Development and Characterization of Novel Floating-Mucoadhesive Tablets Bearing Venlafaxine Hydrochloride.

PubMed

Misra, Raghvendra; Bhardwaj, Peeyush

2016-01-01

The present investigation is concerned about the development of floating bioadhesive drug delivery system of venlafaxine hydrochloride which after oral administration exhibits a unique combination of floating and bioadhesion to prolong gastric residence time and increase drug bioavailability within the stomach. The floating bioadhesive tablets were prepared by the wet granulation method using different ratios of hydroxypropyl methyl cellulose (HPMC K4MCR) and Carbopol 934PNF as polymers. Sodium bicarbonate (NaHCO3) and citric acid were used as gas (CO2) generating agents. Tablets were characterized for floating properties, in vitro drug release, detachment force, and swelling index. The concentration of hydroxypropyl methyl cellulose and Carbopol 934PNF significantly affects the in vitro drug release, floating properties, detachment force, and swelling properties of the tablets. The optimized formulation showed the floating lag time 72 ± 2.49 seconds and duration of floating 24.50 ± 0.74 hr. The in vitro release studies and floating behavior were studied in simulated gastric fluid (SGF) at pH 1.2. Different drug release kinetics models were also applied. The in vitro drug release from tablets was sufficiently sustained (more than 18 hr) and the Fickian transports of the drug from the tablets were confirmed. The radiological evidence suggests that the tablets remained buoyant and altered position in the stomach of albino rabbit and mean gastric residence time was prolonged (more than > 6 hr).

Impact of anti-tacking agents on properties of gas-entrapped membrane and effervescent floating tablets.

PubMed

Kriangkrai, Worawut; Puttipipatkhachorn, Satit; Sriamornsak, Pornsak; Pongjanyakul, Thaned; Sungthongjeen, Srisagul

2014-12-01

Tackiness caused by the gas-entrapped membrane (Eudragit(®)RL 30D) was usually observed during storage of the effervescent floating tablets, leading to failure in floatation and sustained release. In this work, common anti-tacking agents (glyceryl monostearate (GMS) and talc) were used to solve this tackiness problem. The impact of anti-tacking agent on the properties of free films and corresponding floating tablets was investigated. GMS was more effective than talc in reducing tackiness of the film. Addition and increasing amount of anti-tacking agents lowered the film mechanical strength, but the coating films were still strong and flexible enough to resist the generated gas pressure inside the floating tablet. Wettability and water vapor permeability of the film decreased with increasing level of anti-tacking agents as a result of their hydrophobicity. No interaction between anti-tacking agents and polymer was observed as confirmed by Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry studies. Increasing amount of anti-tacking agents decreased time to float and tended to retard drug release of the floating tablets. Floating properties and drug release were also influenced by type of anti-tacking agents. The obtained floating tablets still possessed good floating properties and controlled drug release even though anti-tacking agent had some effects. The results demonstrated that the tackiness problem of the floating tablets could be solved by incorporating anti-tacking agent into the gas-entrapped membrane.

Comparative evaluation of single and bilayered lamotrigine floating tablets

PubMed Central

Lakshmi, PK; Sridhar, M; Shruthi, B

2013-01-01

Aim: The purpose of this study was to prepare lamotrigine (LM) bilayered and single layered floating tablets and to compare their release profiles. Materials and Methods: LM floating tablets were prepared by direct compression method. Drug, hydroxy propyl methyl cellulose K4M, lactose monohydrate and polyvinylpyrrolidone K30 constitute controlled release layer components and floating layer components includes polymers and sodium bicarbonate. The prepared tablets were evaluated for physicochemical parameters such as hardness, friability, weight variation, thickness, floating lag time (FLT), floating time, in vitro buoyancy study, in vitro release studies. The drug-polymer interaction was studied by fourier transform infrared and differential scanning calorimetry. Results and Discussion: The FLT of all the formulations were within the prescribed limits (<3 min). When ethyl cellulose was used as floating layer component, tablets showed good buoyancy effect but eroded within 6-8 h. Hence it was replaced with hydroxypropyl cellulose -M hydrophilic polymer, which showed good FLT and floating duration for 16 h. Formulation LFC4 was found to be optimized with dissolution profile of zero order kinetics showing fickian diffusion. A comparative study of bilayered and single layered tablets of LM showed a highest similarity factor of 83.03, difference factor of 2.74 and t-test (P < 0.05) indicates that there is no significant difference between them. Conclusion: Though bilayered tablet possess many advantages, single layered tablet would be economical, cost-effective and reproducible for large scale production in the industry. However, the results of present study demonstrated that the in vitro development of bilayered gastro retentive floating tablets with controlled drug release profile for LM is feasible. PMID:24167788

A novel automated alternating current biosusceptometry method to characterization of controlled-release magnetic floating tablets of metronidazole.

PubMed

Ferrari, Priscileila Colerato; dos Santos Grossklauss, Dany Bruno Borella; Alvarez, Matheus; Paixão, Fabiano Carlos; Andreis, Uilian; Crispim, Alexandre Giordano; de Castro, Ana Dóris; Evangelista, Raul Cesar; de Arruda Miranda, José Ricardo

2014-08-01

Alternating Current Biosusceptometry is a magnetically method used to characterize drug delivery systems. This work presents a system composed by an automated ACB sensor to acquire magnetic images of floating tablets. The purpose of this study was to use an automated Alternating Current Biosusceptometry (ACB) to characterize magnetic floating tablets for controlled drug delivery. Floating tablets were prepared with hydroxypropyl methylcellulose (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and ferrite as magnetic marker. ACB was used to characterize the floating lag time and the tablet hydration rate, by quantification of the magnetic images to magnetic area. Besides the buoyancy, the floating tablets were evaluated for weight uniformity, hardness, swelling and in vitro drug release. The optimized tablets were prepared with equal amounts of HPMC and ferrite, and began to float within 4 min, maintaining the flotation during more than 24 h. The data of all physical parameters lied within the pharmacopeial limits. Drug release at 24 h was about 40%. The ACB results showed that this study provided a new approach for in vitro investigation of controlled-release dosage forms. Moreover, using automated ACB will also be possible to test these parameters in humans allowing to establish an in vitro.in vivo correlation (IVIVC).

Design and In-vitro Evaluation of Sustained Release Floating Tablets of Metformin HCl Based on Effervescence and Swelling

PubMed Central

Senjoti, Faria Gias; Mahmood, Syed; Jaffri, Juliana Md; Mandal, Uttam Kumar

2016-01-01

An oral sustained-release floating tablet formulation of metformin HCl was designed and developed. Effervescence and swelling properties were attributed on the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination, respectively. Tablet composition was optimized by response surface methodology (RSM). Seventeen (17) trial formulations were analyzed according to Box-Behnken design of experiment where polymer content of HPMC and PEO at 1: 4 ratio (A), amount of sodium bi-carbonate (B), and amount of SSG (C) were adopted as independent variables. Floating lag time in sec (Y1), cumulative percent drug released at 1 h (Y2) and 12 h (Y3) were chosen as response variables. Tablets from the optimized formulation were also stored at accelerated stability condition (40°C and 75% RH) for 3 months to assess their stability profile. RSM could efficiently optimize the tablet composition with excellent prediction ability. In-vitro drug release until 12 h, floating lag time, and duration of floating were dependent on the amount of three selected independent variables. Optimized tablets remained floating for more than 24 h with a floating lag time of less than 4 min. Based on best fitting method, optimized formulation was found to follow Korsmeyer-Peppas release kinetic. Accelerated stability study revealed that optimized formulation was stable for three months without any major changes in assay, dissolution profile, floating lag time and other physical properties. PMID:27610147

[Study on preparation of phenols gastric floating tablet].

PubMed

Zhai, Xiao-Ling; Ni, Jian; Gu, Yu-Long

2008-01-01

To study the preparation of phenols gastric floating tablet. The tablets which were prepared using Eudragit IV, HPMC(K4M), MCC101 and Octadecanol as excipients were evaluated by vitro floatation and releasing performance. The pressure of preparationg was also study to select the optimal preparation. The tablets were successfully prepared in which the drug, Eudragit IV, Octadecanol were 31% respectively,and MCC101 was 7%. And 3-4 kg was found to be the eligible pressure. The study was found to be effective in the process of phenols gastric floating tablet.

Gastroprotective effects of the isopropanol extract of Artemisia princeps and its gastroretentive floating tablets on gastric mucosal injury.

PubMed

Kim, Joo-Il; Park, Sang-Wook; Lim, Jhong-Jae; Sohn, Se-Il; Shin, Ji-Su; Park, Sang Cheol; Jang, Young Pyo; Chung, Eun Kyoung; Lee, Hong-Woo; Lee, Kyung-Tae

2017-12-20

In this study, we investigated the gastroprotective effect of an isopropanol extract from the aerial parts of Artemisia princeps (IPAP) and developed a gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on medium surface with more sustained eupatilin release compared to the non-floating control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared to the non-floating control tablet. Based on these data, our data suggest that IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer.

Preformulation studies and optimization of sodium alginate based floating drug delivery system for eradication of Helicobacter pylori.

PubMed

Diós, Péter; Nagy, Sándor; Pál, Szilárd; Pernecker, Tivadar; Kocsis, Béla; Budán, Ferenc; Horváth, Ildikó; Szigeti, Krisztián; Bölcskei, Kata; Máthé, Domokos; Dévay, Attila

2015-10-01

The aim of this study was to design a local, floating, mucoadhesive drug delivery system containing metronidazole for Helicobacter pylori eradication. Face-centered central composite design (with three factors, in three levels) was used for evaluation and optimization of in vitro floating and dissolution studies. Sodium alginate (X1), low substituted hydroxypropyl cellulose (L-HPC B1, X2) and sodium bicarbonate (X3) concentrations were the independent variables in the development of effervescent floating tablets. All tablets showed acceptable physicochemical properties. Statistical analysis revealed that tablets with 5.00% sodium alginate, 38.63% L-HPC B1 and 8.45% sodium bicarbonate content showed promising in vitro floating and dissolution properties for further examinations. Optimized floating tablets expressed remarkable floating force. Their in vitro dissolution studies were compared with two commercially available non-floating metronidazole products and then microbiologically detected dissolution, ex vivo detachment force, rheological mucoadhesion studies and compatibility studies were carried out. Remarkable similarity (f1, f2) between in vitro spectrophotometrically and microbiologically detected dissolutions was found. Studies revealed significant ex vivo mucoadhesion of optimized tablets, which was considerably increased by L-HPC. In vivo X-ray CT studies of optimized tablets showed 8h gastroretention in rats represented by an animation prepared by special CT technique. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate.

PubMed

Ijaz, Hira; Qureshi, Junaid; Danish, Zeeshan; Zaman, Muhammad; Abdel-Daim, Mohamed; Hanif, Muhammad; Waheed, Imran; Mohammad, Imran Shair

2015-11-01

The purpose of this study was to introduce the technology for the development of rate-controlled oral drug delivery system to overcome various physiological problems. Several approaches are being used for the purpose of increasing the gastric retentive time, including floating drug delivery system. Gastric floating lisinopril maleate and metoprolol tartrate bilayer tablets were formulated by direct compression method using the sodium starch glycolate, crosscarmellose sodium for IR layer. Eudragit L100, pectin, acacia as sustained release polymers in different ratios for SR metoprolol tartrate layer and sodium bicarbonate, citric acid as gas generating agents for the floating extended release layer. The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form. Floating tablets were evaluated for floating lag time, drug contents and in-vitro dissolution profile and different kinetic release models were applied. It was clear that the different ratios of polymers affected the drug release and floating time. L2 and M4 showed good drug release profile and floating behavior. The linear regression and model fitting showed that all formulation followed Higuchi model of drug release model except M4 that followed zero order kinetic. From the study it is evident that a promising controlled release by floating bilyer tablets of lisinopril maleate and metoprolol tartrate can be developed successfully.

Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing.

PubMed

Li, Qijun; Guan, Xiaoying; Cui, Mengsuo; Zhu, Zhihong; Chen, Kai; Wen, Haoyang; Jia, Danyang; Hou, Jian; Xu, Wenting; Yang, Xinggang; Pan, Weisan

2018-01-15

Three dimensional (3D) extrusion-based printing is a paste-based rapid prototyping process, which is capable of building complex 3D structures. The aim of this study was to explore the feasibility of 3D extrusion-based printing as a pharmaceutical manufacture technique for the fabrication of gastro-floating tablets. Novel low-density lattice internal structure gastro-floating tablets of dipyridamole were developed to prolong the gastric residence time in order to improve drug release rate and consequently, improve bioavailability and therapeutic efficacy. Excipients commonly employed in the pharmaceutical study could be efficiently applied in the room temperature 3D extrusion-based printing process. The tablets were designed with three kinds of infill percentage and prepared by hydroxypropyl methylcellulose (HPMC K4M) and hydroxypropyl methylcellulose (HPMC E15) as hydrophilic matrices and microcrystalline cellulose (MCC PH101) as extrusion molding agent. In vitro evaluation of the 3D printed gastro-floating tablets was performed by determining mechanical properties, content uniformity, and weight variation. Furthermore, re-floating ability, floating duration time, and drug release behavior were also evaluated. Dissolution profiles revealed the relationship between infill percentage and drug release behavior. The results of this study revealed the potential of 3D extrusion-based printing to fabricate gastro-floating tablets with more than 8h floating process with traditional pharmaceutical excipients and lattice internal structure design. Copyright © 2017. Published by Elsevier B.V.

Formulation and evaluation of novel coated floating tablets of bergenin and cetirizine dihydrochloride for gastric delivery.

PubMed

He, Shuang; Li, Feng; Zhou, Dan; Du, Junrong; Huang, Yuan

2012-10-01

A novel coated gastric floating drug-delivery system (GFDDS) of bergenin (BN) and cetirizine dihydrochloride (CET) was developed. First, the pharmacodynamic studies were performed and the results revealed that the new compounds of bergenin/cetirizine dihydrochloride had comparative efficacy as commercial products (bergenin/chlorphenamine maleate) but with fewer side effects on central nervous system (CNS). Subsequently, bergenin was formulated as an extended-release core tablet while cetirizine dihydrochloride was incorporated into the gastric coating film for immediate release. The formulation of GFDDS was optimized by CET content uniformity test, in vitro buoyancy and drug release. Herein, the effects of sodium bicarbonate (effervescent), hydroxypropyl methylcellulose (HPMC, matrix polymer) and coating weight gain were investigated respectively. The optimized GFDDS exhibited good floating properties (buoyancy lag time < 2 min; floating duration > 10 h) and satisfactory drug-release profiles (immediate release of CET in 10 min and sustained release of BN for 12 h). In vivo gamma scintigraphy proved that the optimized GFDDS could retain in the stomach with a prolonged gastric retention time (GRT) of 5 h, and the coating layer showed no side effect for gastric retention. The novel coated gastric floating drug-delivery system offers a new approach to enhance BN's absorption at its absorption site and the efficacy of both CET and BN.

Formulation and In Vitro, In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

PubMed Central

Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

2015-01-01

Introduction Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Methodology Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Results and Discussion Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours. Conclusion In conclusion, in order to suggest a better drug delivery system with constant favorable release, resulting in optimized absorption and less side effects, formulated CP-HPMC-SA based imatinib mesylate floating sustained-release tablets can be a promising candidate for cancer chemotherapy. PMID:26035710

New insights on poly(vinyl acetate)-based coated floating tablets: characterisation of hydration and CO2 generation by benchtop MRI and its relation to drug release and floating strength.

PubMed

Strübing, Sandra; Abboud, Tâmara; Contri, Renata Vidor; Metz, Hendrik; Mäder, Karsten

2008-06-01

The purpose of this study was to investigate the mechanism of floating and drug release behaviour of poly(vinyl acetate)-based floating tablets with membrane controlled drug delivery. Propranolol HCl containing tablets with Kollidon SR as an excipient for direct compression and different Kollicoat SR 30 D/Kollicoat IR coats varying from 10 to 20mg polymer/cm2 were investigated regarding drug release in 0.1N HCl. Furthermore, the onset of floating, the floating duration and the floating strength of the device were determined. In addition, benchtop MRI studies of selected samples were performed. Coated tablets with 10mg polymer/cm2 SR/IR, 8.5:1.5 coat exhibited the shortest lag times prior to drug release and floating onset, the fastest increase in and highest maximum values of floating strength. The drug release was delayed efficiently within a time interval of 24 h by showing linear drug release characteristics. Poly(vinyl acetate) proved to be an appropriate excipient to ensure safe and reliable drug release. Floating strength measurements offered the possibility to quantify the floating ability of the developed systems and thus to compare different formulations more efficiently. Benchtop MRI studies allowed a deeper insight into drug release and floating mechanisms noninvasively and continuously.

Influence of different types of low substituted hydroxypropyl cellulose on tableting, disintegration, and floating behaviour of floating drug delivery systems

PubMed Central

Diós, Péter; Pernecker, Tivadar; Nagy, Sándor; Pál, Szilárd; Dévay, Attila

2014-01-01

The object of the present study is to evaluate the effect of application of low-substituted hydroxypropyl cellulose (L-HPC) 11 and B1 as excipients promoting floating in gastroretentive tablets. Directly compressed tablets were formed based on experimental design. Face-centred central composite design was applied with two factors and 3 levels, where amount of sodium alginate (X1) and L-HPC (X2) were the numerical factors. Applied types of L-HPCs and their 1:1 mixture were included in a categorical factor (X3). Studied parameters were floating lag time, floating time, floating force, swelling behaviour of tablets and dissolution of paracetamol, which was used as a model active substance. Due to their physical character, L-HPCs had different water uptake and flowability. Lower flowability and lower water uptake was observed after 60 min at L-HPC 11 compared to L-HPC B1. Shorter floating times were detected at L-HPC 11 and L-HPC mixtures with 0.5% content of sodium alginate, whereas alginate was the only significant factor. Evaluating results of drug release and swelling studies on floating tablets revealed correlation, which can serve to help to understand the mechanism of action of L-HPCs in the field development of gastroretentive dosage forms. PMID:26702261

Magnetic resonance imaging for the in vivo evaluation of gastric-retentive tablets.

PubMed

Steingoetter, Andreas; Weishaupt, Dominik; Kunz, Patrick; Mäder, Karsten; Lengsfeld, Hans; Thumshirn, Miriam; Boesiger, Peter; Fried, Michael; Schwizer, Werner

2003-12-01

To develop a magnetic resonance imaging (MRI) technique for assessing in vivo properties of orally ingested gastric-retentive tablets under physiologic conditions. Tablets with different floating characteristics (tablet A-C) were marked with superparamagnetic Fe3O4 particles to analyze intragastric tablet position and residence time in human volunteers. Optimal Fe3O4 concentration was determined in vitro. Intragastric release characteristic of one slow-release tablet (tablet D) was analyzed by embedding gadolinium chelates (Gd-DOTA) as a drug model into the tablet. All volunteers underwent MRI in the sitting position. Tablet performance was analyzed in terms of relative position of tablet to intragastric meal level (with 100% at meal surface), intragastric residence time (min) and Gd-DOTA distribution volume (% of meal volume). Intragastric tablet floating performance and residence time of tablets (tablet A-D) as well as the intragastric Gd-DOTA distribution of tablet D could be monitored using MRI. Tablet floating performance was different between the tablets (A, 93%(95 - 9%); B, 80%(80 - 68%): C, 38%(63 - 32%); p < 0.05). The intragastric distribution volume of Gd-DOTA was 19.9% proximally and 35.5% distally. The use of MRI allows the assessment of galenic properties of orally ingested tablets in humans in seated position.

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

PubMed

Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed Ma; Hassan, Omiya A

2016-01-01

The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F 10 composed of 28.5% Eudragit RSPM, 3% NaHCO 3 , and 7% citric acid provided sustained drug release. In vitro results showed sustained release of F 10 where the drug release percentage was 96.51%±1.75% after 24 hours ( P =0.031). The pharmacokinetic results indicated that the area under the curve (AUC 0-∞ ) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton ® ) and the relative bioavailability of the sustained-release formulation F 10 increased to 187.80% ( P =0.022). The prepared floating tablets of ITO HCl (F 10 ) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

Study of controlled-release floating tablets of dipyridamole using the dry-coated method.

PubMed

Chen, Kai; Wen, Haoyang; Yang, Feifei; Yu, Yibin; Gai, Xiumei; Wang, Haiying; Li, Pingfei; Pan, Weisan; Yang, Xinggang

2018-01-01

Dipyridamole (DIP), having a short biological half-life, has a narrow absorption window and is primarily absorbed in the stomach. So, the purpose of this study was to prepare controlled-release floating (CRF) tablets of dipyridamole by the dry-coated method. The influence of agents with different viscosity, hydroxypropylmethylcellulose (HPMC) and polyvinylpyrollidon K30 (PVP K30) in the core tablet and low-viscosity HPMC and PVP K30 in the coating layer on drug release, were investigated. Then, a study with a three-factor, three-level orthogonal experimental design was used to optimize the formulation of the CRF tablets. After data processing, the optimized formulation was found to be: 80 mg HPMC K4M in the core tablet, 80 mg HPMC E15 in core tablet and 40 mg PVP K30 in the coating layer. Moreover, an in vitro buoyancy study showed that the optimized formulation had an excellent floating ability and could immediately float without a lag time and this lasted more than 12 h. Furthermore, an in vivo gamma scintigraphic study showed that the gastric residence time of the CRF tablet was about 8 h.

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride

PubMed Central

Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed MA; Hassan, Omiya A

2016-01-01

Purpose The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Materials and methods Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. Results In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031). The pharmacokinetic results indicated that the area under the curve (AUC0–∞) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton®) and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022). Conclusion The prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability. PMID:28008229

Development of Multiple-Unit Floating Drug Delivery System of Clarithromycin: Formulation, in vitro Dissolution by Modified Dissolution Apparatus, in vivo Radiographic Studies in Human Volunteers.

PubMed

Reddy, Arun B; Reddy, Narendar D

2017-07-01

Clarithromycin (CM), a broad spectrum macrolide antibiotic used to eradicate H. pylori in peptic ulcer. Clarithromycin (CM) is well absorbed from the gastrointestinal tract, but has a bioavailability of 50% due to rapid biodegradation. The aim of this investigation was to increase the gastric residence time, and to control the drug release of clarithromycin by formulating into multiple unit floating mini-tablets. Floating tablets were prepared by using direct compression method with HPMC K 4 M and Polyox WSR 1105 as release retarded polymers and sodium bicarbonate as gas generating agent. The prepared mini-tablets were evaluated for thickness, weight variation, friability, hardness, drug content, in vitro buoyancy, swelling studies, in vitro dissolution studies by using modified Rossett-Rice test and in vivo radiographic studies in healthy human volunteers in fasting conditions. DSC analysis revealed that no interaction between drug and excipients. All the physical parameters of the tablets were within the acceptable limits. The optimized formulation (F6) had showed controlled drug release of 99.16±3.22% in 12 h, by zero-order release kinetics, along with floating lag time of 9.5±1.28 s and total floating time of 12±0.14 h. X-ray imaging studies revealed that in vivo gastric residence time of clarithromycin floating mini-tablet in the stomach was about 3.5 h. The results demonstrated that the developed floating mini-tablets of clarithromycin caused significant enhancement in gastric retention time along with sustained effect and increased oral bioavailability. © Georg Thieme Verlag KG Stuttgart · New York.

Development of sustained release floating drug delivery system for norfloxacin: in vitro and in vivo evaluation.

PubMed

Guguloth, Mohan; Bomma, Ramesh; Veerabrahma, Kishan

2011-01-01

Norfloxacin is a drug with an absorption window. Its oral bioavailability is 30-40% and is a case for improvement by appropriate formulation design. In our previous study, gastroretentive floating tablets for norfloxacin were developed employing three different polymers such as HPMC K4M, HPMC K100M, and xanthan gum. The purpose of this investigation is to further improve and evaluate the in vitro and in vivo performance of the prepared floating tablets by inclusion of citric acid as an acidifier, which is also useful in a fed state. The prepared tablets were characterized and found to exhibit satisfactory physico-chemical characteristics. The effects of citric acid at different concentrations on drug release and floating properties were studied. All the prepared batches showed good in vitro buoyancy. It was observed that the tablets remained buoyant for 24 h. The best formulation (F4c), consisting of 1.5% citric acid and 18% HPMC K4M, was selected based on in vitro characteristics and used in vivo radiographic studies by incorporating barium sulphate. These studies revealed that the tablets remained in the stomach for 205 ± 8.4 min in fasting human volunteers. In vivo studies were carried out for the best formulation in eight healthy male human volunteers, and the pharmacokinetic parameters of the developed formulation were compared with marketed conventional (Norbid) tablets. Based on the in vivo performance in a two-way, crossover study design in healthy subjects, the developed floating tablets showed superior bioavailability than the Norbid tablets. The increased bioavailability of developed formulation was found to be 16.27%. Norfloxacin is a broad-spectrum antibiotic used to treat bacterial infections such as respiratory and urinary tract infections. Conventional norfloxacin tablets show incomplete drug absorption resulting in lower bioavailabilty. Norfloxacin is better absorbed in the stomach. The dosage forms that remain in the stomach are referred to as gastroretentive drug delivery systems. Gastroretentive floating tablets of norfloxcin were developed by employing three different polymers, which prolonged the drug release from the dosage forms. Tablet floatation was achieved by an effervescent mechanism. Citric acid at different concentrations was used in formulations to provide an acidic microenvironment. The prepared tablets were characterized for hardness, weight variation, thickness, friability, floating lag time, and dissolution. Around 12 tablet formulations were prepared as a continuation of the previous work. The best formulation (F4c) was selected based on in vitro characteristics and used in vivo radiographic studies by incorporating barium sulphate as a radio-opaque agent. The tablets remained in the stomach for about 205 ± 8.4 min. Bioavailability studies were conducted in healthy male human volunteers, and the pharmacokinetic parameters of the best formulation were compared with that of the marketed conventional (Norbid) tablet. The increased bioavailability of the developed formulation was found to be 16.27%.

Analysis of the meal-dependent intragastric performance of a gastric-retentive tablet assessed by magnetic resonance imaging.

PubMed

Steingoetter, A; Kunz, P; Weishaupt, D; Mäder, K; Lengsfeld, H; Thumshirn, M; Boesiger, P; Fried, M; Schwizer, W

2003-10-01

Modern medical imaging modalities can trace labelled oral drug dosage forms in the gastrointestinal tract, and thus represent important tools for the evaluation of their in vivo performance. The application of gastric-retentive drug delivery systems to improve bioavailability and to avoid unwanted plasma peak concentrations of orally administered drugs is of special interest in clinical and pharmaceutical research. To determine the influence of meal composition and timing of tablet administration on the intragastric performance of a gastric-retentive floating tablet using magnetic resonance imaging in the sitting position. A tablet formulation was labelled with iron oxide particles as negative magnetic resonance contrast marker to allow the monitoring of the tablet position in the food-filled human stomach. Labelled tablet was administered, together with three different solid meals, to volunteers seated in a 0.5-T open-configuration magnetic resonance system. Volunteers were followed over a 4-h period. Labelled tablet was detectable in all subjects throughout the entire study. The tablet showed persistent good intragastric floating performance independent of meal composition. Unfavourable timing of tablet administration had a minor effect on the intragastric tablet residence time and floating performance. Magnetic resonance imaging can reliably monitor and analyse the in vivo performance of labelled gastric-retentive tablets in the human stomach.

Pharmacokinetics and analgesic effect of ketorolac floating delivery system.

PubMed

Radwan, Mahasen A; Abou El Ela, Amal El Sayeh F; Hassan, Maha A; El-Maraghy, Dalia A

2015-05-01

The efficacy of ketorolac tromethamine (KT) floating alginate beads as a drug delivery system for better control of KT release was investigated. The formulation with the highest drug loading, entrapment efficiency, swelling, buoyancy, and in vitro release would be selected for further in vivo analgesic effect in the mice and pharmacokinetics study in rats compared to the tablet dosage form. KT floating alginate beads were prepared by extrusion congealing technique. KT in plasma samples was analyzed using a UPLC MS/MS assay. The percentage yield, drug loading and encapsulation efficiency were increased proportionally with the hydroxypropylmethyl cellulose (HPMC) polymer amount in the KT floating beads. A reverse relationship was observed between HPMC amount in the beads and the KT in vitro release rate. F3-floating beads were selected, due to its better in vitro results (continued floating for >8 h) than others. A longer analgesic effect was observed for F3 in fed mice as compared to the tablets. After F3 administration to rats, the Cmax (2.2 ± 0.3 µg/ml) was achieved at ∼2 h and the decline in KT concentration was slower. F3 showed a significant increase in the AUC (1.89 fold) in rats as compared to the tablets. KT was successfully formulated as floating beads with prolonged in vitro release extended to a better in vivo characteristic with higher bioavailability in rats. KT in floating beads shows a superior analgesic effect over tablets, especially in fed mice.

Floating gastroretentive drug delivery systems: Comparison of experimental and simulated dissolution profiles and floatation behavior.

PubMed

Eberle, Veronika A; Schoelkopf, Joachim; Gane, Patrick A C; Alles, Rainer; Huwyler, Jörg; Puchkov, Maxim

2014-07-16

Gastroretentive drug delivery systems (GRDDS) play an important role in the delivery of drug substances to the upper part of the gastrointestinal tract; they offer a possibility to overcome the limited gastric residence time of conventional dosage forms. The aim of the study was to understand drug-release and floatation mechanisms of a floating GRDDS based on functionalized calcium carbonate (FCC). The inherently low apparent density of the excipient (approx. 0.6 g/cm(3)) enabled a mechanism of floatation. The higher specific surface of FCC (approx. 70 m(2)) allowed sufficient hardness of resulting compacts. The floating mechanism of GRDDS was simulated in silico under simulated acidic and neutral conditions, and the results were compared to those obtained in vitro. United States Pharmacopeia (USP) dissolution methods are of limited usefulness for evaluating floating behavior and drug release of floating dosage forms. Therefore, we developed a custom-built stomach model to simultaneously analyze floating characteristics and drug release. In silico dissolution and floatation profiles of the FCC-based tablet were simulated using a three-dimensional cellular automata-based model. In simulated gastric fluid, the FCC-based tablets showed instant floatation. The compacts stayed afloat during the measurement in 0.1 N HCl and eroded completely while releasing the model drug substance. When water was used as dissolution medium, the tablets had no floating lag time and sank down during the measurement, resulting in a change of release kinetics. Floating dosage forms based on FCC appear promising. It was possible to manufacture floating tablets featuring a density of less than unity and sufficient hardness for further processing. In silico dissolution simulation offered a possibility to understand floating behavior and drug-release mechanism. Copyright © 2014 Elsevier B.V. All rights reserved.

Floating tablets for controlled release of ofloxacin via compression coating of hydroxypropyl cellulose combined with effervescent agent.

PubMed

Qi, Xiaole; Chen, Haiyan; Rui, Yao; Yang, Fengjiao; Ma, Ning; Wu, Zhenghong

2015-07-15

To prolong the residence time of dosage forms within gastrointestinal trace until all drug released at desired rate was one of the real challenges for oral controlled-release drug delivery system. Herein, we developed a fine floating tablet via compression coating of hydrophilic polymer (hydroxypropyl cellulose) combined with effervescent agent (sodium bicarbonate) to achieve simultaneous control of release rate and location of ofloxacin. Sodium alginate was also added in the coating layer to regulate the drug release rate. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated. The optimized formulations were found to immediately float within 30s and remain lastingly buoyant over a period of 12 h in simulated gastric fluid (SGF, pH 1.2) without pepsin, indicating a satisfactory floating and zero-order drug release profile. In addition, the oral bioavailability experiment in New Zealand rabbits showed that, the relative bioavailability of the ofloxacin after administrated of floating tablets was 172.19%, compared to marketed common release tablets TaiLiBiTuo(®). These results demonstrated that those controlled-released floating tables would be a promising gastro-retentive delivery system for drugs acting in stomach. Copyright © 2015 Elsevier B.V. All rights reserved.

In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs

PubMed Central

Kim, Jeong Soo; Cha, Kwang Ho; Kang, Seung Yeob; Won, Donghan; Jang, Sun Woo; Son, Miwon; Son, Moon Ho; Choi, Ho Jung; Lee, Young Won; Kang, Myung Joo

2016-01-01

Objective DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR) tablets of DA-9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR) tablets of DA-9601. Method In vitro buoyancy behavior (floating lag time and duration) and release profile of eupatilin were assessed in acidic medium. The in vivo intragastric behaviors of the barium sulfate-loaded IR and GR tablets were evaluated in beagle dogs by radiographic studies. Local gastroprotective effect was compared in an experimentally induced gastric lesion in beagle dogs after oral administration of IR (three times per day) or GR (twice daily) tablets for 15 days. Results Upon contact with gastric juice, a low-density floating tablet (apparent density of 0.93 g/cm3) was buoyant on the medium and was upheld for 14 hours, providing sustained drug release profile, whereas the IR tablet disintegrated within 10 minutes, showing complete drug release within 2 hours. In vivo radiographic studies showed that the GR tablet was retained for >4 hours in the stomach. Both DA-9601 formulations remarkably alleviated gastric mucosal injury compared to placebo group, when observed by gastric endoscopy. Conclusion Twice-daily GR tablets exhibited a prolonged gastric residence time and a remarkable mucosal restoration effect in animal models. Therefore, the GR system of DA-9601 could be a substitute dosage form for the treatment of gastritis, while reducing the dosing frequency and thus improving patient compliance. PMID:27354765

In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs.

PubMed

Kim, Jeong Soo; Cha, Kwang Ho; Kang, Seung Yeob; Won, Donghan; Jang, Sun Woo; Son, Miwon; Son, Moon Ho; Choi, Ho Jung; Lee, Young Won; Kang, Myung Joo

2016-01-01

DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR) tablets of DA-9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR) tablets of DA-9601. In vitro buoyancy behavior (floating lag time and duration) and release profile of eupatilin were assessed in acidic medium. The in vivo intragastric behaviors of the barium sulfate-loaded IR and GR tablets were evaluated in beagle dogs by radiographic studies. Local gastroprotective effect was compared in an experimentally induced gastric lesion in beagle dogs after oral administration of IR (three times per day) or GR (twice daily) tablets for 15 days. Upon contact with gastric juice, a low-density floating tablet (apparent density of 0.93 g/cm(3)) was buoyant on the medium and was upheld for 14 hours, providing sustained drug release profile, whereas the IR tablet disintegrated within 10 minutes, showing complete drug release within 2 hours. In vivo radiographic studies showed that the GR tablet was retained for >4 hours in the stomach. Both DA-9601 formulations remarkably alleviated gastric mucosal injury compared to placebo group, when observed by gastric endoscopy. Twice-daily GR tablets exhibited a prolonged gastric residence time and a remarkable mucosal restoration effect in animal models. Therefore, the GR system of DA-9601 could be a substitute dosage form for the treatment of gastritis, while reducing the dosing frequency and thus improving patient compliance.

Development of press-coated, floating-pulsatile drug delivery of lisinopril.

PubMed

Jagdale, Swati C; Suryawanshi, Vishnu M; Pandya, Sudhir V; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2014-01-01

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations.

Development of Press-Coated, Floating-Pulsatile Drug Delivery of Lisinopril

PubMed Central

Jagdale, Swati C.; Suryawanshi, Vishnu M.; Pandya, Sudhir V.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

2014-01-01

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations. PMID:24959410

Multi-kinetics and site-specific release of gabapentin and flurbiprofen from oral fixed-dose combination: in vitro release and in vivo food effect.

PubMed

Sonvico, Fabio; Conti, Chiara; Colombo, Gaia; Buttini, Francesca; Colombo, Paolo; Bettini, Ruggero; Barchielli, Marco; Leoni, Barbara; Loprete, Luca; Rossi, Alessandra

2017-09-28

In this work, a fixed-dose combination of gabapentin and flurbiprofen formulated as multilayer tablets has been designed, developed and studied in vitro and in vivo. The aim was to construct a single dosage form of the two drugs, able to perform a therapeutic program involving three release kinetics and two delivery sites, i.e., immediate release of gabapentin, intra-gastric prolonged release of gabapentin and intestinal (delayed) release of flurbiprofen. An oblong three-layer tablet was manufactured having as top layer a floating hydrophilic polymeric matrix for gastric release of gabapentin, as middle layer a disintegrating formulation for immediate release of a gabapentin loading dose and as bottom layer, an uncoated hydrophilic polymeric matrix, swellable but insoluble in gastric fluids, for delayed and prolonged release of flurbiprofen in intestinal environment. The formulations were studied in vitro and in vivo in healthy volunteers. The in vitro release rate assessment confirmed the programmed delivery design. A significant higher bioavailability of gabapentin administered 30min after meal, compared to fasting conditions or to dose administration 10min before meal, argued in favor of the gastro-retention of gabapentin prolonged release layer. The two drugs were delivered at different anatomical sites, since the food presence prolonged the gastric absorption of gabapentin from the floating layer and delayed the flurbiprofen absorption. The attainment of a successful delayed release of flurbiprofen was realized by a matrix based on a polymers' combination. The combined use of three hydrophilic polymers with different pH sensitivity provided the dosage form layer containing flurbiprofen with gastro-resistant characteristics without the use of film coating. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and evaluation of hydrophobic coated buoyant core as floating drug delivery system for sustained release of cisapride

PubMed Central

Jacob, Shery; Nair, Anroop B; Patil, Pandurang N

2010-01-01

An inert hydrophobic buoyant coated–core was developed as floating drug delivery system (FDDS) for sustained release of cisapride using direct compression technology. Core contained low density, porous ethyl cellulose, which was coated with an impermeable, insoluble hydrophobic coating polymer such as rosin. It was further seal coated with low viscosity hydroxypropyl methyl cellulose (HPMC E15) to minimize moisture permeation and better adhesion with an outer drug layer. It was found that stable buoyant core was sufficient to float the tablet more than 8 h without the aid of sodium bicarbonate and citric acid. Sustained release of cisapride was achieved with HPMC K4M in the outer drug layer. The floating lag time required for these novel FDDS was found to be zero, however it is likely that the porosity or density of the core is critical for floatability of these tablets. The in vitro release pattern of these tablets in simulated gastric fluid showed the constant and controlled release for prolonged time. It can be concluded that the hydrophobic coated buoyant core could be used as FDDS for gastroretentive delivery system of cisapride or other suitable drugs. PMID:24825997

Optimization and evaluation of clarithromycin floating tablets using experimental mixture design.

PubMed

Uğurlu, Timucin; Karaçiçek, Uğur; Rayaman, Erkan

2014-01-01

The purpose of the study was to prepare and evaluate clarithromycin (CLA) floating tablets using experimental mixture design for treatment of Helicobacter pylori provided by prolonged gastric residence time and controlled plasma level. Ten different formulations were generated based on different molecular weight of hypromellose (HPMC K100, K4M, K15M) by using simplex lattice design (a sub-class of mixture design) with Minitab 16 software. Sodium bicarbonate and anhydrous citric acid were used as gas generating agents. Tablets were prepared by wet granulation technique. All of the process variables were fixed. Results of cumulative drug release at 8th h (CDR 8th) were statistically analyzed to get optimized formulation (OF). Optimized formulation, which gave floating lag time lower than 15 s and total floating time more than 10 h, was analyzed and compared with target for CDR 8th (80%). A good agreement was shown between predicted and actual values of CDR 8th with a variation lower than 1%. The activity of clarithromycin contained optimizedformula against H. pylori were quantified using well diffusion agar assay. Diameters of inhibition zones vs. log10 clarithromycin concentrations were plotted in order to obtain a standard curve and clarithromycin activity.

A modified emulsion gelation technique to improve buoyancy of hydrogel tablets for floating drug delivery systems.

PubMed

Yom-Tov, Ortal; Seliktar, Dror; Bianco-Peled, Havazelet

2015-10-01

The use of buoyant or floating hydrogel tablets is of particular interest in the sustained release of drugs to the stomach. They have an ability to slow the release rates of drugs by prolonging their absorption window in the upper part of the gastrointestinal (GI) tract. In this study we synthesized bioactive hydrogels that have sustainable release rates for drugs in the stomach based on a hydrogel preparation technique that employs emulsifying surfactants. The emulsion gelation technique, which encapsulates oil droplets within the hydrogels during crosslinking, was used to decrease their specific gravity in aqueous environments, resulting in floating drug release depots. Properties such as swelling, buoyancy, density and drug release were manipulated by changing the polymer concentrations, surfactant percentages and the oil:polymer ratios. The relationship between these properties and the hydrogel's floating lag time was documented. The potential for this material to be used as a floating drug delivery system was demonstrated. Copyright © 2015 Elsevier B.V. All rights reserved.

Design, development and evaluation of clopidogrel bisulfate floating tablets.

PubMed

Rao, K Rama Koteswara; Lakshmi, K Rajya

2014-01-01

The objective of the present work was to formulate and to characterize a floating drug delivery system for clopidogrel bisulphate to improve bioavailability and to minimize the side effects of the drug such as gastric bleeding and drug resistance development. Clopidogrel floating tablets were prepared by direct compression technique by the use of three polymers xanthan gum, hydroxypropyl methylcellulose (HPMC) K15M and HPMC K4M in different concentrations (20%, 25% and 30% w/w). Sodium bicarbonate (15% w/w) and microcrystalline cellulose (30% w/w) were used as gas generating agent and diluent respectively. Studies were carried out on floating behavior and influence of type of polymer on drug release rate. All the formulations were subjected to various quality control and in-vitro dissolution studies in 0.1 N hydrochloric acid (1.2 pH) and corresponding dissolution data were fitted to popular release kinetic equations in order to evaluate release mechanisms and kinetics. All the clopidogrel floating formulations followed first order kinetics, Higuchi drug release kinetics with diffusion as the dominant mechanism of drug release. As per Korsmeyer-Peppas equation, the release exponent "n" ranged 0.452-0.654 indicating that drug release from all the formulations was by non-Fickian diffusion mechanism. The drug release rate of clopidogrel was found to be affected by the type and concentration of the polymer used in the formulation (P < 0.05). As the concentration of the polymer was increased, the drug release was found to be retarded. Based on the results, clopidogrel floating tablets prepared by employing xanthan gum at concentration 25% w/w (formulation F2) was the best formulation with desired in-vitro floating time and drug dissolution.

Dosage form design and in vitro/in vivo evaluation of cevimeline extended-release tablet formulations.

PubMed

Tajiri, Shinichiro; Kanamaru, Taro; Kamada, Makoto; Makoto, Kamada; Konno, Tsutomu; Nakagami, Hiroaki

2010-01-04

The objective of the present work is to develop an extended-release dosage form of cevimeline. Two types of extended-release tablets (simple matrix tablets and press-coated tablets) were prepared and their potential as extended-release dosage forms were assessed. Simple matrix tablets have a large amount of hydroxypropylcellulose as a rate-controlling polymer and the matrix is homogeneous throughout the tablet. The press-coated tablets consisted of a matrix core tablet, which was completely surrounded by an outer shell containing a large amount of hydroxypropylcellulose. The simple matrix tablets could not sustain the release of cevimeline effectively. In contrast, the press-coated tablets showed a slower dissolution rate compared with simple matrix tablets and the release curve was nearly linear. The dissolution of cevimeline from the press-coated tablets was not markedly affected by the pH of the dissolution medium or by a paddle rotating speed over the range of 50-200 rpm. Furthermore, cevimeline was constantly released from the press-coated tablets in the gastrointestinal tract and the steady-state plasma drug levels were maintained in beagle dogs. These results suggested that the designed PC tablets have a potential for extended-release dosage forms.

Design and Optimization of Floating Drug Delivery System of Acyclovir

PubMed Central

Kharia, A. A.; Hiremath, S. N.; Singhai, A. K.; Omray, L. K.; Jain, S. K.

2010-01-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t50%) and 70% (t70%) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t50% and t70% indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. PMID:21694992

Design and optimization of floating drug delivery system of acyclovir.

PubMed

Kharia, A A; Hiremath, S N; Singhai, A K; Omray, L K; Jain, S K

2010-09-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.

Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees.

PubMed

Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele; Đurić, Zorica

2012-05-30

The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

Relationship between diffusivity of water molecules inside hydrating tablets and their drug release behavior elucidated by magnetic resonance imaging.

PubMed

Kikuchi, Shingo; Onuki, Yoshinori; Kuribayashi, Hideto; Takayama, Kozo

2012-01-01

We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.

[Modern polymers in matrix tablets technology].

PubMed

Zimmer, Łukasz; Kasperek, Regina; Poleszak, Ewa

2014-01-01

Matrix tablets are the most popular method of oral drug administration, and polymeric materials have been used broadly in matrix formulations to modify and modulate drug release rate. The main goal of the system is to extend drug release profiles to maintain a constant in vivo plasma drug concentration and a consistent pharmacological effect. Polymeric matrix tablets offer a great potential as oral controlled drug delivery systems. Cellulose derivatives, like hydroxypropyl methylcellulose (HPMC) are often used as matrix formers. However, also other types of polymers can be used for this purpose including: Kollidon SR, acrylic acid polymers such as Eudragits and Carbopols. Nevertheless, polymers of natural origin like: carragens, chitosan and alginates widely used in the food and cosmetics industry are now coming to the fore of pharmaceutical research and are used in matrix tablets technology. Modern polymers allow to obtain matrix tablets by 3D printing, which enables to develop new formulation types. In this paper, the polymers used in matrix tablets technology and examples of their applications were described.

Single and Dual Drug Release Patterns from Shellac Wax-Lutrol Matrix Tablets Fabricated with Fusion and Molding Techniques

PubMed Central

Phaechamud, T.; Choncheewa, C.

2015-01-01

The objective of this investigation was to prepare the shellac wax matrix tablets by fusion and molding technique incorporated with Lutrol in different ratios to modify the hydrophobicity of matrix tablet. The matrix tablets with single drug were loaded either with propranolol hydrochloride or hydrochlorothiazide as hydrophilic and hydrophobic model drugs, and a dual drug formula was also prepared. The single and dual drug release patterns were studied in a dissolution apparatus using distilled water as medium. Propranolol hydrochloride released from matrix was easier than hydrochlorothiazide. Drug release from shellac wax matrix could be enhanced by incorporation of Lutrol. However retardation of drug release from some matrix tablets was evident for the systems that could form dispersion in the dissolution medium. The gel network from high content of Lutrol was hexagonal which was a dense and more compact structure than the other structures found when low amounts of Lutrol were present in the formula. Therefore, the formulae with high content of Lutrol could prolong drug release more efficiently than those containing low content of Lutrol. Hence shellac wax matrix could modulate the drug release with the addition of Lutrol. Sustainable dual drug release was also obtained from these developed matrix tablets. Thus shellac wax-Lutrol component could be used as a potential matrix tablet prepared with fusion and molding technique with excellent controlled drug release. PMID:25767320

Modulation of drug release kinetics of shellac-based matrix tablets by in-situ polymerization through annealing process.

PubMed

Limmatvapirat, Sontaya; Limmatvapirat, Chutima; Puttipipatkhachorn, Satit; Nunthanid, Jurairat; Luangtana-anan, Manee; Sriamornsak, Pornsak

2008-08-01

A new oral-controlled release matrix tablet based on shellac polymer was designed and developed, using metronidazole (MZ) as a model drug. The shellac-based matrix tablets were prepared by wet granulation using different amounts of shellac and lactose. The effect of annealing temperature and pH of medium on drug release from matrix tablets was investigated. The increased amount of shellac and increased annealing temperature significantly affected the physical properties (i.e., tablet hardness and tablet disintegration) and MZ release from the matrix tablets. The in-situ polymerization played a major role on the changes in shellac properties during annealing process. Though the shellac did not dissolve in acid medium, the MZ release in 0.1N HCl was faster than in pH 7.3 buffer, resulting from a higher solubility of MZ in acid medium. The modulation of MZ release kinetics from shellac-based matrix tablets could be accomplished by varying the amount of shellac or annealing temperature. The release kinetics was shifted from relaxation-controlled release to diffusion-controlled release when the amount of shellac or the annealing temperature was increased.

Ketorolac tromethamine floating beads for oral application: Characterization and in vitro/in vivo evaluation

PubMed Central

Abou el Ela, Amal El Sayeh F.; Hassan, Maha A.; El- Maraghy, Dalia A.

2013-01-01

The floating beads have been employed to make a sustained release of the drug in the stomach and to decrease the dose of the drug and hence overcome its side effects. The common benefits of the floating beads were it is easy preparation, without the need of a high temperature, and high percentage of the drug entrapment. In the present work, the Ketorolac tromethamine (KT) floating beads were prepared by extrusion congealing method utilizing calcium carbonate as a gas forming agent. The physical characters of the produced beads were investigated such as KT yield, KT loading, and entrapment efficiency of the drug. In addition, floating behavior, swelling, particle size, morphology and KT stability were also evaluated. In vitro drug release study was carried out, and the kinetics of the release was evaluated using the linear regression method. Furthermore, the in vivo analgesic effect of KT after oral administration of the selected formula of floating beads (F10) was carried out using hot plate and tail flick methods. Oral commercial KT tablets and KT solution were used for the comparison. The prepared beads remained floated for more than 8 h. The optimized formulation (F10) exhibited prolonged drug release (more than 8 h) and the drug release follows the Higuchi kinetic model, with a Fickian diffusion mechanism according to Korsmeyer-Peppas (n = 0.466). Moreover, F10 showed a sustained analgesic effect as compared to the commercial tablet. PMID:25161380

Design and evaluation of a dry coated drug delivery system with floating-pulsatile release.

PubMed

Zou, Hao; Jiang, Xuetao; Kong, Lingshan; Gao, Shen

2008-01-01

The objective of this work was to develop and evaluate a floating-pulsatile drug delivery system intended for chronopharmacotherapy. Floating-pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, we generated the system which consisted of three different parts, a core tablet, containing the active ingredient, an erodible outer shell and a top cover buoyant layer. The dry coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer which is responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with Methocel K4M, Carbopol 934P and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their buoyancy, dissolution and pharmacokinetic, as well gamma-scintigraphically. The results showed that a certain lag time before the drug released generally due to the erosion of the dry coated layer. Floating time was controlled by the quantity and composition of the buoyant layer. Both pharmacokinetic and gamma-scintigraphic data point out the capability of the system of prolonged residence of the tablets in the stomach and releasing drugs after a programmed lag time. (c) 2007 Wiley-Liss, Inc.

Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design.

PubMed

Rapolu, Kishore; Sanka, Krishna; Vemula, Praveen Kumar; Aatipamula, Vinaydas; Mohd, Abdul Bari; Diwan, Prakash V

2013-12-01

One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets. The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole. Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X1), sodium carboxy methylcellulose (X2) and NaHCO3 (X3). The dependent variables were floating lag time (YFLT), cumulative percentage of metronidazole released at 6th h (Y6) and cumulative percentage of metronidazole released at 12th h (Y12). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed. YFLT range was found to be from 1.02 to 12.07 min. The ranges of other responses, Y6 and Y12 were 25.72 ± 2.85 to 77.14 ± 3.42 % and 65.47 ± 1.25 to 99.65 ± 2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage. It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO3 can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.

Study of drug release and tablet characteristics of silicone adhesive matrix tablets.

PubMed

Tolia, Gaurav; Li, S Kevin

2012-11-01

Matrix tablets of a model drug acetaminophen (APAP) were prepared using a highly compressible low glass transition temperature (T(g)) polymer silicone pressure sensitive adhesive (PSA) at various binary mixtures of silicone PSA/APAP ratios. Matrix tablets of a rigid high T(g) matrix forming polymer ethyl cellulose (EC) were the reference for comparison. Drug release study was carried out using USP Apparatus 1 (basket), and the relationship between the release kinetic parameters of APAP and polymer/APAP ratio was determined to estimate the excipient percolation threshold. The critical points attributed to both silicone PSA and EC tablet percolation thresholds were found to be between 2.5% and 5% w/w. For silicone PSA tablets, satisfactory mechanical properties were obtained above the polymer percolation threshold; no cracking or chipping of the tablet was observed above this threshold. Rigid EC APAP tablets showed low tensile strength and high friability. These results suggest that silicone PSA could eliminate issues related to drug compressibility in the formulation of directly compressed oral controlled release tablets of poorly compressible drug powder such as APAP. No routinely used excipients such as binders, granulating agents, glidants, or lubricants were required for making an acceptable tablet matrix of APAP using silicone PSA. Copyright © 2012 Elsevier B.V. All rights reserved.

Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets.

PubMed

Reynolds, Thomas D; Mitchell, Shawn A; Balwinski, Karen M

2002-04-01

The purpose of this study was to investigate the influence of tablet surface area/volume (SA/Vol) on drug release from controlled-release matrix tablets containing hydroxypropylmethylcellulose (HPMC). Soluble drugs (promethazine HCl, diphenhydramine HCl, and propranolol HCl) were utilized in this study to give predominantly diffusion-controlled release. Drug release from HPMC matrix tablets with similar values of SA/Vol was comparable within the same tablet shape (i.e., flat-faced round tablets) and among different shapes (i.e., oval, round concave, flat-faced beveled-edge, and flat-faced round tablets). Tablets having the same surface area but different SA/Vol values did not result in similar drug release; tablets with larger SA/Vol values hadfaster release profiles. Utility of SA/Vol to affect drug release was demonstrated by changing drug doses, and altering tablet shape to adjust SA/Vol. When SA/Vol was held constant, similar release profiles were obtained with f2 metric values greater than 70. Thus, surface area/volume is one of the key variables in controlling drug release from HPMC matrix tablets. Proper use of this variable has practical application by formulators who may need to duplicate drug release profiles from tablets of different sizes and different shapes.

Floating elementary osmotic pump tablet (FEOPT) for controlled delivery of diethylcarbamazine citrate: a water-soluble drug.

PubMed

Khan, Zulfequar Ahamad; Tripathi, Rahul; Mishra, Brahmeshwar

2011-12-01

The present work investigates the feasibility of the design of a novel floating elementary osmotic pump tablet (FEOPT) to prolong the gastric residence of a highly water-soluble drug. Diethylcarbamazine citrate (DEC) was chosen as a model drug. The FEOPT consisted of an osmotic core (DEC, mannitol, and hydrophilic polymers) coated with a semipermeable layer (cellulose acetate) and a gas-generating gelling layer (sodium bicarbonate, hydrophilic polymers) followed by a polymeric film (Eudragit RL 30D). The effect of formulation variables such as concentration of polymers, types of diluent, and coat thickness of semipermeable membrane was evaluated in terms of physical parameters, floating lag time, duration of floatation, and in vitro drug release. The Fourier transform infrared and X-ray diffraction analysis were carried out to study the physicochemical changes in the drug excipients powder blend. The integrity of the orifice and polymeric film layer was confirmed from scanning electron microscopy image. All the developed FEOPT showed floating lag time of less than 8 min and floating duration of 24 h. A zero-order drug release could be attained for DEC. The formulations were found to be stable up to 3 months of stability testing at 40°C/75% relative humidity.

Formulation, development, and evaluation of floating pulsatile drug delivery system of atenolol.

PubMed

Jagdale, Swati C; Sali, Monali S; Barhate, Ajay L; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2013-01-01

The objective of this work was to develop and evaluate a floating-pulsatile drug delivery of atenolol. The floating-pulsatile concept was applied to increase the gastric residence of the dosage form by having lag phase followed by a burst release. The system was generated which consisted of three different parts: a core tablet, containing the active ingredient; an erodible outer shell; and a top cover buoyant layer. The dry, coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with hydroxypropyl methylcellulose (HPMC) K100 M, citric acid, and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their physical properties in vitro release as well as in vivo behavior. The results showed that K3 (180 mg of HPMC K4 M) and K6 (290 mg of HPMC E15 LV) with a buoyant layer were the best formulation, with lag times of 5.2 ± 0.1 h and 4.1 ± 0.2 h, respectively. Floating time was controlled by the quantity and composition of the buoyant layer. In-vitro results point out the capability of the system with its prolonged residence of the tablets in the stomach and release of drug after a programmed lag time. This was confirmed by in vivo x-ray technique. The objective of the present work was to develop a floating-pulsatile oral drug delivery system of atenolol with addition of hydroxylpropyl methylcellulose (HPMC) K100 M, HPMC K4 M, and HPMC E15 LV in different ratios with citric acid and sodium bicarbonate as gas-forming agents. The system consist of three different parts: a core tablet, containing the active ingredient; a bottom layer that erodes; and a top cover floating layer. Atenolol, a β-blocker, is prescribed widely in diverse cardiovascular diseases, for example, hypertension, angina pectoris, arrhythmias, and myocardial infarction. Developed formulations were evaluated for their physical properties and vitro release as well as in vivo behavior. The results showed that K3 (180 mg HPMC K4 M) and K6 (290 mg of HPMC E15 LV) with a buoyant layer were the best formulations with the lag times of 5.2 ± 0.1 h and 4.1 ± 0.2 h, respectively, and were found to be the best choice for manufacturing tablets.

Silicone adhesive matrix of verapamil hydrochloride to provide pH-independent sustained release.

PubMed

Tolia, Gaurav; Li, S Kevin

2014-02-01

Providing pH-independent oral release of weakly basic drugs with conventional matrix tablets can be challenging because of the pH-dependent solubility characteristics of the drugs and the changing pH environment along the gastrointestinal tract. The aim of the present study was to use a hydrophobic polymer to overcome the issue of pH-dependent release of weakly basic model drug verapamil hydrochloride from matrix tablets without the use of organic buffers in the matrix formulations. Silicone pressure-sensitive adhesive (PSA) polymer was evaluated because of its unique properties of low surface energy, hydrophobicity, low glass transition temperature, high electrical resistance, and barrier to hydrogen ion diffusion. Drug release, hydrogen ion diffusion, tablet contact angle, and internal tablet microenvironment pH with matrix tablets prepared using PSA were compared with those using water-insoluble ethyl cellulose (EC). Silicone PSA films showed higher resistance to hydrogen ion diffusion compared with EC films. Verapamil hydrochloride tablets prepared using silicone PSA showed higher hydrophobicity and lower water uptake than EC tablets. Silicone PSA tablets also showed pH-independent release of verapamil and decreased in dimensions during drug dissolution. By contrast, verapamil hydrochloride tablets prepared using EC did not achieve pH-independent release.

Development of swelling/floating gastroretentive drug delivery system based on a combination of hydroxyethyl cellulose and sodium carboxymethyl cellulose for Losartan and its clinical relevance in healthy volunteers with CYP2C9 polymorphism.

PubMed

Chen, Ray-Neng; Ho, Hsiu-O; Yu, Chiao-Ya; Sheu, Ming-Thau

2010-01-31

The aim of this study was to develop an optimal gastroretentive drug delivery system (GRDDS) for administering Losartan. Additionally, the influence of optimized GRDDS on the bioavailability of Losartan and the formation extent of active metabolite E3174 by CYP2C9 polymorphism was investigated. Swellable and floatable GRDDS tablets combining hydroxyethyl cellulose (HEC), sodium carboxymethyl cellulose (NaCMC), and sodium bicarbonate were prepared at various compression pressures for evaluating swelling characteristics and floating capacity. Then Losartan was incorporated into optimized formulations for in vitro and in vivo characterizations. An appropriate ratio of HEC to NaCMC, addition of sodium bicarbonate, and compression at lower pressures resulted in the tablets floating over SGF for more than 16 h and swelling to 2 cm in diameter within 3h. The release patterns of Losartan from these tablets were pH-dependent. Results of the clinical trials showed that the mean bioavailability from GRD-A (HEC 91.67%, sodium bicarbonate 3.33% and Losartan 8.33%) was approximately 164%, relative to the immediate-release product (Cozaar). MRT and t(max) values were greater and C(max) values were lower for the GRDDS tablets compared with Cozaa. The lower bioavailability of Losartan in the CYP2C9*1/*1 subjects than CYP2C9*1/*3 subjects was found and could be due to the variety of enzymatic activity. Copyright 2009 Elsevier B.V. All rights reserved.

Hydration, erosion, and release behavior of guar-based hydrophilic matrix tablets containing total alkaloids of Sophora alopecuroides.

PubMed

Zhao, Wenchang; Song, Lijun; Deng, Hongzhu; Yao, Hui

2009-05-01

It is a challenge to deliver water-soluble drug based on hydrophilic matrix to colon because of swelling and erosion of polysaccharides in contact with media. In our study, guar-based hydrophilic matrix tablets containing water-soluble total alkaloids of Sophora alopecuroides prepared by wet granulation technique were evaluated. A novel method was established to investigate the changes of swelling and volume for guar-based tablets in undynamic state, which generally showed a rapid swelling and volume change in the first 9 h, then the hydrated speed slowed down. On the other hand, the influence of different pH of the media on water uptake and erosion of various guar-based formulations in dynamic state indicated that the hydrated constants in simulated gastric fluid (SGF) was higher than that in SIF, which followed varied mechanism of water penetration by fitting Davidson and Peppas model. The extent of erosion was between 22.4 and 32.6% in SIF within 360 min. In vitro sophoridine release studies in successive different mimicking media showed that the guar matrix tablets released 13.5-25.6% of sophoridine in the first 6 h; therefore it was necessary to develop the bilayer matrix tablet by direct-compressing coating 100 mg guar granula on core tablet. The initial release of coated tablet was retarded and the bilayer matrix tablet was suitable for colon target.

Hydroxyethyl Pachyman as a novel excipient for sustained-release matrix tablets.

PubMed

Zhou, Xiaoju; Wang, Pengyu; Wang, Jiong; Liu, Zhi; Hong, Xuechuan; Xiao, Yuling; Liu, Peng; Hu, Xianming

2016-12-10

This paper addressed the application of hydroxyethyl pachyman (HEP) as a novel matrix for sustained - release tablets, using diclofenac sodium (DS) as a model drug. The studies showed the HEP tablets prepared by wet granulation had much slower drug release as compared to those prepared by direct compression. Meanwhile, increasing the percentage of HEP in the formulations caused a decrease in drug release rates. Moreover, DS release from the HEP tablets was much higher at high pH (6.8) than that at low pH (1.2). Morphology studies proved the HEP tablet formed a continuous gel layer with porous inner structure in the dissolution media. Analysis of DS release profiles revealed that diffusion and matrix erosion occurred in simulated intestinal fluid(SIF, pH=6.8) for all the tablets. The experimental results predict HEP has a potential as a hydrophilic matrix in tablets to prolong drug release. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of matrix type mucoadhesive tablets containing indomethacin for buccal application.

PubMed

Ikeuchi-Takahashi, Yuri; Sasatsu, Masanaho; Onishi, Hiraku

2013-09-10

Nonsteroidal anti-inflammatory drugs (NSAIDs) are administered for pain relief from oral mucositis. However, the systemic administration of NSAIDs is limited due to systemic side effects. To avoid these side effects and treat local lesions effectively, a matrix type mucoadhesive tablet was developed. A mixture of hard fat, ethylcellulose (EC) and polyethylene glycol (PEG) was used as a matrix base, and indomethacin (IMC) was used as the principal agent. In tablets consisting of hard fat, EC and IMC, the drug release was sustained. In tablets consisting of hard fat, EC, considerable amounts of PEG and IMC, the drug release was relatively increased and IMC existed as the molecular phase or in an amorphous state. The in vitro adhesive force of the tablets consisting of hard fat, EC, considerable amounts of PEG and IMC was significantly increased as compared with the tablets consisting of hard fat and IMC. A significantly high tissue concentration and significantly low plasma concentration were observed after buccal administration of this matrix type mucoadhesive tablet as compared with that after oral administration of IMC. Thus, the matrix type mucoadhesive tablet has good potential as a preparation for the treatment of pain due to oral aphtha. Copyright © 2013 Elsevier B.V. All rights reserved.

Lyophilized mucoadhesive-dendrimer enclosed matrix tablet for extended oral delivery of albendazole.

PubMed

Mansuri, Shakir; Kesharwani, Prashant; Tekade, Rakesh Kumar; Jain, Narendra Kumar

2016-05-01

Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06±0.15, 8.17±0.47, 11.04±0.73, 11.49±0.92, 12.52±1.04 and 16.9±1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI-ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40±0.02μg/mL) compared with orally administered free ABZ (0.19±0.07μg/mL) as well as conventional tablet (0.20±0.05μg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ. Copyright © 2015 Elsevier B.V. All rights reserved.

[Preparation of hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata and study on its in vitro release mechanism].

PubMed

Xu, Fang-Fang; Shi, Wei; Zhang, Hui; Guo, Qing-Ming; Wang Zhen-Zhong; Bi, Yu-An; Wang, Zhi-Min; Xiao, Wei

2015-01-01

In this study, hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata were prepared and the in vitro release behavior were also evaluated. The optimal prescription was achieved by studying the main factor of the type and amount of hydroxypropyl methylcellulose (HPMC) using single factor test and evaluating through cumulative release of three lactones. No burst drug release from the obtained matrix tablets was observed. Drug release sustained to 14 h. The release mechanism of three lactones from A. paniculata was accessed by zero-order, first-order, Higuchi and Peppas equation. The release behavior of total lactones from A. paniculata was better agreed with Higuchi model and the drug release from the tablets was controlled by degradation of the matrix. The preparation of hydrophilic matrix sustained release tablets of total lactones from A. paniculata with good performance of drug release was simple.

Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate

PubMed Central

Chen, Ying-Chen; Ho, Hsiu-O; Chiu, Chiao-Chi; Sheu, Ming-Thau

2014-01-01

In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs) of chitosan (CS) and hydroxyethyl cellulose (HEC) at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed. PMID:24403821

Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression.

PubMed

Ofori-Kwakye, Kwabena; Mfoafo, Kwadwo Amanor; Kipo, Samuel Lugrie; Kuntworbe, Noble; Boakye-Gyasi, Mariam El

2016-01-01

The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8-12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.

In vitro studies on guar gum based formulation for the colon targeted delivery of Sennosides.

PubMed

Momin, Munira; Pundarikakshudu, K

2004-09-24

The objective of the present study is to develop colon targeted drug delivery systems for sennosides using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for content uniformity and in vitro drug release study as per BP method. T(50) % value from the dissolution studies was taken for selecting the best formulation. Guar gum matrix tablets released 4-18% sennosides in the physiological environment of gastrointestinal tract depending on the proportion of the guar gum used in the formulation. The matrix tablets containing 50% of guar gum were found to be suitable for targeting of sennosides for local action in the colon. Compared to tablets having 30% and 40% of guar gum, those with 50% guar gum gave better T(50)% (11.7 h) le and fewer amounts (5-8%) of drug release in upper GIT. These tablets with 50% guar gum released 43% and 96% sennosides with and without rat caecal fluids. This suggests the susceptibility of matrix to the colonic micro flora. The similarity factor (f2 value) for drug release with and without rat caecal fluids was found to be less than 30. When hydroxy propyl methylcellulose phthalate (10%) was used as a coat material on the matrix tablets, the initial loss of 5-8% sennosides in stomach could be completely averted. These tablets showed no change in physical appearance, content and dissolution profile upon storage at 45 degrees C / 75% relative humidity for 3 months. The results of our study indicates that matrix tablets containing 50% guar gum and coated with 10% hydroxy propyl methylcellulose phthalate are most suitable for drugs like sennosides which are mainly active in the lower GIT.

Swelling, erosion and drug release characteristics of salbutamol sulfate from hydroxypropyl methylcellulose-based matrix tablets.

PubMed

Chaibva, Faith A; Khamanga, Sandile M M; Walker, Roderick B

2010-12-01

Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.

Optimization studies on compression coated floating-pulsatile drug delivery of bisoprolol.

PubMed

Jagdale, Swati C; Bari, Nilesh A; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 3² full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form.

Optimization Studies on Compression Coated Floating-Pulsatile Drug Delivery of Bisoprolol

PubMed Central

Jagdale, Swati C.; Bari, Nilesh A.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 32 full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form. PMID:24367788

Video- Demonstration of Seltzer Tablet in Water Onboard the International Space Station (ISS)

NASA Technical Reports Server (NTRS)

2002-01-01

Saturday Morning Science, the science of opportunity series of applied experiments and demonstrations, performed aboard the International Space Station (ISS) by Expedition 6 astronaut Dr. Don Pettit, revealed some remarkable findings. In this video clip, Pettit demonstrates dropping an Alka Seltzer tablet into a film of water which becomes a floating ball of activity filled water. Watch the video to see the surprising results!

Modulation of microenvironmental pH for dual release and reduced in vivo gastrointestinal bleeding of aceclofenac using hydroxypropyl methylcellulose-based bilayered matrix tablet.

PubMed

Kang, Won-Ho; Nguyen, Hien Van; Park, Chulhun; Choi, Youn-Woong; Lee, Beom-Jin

2017-05-01

This study was designed to develop a once-daily controlled-release matrix tablet of aceclofenac 200mg (AFC-CR) with dual release characteristics and to investigate the role of an alkalizer in enhancing drug solubility and reducing the occurrence of gastroduodenal mucosal lesions. Two formulation approaches were employed, namely a monolithic matrix tablet and a bilayered tablet. In vitro dissolution studies of AFC-CR tablets were carried out in simulated intestinal fluid (pH6.8 buffer). The in vivo pharmacokinetic studies and drug safety of the immediate-release reference tablet Airtal® 100mg (Daewoong Co., Korea) and the optimized AFC-CR tablet were compared in beagle dogs under fasted condition. The optimally selected AFC-CR formulation displayed the desired dual release characteristics in simulated intestinal fluid with satisfactory micromeritic properties. The swelling action of the optimal matrix tablet, which was visualized by near-infrared (NIR) chemical imaging, occurred rapidly following hydration. Incorporation of sodium carbonate (Na 2 CO 3 ) was found to enhance the release rate of the AFC-CR bilayered tablets at early stages and increase the microenvironmental pH (pH M ). A pharmacokinetic study in beagle dogs indicated a higher drug plasma concentration and a sustained-release pattern for the AFC-CR tablet compared to the Airtal® tablet. AFC-CR was also superior to Airtal® in terms of in vivo drug safety, since no beagle dog receiving AFC-CR experienced gastrointestinal bleeding. The significant enhancement of drug safety was attributed to the size reduction and the increase of pH M of drug particles by means of incorporation of the alkalizer. These findings provide a scientific rationale for developing a novel controlled-release matrix tablet with enhanced patient compliance and better pain control. Copyright © 2017 Elsevier B.V. All rights reserved.

Does the performance of wet granulation and tablet hardness affect the drug dissolution profile of carvedilol in matrix tablets?

PubMed

Košir, Darjan; Ojsteršek, Tadej; Vrečer, Franc

2018-06-14

Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets. One of the most important CQAs is the drug release profile. We studied the influence of granulation process parameters (type of nozzle and water quantity used as granulation liquid) and tablet hardness on the drug release profile. Matrix tablets contained HPMC K4M hydrophilic matrix former and carvedilol as a model drug. The influence of selected HPMC characteristics on the drug release profile was also evaluated using two additional HPMC batches. For statistical evaluation, partial least square (PLS) models were generated for each time point of the drug release profile using the same number of latent factors. In this way, it was possible to evaluate how the importance of factors influencing drug dissolution changes in dependence on time throughout the drug release profile. The results of statistical evaluation show that the granulation process parameters (granulation liquid quantity and type of nozzle) and tablet hardness significantly influence the release profile. On the other hand, the influence of HPMC characteristics is negligible in comparison to the other factors studied. Using a higher granulation liquid quantity and the standard nozzle type results in larger granules with a higher density and lower porosity, which leads to a slower drug release profile. Lower tablet hardness also slows down the release profile.

Sustaining pattern of phenformin hydrochloride using various polymers and waxes.

PubMed

Pandey, V P; Kannappan, N; Manavalan, R; Subburaj, T

2002-01-01

The present study was carried out to formulate matrix tablets of phenformin hydrochloride. Granules of phenformin HCl were prepared by using ethyl cellulose, eudragit RS 100, gum acacia, carnauba wax, stearyl alcohol, glyceryl monostearate and triethanol amine. Thus the granules were compressed and fourteen tablets formulations were prepared. All the physical parameters of granules and matrix tablets were studied including compatibility study. One commercial timed disintegration capsule was also included for study and comparison. The results of in vitro studies showed that sustained release matrix tablet might be prepared using carnauba wax, stearyl alcohol, triethanol amine and magnesium stearate.

Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics

PubMed Central

Bose, Anirbandeep; Wong, Tin Wui; Singh, Navjot

2012-01-01

The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet. PMID:23960836

Formulation and dissolution kinetics study of hydrophilic matrix tablets with tramadol hydrochloride and different co-processed dry binders.

PubMed

Komersová, Alena; Lochař, Václav; Myslíková, Kateřina; Mužíková, Jitka; Bartoš, Martin

2016-12-01

The aim of this study is to present the possibility of using of co-processed dry binders for formulation of matrix tablets with drug controlled release. Hydrophilic matrix tablets with tramadol hydrochloride, hypromellose and different co-processed dry binders were prepared by direct compression method. Hypromelloses Methocel™ K4M Premium CR or Methocel™ K100M Premium CR were used as controlled release agents and Prosolv® SMCC 90 or Disintequik™ MCC 25 were used as co-processed dry binders. Homogeneity of the tablets was evaluated using scanning electron microscopy and energy dispersive X-ray microanalysis. The release of tramadol hydrochloride from prepared formulations was studied by dissolution test method. The dissolution profiles obtained were evaluated by non-linear regression analysis, release rate constants and other kinetic parameters were determined. It was found that matrix tablets based on Prosolv® SMCC 90 and Methocel™ Premium CR cannot control the tramadol release effectively for >12h and tablets containing Disintequik™ MCC 25 and Methocel™ Premium CR >8h. Copyright © 2016 Elsevier B.V. All rights reserved.

Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics.

PubMed

Bose, Anirbandeep; Wong, Tin Wui; Singh, Navjot

2013-04-01

The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

Laser Printing of PCL/Progesterone Tablets for Drug Delivery Applications in Hormone Cancer Therapy

NASA Astrophysics Data System (ADS)

Salmoria, G. V.; Klauss, P.; Kanis, L. A.

2017-09-01

In this study, polycaprolactone (PCL) and progesterone (PG) tablets were produced by selective laser sintering (SLS) using different particle sizes and laser energy. The sintered PCL/PG tablets presented uniform morphology, coalescence of particles and interconnected pores distributed in the polymeric matrix. The EDS analysis confirmed the presence of progesterone recrystallized on the surface of the porous PCL matrix. The crystallinity values for the PCL/PG tablets were lower than that for the pure PCL, suggesting the interaction of components at the molecular level. The PCL/PG tablets fabricated with small particles and high laser energy presented a higher value for the flexural modulus compared with the other specimens. The glass transition temperature (Tg) was -37 °C for the PCL/PG tablet with a high degree of sintering. The fatigue test showed that the PCL/PG blend tablets have high fatigue strength. The drug release mechanism of all tablets studied followed a zero-order kinetics, and drug release rates were dependent on sintering degree and, consequently, on matrix erosion, showing a potential application to controlled drug delivery in hormone cancer therapy.

Preparation and in vitro evaluation of guar gum based triple-layer matrix tablet of diclofenac sodium

PubMed Central

Chavda, H.V.; Patel, M.S.; Patel, C.N.

2012-01-01

The objective of the present study was to design an oral controlled drug delivery system for sparingly soluble diclofenac sodium (DCL) using guar gum as triple-layer matrix tablets. Matrix tablet granules containing 30% (D1), 40% (D2) or 50% (D3) of guar gum were prepared by the conventional wet granulation technique. Matrix tablets of diclofenac sodium were prepared by compressing three layers one by one. Centre layer of sandwich like structure was incorporated with matrix granules containing DCL which was covered on either side by guar gum granule layers containing either 70, 80 or 87% of guar gum as release retardant layers. The tablets were evaluated for hardness, thickness, drug content, and drug release studies. To ascertain the kinetics of drug release, the dissolution profiles were fitted to various mathematical models. The in vitro drug release from proposed system was best explained by the Hopfenberg model indicating that the release of drug from tablets displayed heterogeneous erosion. D3G3, containing 87% of guar gum in guar gum layers and 50% of guar gum in DCL matrix granule layer was found to provide the release rate for prolonged period of time. The results clearly indicate that guar gum could be a potential hydrophilic carrier in the development of oral controlled drug delivery systems. PMID:23181081

Formulation Optimization of Gastro-Retention Tablets of Paeonol and Efficacy in Treatment of Experimental Gastric Ulcer.

PubMed

Zhang, Xitong; Zhang, Yue; Han, Han; Yang, Jun; Xu, Benliang; Wang, Bing; Zhang, Tong

2017-08-01

This study aims to develop a gastroretentive sustained-release drug delivery system of paeonol using floating properties and to investigate its therapeutic effects in rat models. The gastric retention tablets of paeonol (GRT-Ps) were prepared by a direct compression method, and the Box-Behnken design was used to optimize its formulation. The optimized formulation containing 15% NaHCO 3 and a 2 : 1 ratio of paeonol and HPMC-K4M floated within 1 min and remained afloat for more than 8 h in the simulated gastric fluid (200 mL, pH=1.2) and simultaneously showed the desired sustained drug release. Moreover, small tablets (3 mm) were prepared according to the same formulation and the process technology of big tablets (8 mm). A similar drug release behavior was observed between two kinds of tablets (f 2 =52), and then the evaluations of efficacy and retention capacity in vivo were conducted with small tablets. In vivo retention studies showed that the T max (2 h) of GRT-P in rat stomachs was significantly extended compared with the T max (0.5 h) of normal reference preparation. Compared with the model group, low and high doses of GRT-P could significantly inhibit the increase of malondialdehyde (MDA) in serum. Studies showed that the higher MDA content in inflammation tissue increases the inflammatory response. The ulcer inhibition rates of GRT-P in the high-dose group were 59.0 and 64.1% in the ranitidine group. Results indicated that GRT-Ps had the potential for a sustained drug release and an enhanced gastric residence time with relatively high drug concentrations in the tissue distribution.

Effect of degree of esterification of pectin and calcium amount on drug release from pectin-based matrix tablets.

PubMed

Sungthongjeen, Srisagul; Sriamornsak, Pornsak; Pitaksuteepong, Tasana; Somsiri, Atawit; Puttipipatkhachorn, Satit

2004-02-12

The aim of this work was to assess the effect of 2 formulation variables, the pectin type (with different degrees of esterification [DEs]) and the amount of calcium, on drug release from pectin-based matrix tablets. Pectin matrix tablets were prepared by blending indomethacin (a model drug), pectin powder, and various amounts of calcium acetate and then tableting by automatic hydraulic press machine. Differential scanning calorimetry, powder x-ray diffraction, and Fourier transformed-infrared spectroscopy studies of the compressed tablets revealed no drug-polymer interaction and the existence of drug with low crystallinity. The in-vitro release studies in phosphate buffer (United States Pharmacopeia) and tris buffer indicated that the lower the DE, the greater the time for 50% of drug release (T50). This finding is probably because of the increased binding capacity of pectin to calcium. However, when the calcium was excluded, the pectins with different DEs showed similar release pattern with insignificant difference of T50. When the amount of calcium acetate was increased from 0 to 12 mg/tablet, the drug release was significantly slower. However, a large amount of added calcium (ie, 24 mg/tablet) produced greater drug release because of the partial disintegration of tablets. The results were more pronounced in phosphate buffer, where the phosphate ions induced the precipitation of calcium phosphate. In conclusion, both pectin type and added calcium affect the drug release from the pectin-based matrix tablets.

Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

PubMed

Chansanroj, Krisanin; Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele

2011-10-09

Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural network (SOM) was applied for visualizing interrelation among the variables and multilayer perceptron neural networks (MLPs) were employed to generalize the system and predict the drug release properties based on HLB value and concentration of SEs and tablet properties, i.e., tablet porosity, volume and tensile strength. Accurate prediction was obtained after systematically optimizing network performance based on learning algorithm of MLP. Drug release was mainly attributed to the effects of SEs, tablet volume and tensile strength in multi-dimensional interrelation whereas tablet porosity gave a small impact. Ability of system generalization and accurate prediction of the drug release properties proves the validity of SOM and MLPs for the formulation modeling of direct compacted matrix tablets containing controlled release agents of different material properties. Copyright © 2011 Elsevier B.V. All rights reserved.

NMR imaging of high-amylose starch tablets. 1. Swelling and water uptake.

PubMed

Baille, Wilms E; Malveau, Cédric; Zhu, Xiao Xia; Marchessault, Robert H

2002-01-01

Pharmaceutical tablets made of modified high-amylose starch have a hydrophilic polymer matrix into which water can penetrate with time to form a hydrogel. Nuclear magnetic resonance imaging was used to study the water penetration and the swelling of the matrix of these tablets. The tablets immersed in water were imaged at different time intervals on a 300 MHz NMR spectrometer. Radial images show clearly the swelling of the tablets and the water concentration profile. The rate constants for water diffusion and the tablet swelling were extracted from the experimental data. The water diffusion process was found to follow case II kinetics at 25 degrees C. NMR imaging also provided spin density profiles of the water penetrating inside the tablets.

Application of design of experiment for polyox and xanthan gum coated floating pulsatile delivery of sumatriptan succinate in migraine treatment.

PubMed

Jagdale, Swati C; Pawar, Chandrakala R

2014-01-01

Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR 205 and xanthan gum. 3(2) experimental design was applied. Optimized formulation was evaluated for physical characteristics and in-vitro and in-vivo study. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm(2), and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed by in-vivo X-ray study.

Development and optimization of press coated floating pulsatile drug delivery of sumatriptan succinate.

PubMed

Jagdale, Swati C; Pawar, Chandrakala R

2014-01-01

Floating pulsatile is combined approach designed according to circadian rhythm to deliver the drug at right time, in right quantity and at right site as per pathophysiological need of disease with prolong gastric residence and lag phase followed by burst release. As the migraine follows circadian rhythm in which headache is more painful at the awakening time, the dosage form should be given during night time to release drug when pain get worsen. Present work deals with formulation and optimization of floating pulsatile tablet of sumatriptan succinate. Core tablet containing crospovidone as superdisintegrant (10%) showed burst release. Lag time was maintained using swellable polymer as polyoxN12K and xanthum gum. 3(2) experimental design was carried out. Developed formulations were evaluated for physical characteristics, in vitro and in vivo study. Optimized batch F2 with concentration of polyox N12K (73.43%) and xanthum gum (26.56%) of total polymer weight showed floating lag time 15±2 sec, drug content 99.58±0.2 %, hardness 6±0.2 Kg/cm(2) and drug release 99.54±2% with pulsatile manner followed lag period of 7±0.1h. In vivo x-ray study confirms prolong gastric residence of system. Programmable pulsatile release has been achieved by formulation F2 which meet demand of chronotherapeutic objective of migraine.

Formulation development of gastroretentive tablets of lamivudine using the floating-bioadhesive potential of optimized polymer blends.

PubMed

Singh, Bhupinder; Garg, Babita; Chaturvedi, Subhash Chand; Arora, Sharry; Mandsaurwale, Rachana; Kapil, Rishi; Singh, Baljinder

2012-05-01

The current studies entail successful formulation of optimized gastroretentive tablets of lamivudine using the floating-bioadhesive potential of carbomers and cellulosic polymers, and their subsequent in-vitro and in-vivo evaluation in animals and humans. Effervescent floating-bioadhesive hydrophilic matrices were prepared and evaluated for in-vitro drug release, floatation and ex-vivo bioadhesive strength. The optimal composition of polymer blends was systematically chosen using central composite design and overlay plots. Pharmacokinetic studies were carried out in rabbits, and various levels of in-vitro/in-vivo correlation (IVIVC) were established. In-vivo gamma scintigraphic studies were performed in human volunteers using (99m) Tc to evaluate formulation retention in the gastric milieu. The optimized formulation exhibited excellent bioadhesive and floatational characteristics besides possessing adequate drug-release control and pharmacokinetic extension of plasma levels. The successful establishment of various levels of IVIVC substantiated the judicious choice of in-vitro dissolution media for simulating the in-vivo conditions. In-vivo gamma scintigraphic studies ratified the gastroretentive characteristics of the optimized formulation with a retention time of 5 h or more. Besides unravelling the polymer synergism, the study helped in developing an optimal once-a-day gastroretentive drug delivery system with improved bioavailability potential exhibiting excellent swelling, floating and bioadhesive characteristics. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Formulation and evaluation of atenolol floating bioadhesive system using optimized polymer blends

PubMed Central

Siddam, Haritha; Kotla, Niranjan G.; Maddiboyina, Balaji; Singh, Sima; Sunnapu, Omprakash; Kumar, Anil; Sharma, Dinesh

2016-01-01

Introduction: Oral sustained release gastro retentive dosage forms offer several advantages for drugs having absorption from the upper gastrointestinal tract to improve the bioavailability of medications which have narrow absorption window. The aim of the study was to develop a floating bioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong the residence in the stomach using atenolol as a model drug. Methods: Prior to compression, polymeric blend(s) were evaluated for flow properties. The tablets were prepared by direct compression method using bioadhesive polymer like Carbopol 934P and hydrophilic polymers like HPMC K4M, HPMC K15M, and HPMC K100M. The prepared tablets were evaluated for physical characteristics, bioadhesive strength, buoyancy lag time, swelling index and in vitro drug release studies. Results: The mean bioadhesive strength was found to be in the range of 16.2 to 52.1 gm. The optimized blend (F11) showed 92.3% drug releases after 24 hrs. Whilst, increase in concentration of carbopol 934P, bioadhesive strength and swelling index was increased with slow release. The n values of optimized formulations were found in the range of 0.631-0.719 indicating non-fickian anomalous type transport mechanism. Conclusion: The study aided in developing an ideal once-a-day gastro retentive floating drug delivery system with improved floating, swelling and bioadhesive characteristics with better bioavailability. PMID:27051631

[Cost-effective analysis of rotation from sustained-release morphine tablet to transdermal fentanyl of matrix type or sustained-release oxycodone tablet].

PubMed

Ise, Yuya; Wako, Tetsuya; Miura, Yoshihiko; Katayama, Shirou; Shimizu, Hisanori

2009-12-01

The present study was undertaken to determine the pharmacoeconomics of switching from sustained-release morphine tablet to matrix type (MT) of transdermal fontanel or sustained-release Oxycodone tablet. Cost-effective analysis was performed using a simulation model along with decision analysis. The analysis was done from the payer's perspective. The cost-effective ratio/patient of transdermal MT fontanel (22, 539 yen)was lower than that of sustained -release Oxycodone tablet (23, 630 yen), although a sensitivity analysis could not indicate that this result was reliable. These results suggest the possibility that transdermal MT fontanel was much less expensive than a sustained-release Oxycodone tablet.

Zero-order release of aspirin, theophylline and atenolol in water from novel methylcellulose glutarate matrix tablets.

PubMed

Khairuzzaman, A; Ahmed, S U; Savva, M; Patel, N K

2006-08-02

A novel hydrocolloidal polymer, methylcellulose glutarate (MC-GA), was prepared by esterifying methylcellulose with glutaric anhydride. The formation of ester was confirmed by FTIR and NMR spectroscopy, DSC and elemental analysis. The physicochemical properties such as, rate of swelling in water, viscosity and hygroscopicity of MC-GA were determined and compared with those of methycellulose A (MC). Aspirin, theophylline and atenolol tablets were compacted on a Carver press using the wet granulation method. Each tablet contained: 200 mg active, 80 mg anhydrous lactose, 8 mg povidone, 4 mg magnesium stearate, 4 mg talc, 50mg MC or MC-GA (drug-to-polymer ratio, 4:1). Contrary to the first-order release profile of all the drugs from the MC matrix tablets, a zero-order release was obtained from the MC-GA matrix tablets in water.

Development of Maltodextrin-Based Immediate-Release Tablets Using an Integrated Twin-Screw Hot-Melt Extrusion and Injection-Molding Continuous Manufacturing Process.

PubMed

Puri, Vibha; Brancazio, Dave; Desai, Parind M; Jensen, Keith D; Chun, Jung-Hoon; Myerson, Allan S; Trout, Bernhardt L

2017-11-01

The combination of hot-melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited research on its application to formulate crystalline drug-containing immediate-release tablets. Furthermore, studies that have applied the HME-IM process to molded tablets have used a noncontinuous 2-step approach. The present study develops maltodextrin (MDX)-based extrusion-molded immediate-release tablets for a crystalline drug (griseofulvin) using an integrated twin-screw HME-IM continuous process. At 10% w/w drug loading, MDX was selected as the tablet matrix former based on a preliminary screen. Furthermore, liquid and solid polyols were evaluated for melt processing of MDX and for impact on tablet performance. Smooth-surfaced tablets, comprising crystalline griseofulvin solid suspension in the amorphous MDX-xylitol matrix, were produced by a continuous process on a twin-screw extruder coupled to a horizontally opening IM machine. Real-time HME process profiles were used to develop automated HME-IM cycles. Formulation adjustments overcame process challenges and improved tablet strength. The developed MDX tablets exhibited adequate strength and a fast-dissolving matrix (85% drug release in 20 min), and maintained performance on accelerated stability conditions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Matrix-mini-tablets of lornoxicam for targeting early morning peak symptoms of rheumatoid arthritis

PubMed Central

Mohd, Abdul Hadi; Raghavendra Rao, Nidagurthi Guggilla; Avanapu, Srinivasa Rao

2014-01-01

Objective(s): The aim of present research was to develop matrix-mini-tablets of lornoxicam filled in capsule for targeting early morning peak symptoms of rheumatoid arthritis. Materials and Methods: Matrix-mini-tablets of lornoxicam were prepared by direct compression method using microsomal enzyme dependent and pH-sensitive polymers which were further filled into an empty HPMC capsule. To assess the compatibility, FT-IR and DSC studies for pure drug, polymers and their physical mixture were performed. The formulated batches were subjected to physicochemical studies, estimation of drug content, in vitro drug release, drug release kinetics, and stability studies. Results: When FTIR and DSC studies were performed it was found that there was no interaction between lornoxicam and polymers which used. All the physicochemical properties of prepared matrix-mini-tablets were found to be in normal limits. The percentage of drug content was found to be 99.60±0.07%. Our optimized matrix mini-tablets-filled-capsule formulation F30 released lornoxicam after a lag time of 5.02±0.92 hr, 95.48±0.65 % at the end of 8 hr and 99.90±0.83 % at the end of 12 hr. Stability was also found for this formulation as per the guidelines of International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. Conclusion: A novel colon targeted delivery system of lornoxicam was successfully developed by filling matrix-mini-tablets into an empty HPMC capsule shell for targeting early morning peak symptoms of rheumatoid arthritis. PMID:24967065

A comprehensive in vitro and in vivo evaluation of thiolated matrix tablets as a gastroretentive delivery system.

PubMed

Senyigit, Zeynep Ay; Vetter, Anja; Guneri, Tamer; Bernkop-Schnürch, Andreas

2011-08-01

The aim of this study was to investigate the potential of thiolated matrix tablets for gastroretentive delivery systems. Poly(acrylic acid)-cysteine (PAA-Cys) and chitosan-4-thiobuthylamidine (chitosan-TBA) were evaluated as anionic and cationic thiolated polymers and riboflavin was used as a model drug. Tablets were prepared by direct compression and each formulation was characterized in terms of disintegration, swelling, mucoadhesion, and drug release properties. Thereafter, the gastric residence times of tablets were determined with in vivo study in rats. The resulting PAA-Cys and chitosan-TBA conjugates displayed 172.80 ± 30.33 and 371.11 ± 72.74 µmol free thiol groups, respectively. Disintegration studies demonstrated the stability of thiolated tablets up to 24 h, whereas tablets prepared with unmodified PAA and chitosan disintegrated within a time period of 1 h. Mucoadhesion studies showed that mucoadhesion work of PAA-Cys and chitosan-TBA tablets were 1.341- and 2.139-times higher than unmodified ones. The mucoadhesion times of PAA, PAA-Cys, chitosan, and chitosan-TBA tablets were 1.5 ± 0.5, 21 ± 1, 1 ± 0.5, 17 ± 1 h, respectively. These results confirm the theory that thiol groups react with mucin glycoproteins and form covalent bonds to the mucus layer. Release studies indicated that a controlled release was provided with thiolated tablets up to 24 h. These promising in vitro results of thiolated tablets were proved with in vivo studies. The thiolated tablets showed a gastroretention time up to 6 h, whereas unmodified tablets completely disintegrated within 1 h in rat stomach. Consequently, the study suggests that thiolated matrix tablets might be promising formulations for gastroretentive delivery systems.

A new experimental design method to optimize formulations focusing on a lubricant for hydrophilic matrix tablets.

PubMed

Choi, Du Hyung; Shin, Sangmun; Khoa Viet Truong, Nguyen; Jeong, Seong Hoon

2012-09-01

A robust experimental design method was developed with the well-established response surface methodology and time series modeling to facilitate the formulation development process with magnesium stearate incorporated into hydrophilic matrix tablets. Two directional analyses and a time-oriented model were utilized to optimize the experimental responses. Evaluations of tablet gelation and drug release were conducted with two factors x₁ and x₂: one was a formulation factor (the amount of magnesium stearate) and the other was a processing factor (mixing time), respectively. Moreover, different batch sizes (100 and 500 tablet batches) were also evaluated to investigate an effect of batch size. The selected input control factors were arranged in a mixture simplex lattice design with 13 experimental runs. The obtained optimal settings of magnesium stearate for gelation were 0.46 g, 2.76 min (mixing time) for a 100 tablet batch and 1.54 g, 6.51 min for a 500 tablet batch. The optimal settings for drug release were 0.33 g, 7.99 min for a 100 tablet batch and 1.54 g, 6.51 min for a 500 tablet batch. The exact ratio and mixing time of magnesium stearate could be formulated according to the resulting hydrophilic matrix tablet properties. The newly designed experimental method provided very useful information for characterizing significant factors and hence to obtain optimum formulations allowing for a systematic and reliable experimental design method.

Application of Design of Experiment for Polyox and Xanthan Gum Coated Floating Pulsatile Delivery of Sumatriptan Succinate in Migraine Treatment

PubMed Central

Jagdale, Swati C.; Pawar, Chandrakala R.

2014-01-01

Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR 205 and xanthan gum. 32 experimental design was applied. Optimized formulation was evaluated for physical characteristics and in-vitro and in-vivo study. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm2, and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed by in-vivo X-ray study. PMID:25530963

QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil.

PubMed

Bansal, Sanjay; Beg, Sarwar; Garg, Babita; Asthana, Abhay; Asthana, Gyati S; Singh, Bhupinder

2016-10-01

The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.

Strategies to overcome pH-dependent solubility of weakly basic drugs by using different types of alginates.

PubMed

Gutsche, S; Krause, M; Kranz, H

2008-12-01

Weakly basic drugs demonstrate higher solubility at lower pH, thus often leading to faster drug release at lower pH. The objective of this study was to achieve pH-independent release of weakly basic drugs from extended release formulations based on the naturally occurring polymer sodium alginate. Three approaches to overcome the pH-dependent solubility of the weakly basic model drug verapamil hydrochloride were investigated. First, matrix tablets were prepared by direct compression of drug substance with different types of sodium alginate only. Second, pH-modifiers were added to the drug/alginate matrix systems. Third, press-coated tablets consisting of an inner pH-modifier tablet core and an outer drug/sodium alginate coat were prepared. pH-Independent drug release was achieved from matrix tablets consisting of selected alginates and drug substance only. Alginates are better soluble at higher pH. Therefore, they are able to compensate the poor solubility of weakly basic drugs at higher pH as the matrix of the tablets dissolves faster. This approach was successful when using alginates that demonstrated fast hydration and erosion at higher pH. The approach failed for alginates with less-pronounced erosion at higher pH. The addition of fumaric acid to drug/alginate-based matrix systems decreased the microenvironmental pH within the tablets thus increasing the solubility of the weakly basic drug at higher pH. Therefore, pH-independent drug release was achieved irrespective of the type of alginate used. Drug release from press-coated tablets did not provide any further advantages as compound release remained pH-dependent.

Development of theophylline sustained release dosage form based on Kollidon SR.

PubMed

Reza, Md Selim; Quadir, Mohiuddin Abdul; Haider, Syed Shabbir

2002-01-01

Sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl acetate and povidone based matrix retarding polymer) were developed in this study in an attempt to design a dosage form that manifests desirable release profile and thorough adherence to official monographs. Four matrix tablet formulations were prepared by dry blending and direct compression of Kollidon SR and HPMC-15cps (hydroxypropylmethylcellulose) in varying proportion with fixed percentage of theophylline. Tablets containing only Kollidon SR with the active ingredient demonstrated a rapid rate of drug release with an initial burst effect. Incorporation of HPMC-15cps in the matrix tablet prolonged the release of drug with subsequent minimization of burst effect as confirmed by mean dissolution time, T50 and Higuchi release rate data. Among the batches containing HPMC-15 cps, a direct relationship was obtained between release rate and the percentage of HPMC used. A suitable controlled release profile was obtained with the matrix tablets containing 20% Kollidon SR and 30% HPMC-15cps. The formulation showed close resemblance to commercial products and compliance with USP specification. The results were explored and explained by the difference of physico-chemical property and hydration characteristics of the polymers. In addition to this result, the exponential model was applied to characterize the drug release behaviour from polymeric systems. It was found that, Fickian release is predominant in tablets containing Kollidon SR alone and non-Fickian mechanism plays an important role in the release of drug from HPMC containing tablets with a trend towards zero-order or case II release. In vitro release profile of two commercial brands were also undertaken for comparison and modulation of the experimental batches.

Swelling/Floating Capability and Drug Release Characterizations of Gastroretentive Drug Delivery System Based on a Combination of Hydroxyethyl Cellulose and Sodium Carboxymethyl Cellulose

PubMed Central

Chen, Ying-Chen; Ho, Hsiu-O; Liu, Der-Zen; Siow, Wen-Shian; Sheu, Ming-Thau

2015-01-01

The aim of this study was to characterize the swelling and floating behaviors of gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS to incorporate three model drugs with different solubilities (metformin, ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated, and their swelling and floating behaviors were characterized. Influences of media containing various NaCl concentrations on the swelling and floating behaviors and drug solubility were also characterized. Finally, release profiles of the three model drugs from GRDDS formulation (F1-4) and formulation (F1-1) were examined. Results demonstrated when the GRDDS tablets were tested in simulated gastric solution, the degree of swelling at 6 h was decreased for each formulation that contained NaCMC in comparison to those in de-ionized water (DIW). Of note, floating duration was enhanced when in simulated gastric solution compared to DIW. Further, the hydration of tablets was found to be retarded as the NaCl concentration in the medium increased resulting in smaller gel layers and swelling sizes. Dissolution profiles of the three model drugs in media containing various concentrations of NaCl showed that the addition of NaCl to the media affected the solubility of the drugs, and also their gelling behaviors, resulting in different mechanisms for controlling a drug’s release. The release mechanism of the freely water-soluble drug, metformin, was mainly diffusion-controlled, while those of the water-soluble drug, ciprofloxacin, and the slightly water-soluble drug, esomeprazole, were mainly anomalous diffusion. Overall results showed that the developed GRDDS composed of HEC 250HHX and NaCMC of 450 cps possessed proper swelling extents and desired floating periods with sustained-release characteristics. PMID:25617891

Formulation and in vitro evaluation of sustained release matrix tablets using cross-linked natural gum.

PubMed

Jamil, Qurratul Ain; Masood, Muhammad Irfan; Jamil, Muhammad Nauman; Masood, Imran; Iqbal, Shahid Muhammad

2017-03-01

Polysaccharide gums because of their biocompatibility, biodegradability and non-immunogenic properties are considered as the best choice for preparing sustained release tablets as compared to their synthetic counterpart. The cross linking of natural gums in matrix tablets increase the sustained release property of matrix tablets. Isoniazid is a first line therapy of tuberculosis, belongs to BCS I with half-life of 3-4 hours. These characteristics make isoniazid a good candidate for sustained release dosage form. Karaya gum crossed linked with trisodium tri metaphosphate was used as release rate retardant for preparing isoniazid cross-linked matrix tablet. Total 8 sustained release formulations were prepared. Both granules and tablets were evaluated under in vitro condition against different parameters. Dissolution studies were performed with all eight formulations for 12 hours using USP apparatus I. Four formulations designated as F1, F2, F3, F4 have drug and karaya gum while other four formulations F5, F6, F7, F8 have drug and crossed linked polymer in ratios of 1:1, 1:2, 1:3 and 1:4 respectively. Dissolution data was analyzed by using different kinetic models. Best fit model for most efficient formulation was zero order while release mechanism was super case I. Formulation 8 showed sufficiently slow release kinetics and about 83% of drug was released in 10 hours, indicating that cross-linked karaya gum proved efficient in preparing sustained release tablets.

Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage.

PubMed

Kaleemullah, M; Jiyauddin, K; Thiban, E; Rasha, S; Al-Dhalli, S; Budiasih, S; Gamal, O E; Fadli, A; Eddy, Y

2017-07-01

Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor ( f 2 ) value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f 2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05) between the F3 and reference drug in terms of MDT and T50% with p-values of 1.00 and 0.995 respectively.

Influence of sodium dodecyl sulfate on swelling, erosion and release behavior of HPMC matrix tablets containing a poorly water-soluble drug.

PubMed

Zeng, Aiguo; Yuan, Bingxiang; Fu, Qiang; Wang, Changhe; Zhao, Guilan

2009-01-01

The effect of sodium dodecyl sulfate (SDS) on the swelling, erosion and release behavior of HPMC matrix tablets was examined. Swelling and erosion of HPMC matrix tablets were determined by measuring the wet and subsequent dry weights of matrices. The rate of uptake of the dissolution medium by the matrix was quantified using a square root relationship whilst the erosion of the polymer was described using the cube root law. The extent of swelling decreased with increasing SDS concentrations in the dissolution medium but the rate of erosion was found to follow a reverse trend. Such phenomena might have been caused by the attractive hydrophobic interaction between HPMC and SDS as demonstrated by the cloud points of the solutions containing both the surfactant and polymer. Release profiles of nimodipine from HPMC tablets in aqueous media containing different concentrations of SDS were finally studied. Increasing SDS concentrations in the medium was shown to accelerate the release of nimodipine from the tablets, possibly due to increasing nimodipine solubility and increasing rate of erosion by increasing SDS concentrations in the dissolution medium.

Photoimages and the release characteristics of lipophilic matrix tablets containing highly water-soluble potassium citrate with high drug loadings.

PubMed

Cao, Qing-Ri; Kim, Tae-Wan; Lee, Beom-Jin

2007-07-18

Two types of the carnauba wax-based lipophilic matrix tablet using spray-dried granules (SDT) or directly compressible powdered mixtures (DCT) were prepared for sustained release. The model drug was a highly water-soluble potassium citrate and loaded about 74% of the total tablet weight. The SDT slowly eroded and disintegrated during the release study without showing sustained release when the hydrophilic excipients were added. In contrast, the DCT was more efficient for sustained release. The release rate decreased with increasing carnauba wax concentration. In particular, the sustained release rate was markedly pronounced when the lipophilic stearyl alcohol and stearic acid were combined with the carnauba wax. The surface of the intact DCT appeared to be smooth and rusty. The DCT rose to the surface from the bottom of the vessel during the release test, and numerous pores and cracks with no signs of disintegration were also observed after the release test. The release profile was dependent on the formulation composition and preparation method of the matrix tablet. Diffusion-controlled leaching through the channels of the pores and cracks of the lipophilic matrix tablet (DCT) is a key to the sustained release.

Development of controlled drug release systems based on thiolated polymers.

PubMed

Bernkop-Schnürch, A; Scholler, S; Biebel, R G

2000-05-03

The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.

Formulation and evaluation of diclofenac controlled release matrix tablets made of HPMC and Poloxamer 188 polymer: An assessment on mechanism of drug release.

PubMed

Al-Hanbali, Othman A; Hamed, Rania; Arafat, Mosab; Bakkour, Youssef; Al-Matubsi, Hisham; Mansour, Randa; Al-Bataineh, Yazan; Aldhoun, Mohammad; Sarfraz, Muhammad; Dardas, Abdel Khaleq Yousef

2018-01-01

In this study, hydrophilic hydroxypropyl methylcellulose matrices with various concentrations of Poloxamer 188 were used in the development of oral controlled release tablets containing diclofenac sodium. Four formulations of hydrophilic matrix tablets containing 16.7% w/w HPMC and 0, 6.7, 16.7 and 25.0% w/w Poloxamer 188, respectively, were developed. Tablets were prepared by direct compression and characterized for diameter, hardness, thickness, weight and uniformity of content. The influence of various blends of hydroxypropyl methylcellulose and Poloxamer 188 on the in vitro dissolution profile and mechanism of drug release of was investigated. In the four formulations, the rate of drug release decreased with increasing the concentration of Poloxamer 188 at the initial dissolution stages due to the increase in the apparent viscosity of the gel diffusion layer. However, in the late dissolution stages, the rate of drug release increased with increasing Poloxamer 188 concentration due to the increase in wettability and dissolution of the matrix. The kinetic of drug release from the tablets followed non-Fickian mechanism, as predicted by Korsmeyer-Peppas model, which involves diffusion through the gel layer and erosion of the matrix system.

Evaluating vertical concentration profile of carbon source released from slow-releasing carbon source tablets and in situ biological nitrate denitrification activity

NASA Astrophysics Data System (ADS)

Yeum, Y.; HAN, K.; Yoon, J.; Lee, J. H.; Song, K.; Kang, J. H.; Park, C. W.; Kwon, S.; Kim, Y.

2017-12-01

Slow-releasing carbon source tablets were manufactured during the design of a small-scale in situ biological denitrification system to reduce high-strength nitrate (> 30 mg N/L) from a point source such as livestock complexes. Two types of slow-releasing tablets, precipitating tablet (PT, apparent density of 2.0 g/mL) and floating tablet (FT), were prepared to achieve a vertically even distribution of carbon source (CS) in a well and an aquifer. Hydroxypropyl methylcellulose (HPMC) was used to control the release rate, and microcrystalline cellulose pH 101 (MCC 101) was added as a binder. The #8 sand was used as a precipitation agent for the PTs, and the floating agents for the FTs were calcium carbonate and citric acid. FTs floated within 30 min. and remained in water because of the buoyance from carbon dioxide, which formed during the acid-base reaction between citric acid and calcium carbonate. The longevities of PTs with 300 mg of HPMC and FTs with 400 mg of HPMC were 25.4 days and 37.3 days, respectively. We assessed vertical CS profile in a continuous flowing physical aquifer model (release test, RT) and its efficiency on biological nitrate denitrification (denitrification test, DT). During the RT, PTs, FTs and a tracer (as 1 mg rhodamine B/L) were initially injected into a well of physical aquifer model (PAM). Concentrations of CS and the tracer were monitored along the streamline in the PAM to evaluate vertical profile of CS. During the DT, the same experiment was performed as RT, except continuous injection of solution containing 30 mg N/L into the PAM to evaluate biological denitrification activity. As a result of RT, temporal profiles of CS were similar at 3 different depths of monitoring wells. These results suggest that simultaneous addition of PT and FT be suitable for achieving a vertically even distribution of the CS in the injection well and an aquifer. In DT, similar profile of CS was detected in the injection well, and nitrate was biologically denitrified at downstream of the injection well. In conclusion, addition of PT and FT into a well under natural gradient condition may be an effective means for remediating high-strength nitrate in groundwater.

Product Development Studies on Sonocrystallized Curcumin for the Treatment of Gastric Cancer

PubMed Central

Ashif Khan, Mohammad; Akhtar, Nida; Sharma, Vijay; Pathak, Kamla

2015-01-01

Curcumin suffers from the limitation of poor solubility and low dissolution that can lead to limited applications. The investigation was aimed to substantiate the potentiality of melt sonocrystallized gastroretentive tablets of curcumin. Melt sonocrystallized curcumin (MSC CMN) was developed and its therapeutic potential was validated by in vitro cytotoxicity studies against Human oral cancer cell line KB. MSC curcumin was then formulated as floating tablet and evaluated. MSC form of CMN exhibited 2.36-fold and 2.40-fold solubility enhancement in distilled water and phosphate buffer, pH 4.5, respectively, better flow properties and intrinsic dissolution rate (0.242 ± 1.42 and 0.195 ± 1.26 mg/cm2/min) in comparison to its original form. The GI50 value of MSC CMN was found to be less than 10, specifying inhibition of growth more effectively at its least concentration by 50%. The gastroretentive-floating tablet (Formulation F4) displayed controlled drug release (96.22% ± 1.43%) for over 12 h. The present study revealed melt sonocrystallization can be used to produce particles with superior biopharmaceutical properties without the use of organic solvents or the addition of other excipients, and amenable to formulation in to a pharmaceutical dosage form. PMID:25923809

Product development studies on sonocrystallized curcumin for the treatment of gastric cancer.

PubMed

Khan, Mohammad Ashif; Akhtar, Nida; Sharma, Vijay; Pathak, Kamla

2015-04-27

Curcumin suffers from the limitation of poor solubility and low dissolution that can lead to limited applications. The investigation was aimed to substantiate the potentiality of melt sonocrystallized gastroretentive tablets of curcumin. Melt sonocrystallized curcumin (MSC CMN) was developed and its therapeutic potential was validated by in vitro cytotoxicity studies against Human oral cancer cell line KB. MSC curcumin was then formulated as floating tablet and evaluated. MSC form of CMN exhibited 2.36-fold and 2.40-fold solubility enhancement in distilled water and phosphate buffer, pH 4.5, respectively, better flow properties and intrinsic dissolution rate (0.242 ± 1.42 and 0.195 ± 1.26 mg/cm2/min) in comparison to its original form. The GI50 value of MSC CMN was found to be less than 10, specifying inhibition of growth more effectively at its least concentration by 50%. The gastroretentive-floating tablet (Formulation F4) displayed controlled drug release (96.22% ± 1.43%) for over 12 h. The present study revealed melt sonocrystallization can be used to produce particles with superior biopharmaceutical properties without the use of organic solvents or the addition of other excipients, and amenable to formulation in to a pharmaceutical dosage form.

Application of ion exchange resin in floating drug delivery system.

PubMed

Upadhye, Abhijeet A; Ambike, Anshuman A; Mahadik, Kakasaheb R; Paradkar, Anant

2008-10-01

The purpose of this study was to explore the application of low-density ion exchange resin (IER) Tulsion(R) 344, for floating drug delivery system (FDDS), and study the effect of its particle size on rate of complexation, water uptake, drug release, and in situ complex formation. Batch method was used for the preparation of complexes, which were characterized by physical methods. Tablet containing resin with high degree of crosslinking showed buoyancy lag time (BLT) of 5-8 min. Decreasing the particle size of resin showed decrease in water uptake and drug release, with no significant effect on the rate of complexation and in situ complex formation for both preformed complexes (PCs) and physical mixtures (PMs). Thus, low-density and high degree of crosslinking of resin and water uptake may be the governing factor for controlling the initial release of tablet containing PMs but not in situ complex formation. However, further sustained release may be due to in situ complex formation.

Novel swellable polymer of orchidaceae family for gastroretentive drug delivery of famotidine

PubMed Central

Razavi, Mahboubeh; Nyamathulla, Shaik; Karimian, Hamed; Noordin, Mohamed Ibrahim

2014-01-01

This study aimed to develop hydrophilic, gastroretentive matrix tablets of famotidine with good floating and swelling properties. A novel gastroretentive drug delivery formulation was designed using salep, also known as salepi, a flour obtained from grinding dried palmate tubers of Orchis morio var mascula (Orchidaceae family). The main polysaccharide content of salep is glucomannan, highly soluble in cold and hot water, which forms a viscous solution. Salep was characterized for physicochemical properties, thermal stability, chemical interaction, and surface morphology using X-ray diffraction analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Ten different formulations (S1–S10) were prepared using famotidine to salep ratios from 1:0.5 to 1:5. Results demonstrated that all formulations were able to sustain the drug release for more than 24 hours. The S5 formulation, with a famotidine to salep ratio of 1:2.5, had the shortest floating lag time of 35 seconds and 100% drug release within 24 hours. The dissolution data were fitted into popular mathematical models to assess the mechanism of drug release. S5 showed Zero order release (R=0.9746) with Higuchi diffusion (R=0.9428). We conclude that salep, a novel polymer, can be used in controlled release formulations to sustain release for 24 hours, due to inherent swelling and gelling properties. PMID:25246773

Urinary excretion of ciprofloxacin after administration of extended release tablets in healthy volunteers. Swellable drug-polyelectrolyte matrix versus bilayer tablets.

PubMed

Guzmán, M L; Romañuk, C B; Sanchez, M F; Luciani Giacobbe, L C; Alarcón-Ramirez, L P; Battistini, F D; Alovero, F L; Jimenez-Kairuz, A F; Manzo, R H; Olivera, María Eugenia

2018-02-01

This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, t max , area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.

Advances in mechanistic understanding of release rate control mechanisms of extended-release hydrophilic matrix tablets.

PubMed

Timmins, Peter; Desai, Divyakant; Chen, Wei; Wray, Patrick; Brown, Jonathan; Hanley, Sarah

2016-08-01

Approaches to characterizing and developing understanding around the mechanisms that control the release of drugs from hydrophilic matrix tablets are reviewed. While historical context is provided and direct physical characterization methods are described, recent advances including the role of percolation thresholds, the application on magnetic resonance and other spectroscopic imaging techniques are considered. The influence of polymer and dosage form characteristics are reviewed. The utility of mathematical modeling is described. Finally, how all the information derived from applying the developed mechanistic understanding from all of these tools can be brought together to develop a robust and reliable hydrophilic matrix extended-release tablet formulation is proposed.

3D Printing Factors Important for the Fabrication of Polyvinylalcohol Filament-Based Tablets.

PubMed

Tagami, Tatsuaki; Fukushige, Kaori; Ogawa, Emi; Hayashi, Naomi; Ozeki, Tetsuya

2017-01-01

Three-dimensional (3D) printers have been applied in many fields, including engineering and the medical sciences. In the pharmaceutical field, approval of the first 3D-printed tablet by the U.S. Food and Drug Administration in 2015 has attracted interest in the manufacture of tablets and drugs by 3D printing techniques as a means of delivering tailor-made drugs in the future. In current study, polyvinylalcohol (PVA)-based tablets were prepared using a fused-deposition-modeling-type 3D printer and the effect of 3D printing conditions on tablet production was investigated. Curcumin, a model drug/fluorescent marker, was loaded into PVA-filament. We found that several printing parameters, such as the rate of extruding PVA (flow rate), can affect the formability of the resulting PVA-tablets. The 3D-printing temperature is controlled by heating the print nozzle and was shown to affect the color of the tablets and their curcumin content. PVA-based infilled tablets with different densities were prepared by changing the fill density as a printing parameter. Tablets with lower fill density floated in an aqueous solution and their curcumin content tended to dissolve faster. These findings will be useful in developing drug-loaded PVA-based 3D objects and other polymer-based articles prepared using fused-deposition-modeling-type 3D printers.

Development of gastro intestinal sustained release tablet formulation containing acryl-EZE and pH-dependent swelling HPMC K 15 M.

PubMed

Lamoudi, Lynda; Chaumeil, Jean Claude; Daoud, Kamel

2012-05-01

The aim of this study was to evaluate physical properties and release from matrix tablets containing different ratios of HPMC 15 M and Acryl-EZE. A further aim is to assess their suitability for pH dependent controlled release. Matrix tablets containing HPMC 15 M and Acryl-EZE were manufactured using a fluidized bed. The release from this matrix using Sodium Diclofenac (SD) as model drug is studied in two dissolution media (0.1 N HCl or pH = 6.8 phosphate buffer solution); the release rate, mechanism, and pH dependence were characterized by fitting four kinetic models and by using a similarity factor analysis. The obtained results revealed that the presence of Acryl-EZE in the matrix tablets is effective in protecting the dosage forms from release in acid environments such as gastric fluid. In pH = 6.8 phosphate buffer, the drug release rate and mechanism of release from all matrices is mainly controlled by HPMC 15 M. The model of Korsmeyer-Peppas was found to fit experimental dissolution results.

Oral Delivery of Probiotics in Poultry Using pH-Sensitive Tablets.

PubMed

Jiang, Tao; Li, Hui-Shan; Han, Geon Goo; Singh, Bijay; Kang, Sang-Kee; Bok, Jin-Duck; Kim, Dae-Duk; Hong, Zhong-Shan; Choi, Yun-Jaie; Cho, Chong-Su

2017-04-28

As alternatives to antibiotics in livestocks, probiotics have been used, although most of them in the form of liquid or semisolid formulations, which show low cell viability after oral administration. Therefore, suitable dry dosage forms should be developed for livestocks to protect probiotics against the low pH in the stomach such that the products have higher probiotics survivability. Here, in order to develop a dry dosage forms of probiotics for poultry, we used hydroxypropyl methylcellulose phthalate 55 (HPMCP 55) as a tablet-forming matrix to develop probiotics in a tablet form for poultry. Here, we made three different kinds of probiotics-loaded tablet under different compression forces and investigated their characteristics based on their survivability, morphology, disintegration time, and kinetics in simulated gastrointestinal fluid. The results indicated that the probiotics formulated in the tablets displayed higher survival rates in acidic gastric conditions than probiotics in solution. Rapid release of the probiotics from the tablets occurred in simulated intestinal fluid because of fast swelling of the tablets in neutral pH. As a matrix of tablet, HPMCP 55 provided good viability of probiotics after 6 months under refrigeration. Moreover, after oral administration of probiotics-loaded tablets to chicken, more viable probiotics were observed, than with solution type, through several digestive areas of chicken by the tablets.

Influence of formulation technique on acrylate methacrylate copolymer modified paracetamol matrix tablets.

PubMed

Cash-Torunarigha, Omonyemen Edoise; Eichie, Florence Egbomonjiade; Arhewoh, Matthew Ikhuoria

2015-03-01

This work was designed to evaluate the influence of various methods such as dry granulation (DG), wet granulation (using the polymer in an ethanolic solution (WGO) or aqueous dispersion (WGA) and solid dispersion (SD) techniques, on properties of paracetamol matrix tablets prepared using varying concentrations of acrylate methacrylate copolymer. Tablet properties were investigated using official and unofficial standards. Drug dissolution profile assessed at pH 1.2 was studied spectrophotometrically at λ(max) of 245 nm. With the use of various kinetic models, the release mechanism of the drug was analyzed. The parameters, maximum amount of drug release (m(∞)) at time t(∞) were obtained, m(∞) was ≥ 91.36 %, while t(∞) was ≥ 4.5 h. The release rate constant (k) for DG tablets was 15.61 h(sup>-1(/sup>, while, WGO, WGA and SD tablets were 12.90, 11.03 and 10.75 h(-1) respectively. The matrix tablets, which exhibited marked retardation in drug release displayed a Higuchi square root of time model (R(2) > 0.98). The mechanism through which the drug was released was governed by Fickian diffusion release (n values < 0.5). The performance of the drug was affected by the formulation technique in the order of SD > WGO > WGA > DG.

Quantitative evaluation of polymer concentration profile during swelling of hydrophilic matrix tablets using 1H NMR and MRI methods.

PubMed

Baumgartner, Sasa; Lahajnar, Gojmir; Sepe, Ana; Kristl, Julijana

2005-02-01

Many pharmaceutical tablets are based on hydrophilic polymers, which, after exposure to water, form a gel layer around the tablet that limits the dissolution and diffusion of the drug and provides a mechanism for controlled drug release. Our aim was to determine the thickness of the swollen gel layer of matrix tablets and to develop a method for calculating the polymer concentration profile across the gel layer. MR imaging has been used to investigate the in situ swelling behaviour of cellulose ether matrix tablets and NMR spectroscopy experiments were performed on homogeneous hydrogels with known polymer concentration. The MRI results show that the thickest gel layer was observed for hydroxyethylcellulose tablets, followed by definitely thinner but almost equal gel layer for hydroxypropylcellulose and hydroxypropylmethylcellulose of both molecular weights. The water proton NMR relaxation parameters were combined with the MRI data to obtain a quantitative description of the swelling process on the basis of the concentrations and mobilities of water and polymer as functions of time and distance. The different concentration profiles observed after the same swelling time are the consequence of the different polymer characteristics. The procedure developed here could be used as a general method for calculating polymer concentration profiles on other similar polymeric systems.

Formulation and evaluation of polyelectrolyte complex-based matrix tablet of Isosorbide Mononitrate

PubMed Central

Syed, Iizhar Ahmed; Niveditha, P.; Ahmad, Ismail

2014-01-01

Introduction: The polyelectrolyte Complexes (PECs) are based on ionic cross-linking. They have been employed to prepare a sustained release matrix tablets. These systems are based upon the fact that their structure can entrap the drug within them. Isosorbide Mononitrate (ISMN) is an anti-anginal organic nitrate vasodilator used in the treatment of various cardiovascular disorders and prophylaxis of angina Pectoris, which is poorly absorbed from the upper GIT, hence CR formulation is desirable. Materials and Methods: Chitosan (CH)/Sodium alginate (SA), Guar gum (GG), and Xanthan gum (XG) were used as PECs, and were prepared using different proportions i.e., in 1:1 and 1:2 ratio. The optimum ratio of CH: SA, CH: GG and CH: XG was in the ratio was 1:2; these are formed due to electrostatic interaction between oppositely charged poly ions. These normally employ a hydrophilic matrix system. Matrix tablet of ISMN was formulated by using PECs as matrix forming agent by wet granulation technique. Results: The tablets were evaluated for hardness, wt variation, drug content, and in-vitro dissolution studies and found to be within limits. Release kinetics data indicated that ISMN released from the PECs-based matrix tablets of CH-SA, CH-GG and CH-XG CP in 1:1 and 1:2 ratio, followed Fickian and non-Fickian diffusion mechanism respectively. Thus, the drug release rate was extended for over a period of more than 12 h stability studies. There is no significant difference in the mean % drug released from formulation CH-X2 after storing for 3 months at 40°C/75% RH. The FT-IR spectra revealed that there was no interaction between polymers and drug, Statistical analysis showed a significant differences (P < 0.05) for the amount of ISMN released from the formulations (MXG) and formulations (CH-X2). Conclusion: Formulation CH-XG2 (1:2) showed better sustained release of highly water-soluble ISMN with the desired release rate. Thus, the formulated PECs-based matrix tablets seems to be a potential candidate for sustained drug delivery of highly soluble drug ISMN in the symptomatic therapy of angina pectoris. PMID:24678461

Development and experimental design of a novel controlled-release matrix tablet formulation for indapamide hemihydrate.

PubMed

Antovska, Packa; Ugarkovic, Sonja; Petruševski, Gjorgji; Stefanova, Bosilka; Manchevska, Blagica; Petkovska, Rumenka; Makreski, Petre

2017-11-01

Development, experimental design and in vitro in vivo correlation (IVIVC) of controlled-release matrix formulation. Development of novel oral controlled delivery system for indapamide hemihydrate, optimization of the formulation by experimental design and evaluation regarding IVIVC on a pilot scale batch as a confirmation of a well-established formulation. In vitro dissolution profiles of controlled-release tablets of indapamide hemihydrate from four different matrices had been evaluated in comparison to the originator's product Natrilix (Servier) as a direction for further development and optimization of a hydroxyethylcellulose-based matrix controlled-release formulation. A central composite factorial design had been applied for the optimization of a chosen controlled-release tablet formulation. The controlled-release tablets with appropriate physical and technological properties had been obtained with a matrix: binder concentration variations in the range: 20-40w/w% for the matrix and 1-3w/w% for the binder. The experimental design had defined the design space for the formulation and was prerequisite for extraction of a particular formulation that would be a subject for transfer on pilot scale and IVIV correlation. The release model of the optimized formulation has shown best fit to the zero order kinetics depicted with the Hixson-Crowell erosion-dependent mechanism of release. Level A correlation was obtained.

Clinical pharmacokinetic study for the effect of glimepiride matrix tablets developed by quality by design concept.

PubMed

Ahmed, Tarek A; Suhail, Mohammad A A; Hosny, Khaled M; Abd-Allah, Fathy I

2018-01-01

Implementation of a new pharmaceutical technique to improve aqueous solubility and thus dissolution, enhancement of drug permeation, and finally formulation of a controlled release tablet loaded with glimepiride (GLMP). Improve GLMP bioavailability and pharmacokinetics in type II diabetic patients. Different polymers were used to enhance aqueous GLMP solubility of which a saturated polymeric drug solution was prepared and physically adsorbed onto silica. An experimental design was employed to optimize the formulation parameters affecting the preparation of GLMP matrix tablets. A compatibility study was conducted to study components interactions. Scanning electron microscope (SEM) was performed before and after the tablets were placed in the dissolution medium. An in vivo study in human volunteers was performed with the optimized GLMP tablets, which were compared to pure and marketed drug products. Enhancement of GLMP aqueous solubility, using the polymeric drug solution technique, by more than 6-7 times when compared with the binary system. All the studied formulation factors significantly affected the studied variables. No significant interaction was detected among components. SEM illustrated the surface and inner tablet structure, and confirmed the drug release which was attributed to diffusion mechanism. The volunteer group administered the optimized GLMP tablet exhibited higher drug plasma concentration (147.4 ng/mL), longer time to reach maximum plasma concentration (4 h) and longer t 1/2 (7.236 h) compared to other groups. Matrix tablet loaded with a physically modified drug form could represent a key solution for drugs with inconsistent dissolution and absorption profiles.

Release mechanisms of acetaminophen from polyethylene oxide/polyethylene glycol matrix tablets utilizing magnetic resonance imaging.

PubMed

Tajiri, Tomokazu; Morita, Shigeaki; Sakamoto, Ryosaku; Suzuki, Masazumi; Yamanashi, Shigeyuki; Ozaki, Yukihiro; Kitamura, Satoshi

2010-08-16

Release mechanism of acetaminophen (AAP) from extended-release tablets of hydrogel polymer matrices containing polyethylene oxide (PEO) and polyethylene glycol (PEG) were achieved using flow-through cell with magnetic resonance imaging (MRI). The hydrogel forming abilities are observed characteristically and the layer thickness which is corresponding to the diffusion length of AAP has a good correlation with the drug release profiles. In addition, polymeric erosion contribution to AAP releasing from hydrogel matrix tablets was directly quantified using size-exclusion chromatography (SEC). The matrix erosion profile indicates that the PEG erosion kinetic depends primarily on the composition ratio of PEG to PEO. The present study has confirmed that the combination of in situ MRI and SEC should be well suited to investigate the drug release mechanisms of hydrogel matrix such as PEO/PEG. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Application of mixture experimental design in the formulation and optimization of matrix tablets containing carbomer and hydroxy-propylmethylcellulose.

PubMed

Petrovic, Aleksandra; Cvetkovic, Nebojsa; Ibric, Svetlana; Trajkovic, Svetlana; Djuric, Zorica; Popadic, Dragica; Popovic, Radmila

2009-12-01

Using mixture experimental design, the effect of carbomer (Carbopol((R)) 971P NF) and hydroxypropylmethylcellulose (Methocel((R)) K100M or Methocel((R)) K4M) combination on the release profile and on the mechanism of drug liberation from matrix tablet was investigated. The numerical optimization procedure was also applied to establish and obtain formulation with desired drug release. The amount of TP released, release rate and mechanism varied with carbomer ratio in total matrix and HPMC viscosity. Increasing carbomer fractions led to a decrease in drug release. Anomalous diffusion was found in all matrices containing carbomer, while Case - II transport was predominant for tablet based on HPMC only. The predicted and obtained profiles for optimized formulations showed similarity. Those results indicate that Simplex Lattice Mixture experimental design and numerical optimization procedure can be applied during development to obtain sustained release matrix formulation with desired release profile.

Design of sustained release tablet containing fucoidan.

PubMed

Tran, Thao Truong-Dinh; Ngo, Dai Kieu-Phuong; Vo, Toi Van; Tran, Phuong Ha-Lien

2015-01-01

The study introduced a new therapeutic agent, fucoidan, which can offer potential medical treatments including anti-inflammatory and anti-coagulant activities, as well as anti-proliferative effects on cancer cells. Fucoidan was included in sustained release formulations expected for an effective plasma drug concentration for approximately 24 h. The matrices based on the two polymers hydroxypropyl methycellulose (HPMC) and polyethylene oxide (PEO) were prepared with various ratios between the polymers and fucoidan. The dissolution profiles of various matrix tablets performed in enzyme-free simulated intestinal fluid (pH 6.8) for 24 h indicated a higher potential of PEO-based matrix tablets in sustaining release of fucoidan. The swelling and erosion of the tablets were also characterized to elucidate the difference among those dissolution profiles.

Multispectral UV imaging for surface analysis of MUPS tablets with special focus on the pellet distribution.

PubMed

Novikova, Anna; Carstensen, Jens M; Rades, Thomas; Leopold, Prof Dr Claudia S

2016-12-30

In the present study the applicability of multispectral UV imaging in combination with multivariate image analysis for surface evaluation of MUPS tablets was investigated with respect to the differentiation of the API pellets from the excipients matrix, estimation of the drug content as well as pellet distribution, and influence of the coating material and tablet thickness on the predictive model. Different formulations consisting of coated drug pellets with two coating polymers (Aquacoat ® ECD and Eudragit ® NE 30 D) at three coating levels each were compressed to MUPS tablets with various amounts of coated pellets and different tablet thicknesses. The coated drug pellets were clearly distinguishable from the excipients matrix using a partial least squares approach regardless of the coating layer thickness and coating material used. Furthermore, the number of the detected drug pellets on the tablet surface allowed an estimation of the true drug content in the respective MUPS tablet. In addition, the pellet distribution in the MUPS formulations could be estimated by UV image analysis of the tablet surface. In conclusion, this study revealed that UV imaging in combination with multivariate image analysis is a promising approach for the automatic quality control of MUPS tablets during the manufacturing process. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of salt form and molecular weight of chitosan on swelling and drug release from chitosan matrix tablets.

PubMed

Huanbutta, Kampanart; Cheewatanakornkool, Kamonrak; Terada, Katsuhide; Nunthanid, Jurairat; Sriamornsak, Pornsak

2013-08-14

Magnetic resonance imaging (MRI) and gravimetric techniques were used to assess swelling and erosion behaviors of hydrophilic matrix tablets made of chitosan. The impact of salt form, molecular weight (MW) and dissolution medium on swelling behavior and drug (theophylline) release was studied. The matrix tablets made of chitosan glycolate (CGY) showed the greatest swelling in both acid and neutral media, compared to chitosan aspartate, chitosan glutamate and chitosan lactate. MRI illustrated that swelling region of CGY in both media was not different in the first 100 min but glassy region (dry core) in 0.1N HCl was less than in pH 6.8 buffer. The tablets prepared from chitosan with high MW swelled greater than those of low MW. Moreover, CGY can delay drug release in the acid condition due to thick swollen gel and low erosion rate. Therefore, CGY may be suitably applied as sustained drug release polymer or enteric coating material. Copyright © 2013 Elsevier Ltd. All rights reserved.

Release of theophylline and carbamazepine from matrix tablets--consequences of HPMC chemical heterogeneity.

PubMed

Viridén, Anna; Abrahmsén-Alami, Susanna; Wittgren, Bengt; Larsson, Anette

2011-08-01

The release of theophylline and carbamazepine from matrix tablets composed of microcrystalline cellulose, lactose and hydroxypropyl methylcellulose (HPMC) was studied. The aim was to investigate the effect of different substituent heterogeneities of HPMC on the drug release from matrix tablets composed of either 35% or 45% HPMC. The release of the poorly soluble carbamazepine was considerably affected by the HPMC heterogeneity, and the time difference at 80% drug release was more than 12h between the formulations of different HPMC batches. This was explained by slower polymer erosion of the heterogeneous HPMC and the fact that carbamazepine was mainly released by erosion. In addition, results from magnetic resonance imaging showed that the rate of water transport into the tablets was similar. This explained the comparable results of the release of the sparingly soluble theophylline from the two formulations even though the polymer erosion and the swelling of the tablets were considerably different. Thus, it can be concluded that the drug release was highly affected by the substituent heterogeneity, especially in the case of carbamazepine, which was released mainly by erosion. Copyright © 2011 Elsevier B.V. All rights reserved.

The use of a combination of different MR methods to study swelling of hydrophilic xanthan matrix tablets at different pHs.

PubMed

Mikac, U; Sepe, A; Kristl, J; Baumgartner, I

2012-01-01

Modified-release matrix tablets have been extensively used by the pharmaceutical industry as one of the most successful oral drug-delivery systems. The key element in drug release from hydrophilic matrix tablets is the gel layer that regulates the penetration of water and controls drug dissolution and diffusion. Magnetic resonance imaging (MRI) is a powerful, non-invasive technique that can help improve our understanding of the gel layer formed on swellable, polymer-matrix tablets, as well as the layer's properties and its influence on the drug release. The aim was to investigate the effects of pH and ionic strength on swelling and to study the influence of structural changes in xanthan gel on drug release. For this purpose a combination of different MRI methods for accurate determination of penetration, swelling and erosion fronts was used. The position of the penetration and swelling fronts were the same, independently of the different xanthan gel structures formed under different conditions of pH and ionic strength. The position of the erosion front, on the other hand, is strongly dependent on pH and ionic strength, as reflected in different thicknesses of the gel layers.

Controlled release floating multiparticulates of metoprolol succinate by hot melt extrusion.

PubMed

Malode, Vilas N; Paradkar, Anant; Devarajan, Padma V

2015-08-01

We present hot melt extrusion (HME) for the design of floating multiparticulates. Metoprolol succinate was selected as the model drug. Our foremost objective was to optimize the components Eudragit(®) RS PO, polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) to balance both buoyancy and controlled release. Gas generated by sodium bicarbonate in acidic medium was trapped in the polymer matrix to enable floating. Eudragit(®) RS PO and PEO with sodium bicarbonate resulted in multiparticulates which exhibited rapid flotation within 3 min but inadequate total floating time (TFT) of 3h. Addition of HPMC to the matrix did not affect floating lag time (FLT), moreover TFT increased to more than 12h with controlled release of metoprolol succinate. Floating multiparticulates exhibited t50% of 5.24h and t90% of 10.12h. XRD and DSC analysis revealed crystalline state of drug while FTIR suggested nonexistence of chemical interaction between the drug and the other excipients. The assay, FLT, TFT and the drug release of the multiparticulates were unchanged when stored at 40°C/75%RH for 3 months confirming stability. We present floating multiparticulates by HME which could be extrapolated to a range of other drugs. Our approach hence presents platform technology for floating multiparticulates. Copyright © 2015 Elsevier B.V. All rights reserved.

Near-infrared spectroscopic analysis of the breaking force of extended-release matrix tablets prepared by roller-compaction: influence of plasticizer levels and sintering temperature.

PubMed

Dave, Vivek S; Fahmy, Raafat M; Hoag, Stephen W

2015-06-01

The aim of this study was to investigate the feasibility of near-infrared (NIR) spectroscopy for the determination of the influence of sintering temperature and plasticizer levels on the breaking force of extended-release matrix tablets prepared via roller-compaction. Six formulations using theophylline as a model drug, Eudragit® RL PO or Eudragit® RS PO as a matrix former and three levels of TEC (triethyl citrate) as a plasticizer were prepared. The powder blend was roller compacted using a fixed roll-gap of 1.5 mm, feed screw speed to roller speed ratio of 5:1 and roll pressure of 4 MPa. The granules, after removing fines, were compacted into tablets on a Stokes B2 rotary tablet press at a compression force of 7 kN. The tablets were thermally treated at different temperatures (Room Temperature, 50, 75 and 100 °C) for 5 h. These tablets were scanned in reflectance mode in the wavelength range of 400-2500 nm and were evaluated for breaking force. Tablet breaking force significantly increased with increasing plasticizer levels and with increases in the sintering temperature. An increase in tablet hardness produced an upward shift (increase in absorbance) in the NIR spectra. The principle component analysis (PCA) of the spectra was able to distinguish samples with different plasticizer levels and sintering temperatures. In addition, a 9-factor partial least squares (PLS) regression model for tablets containing Eudragit® RL PO had an r(2) of 0.9797, a standard error of calibration of 0.6255 and a standard error of cross validation (SECV) of 0.7594. Similar analysis of tablets containing Eudragit® RS PO showed an r(2) of 0.9831, a standard error of calibration of 0.9711 and an SECV of 1.192.

The influence of heterogeneous nucleation on the surface crystallization of guaifenesin from melt extrudates containing Eudragit L10055 or Acryl-EZE.

PubMed

Bruce, Caroline D; Fegely, Kurt A; Rajabi-Siahboomi, Ali R; McGinity, James W

2010-05-01

The objective of this study was to investigate the influence of talc and humidity conditions during storage on the crystal growth of guaifenesin on the surface of melt-extruded matrix tablets. Tablets consisted of the model drug guaifenesin in a matrix of either Acryl-EZE(R) or Eudragit(R) L10055 and either no talc, 25% or 50% talc. After processing, the hot-melt-extruded matrix tablets were supersaturated with amorphous guaifenesin, which resulted in the development of guaifenesin drug crystals on exposed surfaces of the tablet during storage (all tablets were stored at 24 degrees C). A previously developed, quantitative test was used to assay for surface guaifenesin. In tablets with a drug-to-polymer ratio of 19:81, talc-containing tablets exhibited an earlier onset of crystal growth (storage at 17% relative humidity). The presence of talc also increased the amount of surface crystallization and was independent of the talc concentration, since the talc levels used in this study exceeded the critical nucleant concentration. Additional non-melting components did not have an additive effect on surface crystal growth. High humidity during storage (78%) increased guaifenesin crystallization, but moisture uptake of tablets did not correlate with increased drug recrystallization. When storage at 17% relative humidity was interrupted for 3days by storage at 78% relative humidity before the tablets were returned to their previous low RH storage conditions, crystal growth quickly increased during the high RH interval and remained at an elevated level throughout the remaining storage period. A similar intermediate period of low, 17% relative humidity in tablets stored before and after that time at 78% RH did not affect surface crystallization levels. The effects of humidity and talc on the crystallization of guaifenesin from melt-extruded dosage forms supersaturated with amorphous drug were ascribed to heterogeneous nucleation.

Evaluation of the swelling behaviour of iota-carrageenan in monolithic matrix tablets.

PubMed

Kelemen, András; Buchholcz, Gyula; Sovány, Tamás; Pintye-Hódi, Klára

2015-08-10

The swelling properties of monolithic matrix tablets containing iota-carrageenan were studied at different pH values, with measurements of the swelling force and characterization of the profile of the swelling curve. The swelling force meter was linked to a PC by an RS232 cable and the measured data were evaluated with self-developed software. The monitor displayed the swelling force vs. time curve with the important parameters, which could be fitted with an Analysis menu. In the case of iota-carrageenan matrix tablets, it was concluded that the pH and the pressure did not influence the swelling process, and the first section of the swelling curve could be fitted by the Korsmeyer-Peppas equation. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of two hydrophobic polymers on the release of gliclazide from their matrix tablets.

PubMed

Hussain, Talib; Saeed, Tariq; Mumtaz, Ahmad M; Javaid, Zeeshan; Abbas, Khizar; Awais, Azeema; Idrees, Hafiz Arfat

2013-01-01

Gliclazide is an oral hypoglycemic agent, indicated in non insulin dependent diabetes mellitus and in patients with diabetic retinopathy. It has good tolerability and is a short acting sulfonyl urea that requires large dose to maintain the blood glucose level. So development of a sustained release formulation of gliclazide (GLZ) is required for better patient compliance. This study was conducted to assess the effects of different drug polymer ratios on the release profile of gliclazide from the matrix. Oral matrix tablets of gliclazide were prepared by hot melt method, using pure and blended mixture of glyceryl monostearate (GMS) and stearic acid (SA) in different ratios. In vitro release pattern was studied for 8 h in phosphate buffer media (pH 7.4). Different kinetic models including zero order, first order, Higuchi and Peppas were applied to evaluate drug release behavior. Drug excipient compatibility was evaluated by scanning with DSC and FTIR. Higuchi model was found the most appropriate model for describing the release profile of GLZ and non-Fickian release was found predominant mechanism of drug release. The release of drug from the matrix was greatly controlled by GMS while SA appeared to facilitate the release of drug from matrix tablets. FTIR results showed no chemical interaction between drug and the polymers, and DSC results indicated amorphous state of GLZ and polymers without significant complex formation. The results indicate that matrix tablets of gliclazide using glyceryl monostearate and stearic acid showed marked sustained release properties.

Release from or through a wax matrix system. IV. Generalized expression of the release process for a reservoir device tablet.

PubMed

Yonezawa, Yorinobu; Ishida, Sumio; Suzuki, Shinobu; Sunada, Hisakazu

2002-09-01

Generalization of the release process through the wax matrix layer was examined by use of a reservoir device tablet. The wax matrix layer of the reservoir device tablet was prepared from a physical mixture of lactose and hydrogenated castor oil to simplify the release properties. Release through the wax matrix layer showed zero-order kinetics in a steady state after a given lag time, and could be divided into two stages. The first stage was the formation process of water channel by dissolving the soluble component in the wax matrix layer. The lag time obtained by applying the square root law equation was well connected with the amount of the matrix layer and mixed weight ratio of components in this layer. The second stage was the zero-order release process of drug in the reservoir through the wax matrix layer, because the effective surface area was fixed. The release rate constants were connected with thickness of the matrix layer and permeability coefficient, and the permeability coefficients were connected with the diffusion coefficient of drug and porosity. Hence the release rate constant could be connected with the amount of matrix layer and the mixed weight ratio of components in the matrix layer. It was therefore suggested that the release process could be generalized using the amount of matrix layer and the mixed weight ratio of components in the matrix layer.

Effect of drug particle size in ultrasound compacted tablets. Continuum percolation model approach.

PubMed

Millán, Mónica; Caraballo, Isidoro

2006-03-09

The main objective of this work is to study the influence of the drug particle size on the pharmaceutical availability of ultrasound compacted tablets. Inert matrix systems containing different drug particle sizes were prepared using both, an ultrasound-assisted press and a traditional eccentric machine. Potassium chloride was used as drug model and Eudragit RS-PM as matrix forming excipient. The excipient particle size was kept constant. The cross-sectional microphotographs of ultrasound tablets show the existence of a quasi-continuum medium. Keeping constant the drug load, US-tablets showed very similar release rates, whereas for traditional tablets, an increase in the particle size resulted in a clear decrease in the release rate. In these tablets, the excipient forms an almost continuum medium. In an infinite theoretical system of these characteristics, the size of the drug particles will not modify the percolation threshold. The percolation of the excipient in this system can be assimilated to a continuum percolation model. In accordance with the proposed model, a lower influence of the drug particle size on the drug release rate was obtained for the US-tablets in comparison with traditional tablets. This fact can be indicative of the similarity of the drug percolation thresholds in these systems.

Studies on the compressibility of wax matrix granules of acetaminophen and their admixtures with various tableting bases.

PubMed

Uhumwangho, M U; Okor, R S

2006-04-01

Matrix granules of acetaminophen have been formed by a melt granulation process whereby the acetaminophen powder was triturated with the melted wax--goat wax, glyceryl monostearate or carnuba wax. The compressibility of the matrix granules and their admixture, with diluent granules (lactose, alpha-cellulose or microcrystalline cellulose) was investigated. The granules were compressed to tablets at a constant load (30 arbitrary units on the load scale) of a manesty single punch machine. Resulting tablets were evaluated for tensile strength (T) and disintegration times (DT). Granule flow was determined by measuring their angle of repose when allowed to fall freely on a level surface. Matrix granules prepared by melt granulation with goat wax or glyceryl monostearate were too sticky and therefore did not flow at all. They were also poorly compressible (T values = 0.20MN/m2). Inclusion of the diluent remarkably improved granule flow property and compressibility. The T values of the tablets (measure of compressibility) increased from about 0.24 to 0.65 MN/m2 during increase in diluent (lactose) content from 20 to 80 %w/w. Microcrystalline cellulose and alpha-cellulose were more effective than lactose in promoting compressibility of the granules. By contrast the matrix granules formed with carnuba wax were free flowing (angle of repose, 18.60). Addition of the diluent further improved flowability slightly. The matrix granules (without a diluent) were readily compressible (T value, 1.79MN/m2). Addition of the diluent (80%w/w) reduced T values (MN/m2) slightly to 1.32 (lactose), 1.48 (alpha-cellulose) and 1.74 (microcrystalline cellulose). Tablets of the matrix granules only, disintegrated rapidly within 3 minutes. DT was further reduced to <30 s by addition of any of the diluents. The indication is that the inclusion of the diluents studied can be used to improve the compressibility of the otherwise poorly compressible matrix granules. Based on the flowability, compressibility, and disintegration data, carnuba wax proved most promising in the melt granulation of the test drug for sustained release applications.

Improving energy efficiency in handheld biometric applications

NASA Astrophysics Data System (ADS)

Hoyle, David C.; Gale, John W.; Schultz, Robert C.; Rakvic, Ryan N.; Ives, Robert W.

2012-06-01

With improved smartphone and tablet technology, it is becoming increasingly feasible to implement powerful biometric recognition algorithms on portable devices. Typical iris recognition algorithms, such as Ridge Energy Direction (RED), utilize two-dimensional convolution in their implementation. This paper explores the energy consumption implications of 12 different methods of implementing two-dimensional convolution on a portable device. Typically, convolution is implemented using floating point operations. If a given algorithm implemented integer convolution vice floating point convolution, it could drastically reduce the energy consumed by the processor. The 12 methods compared include 4 major categories: Integer C, Integer Java, Floating Point C, and Floating Point Java. Each major category is further divided into 3 implementations: variable size looped convolution, static size looped convolution, and unrolled looped convolution. All testing was performed using the HTC Thunderbolt with energy measured directly using a Tektronix TDS5104B Digital Phosphor oscilloscope. Results indicate that energy savings as high as 75% are possible by using Integer C versus Floating Point C. Considering the relative proportion of processing time that convolution is responsible for in a typical algorithm, the savings in energy would likely result in significantly greater time between battery charges.

Effect of Quaternary Ammonium Carboxymethylchitosan on Release Rate In-vitro of Aspirin Sustained-release Matrix Tablets

PubMed Central

Meng, Lingbin; Teng, Zhongqiu; Zheng, Nannan; Meng, Weiwei; Dai, Rongji; Deng, Yulin

2013-01-01

The aim of this study was to develop a derivative of chitosan as pharmaceutical excipient used in sustained-release matrix tablets of poorly soluble drugs. A water-soluble quaternary ammonium carboxymethylchitosan was synthesized by a two-step reaction with carboxymethylchitosan (CMCTS), decylalkyl dimethyl ammonium and epichlorohydrin. The elemental analysis showed that the target product with 10.27% of the maximum grafting degree was obtained. To assess the preliminary safety of this biopolymer, cell toxicity assay was employed. In order to further investigate quaternary ammonium carboxymethylchitosan application as pharmaceutical excipient, aspirin was chosen as model drug. The effect of quaternary ammonium CMCTS on aspirin release rate from sustained-release matrix tablets was examined by in-vitro dissolution experiments. The results showed that this biopolymer had a great potential in increasing the dissolution of poorly soluble drug. With the addition of CMCTS-CEDA, the final cumulative release rate of drug rose up to 90%. After 12 h, at the grade of 10, 20 and 50 cps, the drug release rate increased from 58.1 to 90.7%, from 64.1 to 93.9%, from 69.3 to 96.1%, respectively. At the same time, aspirin release rate from sustainedrelease model was found to be related to the amount of quaternary ammonium CMCTS employed. With the increase of CMCTS-CEDA content, the accumulated release rate increased from 69.1% to 86.7%. The mechanism of aspirin release from sustained-release matrix tablets was also preliminary studied to be Fick diffusion. These data demonstrated that the chitosan derivative has positive effect on drug release from sustained-release matrix tablets. PMID:24250627

Formulation of a poorly water-soluble drug in sustained-release hollow granules with a high viscosity water-soluble polymer using a fluidized bed rotor granulator.

PubMed

Asada, Takumi; Yoshihara, Naoki; Ochiai, Yasushi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

2018-04-25

Water-soluble polymers with high viscosity are frequently used in the design of sustained-release formulations of poorly water-soluble drugs to enable complete release of the drug in the gastrointestinal tract. Tablets containing matrix granules with a water-soluble polymer are preferred because tablets are easier to handle and the multiple drug-release units of the matrix granules decreases the influences of the physiological environment on the drug. However, matrix granules with a particle size of over 800 μm sometimes cause a content uniformity problem in the tableting process because of the large particle size. An effective method of manufacturing controlled-release matrix granules with a smaller particle size is desired. The aim of this study was to develop tablets containing matrix granules with a smaller size and good controlled-release properties, using phenytoin as a model poorly water-soluble drug. We adapted the recently developed hollow spherical granule granulation technology, using water-soluble polymers with different viscosities. The prepared granules had an average particle size of 300 μm and sharp particle size distribution (relative width: 0.52-0.64). The values for the particle strength of the granules were 1.86-1.97 N/mm 2 , and the dissolution profiles of the granules were not affected by the tableting process. The dissolution profiles and the blood concentration levels of drug released from the granules depended on the viscosity of the polymer contained in the granules. We succeeded in developing the desired controlled-release granules, and this study should be valuable in the development of sustained-release formulations of poorly water-soluble drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Properties of hot-melt extruded theophylline tablets containing poly(vinyl acetate).

PubMed

Zhang, F; McGinity, J W

2000-09-01

The objectives of this study were to investigate the properties of poly(vinyl acetate) (PVAc) as a retardant polymer and to study the drug release mechanism of theophylline from matrix tablets prepared by hot-melt extrusion. A physical mixture of drug, polymer, and drug release modifiers was fed into the equipment and heated inside the barrel of the extruder. The cylindrical extrudates were either cut into tablets or ground into granules and compressed with other excipients into tablets. Due to the low glass transition temperature of the PVAc, the melt extrusion process was conducted at approximately 70 degrees C. Theophylline was used as the model drug in this study. Theophylline was present in the extrudate in its crystalline form and was released from the tablets by diffusion. The Higuchi diffusion model and percolation theories were applied to the dissolution data to explain the drug release properties of the matrix systems. The release rate was shown to be dependent on the granule size, drug particle size, and drug loading in the tablets. Water-soluble polymers were demonstrated to be efficient release rate modifiers for this system.

Single-dose evaluation of safety, tolerability and pharmacokinetics of newly formulated hydromorphone immediate-release and hydrophilic matrix extended-release tablets in healthy Japanese subjects without co-administration of an opioid antagonist.

PubMed

Toyama, Kaoru; Uchida, Naoki; Ishizuka, Hitoshi; Sambe, Takehiko; Kobayashi, Shinichi

2015-09-01

This single dose, open-label study investigated the safety, tolerability and pharmacokinetics of single oral doses of newly formulated immediate-release (IR) and hydrophilic matrix extended-release (ER) hydromorphone tablets in healthy Japanese subjects without co-administration of an opioid antagonist under fasting and fed conditions. Plasma and urinary concentrations of hydromorphone and metabolites were measured by liquid-chromatography tandem mass-spectroscopy. Following administration of the ER tablet, plasma concentrations of hydromorphone slowly increased with a median tmax of 5.0 h and the Cmax decreased to 37% of the IR tablet, while the AUC0-inf was comparable with that of the IR tablet when administered at the same dose. The degree of fluctuation in the plasma concentration for the ER tablet was much lower than that of the IR tablet and certain levels of plasma concentrations were maintained after 24 h of ER dosing. The AUC0-inf and Cmax increased with food for both IR and ER tablets. The AUC0-inf of hydromorphone-3-glucoside was one-tenth of that of hydromorphone-3-glucuronide. A single oral administration of the hydromorphone tablets would be well-tolerated in healthy Japanese subjects despite a lack of co-administration of an opioid antagonist and the newly developed ER hydromorphone tablets may have the appropriate PK characteristics for once-daily dosing. © 2015, The American College of Clinical Pharmacology.

Implementation of Quality by Design for Formulation of Rebamipide Gastro-retentive Tablet.

PubMed

Ha, Jung-Myung; Seo, Jeong-Woong; Kim, Su-Hyeon; Kim, Ju-Young; Park, Chun-Woong; Rhee, Yun-Seok; Park, Eun-Seok

2017-11-01

The purpose of the present study was to develop a rebamipide (RBM) gastro-retentive (GR) tablet by implementing quality by design (QbD). RBM GR tablets were prepared using a sublimation method. Quality target product profile (QTPP) and critical quality attributes (CQAs) of the RBM GR tablets were defined according to the preliminary studies. Factors affecting the CQAs were prioritized using failure mode and effects analysis (FMEA). Design space and optimum formulation were established through a mixture design. The validity of the design space was confirmed using runs within the area. The QTPP of the RBM GR tablets was the orally administered GR tablet containing 300 mg of RBM taken once daily. Based on the QTPP, dissolution rate, tablet friability, and floating property were chosen as CQAs. According to the risk assessment, the amount of sustained-release agent, sublimating material, and diluent showed high-risk priority number (RPN) values above 40. Based on the RPN, these factors were further investigated using mixture design methodology. Design space of formulations was depicted as an overlaid contour plot and the optimum formulation to satisfy the desired responses was obtained by determining the expected value of each response. The similarity factor (f2) of the release profile between predicted response and experimental response was 89.463, suggesting that two release profiles are similar. The validity of the design space was also confirmed. Consequently, we were able to develop the RBM GR tablets by implementing the QbD concept. These results provide useful information for development of tablet formulations using the QbD.

A novel pH-responsive interpolyelectrolyte hydrogel complex for the oral delivery of levodopa. Part II: characterization and formulation of an IPEC-based tablet matrix.

PubMed

Ngwuluka, Ndidi C; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Khan, Riaz A; Pillay, Viness

2015-03-01

This study was undertaken in order to apply a synthesized interpolyelectrolyte complex (IPEC) of polymethacrylate and carboxymethylcellulose as a controlled release oral tablet matrix for the delivery of the model neuroactive drug levodopa. The IPEC (synthesized in Part I of this work) was characterized by techniques such as Fourier Transform Infra-Red (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), Advanced DSC (ADSC), and Scanning Electron Microscopy (SEM). The tablet matrices were formulated and characterized for their drug delivery properties and in vitro drug release. FTIR confirmed the interaction between the two polymers. The IPEC composite generated tablet matrices with a hardness ranging from 19.152-27.590 N/mm and a matrix resilience ranging between 42 and 46%. An IPEC of polymethacrylate and carboxymethylcellulose was indeed an improvement on the inherent properties of the native polymers providing a biomaterial with the ability to release poorly soluble drugs such as levodopa at a constant rate over a prolonged period of time. © 2014 Wiley Periodicals, Inc.

Matrix tablets for sustained release of repaglinide: Preparation, pharmacokinetics and hypoglycemic activity in beagle dogs.

PubMed

He, Wei; Wu, Mengmeng; Huang, Shiqing; Yin, Lifang

2015-01-15

Repaglinide (RG) is an efficient antihyperglycemic drug; however, due to its short half-life, patients are required to take the marketed products several times a day, which compromises the therapeutic effects. The present study was conducted to develop a hydrophilic sustained release matrix tablet for RG with the aims of prolonging its action time, reducing the required administration times and side effects and improving patient adherence. The matrix tablets were fabricated by a direct compression method, the optimized formulation for which was obtained by screening the factors that affected the drug release. Moreover, studies of the pharmacokinetics and hypoglycemic activity as measured by glucose assay kits were performed in dogs. Sustained drug releases profiles over 10h and a reduced influence of medium pHs on release were achieved with the optimized formulation; moreover, the in vivo performance of extended release formulation was also examined, and better absorption, a one-fold decrease in Cmax, a two-fold increase of Tmax and a prolonged hypoglycemic effect compared to the marketed product were observed. In conclusion, sustained RG release and prolonged action were observed with present matrix tablets, which therefore provide a promising formulation for T2D patients who require long-term treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Formulations of Amlodipine: A Review

PubMed Central

Ahsan, Syed Furqan; Khan, Marium Fatima

2016-01-01

Amlodipine (AD) is a calcium channel blocker that is mainly used in the treatment of hypertension and angina. However, latest findings have revealed that its efficacy is not only limited to the treatment of cardiovascular diseases as it has shown to possess antioxidant activity and plays an important role in apoptosis. Therefore, it is also employed in the treatment of cerebrovascular stroke, neurodegenerative diseases, leukemia, breast cancer, and so forth either alone or in combination with other drugs. AD is a photosensitive drug and requires protection from light. A number of workers have tried to formulate various conventional and nonconventional dosage forms of AD. This review highlights all the formulations that have been developed to achieve maximum stability with the desired therapeutic action for the delivery of AD such as fast dissolving tablets, floating tablets, layered tablets, single-pill combinations, capsules, oral and transdermal films, suspensions, emulsions, mucoadhesive microspheres, gels, transdermal patches, and liposomal formulations. PMID:27822402

Relationships between surface free energy, surface texture parameters and controlled drug release in hydrophilic matrices.

PubMed

Saurí, J; Suñé-Negre, J M; Díaz-Marcos, J; Vilana, J; Millán, D; Ticó, J R; Miñarro, M; Pérez-Lozano, P; García-Montoya, E

2015-01-15

The study of controlled release and drug release devices has been dominated by considerations of the bulk or average properties of material or devices. Yet the outermost surface atoms play a central role in their performance. The objective of this article has been to characterize the surface of hydrophilic matrix tablets using the contact angle (CA) method to ascertain the surface free energy, and atomic force microscopy (AFM) and confocal microscopy (CM) for the physical characterization of the surface of the hydrophilic matrix. The surface free energy results obtained show that hydroxypropylmethylcellulose K15M hinders the spreading of water on the surface of the tablet, such that the concentration of HPMC K15M increases the reaction rate of the hydrophobic interactions between the chains of HPMC K15M which increases with respect to the rate of penetration of water into the tablet. In this study, we developed a new method to characterize the swelling of the tablets and established a relationship between the new method based on microswelling and the swelling ratio parameter. The surface texture parameters have been determined and the morphology of the tablets of the different formulations and the evolution of the surface morphology after interacting with the water, swelling and forming a gel layer were characterized. This work represents significant progress in the characterization of matrix tablets. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of metoprolol tartrate extended-release matrix tablet formulations for regulatory policy consideration.

PubMed

Nellore, R V; Rekhi, G S; Hussain, A S; Tillman, L G; Augsburger, L L

1998-01-02

This research study was designed to develop model extended-release (ER) matrix tablet formulations for metoprolol tartrate (100 mg) sufficiently sensitive to manufacturing variable and to serve as the scientific basis for regulatory policy development on scale-up and post approval changes for modified-release dosage forms (SUPAC-MR). Several grades and levels of hydroxypropyl methylcellulose (Methocel K4M, K15M, K100M and K100LV), fillers and binders and studied. Three granulation processes were evaluated; direct compression, fluid-bed or high-shear granulation. Lubrication was performed in a V-blender and tablets were compressed on an instrumented rotary tablet press. Direct compression formulations exhibited poor flow, picking and sticking problems during tableting. High-shear granulation resulted in the formation of hard granules that were difficult to mill but yielded good tablets. Fluid-bed granulations were made using various binders and appeared to be satisfactory in terms of flow and tableting performance. In vitro drug release testing was performed in pH 6.8 phosphate buffer using USP apparatus 2 (paddle) at 50 rpm. At a fixed polymer level, drug release from the higher viscosity grades (K100M) was slower as compared to the lower viscosity grades (K100LV). In addition, release from K100LV was found to be more sensitive to polymer level changes. Increased in polymer level from 10 to 40% and/or filler change from lactose to dicalcium phosphate resulted in about 25-30% decrease in the amount of metoprolol release after 12 h. The results of this study led to the choice of Methocel K100LV as the hydrophilic matrix polymer and fluid-bed granulation as the process of choice for further evaluation of critical and non-critical formulation and processing variables.

Chitinosans as tableting excipients for modified release delivery systems.

PubMed

Rege, P R; Shukla, D J; Block, L H

1999-04-20

The term 'chitinosans' embraces the spectrum of acetylated poly(N-glucosamines) ranging from chitin to chitosan. Chitinosans (I), at acidic pH, have protonated amines which can interact with oppositely charged drug ions and, thereby, modify drug release from drug delivery systems. Tablets were compressed from a physical mixture containing salicylic acid (II) as the model drug, I, and magnesium stearate. Five commercial I compounds, varying in degree of deacetylation and molecular weight, were selected. Tablets were compressed at 5000, 10 000, and 15 000 psig using a Carver and a single punch tablet press. The differential scanning calorimetry thermograms provided evidence of I-II interaction in the powder blend. Analysis of variance (ANOVA) indicated that the compression pressure did not significantly affect the crushing strength (CS) or the release profile of II from the I-matrix tablets (P?0.05). Furthermore, the ANOVA also indicated that the tablet press used during manufacture did not affect the above properties (P?0.05); however, the chitinosans significantly affected the CS as well as the release profile of II from I-matrix tablets (P<0.05). This study provides further evidence for the use of commercial I compounds as excipients for use in modified release drug delivery systems. Copyright.

Desktop 3D printing of controlled release pharmaceutical bilayer tablets.

PubMed

Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Roberts, Clive J

2014-01-30

Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol(®) 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose(®) (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel(®) 102) and sodium starch glycolate (SSG) (Primojel(®)) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex(®)) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation and in-vivo pharmacokinetic study of a novel extended release compression coated tablets of fenoterol hydrobromide.

PubMed

Elshafeey, Ahmed H; Sami, Elshaimaa I

2008-01-01

The aim of this study was to formulate extended release compression coated core tablets of fenoterol hydrobromide, a selective beta(2) adrenergic receptor agonist, in an attempt to prevent nocturnal asthma. Two hydrophilic polymers viz Kollidon SR, Polyox WSR 303 and a hydrophobic one (Precirol ATO5) were employed. Compression coated tablets were formulated by preparing a core tablet containing 7.5 mg drug and various amounts of polymer and Emcompress then compressed coated with the same polymeric materials. For comparison purpose different matrix tablets were also prepared employing the same polymers. In-vitro release studies were carried out at different pH (1.2 and 6.8). Pharmacokinetics of extended release tablets as well as commercially available immediate release tablets (Berotec) were studied after oral administration to beagle dogs using a new developed LC-MS/MS method with a lower limit of quantification of 1 ng/ml. Fenoterol release from compression coated tablets was significantly lower than matrix tablets. The mechanism of release was changed with the nature and content of polymer. The release pattern of drug from F16 containing 40 mg Kollidon SR divided in the core tablet (15 mg) and the rest in the compressed coat (25 mg) showed a typical zero order release kinetic that could extend drug release >10 h and reasonable time for 75% to be released (t(75)) (8.92 h). When compared to immediate release Berotec tablet the MRT was significantly extended from 7.03 +/- 0.76 to 10.93 +/- 1.25 h (P < 0.001) and HVD(t 50%Cmax) was also significantly extended from 2.71 +/- 0.68 to 6.81 +/- 0.67 h with expected prevention of nocturnal asthma.

Influence of water-soluble channeling agents on the release of diclofenac sodium from Irvingia malayana wax matrix tablets.

PubMed

Yotsawimonwat, Songwut; Charumanee, Suporn; Kaewvichit, Sayam; Sirithunyalug, Jakkapan; Sirisa-Ard, Panee; Piyamongkol, Sirivipa; Siangwong, Kulthawat

2017-05-01

Irvingia malayana wax (IW) is majorly composed of esters of medium chain fatty acids. Its melting point is low and closed to the body temperature. This study aimed at investigating the potential of IW as a matrix-forming agent and evaluate the effect of soluble channeling agents on the release of diclofenac sodium (DS) from IW matrix tablets. The preformulation study by infrared spectroscopy and differential scanning calorimetry showed no incompatibility between IW and DS or soluble channeling agents, namely PEG 4000, PEG 6000 and lactose. IW retarded the release of DS from the matrix tablets more efficiently than carnauba wax due to its greater hydrophobicity and its ability to become partial molten wax at 37° C. Factors affecting the release of DS from IW matrix were drug concentrations, and types and concentrations of channeling agents. The release of DS significantly improved when DS concentration reached approximately 33%. The fast dissolving channeling agent, lactose, could enhance the drug release rate more effectively than PEG 4000 and PEG 6000, respectively. The linear relationship between the DS release rate and the concentration of the chosen channeling agent, PEG 6000, was found (r 2 =0.9866).

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: physicochemical and technological characterisation.

PubMed

Marinich, J A; Ferrero, C; Jiménez-Castellanos, M R

2009-05-01

Nowadays, graft copolymers are being used as an interesting option when developing a direct compression excipient for controlled release matrix tablets. New graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS) were synthesised by free radical polymerization and alternatively dried in a vacuum oven (OD) or freeze-dried (FD). This paper evaluates the performance of these new macromolecules and discusses the effect of the carbohydrate nature and drying process on their physicochemical and technological properties. Grafting of EMA on the carbohydrate backbone was confirmed by IR and NMR spectroscopy, and the grafting yields revealed that graft copolymers present mainly a hydrophobic character. The graft copolymerization also leads to more amorphous materials with larger particle size and lower apparent density and water content than carbohydrates (MS, MHS). All the products show a lack of flow, except MHSEMA derivatives. MSEMA copolymers underwent much plastic flow and less elastic recovery than MHSEMA copolymers. Concerning the effect of drying method, FD derivatives were characterised by higher plastic deformation and less elasticity than OD derivatives. Tablets obtained from graft copolymers showed higher crushing strength and disintegration time than tablets obtained from raw starches. This behaviour suggests that these copolymers could be used as excipients in matrix tablets obtained by direct compression and with a potential use in controlled release.

Swelling kinetics of spray-dried chitosan acetate assessed by magnetic resonance imaging and their relation to drug release kinetics of chitosan matrix tablets.

PubMed

Huanbutta, Kampanart; Sriamornsak, Pornsak; Limmatvapirat, Sontaya; Luangtana-anan, Manee; Yoshihashi, Yasuo; Yonemochi, Etsuo; Terada, Katsuhide; Nunthanid, Jurairat

2011-02-01

Magnetic resonance imaging (MRI) was used to assess in situ swelling behaviors of spray-dried chitosan acetate (CSA) in 0.1N HCl, pH 6.8 and pH 5.0 Tris-HCl buffers. The in vitro drug releases from CSA matrix tablets containing the model drugs, diclofenac sodium and theophylline were investigated in all media using USP-4 apparatus. The effect of chitosan molecular weight, especially in pH 6.8 Tris-HCl, was also studied. In 0.1N HCl, the drug release from the matrix tablets was the lowest in relation to the highest swelling of CSA. The swelling kinetics in Tris-HCl buffers are Fickian diffusion according to their best fit to Higuchi's model as well as the drug release kinetics in all the media. The high swelling rate (k(s)(')) was found to delay the drug release rate (k'). The linear relationship between the swelling and fractions of drug release in Tris-HCl buffers was observed, indicating an important role of the swelling on controlling the drug release mechanism. Additionally, CSA of 200 and 800 kDa chitosan did not swell in pH 6.8 Tris-HCl but disintegrated into fractions, and the drug release from the matrix tablets was the highest. Copyright © 2010 Elsevier B.V. All rights reserved.

Design and in vivo evaluation of a patch system based on thiolated polymers.

PubMed

Hoyer, Herbert; Greindl, Melanie; Bernkop-Schnürch, Andreas

2009-02-01

A new oral patch delivery system has been designed to increase the overall oral bioavailability of drugs within the gastrointestinal tract. The patch system consists of four layered films: a mucoadhesive matrix layer, a water insoluble backing layer, a middle layer and an enteric surface layer. The separation layer between the two matrix layers contained lactose, starch and confectioners' sugar. The matrix layer, exhibiting a diameter of 2.5 mm and a weight of 5 mg, comprised Polycarbophil-cysteine conjugate (49%), fluoresceine isothiocyanate-dextran (26%), glutathione (5%), and mannitol (20%). A standard tablet formulation consisting of the same matrix served as control. Entire fluoresceine isothiocyanate-dextran (FD(4)) was released from the delivery system within 2 h. For in vivo studies patch systems were administered orally to male Sprague-Dawley rats. Maximum FD(4) concentration in blood of the patch system was 46.1 +/- 8.9 ng/mL and was reached 3 h after administration. In contrast c(max) of control tablets displayed 50.5 +/- 14.9 ng/mL after 2 h and the absorption of FD(4) after administration in oral solution was negligible. The absolute bioavailability of orally administered patch systems and control tablets was 0.54% and 0.32% respectively. Results of this study indicate that a prolonged and higher oral bioavailability of FD(4) is obtained with patches than with tablets.

Prolonged release matrix tablet of pyridostigmine bromide: formulation and optimization using statistical methods.

PubMed

Bolourchian, Noushin; Rangchian, Maryam; Foroutan, Seyed Mohsen

2012-07-01

The aim of this study was to design and optimize a prolonged release matrix formulation of pyridostigmine bromide, an effective drug in myasthenia gravis and poisoning with nerve gas, using hydrophilic - hydrophobic polymers via D-optimal experimental design. HPMC and carnauba wax as retarding agents as well as tricalcium phosphate were used in matrix formulation and considered as independent variables. Tablets were prepared by wet granulation technique and the percentage of drug released at 1 (Y(1)), 4 (Y(2)) and 8 (Y(3)) hours were considered as dependent variables (responses) in this investigation. These experimental responses were best fitted for the cubic, cubic and linear models, respectively. The optimal formulation obtained in this study, consisted of 12.8 % HPMC, 24.4 % carnauba wax and 26.7 % tricalcium phosphate, had a suitable prolonged release behavior followed by Higuchi model in which observed and predicted values were very close. The study revealed that D-optimal design could facilitate the optimization of prolonged release matrix tablet containing pyridostigmine bromide. Accelerated stability studies confirmed that the optimized formulation remains unchanged after exposing in stability conditions for six months.

Formulation, in vitro evaluation and study of variables on tri-layered gastro-retentive delivery system of diltiazem HCl.

PubMed

Raut Desai, Shilpa; Rohera, Bhagwan D

2014-03-01

Tri-layered floating tablets using only one grade of polyethylene oxide (PEO) would enable easy manufacturing, reproducibility and controlled release for highly soluble drugs. To evaluate the potential of PEO as a sole polymer for the controlled release and to study the effect of formulation variables on release and gastric retention of highly soluble Diltiazem hydrochloride (DTZ). Tablets were compressed with middle layer consisting of drug and polymer while outer layers consisted of polymer with sodium bicarbonate. Design of formulation to obtain 12 h, zero-order release and rapid floatation was done by varying the grades, quantity of PEO and sodium bicarbonate. Dissolution data were fitted in drug release models and swelling/erosion studies were undertaken to verify the drug release mechanism. Effect of formulation variables and tablet surface morphology using scanning electron microscopy were studied. The optimized formula passed the criteria of USP dissolution test I and exhibited floating lag-time of 3-4 min. Drug release was faster from low molecular weight (MW) PEO as compared to high MW. With an increase in the amount of sodium bicarbonate, faster buoyancy was achieved due to the increased CO2 gas formation. Drug release followed zero-order and gave a good fit to the Korsmeyer-Peppas model, which suggested that drug release was due to diffusion through polymer swelling. Zero-order, controlled release profile with the desired buoyancy can be achieved by using optimum formula quantities of sodium bicarbonate and polymer. The tri-layered system shows promising delivery of DTZ, and possibly other water-soluble drugs.

Matrix Effects in Quantitative Assessment of Pharmaceutical Tablets Using Transmission Raman and Near-Infrared (NIR) Spectroscopy.

PubMed

Sparén, Anders; Hartman, Madeleine; Fransson, Magnus; Johansson, Jonas; Svensson, Olof

2015-05-01

Raman spectroscopy can be an alternative to near-infrared spectroscopy (NIR) for nondestructive quantitative analysis of solid pharmaceutical formulations. Compared with NIR spectra, Raman spectra have much better selectivity, but subsampling was always an issue for quantitative assessment. Raman spectroscopy in transmission mode has reduced this issue, since a large volume of the sample is measured in transmission mode. The sample matrix, such as particle size of the drug substance in a tablet, may affect the Raman signal. In this work, matrix effects in transmission NIR and Raman spectroscopy were systematically investigated for a solid pharmaceutical formulation. Tablets were manufactured according to an experimental design, varying the factors particle size of the drug substance (DS), particle size of the filler, compression force, and content of drug substance. All factors were varied at two levels plus a center point, except the drug substance content, which was varied at five levels. Six tablets from each experimental point were measured with transmission NIR and Raman spectroscopy, and their concentration of DS was determined for a third of those tablets. Principal component analysis of NIR and Raman spectra showed that the drug substance content and particle size, the particle size of the filler, and the compression force affected both NIR and Raman spectra. For quantitative assessment, orthogonal partial least squares regression was applied. All factors varied in the experimental design influenced the prediction of the DS content to some extent, both for NIR and Raman spectroscopy, the particle size of the filler having the largest effect. When all matrix variations were included in the multivariate calibrations, however, good predictions of all types of tablets were obtained, both for NIR and Raman spectroscopy. The prediction error using transmission Raman spectroscopy was about 30% lower than that obtained with transmission NIR spectroscopy.

Geometry of modified release formulations during dissolution--influence on performance of dosage forms with diclofenac sodium.

PubMed

Dorożyński, Przemysław; Kulinowski, Piotr; Jamróz, Witold; Juszczyk, Ewelina

2014-12-30

The objectives of the work included: presentation of magnetic resonance imaging (MRI) and fractal analysis based approach to comparison of dosage forms of different composition, structure, and assessment of the influence of the compositional factors i.e., matrix type, excipients etc., on properties and performance of the dosage form during drug dissolution. The work presents the first attempt to compare MRI data obtained for tablet formulations of different composition and characterized by distinct differences in hydration and drug dissolution mechanisms. The main difficulty, in such a case stems from differences in hydration behavior and tablet's geometry i.e., swelling, cracking, capping etc. A novel approach to characterization of matrix systems i.e., quantification of changes of geometrical complexity of the matrix shape during drug dissolution has been developed. Using three chosen commercial modified release tablet formulations with diclofenac sodium we present the method of parameterization of their geometrical complexity on the base of fractal analysis. The main result of the study is the correlation between the hydrating tablet behavior and drug dissolution - the increase of geometrical complexity expressed as fractal dimension relates to the increased variability of drug dissolution results. Copyright © 2014 Elsevier B.V. All rights reserved.

New release cell for NMR microimaging of tablets. Swelling and erosion of poly(ethylene oxide).

PubMed

Abrahmsén-Alami, Susanna; Körner, Anna; Nilsson, Ingvar; Larsson, Anette

2007-09-05

A small release cell, in the form of a rotating disc, has been constructed to fit into the MRI equipment. The present work show that both qualitative and quantitative information of the swelling and erosion behavior of hydrophilic extended release (ER) matrix tablets may be obtained using this release cell and non-invasive magnetic resonance imaging (MRI) studies at different time-points during matrix dissolution. The tablet size, core size and the gel layer thickness of ER matrix formulations based on poly(ethylene oxide) have been determined. The dimensional changes as a function of time were found to correspond well to observations made with texture analysis (TA) methodology. Most importantly, the results of the present study show that both the erosion (displacement of the gel-dissolution media interface) and the swelling (decrease of dry tablet core size) proceed with a faster rate in radial than in axial direction using the rotating disk set-up. This behavior was attributed to the higher shear forces experienced in the radial direction. The results also indicate that front synchronization (constant gel layer thickness) is associated with the formation of an almost constant polymer concentration profile through the gel layer at different time-points.

Fingerprints, Pharmaceutical and Radical Scavenging Activity Evaluation of an Alzheimer-Targeted Herbal Preparation.

PubMed

Dabaghian, Farid; Khademian, Sedigheh; Azadi, Amir; Zarshenas, Mohammad

2016-05-01

As the most common form of dementia, Alzheimer disease is characterized by progressive loss of memory and deterioration of cognitive functions. It is predicted that about 75.63 million people would suffer from dementia by 2030. Apart from conventional remedies, the application of herbal medicines is on the rise. There are numerous natural medicaments reported in the traditional manuscript of Persian medicine. Accordingly, in the present study, the intended remedy was selected and an appropriate pharmacognostical and pharmaceutical evaluations were performed. By searching through the traditional pharmaceutical manuscripts such as Qarabadeen-e-Salehi, Qarabadeen-e-Azam, Qarabadeen-e-Ghaderi and Canon of Medicine, a simple but proven compound remedy (frankincense and black pepper) was selected. A floating tablet was designed and formulated from those herbal components. Related pharmaceutical assessments such as weight variation, hardness, friability, and disintegration tests as well as pharmacognostical evaluations such as microscopic characterization, TLC, GC/MS, FT/IR fingerprints, and radical scavenging activity assessment (DPPH) were performed. The resulting formulation, as a floating tablet, included 60% of frankincense gum and 15% of black pepper along with appropriate pharmaceutical ingredients (weight variation: 0.219±0.004 g, hardness: 6.50±0.67, friability: 0.45%, disintegration time >30 min). Microscopic characterization demonstrated stone cells, calcium oxalate crystals, sclereids of endocarp and pitted cells of mesocarp of pepper fruits as well as oil drops of frankincense gum. TLC fingerprinting showed classes of secondary metabolites related to both components. GC/MS analysis revealed Acetyl acetate and trans-Caryophyllene as the main constituent. Moderate radical scavenging activity (IC50 >100 µg/ml) was calculated for the methanol extract of tablets. Carrying out and validating a GC method for standardization of the formulated tablet, and having the structure for the effectiveness of these medicinal herbs in Alzheimer may be the horizon for a new Alzheimer-targeted medicine.

Fingerprints, Pharmaceutical and Radical Scavenging Activity Evaluation of an Alzheimer-Targeted Herbal Preparation.

PubMed

Dabaghian, Farid; Khademian, Sedigheh; Azadi, Amir; Zarshenas, Mohammad

2016-05-01

As the most common form of dementia, Alzheimer disease is characterized by progressive loss of memory and deterioration of cognitive functions. It is predicted that about 75.63 million people would suffer from dementia by 2030. Apart from conventional remedies, the application of herbal medicines is on the rise. There are numerous natural medicaments reported in the traditional manuscript of Persian medicine. Accordingly, in the present study, the intended remedy was selected and an appropriate pharmacognostical and pharmaceutical evaluations were performed. By searching through the traditional pharmaceutical manuscripts such as Qarabadeen-e-Salehi, Qarabadeen-e-Azam, Qarabadeen-e-Ghaderi and Canon of Medicine, a simple but proven compound remedy (frankincense and black pepper) was selected. A floating tablet was designed and formulated from those herbal components. Related pharmaceutical assessments such as weight variation, hardness, friability, and disintegration tests as well as pharmacognostical evaluations such as microscopic characterization, TLC, GC/MS, FT/IR fingerprints, and radical scavenging activity assessment (DPPH) were performed. The resulting formulation, as a floating tablet, included 60% of frankincense gum and 15% of black pepper along with appropriate pharmaceutical ingredients (weight variation: 0.219±0.004 g, hardness: 6.50±0.67, friability: 0.45%, disintegration time >30 min). Microscopic characterization demonstrated stone cells, calcium oxalate crystals, sclereids of endocarp and pitted cells of mesocarp of pepper fruits as well as oil drops of frankincense gum. TLC fingerprinting showed classes of secondary metabolites related to both components. GC/MS analysis revealed Acetyl acetate and trans-Caryophyllene as the main constituent. Moderate radical scavenging activity (IC 50 >100 µg/ml) was calculated for the methanol extract of tablets. Carrying out and validating a GC method for standardization of the formulated tablet, and having the structure for the effectiveness of these medicinal herbs in Alzheimer may be the horizon for a new Alzheimer-targeted medicine.

Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum

PubMed Central

Arora, Gurpreet; Malik, Karan; Singh, Inderbir; Arora, Sandeep; Rana, Vikas

2011-01-01

The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w). The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer) and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm2 and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4). Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4) with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations. PMID:22171313

NMR imaging of high-amylose starch tablets. 2. Effect of tablet size.

PubMed

Malveau, Cédric; Baille, Wilms E; Zhu, Xiao Xia; Marchessault, Robert H

2002-01-01

Carbohydrate polymers are widely used for pharmaceutical applications such as the controlled release of drugs. The swelling and water mobility in high-amylose starch tablets are important parameters to be determined for these applications. They have been studied at different time intervals by nuclear magnetic resonance imaging (NMRI) after the immersion of the samples in water. These tablets have a hydrophilic matrix, which swells anisotropically and forms a hydrogel in water. NMRI shows clearly the anisotropy of the water penetration and the swelling along the radial and axial dimensions of the tablets. Empirical relationships are established to describe the kinetics of water penetration and swelling of the tablets. Results show that water uptake and tablet swelling strongly depend on the size of the tablets. Gravimetric measurements of water uptake were also performed in comparison with the NMRI results.

The floating-gate non-volatile semiconductor memory--from invention to the digital age.

PubMed

Sze, S M

2012-10-01

In the past 45 years (from 1967 to 2012), the non-volatile semiconductor memory (NVSM) has emerged from a floating-gate concept to the prime technology driver of the largest industry in the world-the electronics industry. In this paper, we briefly review the historical development of NVSM and project its future trends to the year 2020. In addition, we consider NVSM's wide-range of applications from the digital cellular phone to tablet computer to digital television. As the device dimension is scaled down to the deca-nanometer regime, we expect that many innovations will be made to meet the scaling challenges, and NVSM-inspired technology will continue to enrich and improve our lives for decades to come.

Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation

PubMed Central

Shah, Kifayat Ullah; Khan, Gul Majid

2012-01-01

The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC) and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P) ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP) as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4) using PharmaTest dissolution apparatus at constant temperature of 37°C ± 0.1. Similarity factor f 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including C max⁡, T max⁡ and AUC0-t were compared which showed an optimized C max⁡ and T max⁡ (P < 0.05). A good correlation was obtained between in vitro drug release and in vivo drug absorption with correlation value (R 2 = 0.934). Relative bioavailability was found to be 93%. Reproducibility of manufacturing process and accelerated stability of the developed tablets were performed in stability chamber at 40 ± 2°C and 75 ± 5% relative humidity for a period of 6 months and were found to be stable throughout the stability period. PMID:22649325

Elucidation of release characteristics of highly soluble drug trimetazidine hydrochloride from chitosan-carrageenan matrix tablets.

PubMed

Li, Liang; Wang, Linlin; Shao, Yang; Tian, Ye; Li, Conghao; Li, Ying; Mao, Shirui

2013-08-01

The aim of this study was to better understand the underlying drug release characteristics from matrix tablets based on the combination of chitosan (CS) and different types of carrageenans [kappa (κ)-CG, iota (ι)-CG, and lambda (λ)-CG]. Highly soluble trimetazidine hydrochloride (TH) was used as a model drug. First, characteristics of drug release from different formulations were investigated, and then in situ complexation capacity of CG with TH and CS was studied by differential scanning calorimetry and Fourier transform infrared spectroscopy. Erosion and swelling of matrix were also characterized to better understand the drug-release mechanisms. Effects of pH and ionic strength on drug release were also studied. It was found that not only ι-CG and λ-CG could reduce the burst release of TH by the effect of TH-CG interaction, CS-ι-CG- and CS-λ-CG-based polyelectrolyte film could further modify the controlled-release behavior, but not CS-κ-CG. High pH and high ionic strength resulted in faster drug release from CS-κ-CG- and CS-ι-CG-based matrix, but drug release from CS-λ-CG-based matrix was less sensitive to pH and ionic strength. In conclusion, CS-λ-CG-based matrix tablets are quite promising as controlled-release drug carrier based on multiple mechanisms. Copyright © 2013 Wiley Periodicals, Inc.

Effect of matrix composition and process conditions on casein-gelatin beads floating properties.

PubMed

Bulgarelli, E; Forni, F; Bernabei, M T

2000-04-05

Casein-gelatin beads have been prepared by emulsification extraction method and cross-linked with D,L-glyceraldehyde in an acetone-water mixture 3:1 (v/v). Casein emulsifying properties cause air bubble incorporation and the formation of large holes in the beads. The high porosity of the matrix influences the bead properties such as drug loading, drug release and floatation. These effects have been stressed by comparison with low porous beads, artificially prepared without cavities. The percentage of casein in the matrix increases the drug loading of both low and high porous matrices, although the loading of high porous matrices is lower than that of low porous matrices. As a matter of fact, the drug should be more easily removed during washing and recovery because of the higher superficial pore area of the beads. This can explain the drug release rate increase, observed in high porous matrix, in comparison with beads without cavities. This is due to the rapid diffusion of the drug through water filled pores. The study shows that cavities act as an air reservoir and enable beads to float. Therefore, casein seems to be a material suitable to the inexpensive formation of an air reservoir for floating systems.

Aqueous film coating to reduce recrystallization of guaifenesin from hot-melt extruded acrylic matrices.

PubMed

Bruce, Caroline D; Fegely, Kurt A; Rajabi-Siahboomi, Ali R; McGinity, James W

2010-02-01

This study investigated the effect of aqueous film coating on the recrystallization of guaifenesin from acrylic, hot-melt extruded matrix tablets. After hot-melt extrusion, matrix tablets were film-coated with either hypromellose or ethylcellulose. The effects of the coating polymer, curing and storage conditions, polymer weight gain, and core guaifenesin concentration on guaifenesin recrystallization were investigated. The presence of either film coating on the guaifenesin-containing tablets was found to prolong the onset time of drug crystallization. The coating polymer was the most important factor determining the delay in the onset of crystallization, with the more hydrophilic polymer, hypromellose, having a higher solubilization potential for the guaifenesin and delaying crystallization for longer period (3 or 6 months in tablets stored at 40 degrees C or 25 degrees C, respectively) than the more hydrophobic ethylcellulose, which displayed a lower solubilization potential for guaifenesin (crystal growth on tablets cured for 2 hours at 60 degrees C occurred within 3 weeks, whereas uncoated tablets displayed surface crystal growth after 30 minutes). Crystal morphology was also affected by the film coating. Elevated temperatures during both curing and storage, incomplete film coalescence, and high core drug concentrations all contributed to an earlier onset of crystal growth.

Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.

PubMed

Duque, Marcelo Dutra; Kreidel, Rogério Nepomuceno; Taqueda, Maria Elena Santos; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Consiglieri, Vladi Olga

2013-01-01

A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

Influence of Carbopol 71G-NF on the release of dextromethorphan hydrobromide from extended-release matrix tablets.

PubMed

Fayed, Mohamed H; Mahrous, Gamal M; Ibrahim, Mohamed A; Sakr, Adel

2013-01-01

The objective of this study was to evaluate the potential of Carbopol(®) 71G-NF on the release of dextromethorphan hydrobromide (DM) from matrix tablets in comparison with hydroxypropyl methylcellulose (HPMC(®) K15M) and Eudragit(®) L100-55 polymers. Controlled release DM matrix tablets were prepared using Carbopol 71G-NF, HPMC K15M, and Eudragit L100-55 at different drug to polymer ratios by direct compression technique. The mechanical properties of the tablets as tested by crushing strength and friability tests were improved as the concentration of Carbopol, HPMC, and Eudragit increased. However, Carbopol-based tablets showed a significantly (P<0.05) higher crushing strength and a lower friability than HPMC and Eudragit tablets. No significant differences in weight uniformity and thickness values were observed between the different formulations. It was also found that Carbopol significantly (P<0.05) delayed the release of DM in comparison with HPMC K15M and Eudragit L100-55. A combination of HPMC K15M and Eudragit L100-55 in a 1:1 ratio at 20 and 30% significantly (P<0.05) delayed the release of DM than Eudragit L100-55 alone. Moreover, blends of Carbopol and HPMC at a 1:1 ratio at the 10, 20, and 30% total polymer concentration were investigated. The blend of Carbopol and HPMC at 10% level significantly (P<0.05) slowed the release of DM than Carbopol or HPMC alone, whereas blends at 20 and 30% level significantly (P<0.05) delayed the release of DM compared with HPMC or Carbopol alone. The results with these polymer blends showed that it was possible to reduce the total amount of polymers when used as a combination in formulation.

A study of compressibility and compactibility of directly compressible tableting materials containing tramadol hydrochloride.

PubMed

Mužíková, Jitka; Kubíčková, Alena

2016-09-01

The paper evaluates and compares the compressibility and compactibility of directly compressible tableting materials for the preparation of hydrophilic gel matrix tablets containing tramadol hydrochloride and the coprocessed dry binders Prosolv® SMCC 90 and Disintequik™ MCC 25. The selected types of hypromellose are Methocel™ Premium K4M and Methocel™ Premium K100M in 30 and 50 % concentrations, the lubricant being magnesium stearate in a 1 % concentration. Compressibility is evaluated by means of the energy profile of compression process and compactibility by the tensile strength of tablets. The values of total energy of compression and plasticity were higher in the tableting materials containing Prosolv® SMCC 90 than in those containing Disintequik™ MCC 25. Tramadol slightly decreased the values of total energy of compression and plasticity. Tableting materials containing Prosolv® SMCC 90 yielded stronger tablets. Tramadol decreased the strength of tablets from both coprocessed dry binders.

Floating Node Method and Virtual Crack Closure Technique for Modeling Matrix Cracking-Delamination Interaction

NASA Technical Reports Server (NTRS)

DeCarvalho, N. V.; Chen, B. Y.; Pinho, S. T.; Baiz, P. M.; Ratcliffe, J. G.; Tay, T. E.

2013-01-01

A novel approach is proposed for high-fidelity modeling of progressive damage and failure in composite materials that combines the Floating Node Method (FNM) and the Virtual Crack Closure Technique (VCCT) to represent multiple interacting failure mechanisms in a mesh-independent fashion. In this study, the approach is applied to the modeling of delamination migration in cross-ply tape laminates. Delamination, matrix cracking, and migration are all modeled using fracture mechanics based failure and migration criteria. The methodology proposed shows very good qualitative and quantitative agreement with experiments.

Floating Node Method and Virtual Crack Closure Technique for Modeling Matrix Cracking-Delamination Migration

NASA Technical Reports Server (NTRS)

DeCarvalho, Nelson V.; Chen, B. Y.; Pinho, Silvestre T.; Baiz, P. M.; Ratcliffe, James G.; Tay, T. E.

2013-01-01

A novel approach is proposed for high-fidelity modeling of progressive damage and failure in composite materials that combines the Floating Node Method (FNM) and the Virtual Crack Closure Technique (VCCT) to represent multiple interacting failure mechanisms in a mesh-independent fashion. In this study, the approach is applied to the modeling of delamination migration in cross-ply tape laminates. Delamination, matrix cracking, and migration are all modeled using fracture mechanics based failure and migration criteria. The methodology proposed shows very good qualitative and quantitative agreement with experiments.

Using quantitative magnetic resonance methods to understand better the gel-layer formation on polymer-matrix tablets.

PubMed

Mikac, Urša; Kristl, Julijana; Baumgartner, Saša

2011-05-01

Magnetic resonance imaging is a powerful, non-invasive technique that can help improve our understanding of the hydrogel layer formed on swellable, polymer-matrix tablets, as well as the layer's properties and its influence on drug release. In this paper, the authors review the NMR and MRI investigations of hydrophilic, swellable polymers published since 1994. The review covers NMR studies on the properties of water and drugs within hydrated polymers. In addition, MRI studies using techniques for determining the different moving-front positions within the swollen tablets, the polymer concentration profiles across them, the influence of the incorporated drug, and so on, are presented. Some complementary methods are also briefly presented and discussed. Using MRI, the formation of a hydrogel along with simultaneous determination of the drug's position within it can be observed non-invasively. However, the MRI parameters can influence the signal's intensity and therefore they need to be considered carefully in order to prevent any misinterpretation of the results. MRI makes possible an in situ investigation of swollen-matrix tablets and provides valuable information that can lead, when combined with other techniques, to a better understanding of polymeric systems and a more effective development of optimal dosage forms.

Conceptuation, formulation and evaluation of sustained release floating tablets of captopril compression coated with gastric dispersible hydrochlorothiazide using 23 factorial design

PubMed Central

Sirisha, Pathuri Lakshmi; Babu, Govada Kishore; Babu, Puttagunta Srinivasa

2014-01-01

Ambulatory blood pressure monitoring is regarded as the gold standard for hypertensive therapy in non-dipping hypertension patients. A novel compression coated formulation of captopril and hydrochlorothiazide (HCTZ) was developed in order to improve the efficacy of antihypertensive therapy considering the half-life of both drugs. The synergistic action using combination therapy can be effectively achieved by sustained release captopril (t1/2= 2.5 h) and fast releasing HCTZ (average t1/2= 9.5 h). The sustained release floating tablets of captopril were prepared by using 23 factorial design by employing three polymers i.e., ethyl cellulose (EC), carbopol and xanthan gum at two levels. The formulations (CF1-CF8) were optimized using analysis of variance for two response variables, buoyancy and T50%. Among the three polymers employed, the coefficients and P values for the response variable buoyancy and T50% using EC were found to be 3.824, 0.028 and 0.0196, 0.046 respectively. From the coefficients and P values for the two response variables, formulation CF2 was optimized, which contains EC polymer alone at a high level. The CF2 formulation was further compression coated with optimized gastric dispersible HCTZ layer (HF9). The compression coated tablet was further evaluated using drug release kinetics. The Q value of HCTZ layer is achieved within 20 min following first order release whereas the Q value of captopril was obtained at 6.5 h following Higuchi model, from which it is proved that rapid release HCTZ and slow release of captopril is achieved. The mechanism of drug release was analyzed using Peppas equation, which showed an n >0.90 confirming case II transportation mechanism for drug release. PMID:25006552

Mechanistic understanding of the link between Sodium Starch Glycolate properties and the performance of tablets made by wet granulation.

PubMed

Wren, S A C; Alhusban, F; Barry, A R; Hughes, L P

2017-08-30

The impact of varying Sodium Starch Glycolate (SSG) grade and wet granulation intensity on the mechanism of disintegration and dissolution of mannitol-based Immediate Release (IR) placebo tablets was investigated. MRI and 1 H NMR provided mechanistic insight, and revealed a four-fold range in both tablet disintegration and dissolution rates. MRI was used to quantify the rates of change in tablet volumes and the data fitted to a hydration/erosion model. Reduced levels of cross-linking change SSG from a swelling to a gelling matrix. The tablet hydration and dissolution rates are related to the viscosity at the tablet-solution interface, with high viscosities limiting mass transport. Copyright © 2017 Elsevier B.V. All rights reserved.

An empirical model for dissolution profile and its application to floating dosage forms.

PubMed

Weiss, Michael; Kriangkrai, Worawut; Sungthongjeen, Srisagul

2014-06-02

A sum of two inverse Gaussian functions is proposed as a highly flexible empirical model for fitting of in vitro dissolution profiles. The model was applied to quantitatively describe theophylline release from effervescent multi-layer coated floating tablets containing different amounts of the anti-tacking agents talc or glyceryl monostearate. Model parameters were estimated by nonlinear regression (mixed-effects modeling). The estimated parameters were used to determine the mean dissolution time, as well as to reconstruct the time course of release rate for each formulation, whereby the fractional release rate can serve as a diagnostic tool for classification of dissolution processes. The approach allows quantification of dissolution behavior and could provide additional insights into the underlying processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Release from or through a wax matrix system. I. Basic release properties of the wax matrix system.

PubMed

Yonezawa, Y; Ishida, S; Sunada, H

2001-11-01

Release properties from a wax matrix tablet was examined. To obtain basic release properties, the wax matrix tablet was prepared from a physical mixture of drug and wax powder (hydrogenated caster oil) at a fixed mixing ratio. Properties of release from the single flat-faced surface or curved side surface of the wax matrix tablet were examined. The applicability of the square-root time law and of Higuchi equations was confirmed. The release rate constant obtained as g/min(1/2) changed with the release direction. However, the release rate constant obtained as g/cm2 x min(1/2) was almost the same. Hence it was suggested that the release property was almost the same and the wax matrix structure was uniform independent of release surface or direction at a fixed mixing ratio. However, these equations could not explain the entire release process. The applicability of a semilogarithmic equation was not as good compared with the square-root time law or Higuchi equation. However, it was revealed that the semilogarithmic equation was available to simulate the entire release process, even though the fit was somewhat poor. Hence it was suggested that the semilogarithmic equation was sufficient to describe the release process. The release rate constant was varied with release direction. However, these release rate constants were expressed by a function of the effective surface area and initial amount, independent of the release direction.

Terahertz Pulsed Imaging and Magnetic Resonance Imaging as Tools to Probe Formulation Stability

PubMed Central

Zhang, Qilei; Gladden, Lynn F.; Avalle, Paolo; Zeitler, J. Axel; Mantle, Michael D.

2013-01-01

Dissolution stability over the entire shelf life duration is of critical importance to ensure the quality of solid dosage forms. Changes in the drug release profile during storage may affect the bioavailability of drug products. This study investigated the stability of a commercial tablet (Lescol® XL) when stored under accelerated conditions (40 °C/75% r.h.). Terahertz pulsed imaging (TPI) was used to investigate the structure of the tablet coating before and after the accelerated aging process. The results indicate that the coating was reduced in thickness and exhibited a higher density after being stored under accelerated conditions for four weeks. In situ magnetic resonance imaging (MRI) of the water penetration processes during tablet dissolution in a USP-IV dissolution cell equipped with an in-line UV-vis analyzer was carried out to study local differences in water uptake into the tablet matrix between the stressed and unstressed state. The drug release profiles of the Lescol® XL tablet before and after the accelerated storage stability testing were compared using a “difference” factor f1 and a “similarity” factor f2. The results reveal that even though the physical properties of the coating layers changed significantly during the stress testing, the coating protected the tablet matrix and the densification of the coating polymer had no adverse effect on the drug release performance. PMID:24300564

Nonvolatile memory with Co-SiO2 core-shell nanocrystals as charge storage nodes in floating gate

NASA Astrophysics Data System (ADS)

Liu, Hai; Ferrer, Domingo A.; Ferdousi, Fahmida; Banerjee, Sanjay K.

2009-11-01

In this letter, we reported nanocrystal floating gate memory with Co-SiO2 core-shell nanocrystal charge storage nodes. By using a water-in-oil microemulsion scheme, Co-SiO2 core-shell nanocrystals were synthesized and closely packed to achieve high density matrix in the floating gate without aggregation. The insulator shell also can help to increase the thermal stability of the nanocrystal metal core during the fabrication process to improve memory performance.

A gastro-resistant ovalbumin bi-layered mini-tablet-in-tablet system for the delivery of Lactobacillus acidophilus probiotic to simulated human intestinal and colon conditions.

PubMed

Govender, Mershen; Choonara, Yahya Essop; van Vuuren, Sandy; Kumar, Pradeep; du Toit, Lisa Claire; Pillay, Viness

2015-07-01

The viability of probiotic bacteria during formulation processes and delivery is vital to ensure health benefits. This study focuses on the use of gastro-resistant denatured ovalbumin for the targeted delivery of probiotic Lactobacillus acidophilus to simulated human intestinal and colon conditions through a bi-layered mini-tablet-in-tablet system (BMTTS). The BMTTS consists of two gastro-resistant ovalbumin mini-tablets containing L. acidophilus suspended in lactose and eudragit S100 for targeted intestinal and colonic delivery respectively. Luminescence has been utilized to ensure probiotic viability during formulation processes in addition to determining all probiotic release profiles. The mechanism of probiotic release from the ovalbumin matrix was ascertained using mathematical modelling and molecular docking studies. Magnetic resonance imaging and differential scanning calorimetry are also included as part of the in-vitro characterization of the ovalbumin system. The BMTTS was effective in the delivery of L. acidophilus to simulated human intestinal and colon conditions. Formulation processes were furthermore determined to maintain probiotic viability. Statistical analysis of the release data noted a significant effect of pH denaturation on the release properties of ovalbumin. Magnetic resonance imaging results have indicated a decrease in ovalbumin matrix size upon exposure to simulated intestinal fluid. Molecular docking studies carried out depicted the interaction and binding positions inherent to the ovalbumin-pancreatic trypsin interaction complex indicating the possible enzymatic degradation of ovalbumin leading to the release of the probiotic from the protein matrix. The BMTTS has been determined to be effective in the protection and delivery of probiotic L. acidophilus to simulated human intestinal and colonic conditions. Molecular docking analysis has noted that pancreatin exerts a significant effect on probiotic release from the gastro-resistant ovalbumin matrix. © 2015 Royal Pharmaceutical Society.

Release mechanism of doxazosin from carrageenan matrix tablets: Effect of ionic strength and addition of sodium dodecyl sulphate.

PubMed

Kos, Petra; Pavli, Matej; Baumgartner, Saša; Kogej, Ksenija

2017-08-30

The polyelectrolyte matrix tablets loaded with an oppositely charged drug exhibit complex drug-release mechanisms. In this study, the release mechanism of a cationic drug doxazosin mesylate (DM) from matrix tablets based on an anionic polyelectrolyte λ-carrageenan (λ-CARR) is investigated. The drug release rates from λ-CARR matrices are correlated with binding results based on potentiometric measurements using the DM ion-sensitive membrane electrode and with molecular characteristics of the DM-λ-CARR-complex particles through hydrodynamic size measurements. Experiments are performed in solutions with different ionic strength and with the addition of an anionic surfactant sodium dodecyl sulphate (SDS). It is demonstrated that in addition to swelling and erosion of tablets, the release rates depend strongly on cooperative interactions between DM and λ-CARR. Addition of SDS at concentrations below its critical micelle concentration (CMC) slows down the DM release through hydrophobic binding of SDS to the DM-λ-CARR complex. On the contrary, at concentrations above the CMC SDS pulls DM from the complex by forming mixed micelles with it and thus accelerates the release. Results involving SDS show that the concentration of surfactants that are naturally present in gastrointestinal environment may have a great impact on the drug release process. Copyright © 2017 Elsevier B.V. All rights reserved.

Architecture of Columnar Nacre, and Implications for Its Formation Mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Metzler, Rebecca A.; Olabisi, Ronke M.; Coppersmith, Susan N.

2007-06-29

We analyze the structure of Haliotis rufescens nacre, or mother-of-pearl, using synchrotron spectromicroscopy and x-ray absorption near-edge structure spectroscopy. We observe imaging contrast between adjacent individual nacre tablets, arising because different tablets have different crystal orientations with respect to the radiation's polarization vector. Comparing previous data and our new data with models for columnar nacre growth, we find the data are most consistent with a model in which nacre tablets are nucleated by randomly distributed sites in the organic matrix layers.

Risperidone mucoadhesive buccal tablets: formulation design, optimization and evaluation

PubMed Central

Çelik, Burak

2017-01-01

The aim of this study was to design and optimize risperidone (RIS) mucoadhesive buccal tablets for systemic delivery as an alternative route. Direct compression method was used for the preparation of buccal tablets, and screening studies were conducted with different polymers to determine their effects on tablet characteristics. Carbopol® (CP) and sodium alginate (SA) were selected as two polymer types for further optimization studies by applying response surface methodology. Tablet hardness (TH), ex vivo residence time (RT), and peak detachment force (DF) from buccal mucosa were selected as three important responses. Physicochemical compatibility of formulation excipients and RIS was evaluated by using Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) analysis. In vitro drug release profiles and release kinetics were investigated; swelling index and matrix erosion studies were conducted. Optimum formulation consisted of 16.4% CP and 20.3% SA, which provided 7.67±0.29 hour ex vivo RT, 45.52±4.85 N TH, and 2.12±0.17 N DF. FT-IR spectroscopy and DSC analysis revealed that there was no chemical interaction present between tablet ingredients. Cumulative RIS release of >90% was achieved after 8 hours of in vitro dissolution studies, which was supported by swelling and matrix erosion analysis. Mechanism of RIS release was fitted best to zero-order model, while release exponent (n) value of 0.77 demonstrated an anomalous (non-Fickian) release, indicating combined erosion and swelling mechanism. The results suggested that optimized buccal tablets of RIS would be a promising and alternative delivery system for the treatment of schizophrenia. PMID:29225461

Predictability of drug release from water-insoluble polymeric matrix tablets.

PubMed

Grund, Julia; Körber, Martin; Bodmeier, Roland

2013-11-01

The purpose of this study was to extend the predictability of an established solution of Fick's second law of diffusion with formulation-relevant parameters and including percolation theory. Kollidon SR (polyvinyl acetate/polyvinylpyrrolidone, 80/20 w/w) matrix tablets with various porosities (10-30% v/v) containing model drugs with different solubilities (Cs=10-170 mg/ml) and in different amounts (A=10-90% w/w) were prepared by direct compression and characterized by drug release and mass loss studies. Drug release was fitted to Fick's second law to obtain the apparent diffusion coefficient. Its changes were correlated with the total porosity of the matrix and the solubility of the drug. The apparent diffusion coefficient was best described by a cumulative normal distribution over the range of total porosities. The mean of the distribution coincided with the polymer percolation threshold, and the minimum and maximum of the distribution were represented by the diffusion coefficient in pore-free polymer and in aqueous medium, respectively. The derived model was verified, and the applicability further extended to a drug solubility range of 10-1000 mg/ml. The developed mathematical model accurately describes and predicts drug release from Kollidon SR matrix tablets. It can efficiently reduce experimental trials during formulation development. Copyright © 2013 Elsevier B.V. All rights reserved.

Development and in vitro evaluation of expandable gastroretentive dosage forms based on compressed collagen sponges.

PubMed

Gröning, R; Cloer, C; Müller, R S

2006-07-01

The objective of this study was to develop and evaluate new collagen gastroretentive dosage forms (GRDFs) which expand in the stomach after contact with gastric fluids. The GRDFs should remain in the stomach for a prolonged period of time due to their size. The dosage forms were prepared from collagen sponges. The sponges were manufactured by freeze-drying a riboflavin-containing collagen solution. A computer controlled material supply was constructed to transport precompressed collagen into a tablet machine. A second type of tablet was manufactured by combining compressed collagen sponges with hydrophilic matrix layers of hydroxypropylmethylcellulose. Matrix layers containing captopril or aciclovir were developed. In vitro experiments were performed with both types of dosage forms. The collagen tablets expand within a few minutes after contact with artificial gastric juice and form a drug delivery system with a size of 8 mm x 18 mm x 60 mm. Riboflavin is released over 16 h. If two layer tablets are used, the release of aciclovir or captopril can be controlled by the composition of the sustained release layer.

Formulation of bi-layer matrix tablets of tramadol hydrochloride: Comparison of rate retarding ability of the incorporated hydrophilic polymers.

PubMed

Arif, Hasanul; Al-Masum, Abdullah; Sharmin, Florida; Reza, Selim; Sm Islam, Sm Ashraful

2015-05-01

Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique. Each tablet contains an instant release layer with a sustained release layer. The instant release layer was found to release the initial dose immediately within minutes. The instant release layer was combined with sustained release matrix made of varying quantity of Methocel K4M, Methocel K15MCR and Carbomer 974P. Bi-layer tablets were evaluated for various physical tests including weight variation, thickness and diameter, hardness and percent friability. Drug release from bi-layer tablet was studied in acidic medium and buffer medium for two and six hours respectively. Sustained release of tramadol hydrochloride was observed with a controlled fashion that was characteristic to the type and extent of polymer used. % Drug release from eight-hour dissolution study was fitted with several kinetic models. Mean dissolution time (MDT) and fractional dissolution values (T25%, T50% and T80%) were also calculated as well, to compare the retarding ability of the polymers. Methocel K15MCR was found to be the most effective in rate retardation of freely water-soluble tramadol hydrochloride compared to Methocel K4M and Capbomer 974P, when incorporated at equal ratio in the formulation.

Continuous manufacturing of extended release tablets via powder mixing and direct compression.

PubMed

Ervasti, Tuomas; Simonaho, Simo-Pekka; Ketolainen, Jarkko; Forsberg, Peter; Fransson, Magnus; Wikström, Håkan; Folestad, Staffan; Lakio, Satu; Tajarobi, Pirjo; Abrahmsén-Alami, Susanna

2015-11-10

The aim of the current work was to explore continuous dry powder mixing and direct compression for manufacturing of extended release (ER) matrix tablets. The study was span out with a challenging formulation design comprising ibuprofen compositions with varying particle size and a relatively low amount of the matrix former hydroxypropyl methylcellulose (HPMC). Standard grade HPMC (CR) was compared to a recently developed direct compressible grade (DC2). The work demonstrate that ER tablets with desired quality attributes could be manufactured via integrated continuous mixing and direct compression. The most robust tablet quality (weight, assay, tensile strength) was obtained using high mixer speed and large particle size ibuprofen and HPMC DC2 due to good powder flow. At low mixer speed it was more difficult to achieve high quality low dose tablets. Notably, with HPMC DC2 the processing conditions had a significant effect on drug release. Longer processing time and/or faster mixer speed was needed to achieve robust release with compositions containing DC2 compared with those containing CR. This work confirms the importance of balancing process parameters and material properties to find consistent product quality. Also, adaptive control is proven a pivotal means for control of continuous manufacturing systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Designing an extended release waxy matrix tablet containing nicardipine–hydroxy propyl β cyclodextrin complex

PubMed Central

Al-Zein, Hind; Sakeer, Khalil; Alanazi, Fars K.

2011-01-01

Aim The current study aimed to prepare a sustained release tablet for a drug which has poor solubility in alkaline medium using complexation with cyclodextrin. Nicardipine hydrochloride (NC) a weak basic drug was chosen as a model drug for this study. Method Firstly the most suitable binary system NC-HPβCD was selected in order to improve drug solubility in the intestinal media and then embedding the complexed drug into a plastic matrix, by fusion method, consists of glycerol monostearate (GMS) as an inert waxy substance and polyethylene glycol 4000 (PEG4000) as a channeling agent, after that the final solid dispersion [(NC:HPβCD):GMS:PEG4000] which was prepared at different ratios was mixed with other excipients, avicel PH101, lactose, and talc, to get a tablet owning dissolution profile complying with the FDA and USP requirements for the extended release solid dosage forms. Results Infrared spectroscopy (IR), differential scanning colorimetry (DSC), polarized microscopy and X-ray diffractometry proved that the coevaporation technique was effective in preparing amorphous cyclodextrin complexes with NC and trapping of NC within the HPβCD cavity by dissolving both in ethanol and evaporate the solvent using a rotavapor at 65 °C. Dissolution profile of NC enhanced significantly in pH 6.8 from NC:HPβCD inclusion complex prepared by the rotavapor (t-test Student p < 0.05). The release of NC from tablet containing [(NC:HPβCD):GMS:PEG4000] [(1):0.75:0.5] (w/w/w) solid dispersion (F8) was complying with the FDA dissolution requirements for extended release dosage forms, and studying the kinetics of the release showed that the diffusional contribution is the major factor controlling the drug release from that formula. Conclusion The prepared waxy matrix tablet containing NC complexes with CD shows promising results as extended release tablets. PMID:23960765

Continuous direct compression as manufacturing platform for sustained release tablets.

PubMed

Van Snick, B; Holman, J; Cunningham, C; Kumar, A; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

2017-03-15

This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard Methocel CR and directly compressible Methocel DC2. The feeding behavior of each formulation component was investigated by deriving feed factor profiles. The maximum feed factor was used to estimate the drive command and depended strongly upon the density of the material. Furthermore, the shape of the feed factor profile allowed definition of a customized refill regime for each material. Inline NIRs was used to estimate the residence time distribution (RTD) in the mixer and monitor blend uniformity. Tablet content and weight variability were determined as additional measures of mixing performance. For Methocel CR, the best axial mixing (i.e. feeder fluctuation dampening) was achieved when an impeller with high number of radial mixing blades operated at low speed. However, the variability in tablet weight and content uniformity deteriorated under this condition. One can therefore conclude that balancing axial mixing with tablet quality is critical for Methocel CR. However, reformulating with the direct compressible Methocel DC2 as matrix former improved tablet quality vastly. Furthermore, both process and product were significantly more robust to changes in process and design variables. This observation underpins the importance of flowability during continuous blending and die-filling. At the compaction stage, blends with Methocel CR showed better tabletability driven by a higher compressibility as the smaller CR particles have a higher bonding area. However, tablets of similar strength were achieved using Methocel DC2 by targeting equal porosity. Compaction pressure impacted tablet properties and dissolution. Hence controlling thickness during continuous manufacturing of sustained release tablets was crucial to ensure reproducible dissolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Gamma scintigraphic evaluation of floating gastroretentive tablets of metformin HCl using a combination of three natural polymers in rabbits

PubMed Central

Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Chung, Lip Yong; Nyamathulla, Shaik; Noordin, Mohamed Ibrahim

2015-01-01

The present research was aimed at formulating a metformin HCl sustained-release formulation from a combination of polymers, using the wet granulation technique. A total of 16 formulations (F1–F16) were produced using different combinations of the gel-forming polymers: tamarind kernel powder, salep (palmate tubers of Orchis morio), and xanthan. Post-compression studies showed that there were no interactions between the active drug and the polymers. Results of in vitro drug-release studies indicated that the F10 formulation which contained 5 mg of tamarind kernel powder, 33.33 mg of xanthan, and 61.67 mg of salep could sustain a 95% release in 12 hours. The results also showed that F2 had a 55% similarity factor with the commercial formulation (C-ER), and the release kinetics were explained with zero order and Higuchi models. The in vivo study was performed in New Zealand White rabbits by gamma scintigraphy; the F10 formulation was radiolabeled using samarium (III) oxide (153Sm2O3) to trace transit of the tablets in the gastrointestinal tract. The in vivo data supported the retention of F10 formulation in the gastric region for 12 hours. In conclusion, the use of a combination of polymers in this study helped to develop an optimal gastroretentive drug-delivery system with improved bioavailability, swelling, and floating characteristics. PMID:26273196

Development of sustained release antipsychotic tablets using novel polysaccharide isolated from Delonix regia seeds and its pharmacokinetic studies

PubMed Central

Krishnaraj, Kaliaperumal; Chandrasekar, Mulla Joghi Nanjan; Nanjan, Mulla Joghi; Muralidharan, Selvadurai; Manikandan, Duraikannu

2011-01-01

A natural polysaccharide was isolated from the seeds of Delonix regia. The isolated polysaccharide could maintain aqueous equilibrium between the dosage form and the surrounding medium due to its massive competence of water absorption (80.72%) and swelling index (266.7%). The Scanning Electron Micrograph of a polysaccharide exhibits rough surface with pores and crevices, hence, the drug release will be retarded because of the drug particles entrapment in the pores and crevices. Further, the surface tension of polysaccharide is higher than that of water, which may facilitate sustained release of drugs from dosage forms. An antipsychotic drug, quetiapine fumarate has a short half-life of 6 h and administered multiple times per day. Hence the quetiapine fumarate oral sustained release tablets were formulated using this polysaccharide in the concentration of 5–30% to avoid the side effects and increase patient compliance. Dissolution of the developed tablets with 25% polysaccharide content showed a better release profile than the other batches (5–20%) at the end of 12 h. The strong matrix complex has low solubility in water, it does not dissolve rapidly and the drug continues to diffuse through the gel layer at a consistent rate. Drug release from the matrix tablets follows matrix type except F-4 and F-5 which follow first order and Hix.crow type. The bioavailability study was carried out using healthy male New Zealand white rabbits that show the AUC(0–inf) value for developed SR tablets is 1.44 times higher than the reference thus, indicating more efficient and sustained drug delivery capable of maintaining plasma drug levels better. PMID:24115903

Formulation and in vitro characterization of xanthan gum-based sustained release matrix tables of isosorbide-5- mononitrate.

PubMed

Kar, Rajat; Mohapatra, Snehamayee; Bhanja, Satyabrata; Das, Debjyoti; Barik, Bhaktibhusan

2010-01-01

In the present investigation an attempt has been made to increase therapeutic efficacy, to reduce frequency of administration and to improve patient compliance by developing a sustained release matrix tablets of isosorbide-5-mononitrate. Sustained release matrix tablets of isosorbide-5-mononitrate were developed by using different drug: polymer ratios, such in F1 (1:0.75), F2 (1:1), F3 (1:1.5), F4 (1:1.75) and F6 (1:2). Xanthan gum was used as matrix former and microcrystalline cellulose as diluent. All the lubricated formulations were compressed, using 8mm flat faced punches. Compressed tablets were evaluated for uniformity of weight, content of active ingredient, friability, hardness, thickness, in vitro dissolution study using basket method and swelling index. Each formulation showed compliance with pharmacopoeial standards. Among all formulations, F5 showed a greater sustained release pattern of drug over a 12 h period with 92.12% of drug being released. The kinetic studies showed that drug release follows the Higuchi model (r(2) =0.9851). Korsemeyer and Peppas equation gave an n-value of 0.4566, which was close to 0.5, indicating that drug release follows the Fickian diffusion. Thus, xanthan gum can be used as an effective matrix former to extend the release of isosorbide-5-mononitrate. No significant difference was observed in the dissolution profile of optimized formulation, using basket and paddle apparatus.

Effect of HPMC - E15 LV premium polymer on release profile and compression characteristics of chitosan/ pectin colon targeted mesalamine matrix tablets and in vitro study on effect of pH impact on the drug release profile.

PubMed

Newton, A M J; Lakshmanan, Prabakaran

2014-04-01

The study was designed to investigate the in vitro dissolution profile and compression characteristics of colon targeted matrix tablets prepared with HPMC E15 LV in combination with pectin and Chitosan. The matrix tablets were subjected to two dissolution models in various simulated fluids such as pH 1.2, 6, 6.8, 7.2, 5.5. The fluctuations in colonic pH conditions during IBD (inflammatory bowel disease) and the nature of less fluid content in the colon may limit the expected drug release in the polysaccharide-based matrices when used alone. The Hydrophilic hydroxyl propyl methylcellulose ether premium polymer (HPMC E15 LV) of low viscosity grade was used in the formulation design, which made an excellent modification in physical and compression characteristics of the granules. The release studies indicated that the prepared matrices could control the drug release until the dosage form reaches the colon and the addition HPMC E15 LV showed the desirable changes in the dissolution profile by its hydrophilic nature since the colon is known for its less fluid content. The hydrophilic HPMC E15 LV allowed the colonic fluids to enter into the matrix and confirmed the drug release at the target site from a poorly water soluble polymer such as Chitosan and also from water soluble Pectin. The dramatic changes occurred in the drug release profile and physicochemical characteristics of the Pectin, Chitosan matrix tablets when a premium polymer HPMC E15 LV added in the formulation design in the optimized concentration. Various drug release mechanisms used for the examination of drug release characteristics. Drug release followed the combined mechanism of diffusion, erosion, swelling and polymer entanglement. In recent decade, IBD attracts many patents in novel treatment methods by using novel drug delivery systems.

A non-destructive method for quality control of the pellet distribution within a MUPS tablet by terahertz pulsed imaging.

PubMed

Novikova, Anna; Markl, Daniel; Zeitler, J Axel; Rades, Thomas; Leopold, Claudia S

2018-01-01

Terahertz pulsed imaging (TPI) was applied to analyse the inner structure of multiple unit pellet system (MUPS) tablets. MUPS tablets containing different amounts of theophylline pellets coated with Eudragit® NE 30 D and with microcrystalline cellulose (MCC) as cushioning agent were analysed. The tablets were imaged by TPI and the results were compared to X-ray microtomography. The terahertz pulse beam propagates through the tablets and is back-reflected at the interface between the MCC matrix and the coated pellets within the tablet causing a peak in the terahertz waveform. Cross-section images of the tablets were extracted at different depths and parallel to the tablet faces from 3D terahertz data to visualise the surface-near structure of the MUPS tablets. The images of the surface-near structure of the MUPS tablets were compared to X-ray microtomography images at the same depths. The surface-near structure could be clearly resolved by TPI at depths between 24 and 152μm below the tablet surface. An increasing amount of pellets within the MUPS tablets appears to slightly decrease the detectability of the pellets within the tablets by TPI. TPI was shown to be a non-destructive method for the detection of pellets within the tablets and could resolve structures thicker than 30μm. In conclusion, a proof-of-concept was provided for TPI as a method of quality control for MUPS tablets. Copyright © 2017 Elsevier B.V. All rights reserved.

Terahertz Technology: A Boon to Tablet Analysis

PubMed Central

Wagh, M. P.; Sonawane, Y. H.; Joshi, O. U.

2009-01-01

The terahertz gap has a frequency ranges from ∼0.3 THz to ∼10 THz in the electromagnetic spectrum which is in between microwave and infrared. The terahertz radiations are invisible to naked eye. In comparison with x-ray they are intrinsically safe, non-destructive and non-invasive. Terahertz spectroscopy enables 3D imaging of structures and materials, and the measurement of the unique spectral fingerprints of chemical and physical forms. Terahertz radiations are produced by a dendrimer based high power terahertz source and spectroscopy technologies. It resolves many of the questions left unanswered by complementary techniques, such as optical imaging, Raman and infrared spectra. In the pharmaceutical industries it enables nondestructive, internal, chemical analysis of tablets, capsules, and other dosage forms. Tablet coatings are a major factor in drug bioavailability. Therefore tablet coatings integrity and uniformity are of crucial importance to quality. Terahertz imaging gives an unparalleled certainty about the integrity of tablet coatings and the matrix performance of tablet cores. This article demonstrates the potential of terahertz pulse imaging for the analysis of tablet coating thickness by illustrating the technique on tablets. PMID:20490288

Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs.

PubMed

Nart, Viviane; Beringhs, André O'Reilly; França, Maria Terezinha; de Espíndola, Brenda; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

2017-01-01

Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (<0.1%). The melt-granulated captopril in matrix systems containing 50% EC (45P, 100P or 100FP) and the melt-granulated metformin hydrochloride in reservoir systems coated with Kollicoat® SR 30D and Opadry® II (80:20 with 10% weight gain or 70:30 with 20% weight gain) exhibited release profiles adequate to sustained release formulations, for over 450min. Therefore, carnauba wax proved to be a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of soluble drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of matrix-based theophylline sustained-release microtablets.

PubMed

Rey, H; Wagner, K G; Wehrlé, P; Schmidt, P C

2000-01-01

Microtablets containing high theophylline content (from 60% to 80%) based on a Eudragit RS PO matrix were produced on a rotary tablet press. The influence of the compaction pressure, the plasticizer content used for the granulation of theophylline particles, and the amount of theophylline on the drug release were investigated. The effects of surface area and the addition of magnesium stearate as a hydrophobic agent on the drug release were studied. The storage stabilities of the release rate at room temperature and at 50 degrees C were also determined. Dissolution profiles expressed as percentage of theophylline dissolved were obtained over 8 hr in 900 ml of purified water at 37 degrees C and 75 rpm. It was observed that the compaction pressure (from 200 MPa to 250 MPa) had no effect on the theophylline release. The use of triethyl citrate (TEC) as a plasticizer in the granulation of theophylline enhanced the physical properties of the microtablets. Theophylline content in the range 60% to 80% did not affect the drug release. The theophylline release obtained was a function of the quotient surface area/tablet weight and therefore was dependent on the tablet diameter. To reduce the dissolution rates, magnesium stearate was added in a concentration up to 50% of the matrix material. Tablets of this hydrophobic formulation fulfilled the requirements of USP 23 for theophylline sustained-release preparations. Storage at room temperature for 3 months and at 50 degrees C for 2 months showed no significant influence on the theophylline release.

Substituted amylose matrices for oral drug delivery

NASA Astrophysics Data System (ADS)

Moghadam, S. H.; Wang, H. W.; Saddar El-Leithy, E.; Chebli, C.; Cartilier, L.

2007-03-01

High amylose corn starch was used to obtain substituted amylose (SA) polymers by chemically modifying hydroxyl groups by an etherification process using 1,2-epoxypropanol. Tablets for drug-controlled release were prepared by direct compression and their release properties assessed by an in vitro dissolution test (USP XXIII no 2). The polymer swelling was characterized by measuring gravimetrically the water uptake ability of polymer tablets. SA hydrophilic matrix tablets present sequentially a burst effect, typical of hydrophilic matrices, and a near constant release, typical of reservoir systems. After the burst effect, surface pores disappear progressively by molecular association of amylose chains; this allows the creation of a polymer layer acting as a diffusion barrier and explains the peculiar behaviour of SA polymers. Several formulation parameters such as compression force, drug loading, tablet weight and insoluble diluent concentration were investigated. On the other hand, tablet thickness, scanning electron microscope analysis and mercury intrusion porosimetry showed that the high crushing strength values observed for SA tablets were due to an unusual melting process occurring during tabletting although the tablet external layer went only through densification, deformation and partial melting. In contrast, HPMC tablets did not show any traces of a melting process.

Assessment of intra-granular and extra-granular fracture in the development of tablet tensile strength.

PubMed

Mitra, Biplob; Hilden, Jon; Litster, James D

2018-05-24

When a tablet is compacted from deformable granules and then broken, the fracture plane may cleave granules in two (intra-granular fracture) or separate neighboring granules (extra-granular fracture). In this study, a novel method was developed to quantify the extent of intra- versus extra-granular fracture by compacting tablets from multi-colored ideal granules and evaluating fracture surfaces. The proportions of intra-granular and extra-granular fracture were quantified and modeled in light of a new metric, the deformation potential, Δ, reflecting the solid fraction increase as an initial granule bed is compressed into a final tablet. Results show that a measurable tablet strength is achieved at Δ > 0.18, but intra-granular fracture is not observed until Δ > 0.21. At very large Δ, tablets experience almost exclusively intra-granular fracture, yet the tablet tensile strength is considerably lower than that of a tablet compacted from raw powders versus pre-compacted granules. Thus, secondary compaction of granules appears to weaken the granule matrix, leading to reduced tablet tensile strength even in the presence of strong extra-granular bonding. Copyright © 2018. Published by Elsevier Inc.

Pharmaceutical acrylic beads obtained by suspension polymerization containing cellulose nanowhiskers as excipient for drug delivery.

PubMed

Villanova, J C O; Ayres, E; Carvalho, S M; Patrício, P S; Pereira, F V; Oréfice, R L

2011-03-18

Direct compression is one of the most popular techniques to prepare tablets but only a few commercial excipients are well adapted for this process into controlled release formulations. In the last years, the introduction of new materials for drug delivery matrix tablets has become more important. This paper evaluated the physicochemical and flow properties of new polymeric excipient of ethyl acrylate, methyl methacrylate and butyl metacrylate, synthesized by suspension polymerization using cellulose nanowhiskers as co-stabilizer, to be used as direct compression for modified release tablets. Infrared spectroscopy (FTIR) confirmed the success of the copolymerization reaction. Scanning electron microscopy (SEM) showed that excipient was obtained how spherical beads. Thermal properties of the beads were characterized by thermogravimetric (TG) analysis. Particle size analysis of the beads with cellulose nanowhiskers (CNWB) indicated that the presence of the nanowhiskers led to a reduction of particle size and to a narrower size distribution. In vitro test showed that the nanowhiskers and beads produced are nontoxic. Parameters such as Hausner ratio, Carr's index and cotangent of angle α were employed to characterize the flow properties of CNWB beads. Furthermore, the beads are used to produce tablets by direct compression contained propranolol hydrochloride as model drug. Dissolution tests performed suggested that beads could be used as excipient in matrix tablets with a potential use in drug controlled release. Copyright © 2011 Elsevier B.V. All rights reserved.

Modeling drug release from PVAc/PVP matrix tablets.

PubMed

Siepmann, F; Eckart, K; Maschke, A; Kolter, K; Siepmann, J

2010-01-25

Kollidon SR-based matrix tablets containing various amounts of diprophylline were prepared and thoroughly characterized in vitro. This includes drug release measurements in 0.1M HCl and phosphate buffer pH 7.4, monitoring of changes in the tablet's height and diameter, morphology as well as dry mass upon exposure to the release media. Based on these experimental results, a mechanistic realistic mathematical theory is proposed, taking into account the given initial and boundary conditions as well as radial and axial mass transport in cylinders. Importantly, good agreement between theory and experiment was obtained in all cases, indicating that drug diffusion with constant diffusivity is the dominant mass transport mechanism in these systems. Furthermore, the proposed theory was used to quantitatively predict the effects of the initial tablet height and diameter on the resulting drug release patterns. These theoretical predictions were compared with independently measured drug release kinetics. Good agreement was observed in all cases, proving the validity of the mathematical theory and illustrating the latter's practical benefit: The model can help to significantly facilitate the recipe optimization of this type of advanced drug delivery systems in order to achieve a desired release profile. Copyright 2009 Elsevier B.V. All rights reserved.

Alginate/cashew gum floating bead as a matrix for larvicide release.

PubMed

Paula, Haroldo C B; de Oliveira, Erick F; Abreu, Flávia O M S; de Paula, Regina C M

2012-08-01

A polymeric floating system composed of Alginate (ALG) and Cashew gum (CG), loaded with an essential oil (Lippia sidoides-Ls) was prepared by ionotropic gelation, characterized regarding its physical-chemistry properties and evaluated on its potential as a controlled release system. The influence of process parameters on the buoyancy, loading, swelling and in vitro and in vivo release kinetics, was investigated. Results showed that beads produced with carbonate and Ls at high level contents exhibit good floatability (up to 5 days) and loading capacity (15.2-23.8%). In vitro release data showed a Fickian diffusion profile and in vivo experiments showed that ALG-CG floating system presented a superior and prolonged larvicide effect, in comparison with non-floating ones, presenting larvae mortality values of 85% and 33%, respectively, after 48 h. These results indicate that ALG-CG floating beads loaded with Ls presented enhanced oil entrapment efficiency, excellent floating ability, and suitable larvicide release pattern. Copyright © 2012 Elsevier B.V. All rights reserved.

Floating-Point Units and Algorithms for field-programmable gate arrays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Underwood, Keith D.; Hemmert, K. Scott

2005-11-01

The software that we are attempting to copyright is a package of floating-point unit descriptions and example algorithm implementations using those units for use in FPGAs. The floating point units are best-in-class implementations of add, multiply, divide, and square root floating-point operations. The algorithm implementations are sample (not highly flexible) implementations of FFT, matrix multiply, matrix vector multiply, and dot product. Together, one could think of the collection as an implementation of parts of the BLAS library or something similar to the FFTW packages (without the flexibility) for FPGAs. Results from this work has been published multiple times and wemore » are working on a publication to discuss the techniques we use to implement the floating-point units, For some more background, FPGAS are programmable hardware. "Programs" for this hardware are typically created using a hardware description language (examples include Verilog, VHDL, and JHDL). Our floating-point unit descriptions are written in JHDL, which allows them to include placement constraints that make them highly optimized relative to some other implementations of floating-point units. Many vendors (Nallatech from the UK, SRC Computers in the US) have similar implementations, but our implementations seem to be somewhat higher performance. Our algorithm implementations are written in VHDL and models of the floating-point units are provided in VHDL as well. FPGA "programs" make multiple "calls" (hardware instantiations) to libraries of intellectual property (IP), such as the floating-point unit library described here. These programs are then compiled using a tool called a synthesizer (such as a tool from Synplicity, Inc.). The compiled file is a netlist of gates and flip-flops. This netlist is then mapped to a particular type of FPGA by a mapper and then a place- and-route tool. These tools assign the gates in the netlist to specific locations on the specific type of FPGA chip used and constructs the required routes between them. The result is a "bitstream" that is analogous to a compiled binary. The bitstream is loaded into the FPGA to create a specific hardware configuration.« less

Tablet disintegration studied by high-resolution real-time magnetic resonance imaging.

PubMed

Quodbach, Julian; Moussavi, Amir; Tammer, Roland; Frahm, Jens; Kleinebudde, Peter

2014-01-01

The present work employs recent advances in high-resolution real-time magnetic resonance imaging (MRI) to investigate the disintegration process of tablets containing disintegrants. A temporal resolution of 75 ms and a spatial resolution of 80 × 80 µm with a section thickness of only 600 µm were achieved. The histograms of MRI videos were quantitatively analyzed with MATLAB. The mechanisms of action of six commercially available disintegrants, the influence of relative tablet density, and the impact of disintegrant concentration were examined. Crospovidone seems to be the only disintegrant acting by a shape memory effect, whereas the others mainly swell. A higher relative density of tablets containing croscarmellose sodium leads to a more even distribution of water within the tablet matrix but hardly impacts the disintegration kinetics. Increasing the polacrilin potassium disintegrant concentration leads to a quicker and more thorough disintegration process. Real-time MRI emerges as valuable tool to visualize and investigate the process of tablet disintegration.

Spray-dried chitosan as a direct compression tableting excipient.

PubMed

Chinta, Dakshinamurthy Devanga; Graves, Richard A; Pamujula, Sarala; Praetorius, Natalie; Bostanian, Levon A; Mandal, Tarun K

2009-01-01

The objective of this study was to prepare and evaluate a novel spray-dried tableting excipient using a mixture of chitosan and lactose. Three different grades of chitosan (low-, medium-, and high-molecular-weight) were used for this study. Propranolol hydrochloride was used as a model drug. A specific amount of chitosan (1, 1.9, and 2.5 g, respectively) was dissolved in 50 mL of an aqueous solution of citric acid (1%) and later mixed with 50 mL of an aqueous solution containing lactose (20, 19.1, and 18.5 g, respectively) and propanolol (2.2 g). The resultant solution was sprayed through a laboratory spray drier at 1.4 mL/min. The granules were evaluated for bulk density, tap density, Carr index, particle size distribution, surface morphology, thermal properties, and tableting properties. Bulk density of the granules decreased from 0.16 to 0.13 g/mL when the granules were prepared using medium- or high-molecular-weight chitosan compared with the low-molecular-weight chitosan. The relative proportion of chitosan also showed a significant effect on the bulk density. The granules prepared with 1 g of low-molecular-weight chitosan showed the minimum Carr index (11.1%) indicating the best flow properties among all five formulations. All three granules prepared with 1 g chitosan, irrespective of their molecular weight, showed excellent flow properties. Floating tablets prepared by direct compression of these granules with sodium bicarbonate showed 50% drug release between 30 and 35 min. In conclusion, the spray-dried granules prepared with chitosan and lactose showed excellent flow properties and were suitable for tableting.

Development of starch based mucoadhesive vaginal drug delivery systems for application in veterinary medicine.

PubMed

Gök, Mehmet Koray; Özgümüş, Saadet; Demir, Kamber; Cirit, Ümüt; Pabuccuoğlu, Serhat; Cevher, Erdal; Özsoy, Yıldız; Bacınoğlu, Süleyman

2016-01-20

The aim of this study was to prepare and evaluate the mucoadhesive, biocompatible and biodegradable progesterone containing vaginal tablets based on modified starch copolymers for the estrus synchronization of ewes. Starch-graft-poly(acrylic acid) copolymers (S-g-PAA) were synthesized and characterized. The vaginal tablets were fabricated with S-g-PAA and their equilibrium swelling degree (Qe) and matrix erosion (ME%) were determined in lactate buffer solution. In vitro, mucoadhesive properties of the tablets were investigated by using ewe vaginal mucosa and in vivo residence time were also investigated. In vitro and in vivo progesterone release profiles from the tablets were compared with two commercial products. Tablet formulation containing wheat starch based grafted copolymer (WS-g-PAA)gc indicated promising results and might be convenient as an alternative product to the commercial products in veterinary medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Review of Disintegrants and the Disintegration Phenomena.

PubMed

Desai, Parind Mahendrakumar; Liew, Celine Valeria; Heng, Paul Wan Sia

2016-09-01

Disintegrant is one of the most important components in a typical tablet dosage form. It is responsible for ensuring the break-up of the tablet matrix upon ingestion. Disintegrants act by different mechanisms, and a number of factors may affect their performance. It is important for formulators to understand how disintegrants function so as to be able to judiciously use disintegrants to develop optimized formulations. If the formulator is required to implement the quality by design paradigm while developing a tablet formulation, it would be important to determine the impact of component ranges and process variations on tablet performance and of particular importance, tablet disintegration. Thus, a better understanding of the mechanisms of disintegrants and the tablet disintegration processes can be critical to product design success. This review aims to provide an overview of tablet disintegrants and the disintegration processes with particular focus on the factors affecting the functionalities of disintegrants. An updated compendium of different techniques employed to evaluate disintegrant action and measure disintegration time is also provided. The objective of this review is to assemble the knowledge about disintegrants and the measurement of tablet disintegratability so that the information provided could be of help to tablet formulation development. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Time-oriented experimental design method to optimize hydrophilic matrix formulations with gelation kinetics and drug release profiles.

PubMed

Shin, Sangmun; Choi, Du Hyung; Truong, Nguyen Khoa Viet; Kim, Nam Ah; Chu, Kyung Rok; Jeong, Seong Hoon

2011-04-04

A new experimental design methodology was developed by integrating the response surface methodology and the time series modeling. The major purposes were to identify significant factors in determining swelling and release rate from matrix tablets and their relative factor levels for optimizing the experimental responses. Properties of tablet swelling and drug release were assessed with ten factors and two default factors, a hydrophilic model drug (terazosin) and magnesium stearate, and compared with target values. The selected input control factors were arranged in a mixture simplex lattice design with 21 experimental runs. The obtained optimal settings for gelation were PEO, LH-11, Syloid, and Pharmacoat with weight ratios of 215.33 (88.50%), 5.68 (2.33%), 19.27 (7.92%), and 3.04 (1.25%), respectively. The optimal settings for drug release were PEO and citric acid with weight ratios of 191.99 (78.91%) and 51.32 (21.09%), respectively. Based on the results of matrix swelling and drug release, the optimal solutions, target values, and validation experiment results over time were similar and showed consistent patterns with very small biases. The experimental design methodology could be a very promising experimental design method to obtain maximum information with limited time and resources. It could also be very useful in formulation studies by providing a systematic and reliable screening method to characterize significant factors in the sustained release matrix tablet. Copyright © 2011 Elsevier B.V. All rights reserved.

Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®.

PubMed

Caccavo, D; Barba, A A; d'Amore, M; De Piano, R; Lamberti, G; Rossi, A; Colombo, P

2017-12-01

The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used asa fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped. Copyright © 2017 Elsevier B.V. All rights reserved.

Formulation and in vitro evaluation of theophylline matrix tablets prepared by direct compression: Effect of polymer blends

PubMed Central

El-Bagory, Ibrahim; Barakat, Nahla; Ibrahim, Mohamed A.; El-Enazi, Fouza

2011-01-01

The deformation mechanism of pharmaceutical powders, used in formulating directly compressed matrix tablets, affects the characteristics of the formed tablets. Three polymers of different deformation mechanisms were tested for their impact on theophylline directly compressed tablets namely Kollidon SR (KL SR, plastic deformation), Ethylcellulose (EC, elastic deformation) and Carnauba wax (CW, brittle deformation) at different compression forces. However, tablets based mainly on KL SR, the plastically deformed polymer (TN1) exhibited the highest hardness values compared to the other formulae which are based on either blends of KL SR with CW, the very brittle deformed polymer. The upper detected force for TN formulae and the lower punch force were found to dependent mainly on the powder deformation. This difference is attributed to the work done during the compression phase as well as the work lost during the decompression phase. Furthermore, the release profiles of TN from formulae TN2 and TN4 that are based on the composition (2KL SR:1EC) and (1KL SR:2EC), respectively, were consistent with different deformation mechanisms of KL SR and EC and on the physicochemical properties like the water absorptive capacity of EC. Upon increasing the weight ratio of KL SR (TN2), the release rate was greatly retarded (39.4%, 37.1%, 35.0% and 33.6% released after 8 h at 5, 10, 15 and 20 kN. PMID:24115902

Multimodal approach to characterization of hydrophilic matrices manufactured by wet and dry granulation or direct compression methods.

PubMed

Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Obrał, Jadwiga; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Jachowicz, Renata; Wyszogrodzka, Gabriela; Klaja, Jolanta; Dorożyński, Przemysław P

2016-02-29

The purpose of the research was to investigate the effect of the manufacturing process of the controlled release hydrophilic matrix tablets on their hydration behavior, internal structure and drug release. Direct compression (DC) quetiapine hemifumarate matrices and matrices made of powders obtained by dry granulation (DG) and high shear wet granulation (HS) were prepared. They had the same quantitative composition and they were evaluated using X-ray microtomography, magnetic resonance imaging and biorelevant stress test dissolution. Principal results concerned matrices after 2 h of hydration: (i) layered structure of the DC and DG hydrated tablets with magnetic resonance image intensity decreasing towards the center of the matrix was observed, while in HS matrices layer of lower intensity appeared in the middle of hydrated part; (ii) the DC and DG tablets retained their core and consequently exhibited higher resistance to the physiological stresses during simulation of small intestinal passage than HS formulation. Comparing to DC, HS granulation changed properties of the matrix in terms of hydration pattern and resistance to stress in biorelevant dissolution apparatus. Dry granulation did not change these properties-similar hydration pattern and dissolution in biorelevant conditions were observed for DC and DG matrices. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation and characterization of a compacted multiparticulate system for modified release of water-soluble drugs--Part II theophylline and cimetidine.

PubMed

Cantor, Stuart L; Hoag, Stephen W; Augsburger, Larry L

2009-05-01

The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and different film-coating polymers in delaying drug release from compacted multiparticulate systems. Formulations containing theophylline or cimetidine granulated with Eudragit RS 30D were developed and beads were produced by extrusion-spheronization. Drug beads were coated using 15% wt/wt Surelease or Eudragit NE 30D and were evaluated for true density, particle size, and sphericity. Lipid-based placebo beads and drug beads were blended together and compacted on an instrumented Stokes B2 rotary tablet press. Although placebo beads were significantly less spherical, their true density of 1.21 g/cm(3) and size of 855 mum were quite close to Surelease-coated drug beads. Curing improved the crushing strength and friability values for theophylline tablets containing Surelease-coated beads; 5.7 +/- 1.0 kP and 0.26 +/- 0.07%, respectively. Dissolution profiles showed that the EC matrix only provided 3 h of drug release. Although tablets containing Surelease-coated theophylline beads released drug fastest overall (t(44.2%) = 8 h), profiles showed that coating damage was still minimal. Size and density differences indicated a minimal segregation potential during tableting for blends containing Surelease-coated drug beads. Although modified release profiles >8 h were achievable in tablets for both drugs using either coating polymer, Surelease-coated theophylline beads released drug fastest overall. This is likely because of the increased solubility of theophylline and the intrinsic properties of the Surelease films. Furthermore, the lipid-based placebos served as effective cushioning agents by protecting coating integrity of drug beads under a number of different conditions while tableting.

Evaluation of Matrix Tablets Based on Eudragit®E100/Carbopol®971P Combinations for Controlled Release and Improved Compaction Properties of Water Soluble Model Drug Paracetamol.

PubMed

Obeidat, Wasfy M; Nokhodchi, Ali; Alkhatib, Hatim

2015-10-01

The purpose of this work was to investigate the influence of Eudragit®E100 polymer in modifying the release rates and compaction properties of water soluble model drug paracetamol from Carbopol®971P NF polymer matrix tablets prepared by direct compression. The effects of the ratio of the two polymers, the total polymeric content, and the tablets mechanical strength on paracetamol release rates were investigated. Dissolution studies were conducted using USP XX Π rotating paddle apparatus at 50 rpm and 37°C at three different stages (pH 1.2, 4.8, and 6.8). Results showed that the polymers combination improved significantly the compaction properties of paracetamol tablets as evident by the higher crushing strengths (8.3 ± 0.4 Kp) compared to polymer-free tablets (3.4 ± 0.2 Kp) at intermediate compression pressure of 490 MPa. When combined with Carbopol®971P NF, Eudragit®E100 was found to be capable of extending paracetamol release for more than 12 h compared to 1 h for polymers-free tablets. The combined polymers were able to control paracetamol release in a pH independent pattern. The f2 (similarity factor) analysis showed that the ratio between the polymers and the total polymer concentration exhibited significant impact on drug release rates. In conclusion, Eudragit®E100 when combined with Carbopol®971P NF was capable of improving the compaction and sustained release properties of paracetamol. Korsmeyer-Peppas model was found to be the most suitable for fitting drug release data. The polymer combinations can potentially be used to control the release rates of highly water soluble drugs.

In vitro evaluation of mucoadhesive vaginal tablets of antifungal drugs prepared with thiolated polymer and development of a new dissolution technique for vaginal formulations.

PubMed

Baloglu, Esra; Ay Senyıgıt, Zeynep; Karavana, Sinem Yaprak; Vetter, Anja; Metın, Dilek Yesim; Hilmioglu Polat, Suleyha; Guneri, Tamer; Bernkop-Schnurch, Andreas

2011-01-01

The main objective of this work was to develop antifungal matrix tablet for vaginal applications using mucoadhesive thiolated polymer. Econazole nitrate (EN) and miconazole nitrate (MN) were used as antifungal drugs to prepare the vaginal tablet formulations. Thiolated poly(acrylic acid)-cysteine (PAA-Cys) conjugate was synthesized by the covalent attachment of L-cysteine to PAA with the formation of amide bonds between the primary amino group of L-cysteine and the carboxylic acid group of the polymer. Vaginal mucoadhesive matrix tablets were prepared by direct compression technique. The investigation focused on the influence of modified polymer on water uptake behavior, mucoadhesive property and release rate of drug. Thiolated polymer increased the water uptake ratio and mucoadhesive property of the formulations. A new simple dissolution technique was developed to simulate the vaginal environment for the evaluation of release behavior of vaginal tablets. In this technique, daily production amount and rate of the vaginal fluid was used without any rotational movement. The drug release was found to be slower from PAA-Cys compared to that from PAA formulations. The similarity study results confirmed that the difference in particle size of EN and MN did not affect their release profile. The release process was described by plotting the fraction released drug versus time and n fitting data to the simple exponential model: M(t)/M(∞)=kt(n). The release kinetics were determined as Super Case II for all the formulations prepared with PAA or PAA-Cys. According to these results the mucoadhesive vaginal tablet formulations prepared with PAA-Cys represent good example for delivery systems which prolong the residence time of drugs at the vaginal mucosal surface.

Development of a simple analytical methodology for determination of glucosamine release from modified release matrix tablets.

PubMed

Wu, Yunqi; Hussain, Munir; Fassihi, Reza

2005-06-15

A simple spectrophotometric method for determination of glucosamine release from sustained release (SR) hydrophilic matrix tablet based on reaction with ninhydrin is developed, optimized and validated. The purple color (Ruhemann purple) resulted from the reaction was stabilized and measured at 570 nm. The method optimization was essential as many procedural parameters influenced the accuracy of determination including the ninhydrin concentration, reaction time, pH, reaction temperature, purple color stability period, and glucosamine/ninhydrin ratio. Glucosamine tablets (600 mg) with different hydrophilic polymers were formulated and manufactured on a rotary press. Dissolution studies were conducted (USP 26) using deionized water at 37+/-0.2 degrees C with paddle rotation of 50 rpm, and samples were removed manually at appropriate time intervals. Under given optimized reaction conditions that appeared to be critical, glucosamine was quantitatively analyzed and the calibration curve in the range of 0.202-2.020 mg (r=0.9999) was constructed. The recovery rate of the developed method was 97.8-101.7% (n=6). Reproducible dissolution profiles were achieved from the dissolution studies performed on different glucosamine tablets. The developed method is easy to use, accurate and highly cost-effective for routine studies relative to HPLC and other techniques.

The influence of product brand-to-brand variability on superdisintegrant Performance. A case study with croscarmellose sodium.

PubMed

Zhao, Na; Augsburger, L L

2006-01-01

The purpose of this study is to investigate factors influencing croscarmellose sodium functionality with special emphasis on developing a discriminating model tablet formulation to evaluate product brand-to-brand variability. The particle size distribution, water uptake, and swelling properties of five brands of croscarmellose sodium in either neutral water or 0.1 N HCl were studied. Differences were observed in all properties between brands. Media with acidic pH had a negative impact, but to different extents, on both the water uptake and swelling of all croscarmellose sodium brands due to the presence of carboxymethyl sodium substituents. A tablet matrix composed of lactose (75% w/w) and dicalcium phosphate (25% wt/wt) was used to compare the functional equivalency of the five brands of croscarmellose sodium. The tablet disintegration times were inversely proportional to the swelling ability of superdisintegrant in the testing medium regardless of medium temperature and disintegrant concentration. In conclusion; the particle size, total degree of substitution, and the ratio of basic to acidic substituents are important factors that should be considered during product optimization. The tablet matrix composed of lactose and dicalcium phosphate at a weight ratio of 3:1 can be used as a model formulation for product lot-to-lot consistency and product brand-to-brand comparison purposes.

Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine.

PubMed

Tanaka, Nobuyuki; Imai, Keiji; Okimoto, Kazuto; Ueda, Satoshi; Tokunaga, Yuji; Ohike, Atsuo; Ibuki, Rinta; Higaki, Kazutaka; Kimura, Toshikiro

2005-11-28

The goal of this study is to develop a novel sustained-release (SR) system for poorly water-soluble drugs by applying solid dispersion (SD) technique for improving the solubility. The developed SR system, disintegration-controlled matrix tablet (DCMT), consists of hydrogenated soybean oil (HSO) as wax and SD granules containing low-substituted hydroxypropylcellulose (L-HPC) as a disintegrant. In this study, nilvadipine (NiD) was chosen as a model compound. Sustained-release profiles of NiD from DCMT were identically controlled in several dissolution mediums in spite of varying pH and agitation speed. The release of NiD from DCMT was sustained more effectively by increasing the amount of wax or by decreasing the amount of disintegrant, and supersaturation of NiD was achieved without any re-crystallization in dissolution medium. The release rate of NiD from DCMT was controlled by the disintegration rate of tablet. The release profile of NiD was described by the Hixson-Crowell's model better than zero-order kinetics, first-order kinetics and Higuchi's model, which supports that the release of NiD from DCMT is regulated by the disintegration of the tablet. From this study, it was clarified that DCMT was one of the promising SR systems applying SD for the poorly water-soluble drugs.

The Impact of Amorphisation and Spheronization Techniques on the Improved in Vitro & in Vivo Performance of Glimepiride Tablets

PubMed Central

Makar, Rana Refaat; Latif, Randa; Hosni, Ehab Ahmed; El Gazayerly, Omaima Naim

2017-01-01

Purpose: Triple solid dispersion adsorbates (TSDads) and spherical agglomerates (SA) present new techniques that extensively enhance dissolution of poorly soluble drugs. The aim of the present study is to hasten the onset of hypoglycemic effect of glimepiride through enhancing its rate of release from tablet formulation prepared from either technique. Methods: Drug release from TSDads or SA tablets with different added excipients was explored. Scanning electron microscopy (SEM) and effect of compression on dissolution were illustrated. Pharmacodynamic evaluation was performed on optimized tablets. Results: TSDads & SA tablets with Cross Povidone showed least disintegration times of 1.48 and 0.5 min. respectively. Kinetics of drug release recorded least half-lives (54.13 and 59.83min for both techniques respectively). Cross section in tablets displayed an organized interconnected matrix under SEM, accounting for the rapid access of dissolution media to the tablet core. Components of tablets filled into capsules showed a similar release profile to that of tablets after compression as indicated by similarity factor. The onset time of maximum reduction in blood glucose in male albino rabbits was hastened to 2h instead of 3h for commercial tablets. Conclusion: After optimization of tablet excipients that interacted differently with respect to their effect on drug release, we could conclude that both amorphisation and spheronization were equally successful in promoting in vitro dissolution enhancement as well as providing a more rapid onset time for drug action in vivo. PMID:29399545

Dual release and molecular mechanism of bilayered aceclofenac tablet using polymer mixture.

PubMed

Van Nguyen, Hien; Nguyen, Van Hong; Lee, Beom-Jin

2016-12-30

The objectives of the present study were to develop a controlled-release bilayered tablet of aceclofenac (AFN) 200mg with dual release and to gain a mechanistic understanding of the enhanced sustained release capability achieved by utilizing a binary mixture of the sustained release materials. Different formulations of the sustained-release layer were formulated by employing hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) as the major retarding polymers. The in vitro dissolution studies of AFN bilayered tablets were carried out in intestinal fluid (pH 6.8 buffer). The mechanism of the synergistic rate-retarding effect of the polymer mixture containing HPC and carbomer was elucidated by the rate of swelling and erosion in intestinal fluid and the molecular interactions in the polymer network. The optimized bilayered tablets had similar in vitro dissolution profiles to the marketed tablet Clanza ® CR based on the similarity factor (f2) in combination with their satisfactory micromeritic, physicochemical properties, and stability profiles. Drug release from HPMC-based matrix was controlled by non-Fickian transport, while drug release from HPC-based matrix was solely governed by drug diffusion. The swelling and erosion data exhibited a dramatic increase of water uptake and a reduction of weight loss in the polymer mixture-loaded tablet. Fourier transform infrared (FTIR) spectra revealed strong hydrogen bonding between HPC and carbomer in the polymer mixture. Regarding spatial distribution of polymers in the polymer mixture-loaded tablet, carbomer was found to be the main component of the gel layer during the first 2h of the hydration process, which was responsible for retarding drug release at initial stage. This process was then followed by a gradual transition of HPC from the glassy core to the gel layer for further increasing gel strength. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

PubMed

Khamanga, Sandile M; Walker, Roderick B

2006-01-01

Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

Drug Release Kinetics and Front Movement in Matrix Tablets Containing Diltiazem or Metoprolol/λ-Carrageenan Complexes

PubMed Central

Bonferoni, Maria Cristina; Colombo, Paolo; Zanelotti, Laura; Caramella, Carla

2014-01-01

In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer. PMID:25045689

Drug release kinetics and front movement in matrix tablets containing diltiazem or metoprolol/λ-carrageenan complexes.

PubMed

Bettini, Ruggero; Bonferoni, Maria Cristina; Colombo, Paolo; Zanelotti, Laura; Caramella, Carla

2014-01-01

In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer.

Injection molding as a one-step process for the direct production of pharmaceutical dosage forms from primary powders.

PubMed

Eggenreich, K; Windhab, S; Schrank, S; Treffer, D; Juster, H; Steinbichler, G; Laske, S; Koscher, G; Roblegg, E; Khinast, J G

2016-05-30

The objective of the present study was to develop a one-step process for the production of tablets directly from primary powder by means of injection molding (IM), to create solid-dispersion based tablets. Fenofibrate was used as the model API, a polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol graft co-polymer served as a matrix system. Formulations were injection-molded into tablets using state-of-the-art IM equipment. The resulting tablets were physico-chemically characterized and the drug release kinetics and mechanism were determined. Comparison tablets were produced, either directly from powder or from pre-processed pellets prepared via hot melt extrusion (HME). The content of the model drug in the formulations was 10% (w/w), 20% (w/w) and 30% (w/w), respectively. After 120min, both powder-based and pellet-based injection-molded tablets exhibited a drug release of 60% independent of the processing route. Content uniformity analysis demonstrated that the model drug was homogeneously distributed. Moreover, analysis of single dose uniformity also revealed geometric drug homogeneity between tablets of one shot. Copyright © 2016 Elsevier B.V. All rights reserved.

Fused deposition modeling provides solution for magnetic resonance imaging of solid dosage form by advancing design quickly from prototype to final product.

PubMed

Charest, Ken; Mak-Jurkauskas, Melody L; Cinicola, Daniel; Clausen, Andrew M

2013-02-01

The release profile of active pharmaceutical ingredient (API) from its solid dosage form is an important aspect of drug development as it is often used to predict potential drug release characteristics of a product in vivo. In recent years, magnetic resonance imaging has emerged as a nondestructive technique that captures the physical changes of solid dosage forms during dissolution. An example that highlights this application is in the dissolution of modified-release tablet studies. As the tablet dissolves, API disperses in a hydrogel matrix within the tablet, and swelling of the hydrogel layer eventually leads to release of API over time. To achieve optimum signal-to-noise ratios, the tablet should be placed in the most homogeneous region of the magnet and remain there throughout the dissolution experiment. Moreover, the tablet holder must maintain the tablet position without interfering with the natural dissolution process, such as by crushing the softened tablet. This can be difficult because the size, shape, and rigidity of the tablet change during dissolution. This article describes the process, material, and manufacture of a novel device that meets these challenges, with emphasis on how additive manufacturing on a 3D printer enabled an efficient and inexpensive process of design improvements.

Integrated hot-melt extrusion - injection molding continuous tablet manufacturing platform: Effects of critical process parameters and formulation attributes on product robustness and dimensional stability.

PubMed

Desai, Parind M; Hogan, Rachael C; Brancazio, David; Puri, Vibha; Jensen, Keith D; Chun, Jung-Hoon; Myerson, Allan S; Trout, Bernhardt L

2017-10-05

This study provides a framework for robust tablet development using an integrated hot-melt extrusion-injection molding (IM) continuous manufacturing platform. Griseofulvin, maltodextrin, xylitol and lactose were employed as drug, carrier, plasticizer and reinforcing agent respectively. A pre-blended drug-excipient mixture was fed from a loss-in-weight feeder to a twin-screw extruder. The extrudate was subsequently injected directly into the integrated IM unit and molded into tablets. Tablets were stored in different storage conditions up to 20 weeks to monitor physical stability and were evaluated by polarized light microscopy, DSC, SEM, XRD and dissolution analysis. Optimized injection pressure provided robust tablet formulations. Tablets manufactured at low and high injection pressures exhibited the flaws of sink marks and flashing respectively. Higher solidification temperature during IM process reduced the thermal induced residual stress and prevented chipping and cracking issues. Polarized light microscopy revealed a homogeneous dispersion of crystalline griseofulvin in an amorphous matrix. DSC underpinned the effect of high tablet residual moisture on maltodextrin-xylitol phase separation that resulted in dimensional instability. Tablets with low residual moisture demonstrated long term dimensional stability. This study serves as a model for IM tablet formulations for mechanistic understanding of critical process parameters and formulation attributes required for optimal product performance. Copyright © 2017 Elsevier B.V. All rights reserved.

Release and diffusional modeling of metronidazole lipid matrices.

PubMed

Ozyazici, Mine; Gökçe, Evren H; Ertan, Gökhan

2006-07-01

In this study, the first aim was to investigate the swelling and relaxation properties of lipid matrix on diffusional exponent (n). The second aim was to determine the desired release profile of metronidazole lipid matrix tablets. We prepared metronidazole lipid matrix granules using Carnauba wax, Beeswax, Stearic acid, Cutina HR, Precirol ATO 5, and Compritol ATO 888 by hot fusion method and pressed the tablets of these granules. In vitro release test was performed using a standard USP dissolution apparatus I (basket method) with a stirring rate of 100 rpm at 37 degrees C in 900 ml of 0.1 N hydrochloric acid, adjusted to pH 1.2, as medium for the formulations' screening. Hardness, diameter-height ratio, friability, and swelling ratio were determined. Target release profile of metronidazole was also drawn. Stearic acid showed the highest and Carnauba wax showed the lowest release rates in all formulations used. Swelling ratios were calculated after the dissolution of tablets as 9.24%, 6.03%, 1.74%, and 1.07% for Cutina HR, Beeswax, Precirol ATO 5, and Compritol ATO 888, respectively. There was erosion in Stearic acid, but neither erosion nor swelling in Carnauba wax, was detected. According to the power law analysis, the diffusion mechanism was expressed as pure Fickian for Stearic acid and Carnauba wax and the coupling of Fickian and relaxation contributions for other Cutina HR, Beeswax, Compritol ATO 888, and Precirol ATO 5 tablets. It was found that Beeswax (kd=2.13) has a very close drug release rate with the target profile (kt=1.95). Our results suggested that swelling and relaxation properties of lipid matrices should be examined together for a correct evaluation on drug diffusion mechanism of insoluble matrices.

Optimization of metformin HCl 500 mg sustained release matrix tablets using Artificial Neural Network (ANN) based on Multilayer Perceptrons (MLP) model.

PubMed

Mandal, Uttam; Gowda, Veeran; Ghosh, Animesh; Bose, Anirbandeep; Bhaumik, Uttam; Chatterjee, Bappaditya; Pal, Tapan Kumar

2008-02-01

The aim of the present study was to apply the simultaneous optimization method incorporating Artificial Neural Network (ANN) using Multi-layer Perceptron (MLP) model to the development of a metformin HCl 500 mg sustained release matrix tablets with an optimized in vitro release profile. The amounts of HPMC K15M and PVP K30 at three levels (-1, 0, +1) for each were selected as casual factors. In vitro dissolution time profiles at four different sampling times (1 h, 2 h, 4 h and 8 h) were chosen as output variables. 13 kinds of metformin matrix tablets were prepared according to a 2(3) factorial design (central composite) with five extra center points, and their dissolution tests were performed. Commercially available STATISTICA Neural Network software (Stat Soft, Inc., Tulsa, OK, U.S.A.) was used throughout the study. The training process of MLP was completed until a satisfactory value of root square mean (RSM) for the test data was obtained using feed forward back propagation method. The root mean square value for the trained network was 0.000097, which indicated that the optimal MLP model was reached. The optimal tablet formulation based on some predetermined release criteria predicted by MLP was 336 mg of HPMC K15M and 130 mg of PVP K30. Calculated difference (f(1) 2.19) and similarity (f(2) 89.79) factors indicated that there was no difference between predicted and experimentally observed drug release profiles for the optimal formulation. This work illustrates the potential for an artificial neural network with MLP, to assist in development of sustained release dosage forms.

Inelastic behaviour of collagen networks in cell-matrix interactions and mechanosensation.

PubMed

Mohammadi, Hamid; Arora, Pamma D; Simmons, Craig A; Janmey, Paul A; McCulloch, Christopher A

2015-01-06

The mechanical properties of extracellular matrix proteins strongly influence cell-induced tension in the matrix, which in turn influences cell function. Despite progress on the impact of elastic behaviour of matrix proteins on cell-matrix interactions, little is known about the influence of inelastic behaviour, especially at the large and slow deformations that characterize cell-induced matrix remodelling. We found that collagen matrices exhibit deformation rate-dependent behaviour, which leads to a transition from pronounced elastic behaviour at fast deformations to substantially inelastic behaviour at slow deformations (1 μm min(-1), similar to cell-mediated deformation). With slow deformations, the inelastic behaviour of floating gels was sensitive to collagen concentration, whereas attached gels exhibited similar inelastic behaviour independent of collagen concentration. The presence of an underlying rigid support had a similar effect on cell-matrix interactions: cell-induced deformation and remodelling were similar on 1 or 3 mg ml(-1) attached collagen gels while deformations were two- to fourfold smaller in floating gels of high compared with low collagen concentration. In cross-linked collagen matrices, which did not exhibit inelastic behaviour, cells did not respond to the presence of the underlying rigid foundation. These data indicate that at the slow rates of collagen compaction generated by fibroblasts, the inelastic responses of collagen gels, which are influenced by collagen concentration and the presence of an underlying rigid foundation, are important determinants of cell-matrix interactions and mechanosensation. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Inelastic behaviour of collagen networks in cell–matrix interactions and mechanosensation

PubMed Central

Mohammadi, Hamid; Arora, Pamma D.; Simmons, Craig A.; Janmey, Paul A.; McCulloch, Christopher A.

2015-01-01

The mechanical properties of extracellular matrix proteins strongly influence cell-induced tension in the matrix, which in turn influences cell function. Despite progress on the impact of elastic behaviour of matrix proteins on cell–matrix interactions, little is known about the influence of inelastic behaviour, especially at the large and slow deformations that characterize cell-induced matrix remodelling. We found that collagen matrices exhibit deformation rate-dependent behaviour, which leads to a transition from pronounced elastic behaviour at fast deformations to substantially inelastic behaviour at slow deformations (1 μm min−1, similar to cell-mediated deformation). With slow deformations, the inelastic behaviour of floating gels was sensitive to collagen concentration, whereas attached gels exhibited similar inelastic behaviour independent of collagen concentration. The presence of an underlying rigid support had a similar effect on cell–matrix interactions: cell-induced deformation and remodelling were similar on 1 or 3 mg ml−1 attached collagen gels while deformations were two- to fourfold smaller in floating gels of high compared with low collagen concentration. In cross-linked collagen matrices, which did not exhibit inelastic behaviour, cells did not respond to the presence of the underlying rigid foundation. These data indicate that at the slow rates of collagen compaction generated by fibroblasts, the inelastic responses of collagen gels, which are influenced by collagen concentration and the presence of an underlying rigid foundation, are important determinants of cell–matrix interactions and mechanosensation. PMID:25392399

Ocean Spectral Data Assimilation Without Background Error Covariance Matrix

DTIC Science & Technology

2016-01-01

float data (Chu et al. 2007 ), and 97 temporal and spatial variability of the global upper ocean heat content (Chu 2011) from the data 98 of the Global...Melnichenko OV, Wells NC ( 2007 ) Long baroclinic Rossby waves in the 558 tropical North Atlantic observed from profiling floats. J Geophys Res...Hall, J, Harrison D.E. and Stammer , D., Eds., ESA Publication WPP-610 306. 611 612 Tang Y, Kleeman R (2004) SST assimilation experiments in a

Discrete element modeling of microstructure of nacre

NASA Astrophysics Data System (ADS)

Chandler, Mei Qiang; Cheng, Jing-Ru C.

2018-04-01

The microstructure of nacre consists of polygon-shaped aragonite mineral tablets bonded by very thin layers of organic materials and is organized in a brick-mortar morphology. In this research, the discrete element method was utilized to model this structure. The aragonite mineral tablets were modeled with three-dimensional polygon particles generated by the Voronoi tessellation method to represent the Voronoi-like patterns of mineral tablets assembly observed in experiments. The organic matrix was modeled with a group of spring elements. The constitutive relations of the spring elements were inspired from the experimental results of organic molecules from the literature. The mineral bridges were modeled with simple elastic bonds with the parameters based on experimental data from the literature. The bulk stress-strain responses from the models agreed well with experimental results. The model results show that the mineral bridges play important roles in providing the stiffness and yield strength for the nacre, while the organic matrix in providing the ductility for the nacre. This work demonstrated the suitability of particle methods for modeling microstructures of nacre.

Modified release matrix prepared by compaction of spheres containing waxy material.

PubMed

Bado, L; Ghaly, E S

1995-09-01

In this study, chlorpheniramine maleate spheres were prepared by the extruder/marumerizer. A new waxy material, Gelucire 50/02 at three levels (10%, 30% and 50%) was added and Avicel PH-101 was used as spheronizing material. The drug was incorporated into the waxy material by two methods. The first was the direct method, in which the drug (10%), wax and Avicel PH-101 were mixed together. The second was the fusion method, in which the drug was dispersed in the melted wax and the solidified mass was milled and mixed with Avicel PH-101. The data obtained indicated that simple addition of waxy material into chlorpheniramine maleate-Avicel PH-101 spheres interrupted matrix formation and increased drug release. Also in this study, a multiparticulate delivery system was prepared successfully by compaction of spheres into tablets. Tablets compacted from spheres prepared by fusion method gave less drug release than those compacted from spheres of the same composition but prepared with direct method. As the level of wax was increased in tablet formulation, drug release was decreased.

Formulation and in-vitro evaluation of directly compressed controlled release matrices of Losartan Potassium using Ethocel Grade 100 as rate retarding agent.

PubMed

Khan, Kamran Ahmad; Khan, Gul Majid; Zeeshan Danish, Muhammad; Akhlaq; Khan, Haroon; Rehman, Fazal; Mehsud, Saifullah

2015-12-30

Current study was aimed to develop 200mg controlled release matrix tablets of Losartan Potassium using Ethocel 100 Premium and Ethocel 100 FP Premium as rate controlling polymer. In-vitro studies were performed according to USP Method-I in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature of the dissolution medium was kept constant at 37±0.5°C at 100rpm. Flow properties, physical quality control tests, effect of polymer size and drug-to-polymers ratios were studied using different kinetics models such as 1st-order, zero-order, Hixon Crowell model, Highuchi model and Power law. Difference factor f1 and similarity factor f2 were applied for dissolution profiles against Cardaktin® tablets used as a reference formulation. The matrices with polymer ethocel 100 FP Premiums have prolonged the drug release rate as compared to polymer ethocel 100 Premiums. The n values matrices with polymer ethocel grade 100 ranged from 0.603 to 0.857 indicating that the drug release occurred by anomalous non fickian diffusion kinetics while then value of reference Cardaktin® tablet was measured as 0.125 indicating that these tablets do not follow power law. The dissolution profiles of test formulations were different than that of reference Cardaktin®. This suggests the polymer Ethocel grade 100 can be proficiently incorporated in fabrication and development of once a day controlled release matrix tablets. Copyright © 2015. Published by Elsevier B.V.

Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet

PubMed Central

Mortazavi, Seyed Alireza; Jafariazar, Zahra; Ghadjahani, Yasaman; Mahmoodi, Hoda; Mehtarpour, Farzaneh

2014-01-01

The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were prepared by through mixing of the ingredients, followed by direct compression. All the prepared formulations were evaluated in terms of physicochemical tests, including uniformity of weight, thickness, crushing strength, friability and in-vitro drug release. Four groups of formulations were prepared. The presence of different amounts of cellulose derivatives or Carbopol 971P, alone, was studied in group A formulations. In group B formulations, the effect of adding Carbopol 971P alongside different cellulose derivatives was investigated. Group C formulations were made by including mannitol as the solubilizing agent, alongside Carbopol 971P and a cellulose derivative. In group D formulations, mini-tablets were made using Carbopol 971P, alongside two different cellulose derivative. The selected formulation (C1) contained ethyl cellulose, Carbopol 971P, mannitol and magnesium stearate, which showed almost 100% drug release over 5 h. Based on kinetic studies, this formulation was found to best fit the zero-order model of drug release. However, the Higuchi and Hixson -Crowell models also showed a good fit. Hence, overall, formulation C1 was chosen as the best formulation. PMID:24734053

Overcoming Matrix Effects in a Complex Sample: Analysis of Multiple Elements in Multivitamins by Atomic Absorption Spectroscopy

ERIC Educational Resources Information Center

Arnold, Randy J.; Arndt, Brett; Blaser, Emilia; Blosser, Chris; Caulton, Dana; Chung, Won Sog; Fiorenza, Garrett; Heath, Wyatt; Jacobs, Alex; Kahng, Eunice; Koh, Eun; Le, Thao; Mandla, Kyle; McCory, Chelsey; Newman, Laura; Pithadia, Amit; Reckelhoff, Anna; Rheinhardt, Joseph; Skljarevski, Sonja; Stuart, Jordyn; Taylor, Cassie; Thomas, Scott; Tse, Kyle; Wall, Rachel; Warkentien, Chad

2011-01-01

A multivitamin tablet and liquid are analyzed for the elements calcium, magnesium, iron, zinc, copper, and manganese using atomic absorption spectrometry. Linear calibration and standard addition are used for all elements except calcium, allowing for an estimate of the matrix effects encountered for this complex sample. Sample preparation using…

Water hyacinth: a possible alternative rate retarding natural polymer used in sustained release tablet design

PubMed Central

Khatun, Sabera; Sutradhar, Kumar B.

2014-01-01

In recent years natural polymers have been widely used because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5, 10, 15, 20, 25 and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr's Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM) studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37°C ± 0.5 temperature for 8 h. Though all the formulations comply with both BP and USP requirements, formulation F-1 (5% of Water hyacinth) was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell, and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations. PMID:24966835

Roller compaction of hydrophilic extended release tablets-combined effects of processing variables and drug/matrix former particle size.

PubMed

Heiman, Johanna; Tajarobi, Farhad; Gururajan, Bindhumadhavan; Juppo, Anne; Abrahmsén-Alami, Susanna

2015-04-01

The present study shows that roller compaction (RC) can successfully be used as a granulation method to prepare hydroxypropyl methylcellulose (HPMC)-based extended release matrix tablets containing a high drug load, both for materials deforming mainly by fragmentation (paracetamol) as for those having mainly plastic deformation (ibuprofen). The combined effect of RC process variables and composition on the manufacturability of HPMC tablets was investigated. Standard wet granulation grade HPMC was compared with a larger particle size direct compressible HPMC grade. Higher roll pressure was found to result in larger paracetamol granules and narrower granule particle size distributions, especially for formulations containing smaller size HPMC. However, for ibuprofen, no clear effect of roll pressure was observed. High roll pressure also resulted in denser ribbon and less bypass fines during RC. Loss of compactibility was observed for granules compared to powder blends, which was found to be related to differences in granule porosity and morphology. Using the large-sized HPMC grade did in some cases result in lower tensile strength tablets but had the advantage to improve the powder flow into the roller compactor. This work also indicates that when the HPMC level lies near the percolation threshold, significant changes can occur in the drug release rate due to changes in other factors (raw material characteristics and processing).

High-amylose sodium carboxymethyl starch matrices for oral, sustained drug-release: formulation aspects and in vitro drug-release evaluation.

PubMed

Brouillet, F; Bataille, B; Cartilier, L

2008-05-22

High-amylose sodium carboxymethyl starch (HASCA), produced by spray-drying (SD), was previously shown to have interesting properties as a promising pharmaceutical sustained drug-release tablet excipient for direct compression, including ease of manufacture and high crushing strength. This study describes the effects of some important formulation parameters, such as compression force (CF), tablet weight (TW), drug-loading and electrolyte particle size, on acetaminophen-release performances from sustained drug-release matrix tablets based on HASCA. An interesting linear relationship between TW and release time was observed for a typical formulation of the system consisting of 40% (w/w) acetaminophen as model drug and 27.5% NaCl as model electrolyte dry-mixed with HASCA. Application of the Peppas and Sahlin model gave a better understanding of the mechanisms involved in drug-release from the HASCA matrix system, which is mainly controlled by surface gel layer formation. Indeed, augmenting TW increased the contribution of the diffusion mechanism. CFs ranging from 1 to 2.5 tonnes/cm(2) had no significant influence on the release properties of tablets weighing 400 or 600 mg. NaCl particle size did not affect the acetaminophen-release profile. Finally, these results prove that the new SD process developed for HASCA manufacture is suitable for obtaining similar-quality HASCA in terms of release and compression performances.

General Classification Handbook for Floodplain Vegetation in Large River Systems. Chapter 1 of Book 2, Collection of Environmental Data

DTIC Science & Technology

2004-01-01

chlorophyll content, and the more vigorous the growth , the greater the reflectance. This helps the photointerpreter to better distinguish between plant and...land cover map and the field determinations for each class. Based on the error matrix, the accuracy rate for classifying each map class can be...duck- weed (Lemna, Spirodela, and Wolffia) and other nonrooted- floating aquatics. Because duckweed is free-floating, it can relocate day-to-day

Investigation of water mobility and diffusivity in hydrating micronized low-substituted hydroxypropyl cellulose, hydroxypropylmethyl cellulose, and hydroxypropyl cellulose matrix tablets by magnetic resonance imaging (MRI).

PubMed

Kojima, Masazumi; Nakagami, Hiroaki

2002-12-01

The water mobility and diffusivity in the gel-layer of hydrating low-substituted hydroxypropyl cellulose (LH41) tablets with or without a drug were investigated by magnetic resonance imaging (MRI) and compared with those properties in the gel-layer of hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) tablets. For this purpose, a localized image-analysis method was newly developed, and the spin-spin relaxation time (T(2)) and apparent self-diffusion coefficient (ADC) of water in the gel-layer were visualized in one-dimensional maps. Those maps showed that the extent of gel-layer growth in the tablets was in the order of HPC>HPMC>LH41, and there was a water mobility gradient across the gel-layers of all three tablet formulations. The T(2) and ADC in the outer parts of the gel-layers were close to those of free water. In contrast, these values in the inner parts of the gel-layer decreased progressively; suggesting that the water mobility and diffusivity around the core interface were highly restricted. Furthermore, the correlation between the T(2) of (1)H proton in the gel-layer of the tablets and the drug release rate from the tablets was observed.

4K Video of Colorful Liquid in Space

NASA Image and Video Library

2015-10-09

Once again, astronauts on the International Space Station dissolved an effervescent tablet in a floating ball of water, and captured images using a camera capable of recording four times the resolution of normal high-definition cameras. The higher resolution images and higher frame rate videos can reveal more information when used on science investigations, giving researchers a valuable new tool aboard the space station. This footage is one of the first of its kind. The cameras are being evaluated for capturing science data and vehicle operations by engineers at NASA's Marshall Space Flight Center in Huntsville, Alabama.

Compacted Multiparticulate Systems for Colon-Specific Delivery of Ketoprofen.

PubMed

de Alencar, Rodrigo Gomes; de Oliveira, Aline Carlos; Lima, Eliana Martins; da Cunha-Filho, Marcílio Sérgio Soares; Taveira, Stephânia Fleury; Marreto, Ricardo Neves

2017-08-01

Pellet-containing tablets for colon-specific drug delivery present higher targeting efficiency and lower costs when compared with monolithic tablets and pellet-filled capsules, respectively. In this study, pellets containing ketoprofen were coated with different acrylic polymers and submitted to compaction. The influence of formulation and process factors on film integrity was then evaluated. Pellets were prepared via extrusion-spheronization and coated using two acrylic polymers (Eudragit® FS 30 D and Opadry® 94 k28327, PMMA and PMA, respectively). The resulting pellets were mixed with placebo granules and compressed in a hydraulic press. Multiple regression showed that ketoprofen release from pellet-containing tablets is predominantly influenced by pellet content, hardness, friability, and disintegration time. PMA-containing tablets prepared under low compaction force or with low pellet content showed rapid disintegration (<1 min) and ketoprofen release similar to those of uncompressed coated pellets (∼30% at 360 min of experiment). On the other hand, PMMA-containing tablets showed a higher rupture level, and those prepared with higher pellet content gave rise to a non-disintegrating matrix. Coated pellets were shown to be able to target ketoprofen to the colonic region. Targeting capacity was dependent on the physicochemical characteristics of the tablets.

Tablet fragmentation without a disintegrant: A novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets.

PubMed

Arafat, Basel; Wojsz, Magdalena; Isreb, Abdullah; Forbes, Robert T; Isreb, Mohammad; Ahmed, Waqar; Arafat, Tawfiq; Alhnan, Mohamed A

2018-06-15

Fused deposition modelling (FDM) 3D printing has shown the most immediate potential for on-demand dose personalisation to suit particular patient's needs. However, FDM 3D printing often involves employing a relatively large molecular weight thermoplastic polymer and results in extended release pattern. It is therefore essential to fast-track drug release from the 3D printed objects. This work employed an innovative design approach of tablets with unique built-in gaps (Gaplets) with the aim of accelerating drug release. The novel tablet design is composed of 9 repeating units (blocks) connected with 3 bridges to allow the generation of 8 gaps. The impact of size of the block, the number of bridges and the spacing between different blocks was investigated. Increasing the inter-block space reduced mechanical resistance of the unit, however, tablets continued to meet pharmacopeial standards for friability. Upon introduction into gastric medium, the 1 mm spaces gaplet broke into mini-structures within 4 min and met the USP criteria of immediate release products (86.7% drug release at 30 min). Real-time ultraviolet (UV) imaging indicated that the cellulosic matrix expanded due to swelling of hydroxypropyl cellulose (HPC) upon introduction to the dissolution medium. This was followed by a steady erosion of the polymeric matrix at a rate of 8 μm/min. The design approach was more efficient than a comparison conventional formulation approach of adding disintegrants to accelerate tablet disintegration and drug release. This work provides a novel example where computer-aided design was instrumental at modifying the performance of solid dosage forms. Such an example may serve as the foundation for a new generation of dosage forms with complicated geometric structures to achieve functionality that is usually achieved by a sophisticated formulation approach. Copyright © 2018 Elsevier B.V. All rights reserved.

Assembled modules technology for site-specific prolonged delivery of norfloxacin.

PubMed

Oliveira, Paulo Renato; Bernardi, Larissa Sakis; Strusi, Orazio Luca; Mercuri, Salvatore; Segatto Silva, Marcos A; Colombo, Paolo; Sonvico, Fabio

2011-02-28

The aim of this research was to design and study norfloxacin (NFX) release in floating conditions from compressed hydrophilic matrices of hydroxypropylmethylcellulose (HPMC) or poly(ethylene oxide) (PEO). Module assembling technology for drug delivery system manufacturing was used. Two differently cylindrical base curved matrix/modules, identified as female and male, were assembled in void configuration by friction interlocking their concave bases obtaining a floating release system. Drug release and floatation behavior of this assembly was investigated. Due to the higher surface area exposed to the release medium, faster release was observed for individual modules compared to their assembled configuration, independently on the polymer used and concentration. The release curves analyzed using the Korsmeyer exponential equation and Peppas & Sahlin binomial equation showed that the drug release was controlled both by drug diffusion and polymer relaxation or erosion mechanisms. However, convective transport was predominant with PEO and at low content of polymers. NFX release from PEO polymeric matrix was more erosion dependent than HPMC. The assembled systems were able to float in vitro for up to 240min, indicating that this drug delivery system of norfloxacin could provide gastro-retentive site-specific release for increasing norfloxacin bioavailability. Copyright © 2010. Published by Elsevier B.V.

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethyl cellulose matrix tablets in situ.

PubMed

Kulinowski, Piotr; Młynarczyk, Anna; Dorożyński, Przemysław; Jasiński, Krzysztof; Gruwel, Marco L H; Tomanek, Bogusław; Węglarz, Władysław P

2012-12-01

To resolve contradictions found in morphology of hydrating hydroxypropylmethyl cellulose (HPMC) matrix as studied using Magnetic Resonance Imaging (MRI) techniques. Until now, two approaches were used in the literature: either two or three regions that differ in physicochemical properties were identified. Multiparametric, spatially and temporally resolved T(2) MR relaxometry in situ was applied to study the hydration progress in HPMC matrix tablets using a 11.7 T MRI system. Two spin-echo based pulse sequences-one of them designed to specifically study short T(2) signals-were used. Two components in the T(2) decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T(2) values, were obtained. Based on the data, five different regions and their temporal evolution were identified: dry glassy, hydrated solid like, two interface layers and gel layer. The regions were found to be separated by four evolving fronts identified as penetration, full hydration, total gelification and apparent erosion. The MRI results showed morphological details of the hydrating HPMC matrices matching compound theoretical models. The proposed method will allow for adequate evaluation of controlled release polymeric matrix systems loaded with drug substances of different solubility.

The effect of pH, buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends.

PubMed

Hamed, Rania; AlJanabi, Reem; Sunoqrot, Suhair; Abbas, Aiman

2017-08-01

The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel ® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol ® HD5 ATO). The two formulations attained release profiles of QF over 24 h similar to that of Seroquel ® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel ® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro-in vivo correlations.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: drug release and fronts movement kinetics.

PubMed

Marinich, J A; Ferrero, C; Jiménez-Castellanos, M R

2012-04-01

A previous paper deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility. The influence of the carbohydrate nature, drying procedure and initial pore network on drug release kinetics was also evaluated. Drug release experiments were performed from free tablets. Radial drug release and fronts movement kinetics were also analysed, and several mathematical models were employed to ascertain the drug release mechanisms. The drug release markedly depends on the drug solubility and the carbohydrate nature but is practically not affected by the drying process and the initial matrix porosity. A faster drug release is observed for matrices containing diltiazem HCl compared with those containing anhydrous theophylline, in accordance with the higher drug solubility and the higher friability of diltiazem matrices. In fact, although diffusion is the prevailing drug release mechanism for all matrices, the erosion mechanism seems to have some contribution in several formulations containing diltiazem. A reduction in the surface exposed to the dissolution medium (radial release studies) leads to a decrease in the drug release rate, but the release mechanism is not essentially modified. The nearly constant erosion front movement confirms the behaviour of these systems as inert matrices where the drugs are released mainly by diffusion through the porous structure. Copyright © 2011 Elsevier B.V. All rights reserved.

Interaction between fed gastric media (Ensure Plus®) and different hypromellose based caffeine controlled release tablets: comparison and mechanistic study of caffeine release in fed and fasted media versus water using the USP dissolution apparatus 3.

PubMed

Franek, Frans; Holm, Per; Larsen, Frank; Steffansen, Bente

2014-01-30

The aim of the study was to investigate caffeine release in fed and fasted state media from three controlled release matrix tablets containing different HPMC viscosity grades. The biorelevant in vitro dissolution methods utilize the USP 3 dissolution apparatus and biorelevant media to simulate fed and fasted gastro-intestinal dissolution conditions. The effect of tablet reciprocation rate (dip speed) in dissolution media (10 and 15 dips per minute) and media (water, fed and fasted) on caffeine release rate from - and erosion rate of - 100, 4000 and 15,000 mPa s HPMC viscosity tablets was investigated using factorial designed experiments. Furthermore, the mechanism of release in Ensure Plus(®), a nutrition drink similar in composition to the FDA standard meal, was investigated by studying tablet swelling using texture analysis. Altering dip speed has negligible effect on release and erosion rates. Using fasted media instead of water slightly decreases caffeine release from 100 and 4000 mPa s HPMC viscosity tablets as well as erosion rates, while 15,000 mPa s tablets remain unaffected. Fed compared to fasted media decreases caffeine release rate, and the food effect is greater for the 100 mPa s viscosity tablets compared to the 4000 and 15,000 mPa s viscosity tablets. The investigation using texture analysis indicates that Ensure Plus(®) becomes rate-limiting for caffeine release from HPMC tablets by forming a hydrophobic barrier around the tablets. The barrier decreases tablet water permeation, which decreases erosion rate in 100 mPa s viscosity tablets, swelling in 15,000 mPa s viscosity tablets and caffeine release from both tablets. This observed interaction between Ensure Plus(®) and the HPMC tablets may translate into decreased drug release rate in the fed stomach, which may decrease the amount of drug available for absorption in the small intestine and thus reduce systemic drug exposure and maximum plasma concentration. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of pore forming agents on chitosan-graft-poly(N-vinylpyrrolidone) hydrogel properties for use as a matrix for floating drug delivery

NASA Astrophysics Data System (ADS)

Budianto, E.; Al-Shidqi, M. F.; Cahyana, A. H.

2017-07-01

Eradicating H. pylori-based infection by using conventional oral dosage form of amoxicillin trihydrate finds difficulties to overcome rapid gastric retention time. Encapsulating amoxicillin trihydrate in floating drug delivery system may solve the problem. In this research, the floating drug delivery system of amoxicillin trihydrate encapsulated in floating chitosan-graft-poly(N-vinyl pyrrolidone) hydrogels containing CaCO3 and NaHCO3 as pore forming agents has been successfully prepared. Pore forming agents used was varied with the ratio of 10 to 25% pore forming agents to total mass of the used materials. The hydrogel were characterizedusing FTIR spectrophotometer and stereo microscope. As pore forming agents compositions increased, the porosity (%) and floating properties increased but followed by decrease in drug entrapment efficiency. Most of the floating hydrogels possessed floating ability longer than 180 min and the highest porosity was found in hydrogel containing 25% NaHCO3. Hydrogel containing CaCO3 showed sustained drug release profile than hydrogel containing NaHCO3. However, the optimum formulation was achieved at composition of 10% NaHCO3 with 57% of drug entrapped within the hydrogel and 43% drug released. The results of these studies show that NaHCO3 is an effective pore forming agents for chitosan-graft-poly(N-vinyl pyrrolidone) hydrogel preparation as compare to CaCO3.

Modulation of venlafaxine hydrochloride release from press coated matrix tablet.

PubMed

Gohel, M C; Soni, C D; Nagori, S A; Sarvaiya, K G

2008-01-01

The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3(2) full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

A study of a novel coprocessed dry binder composed of α-lactose monohydrate, microcrystalline cellulose and corn starch.

PubMed

Mužíková, Jitka; Srbová, Alena; Svačinová, Petra

2017-12-01

This paper deals with a study of the novel coprocessed dry binder Combilac®, which contains 70% of α-lactose monohydrate, 20% of microcrystalline cellulose and 10% of native corn starch. These tests include flow properties, compressibility, lubricant sensitivity, tensile strength and disintegration time of tablets. Compressibility is evaluated by means of the energy profile of compression process, test of stress relaxation and tablet strength. The above-mentioned parameters are also evaluated in the physical mixture of α-lactose monohydrate, microcrystalline cellulose and native corn starch and compared with Combilac. Combilac shows much better flowability than the physical mixture of the used dry binders. Its compressibility is better, tablets possess a higher tensile strength. Neither Combilac, nor the physical mixture can be compressed without lubricants due to high friction and sticking to the matrix. Combilac has a higher lubricant sensitivity than the physical mixture of the dry binders. Disintegration time of Combilac tablets is comparable with the disintegration time of tablets made from the physical mixture.

Multiway analysis methods applied to the fluorescence excitation-emission dataset for the simultaneous quantification of valsartan and amlodipine in tablets

NASA Astrophysics Data System (ADS)

Dinç, Erdal; Ertekin, Zehra Ceren; Büker, Eda

2017-09-01

In this study, excitation-emission matrix datasets, which have strong overlapping bands, were processed by using four different chemometric calibration algorithms consisting of parallel factor analysis, Tucker3, three-way partial least squares and unfolded partial least squares for the simultaneous quantitative estimation of valsartan and amlodipine besylate in tablets. In analyses, preliminary separation step was not used before the application of parallel factor analysis Tucker3, three-way partial least squares and unfolded partial least squares approaches for the analysis of the related drug substances in samples. Three-way excitation-emission matrix data array was obtained by concatenating excitation-emission matrices of the calibration set, validation set, and commercial tablet samples. The excitation-emission matrix data array was used to get parallel factor analysis, Tucker3, three-way partial least squares and unfolded partial least squares calibrations and to predict the amounts of valsartan and amlodipine besylate in samples. For all the methods, calibration and prediction of valsartan and amlodipine besylate were performed in the working concentration ranges of 0.25-4.50 μg/mL. The validity and the performance of all the proposed methods were checked by using the validation parameters. From the analysis results, it was concluded that the described two-way and three-way algorithmic methods were very useful for the simultaneous quantitative resolution and routine analysis of the related drug substances in marketed samples.

Investigation of the effect of hydroxypropyl methylcellulose on the phase transformation and release profiles of carbamazepine-nicotinamide cocrystal.

PubMed

Li, Mingzhong; Qiu, Shi; Lu, Yan; Wang, Ke; Lai, Xiaojun; Rehan, Mohammad

2014-09-01

The aim of this work was to investigate the influence of hydroxypropyl methylcellulose (HPMC) on the phase transformation and release profile of carbamazepine-nicotinamide (CBZ-NIC) cocrystal in solution and in sustained release matrix tablets. The polymorphic transitions of the CBZ-NIC cocrystal and its crystalline properties were examined by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Raman spectroscopy, and scanning electron microscopy (SEM). The apparent CBZ solubility and dissolution rate of CBZ-NIC cocrystal were constant in different concentrations of HPMC solutions. In a lower percentage of HPMC in the matrix tablets, the CBZ release profile of the CBZ-NIC cocrystal was nonlinear and declined over time. With an increased HPMC content in the tablets, the CBZ-NIC cocrystal formulation showed a significantly higher CBZ release rate in comparison with the other two formulations of CBZ III and the physical mixture. Because of a significantly improved dissolution rate of the CBZ-NIC cocrystal, the rate of CBZ entering into solution is significantly faster than the rate of formation of the CBZ-HPMC soluble complex in solution, leading to a higher supersaturation level of CBZ and subsequently precipitation of CBZ dihydrate.

[Mechanism of Tongsaimai tablet for atherosclerosis based on network pharmacology].

PubMed

Li, Na; Zhang, Xin-Zhuang; Wang, Yan-Ru; Cao, Liang; Ding, Gang; Wang, Zhen-Zhong; Xiao, Wei; Xu, Xiao-Jie

2016-05-01

Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Tongsaimai tablets for atherosclerosis. In molecular docking and molecular-target protein network analysis, 97 molecules in Tongsaimai tablets showed good interaction with the atherosclerosis-related target protein (docking score ≥ 7), and 37 molecules of them could act on more than 2 targets (≥ 2) with higher betweenness, suggesting that these 37 molecules might be the main active compounds group in Tongsaimai tablets for atherosclerosis treatment. Furthermore, the predicted active compounds contained more flavonoids and saponins, reminding more attention should be paid on flavonoids and saponins in study of effective compounds and quality standards of Tongsaimai tablets. Targets network analysis showed that, the active compounds of Tongsaimai tablets could regulate inflammation, stabilize plaque, protect vascular endothelial cell, regulate blood lipid and inhibit blood coagulation through acting on the main 22 target proteins, such as Toll-like receptors (TLR1, TLR2), matrix metalloproteinase (MMP1, MMP2, MMP3, MMP9), angiotensin converting enzyme (ACE), leukotriene A4 hydrolase (LTA4-H), 5-lipoxidase (5-LOX), peroxisome proliferators-activated receptors (PPARα, PPARγ). These active compounds can participate in regulating different pathologic stages of atherosclerosis and thus treat atherosclerosis finally. This study revealed the main active compounds and possible mechanism of Tongsaimai tablets for treatment of atherosclerosis and meanwhile, verified the characteristics of multi-components, multi-targets and integral regulation for Tongsaimai tablets, providing theoretical references for the following systematic laboratory experiments on effective compounds and action mechanism of Tongsaimai Tablet. Copyright© by the Chinese Pharmaceutical Association.

Spatial Distribution of Trehalose Dihydrate Crystallization in Tablets by X-ray Diffractometry.

PubMed

Thakral, Naveen K; Yamada, Hiroyuki; Stephenson, Gregory A; Suryanarayanan, Raj

2015-10-05

Crystallization of trehalose dihydrate (C12H22O11·2H2O) was induced by storing tablets of amorphous anhydrous trehalose (C12H22O11) at 65% RH (RT). Our goal was to evaluate the advantages and limitations of two approaches of profiling spatial distribution of drug crystallization in tablets. The extent of crystallization, as a function of depth, was determined in tablets stored for different time-periods. The first approach was glancing angle X-ray diffractometry, where the penetration depth of X-rays was modulated by the incident angle. Based on the mass attenuation coefficient of the matrix, the depth of X-ray penetration was calculated as a function of incident angle, which in turn enabled us to "calculate" the extent of crystallization to different depths. In the second approach, the tablets were split into halves and the split surfaces were analyzed directly. Starting from the tablet surface and moving toward the midplane, XRD patterns were collected in 36 "regions", in increments of 0.05 mm. The results obtained by the two approaches were, in general, in good agreement. Additionally, the results obtained were validated by determining the "average" crystallization in the entire tablet by using synchrotron radiation in the transmission mode. The glancing angle method could detect crystallization up to ∼650 μm and had a "surface bias". Being a nondestructive technique, this method will permit repeated analyses of the same tablet at different time points, for example, during a stability study. However, split tablet analyses, while a "destructive" technique, provided comprehensive and unbiased depth profiling information.

A study on maize proteins as a potential new tablet excipient.

PubMed

Georget, Dominique M R; Barker, Susan A; Belton, Peter S

2008-06-01

This investigation has examined the use of zein proteins from maize as the major component in oral controlled-release tablets, such formulations often being required to improve patient compliance. Tablets containing ground zein proteins, calcium hydrogen orthophosphate, polyvinyl pyrrolidone, theophylline and magnesium stearate were produced by wet granulation and compression on a single station tablet press and were compared to directly compressed tablets based on zein proteins, calcium hydrogen orthophosphate and theophylline. Non invasive techniques such as Fourier Transform infrared spectroscopy and Fourier Transform Raman spectroscopy were employed to investigate any changes in the secondary structure of zein proteins during tablet production. Random coils, alpha helices and beta sheets predominated and their relative content remained unaffected during grinding, wet granulation and compression, indicating that formulations based on zeins will be robust, i.e. insensitive to minor changes in the production conditions. Drug release from the tablets was studied using a standard pharmacopoeial dissolution test. Dissolution profiles in water, 0.1M HCl (pH=1) and phosphate buffer (pH=6.8) show that only a limited amount of theophylline was released after 4.5h, suggesting that zein proteins could act as a potential vehicle for oral controlled drug release. Analysis of the theophylline release profiles using the Peppas and Sahlin model reveals that diffusion and polymer relaxation occurred in acidic (pH=1) and buffered (pH=6.8) conditions for wet granulated tablets, whereas diffusion was predominant in directly compressed tablets. In conclusion, the present study has shown that zeins can be successfully used as a pharmaceutical excipient, and in particular as a matrix in monolithic controlled release tablets.

A simple and rapid approach to evaluate the in vitro in vivo role of release controlling agent ethyl cellulose ether derivative polymer.

PubMed

Akhlaq, Muhammad; Khan, Gul Majid; Jan, Syed Umer; Wahab, Abdul; Hussain, Abid; Nawaz, Asif; Abdelkader, Hamdy

2014-11-01

Diclofenac sodium (DCL-Na) conventional oral tablets exhibit serious side effects when given for a longer period leading to noncompliance. Controlled release matrix tablets of diclofenac sodium were formulated using simple blending (F-1), solvent evaporation (F-2) and co-precipitation techniques (F-3). Ethocel® Standard 7 FP Premium Polymer (15%) was used as a release controlling agent. Drug release study was conducted in 7.4 pH phosphate buffer solutions as dissolution medium in vitro. Pharmacokinetic parameters were evaluated using albino rabbits. Solvent evaporation technique was found to be the best release controlling technique thereby prolonging the release rate up to 24 hours. Accelerated stability studies of the optimized test formulation (F-2) did not show any significant change (p<0.05) in the physicochemical characteristics and release rate when stored for six months. A simple and rapid method was developed for DCL-Na active moiety using HPLC-UV at 276nm. The optimized test tablets (F-2) significantly (p<0.05) exhibited peaks plasma concentration (cmax=237.66±1.98) and extended the peak time (tmax=4.63±0.24). Good in-vitro in vivo correlation was found (R(2)=0.9883) against drug absorption and drug release. The study showed that once-daily controlled release matrix tablets of DCL-Na were successfully developed using Ethocel® Standard 7 FP Premium.

Development of Polyethylene Glycol and Hard Fat-Based Mucoadhesive Tablets Containing Various Types of Polyvinyl Alcohols as Mucoadhesive Polymers for Buccal Application.

PubMed

Ikeuchi-Takahashi, Yuri; Kobayashi, Ayaka; Onishi, Hiraku

2017-06-01

Topical drug application has the advantage of avoiding systemic side effects. We attempted to develop a long-acting matrix-type tablet containing indomethacin (IM) with low physical stimulus and potent mucoadhesive force to treat pain caused by oral aphtha. A mixture of polyethylene glycol (PEG) and hard fat was used as the tablet base. Ethylcellulose was added to the base in an attempt to control drug release. Tablets with PEG as a base were also prepared for comparison. Polyvinyl alcohols (PVAs) with various degrees of saponification were added to increase the mucoadhesive force. From the optical microscopic observations, formulations using PEG and hard fat exhibit PEG/hard fat dispersions caused by the stabilizing effects of PVA. Although the tablets using PEG and hard fat showed sufficient adhesiveness and sustained drug release, those using PEG as the base did not. Drug release was controlled by the amount of hard fat and the saponification degree of PVA. The drug release rate was most increased in a tablet containing PVA with an intermediate degree of saponification, PEG and hard fat. From differential scanning calorimetry and powder X-ray diffraction, IM was considered to exist in the molecular phase. From the results of buccal administration of tablets to rats, highest tissue concentrations were observed in the tablet containing PVA with the intermediate degree of saponification using PEG and hard fat, and the plasma concentrations were sufficiently low in comparison.

Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

PubMed Central

Campos, Michel Leandro; Rosa, Talita Atanazio; Padilha, Elias Carvalho; Alzate, Alejandro Henao; Rolim, Larissa Araújo; Rolim-Neto, Pedro José

2016-01-01

Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentration in vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease. PMID:26883698

pH responsive alginate polymeric rafts for controlled drug release by using box behnken response surface design

PubMed Central

Abbas, Ghulam; Hanif, Muhammad; Khan, Mahtab Ahmad

2017-01-01

Abstract Aim of the present work was to develop alginate raft forming tablets for controlled release pantoprazole sodium sesquihydrate (PSS). Box behnken design was used to optimize 15 formulations with three independent and three dependent variables. Physical tests of all formulations were within pharmacopoeial limits. Raft was characterized by their strength, thickness, resilience, acid neutralizing capacity, floating lag time and total floating time. Raft strength, thickness and resilience of optimized formulation AR9 were 7.43 ± 0.019 g, 5.8 ± 0.245 cm and greater than 480 min, respectively. Buffering and neutralizing capacity were 11.2 ± 1.01 and 6.5 ± 0.56 meq, respectively. Dissolution studies were performed by using simulated gastric fluid pH 1.2 and cumulative percentage release of optimized formulation AR9 was found 98%. First order release kinetics were followed and non-fickian diffusion was observed as value of n was greater than 0.45 in korsmeyer-peppas model. PSS, polymers, tablets and rafts were further characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). FTIR spectra of PSS, polymers and raft of optimized formulation AR9 showed peaks at 3223.09, 1688.17, 1586.67, 1302.64 and 1027.74 cm−1 due to –OH stretching, ester carbonyl group (C=O) stretching, existence of water and carboxylic group in raft, C–N stretching and –OH bending vibration showed no interaction between them. XRD showed diffraction lines indicates crystalline nature of PSS. DSC thermogram showed endothermic peaks at 250 °C for PSS. The developed raft was suitable for controlled release delivery of PSS. PMID:29491774

Floating-point scaling technique for sources separation automatic gain control

NASA Astrophysics Data System (ADS)

Fermas, A.; Belouchrani, A.; Ait-Mohamed, O.

2012-07-01

Based on the floating-point representation and taking advantage of scaling factor indetermination in blind source separation (BSS) processing, we propose a scaling technique applied to the separation matrix, to avoid the saturation or the weakness in the recovered source signals. This technique performs an automatic gain control in an on-line BSS environment. We demonstrate the effectiveness of this technique by using the implementation of a division-free BSS algorithm with two inputs, two outputs. The proposed technique is computationally cheaper and efficient for a hardware implementation compared to the Euclidean normalisation.

Influence of hydroxypropyl methylcellulose on drug release pattern of a gastroretentive floating drug delivery system using a 3(2) full factorial design.

PubMed

Swain, Kalpana; Pattnaik, Satyanarayan; Mallick, Subrata; Chowdary, Korla Appana

2009-01-01

In the present investigation, controlled release gastroretentive floating drug delivery system of theophylline was developed employing response surface methodology. A 3(2) randomized full factorial design was developed to study the effect of formulation variables like various viscosity grades and contents of hydroxypropyl methylcellulose (HPMC) and their interactions on response variables. The floating lag time for all nine experimental trial batches were less than 2 min and floatation time of more than 12 h. Theophylline release from the polymeric matrix system followed non-Fickian anomalous transport. Multiple regression analysis revealed that both viscosity and content of HPMC had statistically significant influence on all dependent variables but the effect of these variables found to be nonlinear above certain threshold values.

A unified multicomponent stress-diffusion model of drug release from non-biodegradable polymeric matrix tablets.

PubMed

Salehi, Ali; Zhao, Jin; Cabelka, Tim D; Larson, Ronald G

2016-02-28

We propose a new transport model of drug release from hydrophilic polymeric matrices, based on Stefan-Maxwell flux laws for multicomponent transport. Polymer stress is incorporated in the total mixing free energy, which contributes directly to the diffusion driving force while leading to time-dependent boundary conditions at the tablet interface. Given that hydrated matrix tablets are dense multicomponent systems, extended Stefan-Maxwell (ESM) flux laws are adopted to ensure consistency with the Onsager reciprocity principle and the Gibbs-Duhem thermodynamic constraint. The ESM flux law for any given component takes into account the friction exerted by all other species and is invariant with respect to reference velocity, thus satisfying Galilean translational invariance. Our model demonstrates that penetrant-induced plasticization of polymer chains partially or even entirely offsets the steady decline of chemical potential gradients at the tablet-medium interface that drive drug release. Utilizing a Flory-Huggins thermodynamic model, a modified form of the upper convected Maxwell constitutive equation for polymer stress and a Fujita-type dependence of mutual diffusivities on composition, depending on parameters, Fickian, anomalous or case II drug transport arises naturally from the model, which are characterized by quasi-power-law release profiles with exponents ranging from 0.5 to 1, respectively. A necessary requirement for non-Fickian release in our model is that the matrix stress relaxation time is comparable to the time scale for water diffusion. Mutual diffusivities and their composition dependence are the most decisive factors in controlling drug release characteristics in our model. Regression of the experimental polymer dissolution and drug release profiles in a system of Theophylline/cellulose (K15M) demonstrate that API-water mutual diffusivity in the presence of excipient cannot generally be taken as a constant. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of processing on the release profiles of matrix systems containing 5-aminosalicylic acid.

PubMed

Korbely, Anita; Kelemen, András; Kása, Péter; Pintye-Hódi, Klára

2012-12-01

The aim of this study was to investigate the influence of different processing methods on the profiles of 5-aminosalicylic acid dissolution from controlled-release matrix systems based on Eudragit® RL and Eudragit® RS water-insoluble polymers. The pure polymers and their mixtures were studied as matrix formers using different processing methods, i.e., direct compression, wet granulation of the active ingredient with the addition of polymer(s) to the external phase, wet granulation with water, and wet granulation with aqueous dispersions. In comparison with the directly compressed tablets, tablets made by wet granulation with water demonstrated a 6-19% increase in final drug dissolution, whereas when polymers were applied in the external phase during compression, a 0-13% decrease was observed in the amount of drug released. Wet granulation with aqueous polymer dispersions delayed the release of the drug; this was especially marked (a 54-56% decrease in drug release) in compositions, which contained a high amount of Eudragit RL 30D. The release profiles were mostly described by the Korsmeyer-Peppas model or the Hopfenberg model.

Soft, chewable gelatin-based pharmaceutical oral formulations: a technical approach.

PubMed

Dille, Morten J; Hattrem, Magnus N; Draget, Kurt I

2018-06-01

Hard tablets and capsules for oral drug delivery cause problems for people experiencing dysphagia. This work describes the formulation and properties of a gelatin based, self-preserved, and soft chewable tablet as an alternative and novel drug delivery format. Gelatin (8.8-10% in 24.7-29% water) constituted the matrix of the soft, semi-solid tablets. Three different pharmaceuticals (Ibuprofen 10%, Acetaminophen 15%, and Meloxicam 1.5%) were tested in this formulation. Microbial stability was controlled by lowering the water activity with a mixture of sorbitol and xylitol (45.6-55%). Rheological properties were tested applying small strain oscillation measurements. Taste masking of ibuprofen soft-chew tablets was achieved by keeping the ibuprofen insoluble at pH 4.5 and keeping the processing temperature below the crystalline-to-amorphous transition temperature. Soft-chew formulations showed good stability for all three pharmaceuticals (up to 24 months), and the ibuprofen containing formulation exhibited comparable dissolution to a standard oral tablet as well as good microbial stability. The rheological properties of the ibuprofen/gelatin formulation had the fingerprint of a true gelatin gel, albeit higher moduli, and melting temperature. The results suggest that easy-to-swallow and well taste-masked soft chewable tablet formulations with extended shelf life are within reach for several active pharmaceutical ingredients (APIs).

Theoretical characterization of a model of aragonite crystal orientation in red abalone nacre

NASA Astrophysics Data System (ADS)

Coppersmith, S N; Gilbert, P U P A; Metzler, R A

2009-03-01

Nacre, commonly known as mother-of-pearl, is a remarkable biomineral that in red abalone consists of layers of 400 nm thick aragonite crystalline tablets confined by organic matrix sheets, with the [0 0 1] crystal axes of the aragonite tablets oriented to within ±12° from the normal to the layer planes. Recent experiments demonstrate that greater orientational order develops over a distance of tens of layers from the prismatic boundary at which nacre formation begins. Our previous simulations of a model in which the order develops because of differential tablet growth rates (oriented tablets growing faster than misoriented ones) yield patterns of tablets that agree qualitatively and quantitatively with the experimental measurements. This paper presents an analytical treatment of this model, focusing on how the dynamical development and eventual degree of order depend on model parameters. Dynamical equations for the probability distributions governing tablet orientations are introduced whose form can be determined from symmetry considerations and for which substantial analytic progress can be made. Numerical simulations are performed to relate the parameters used in the analytic theory to those in the microscopic growth model. The analytic theory demonstrates that the dynamical mechanism is able to achieve a much higher degree of order than naive estimates would indicate.

Raman chemical mapping of magnesium stearate delivered by a punch-face lubrication system on the surface of placebo and active tablets.

PubMed

Šašiċ, Slobodan; Ojakovo, Peter; Warman, Martin; Sanghvi, Tapan

2013-09-01

Raman chemical mapping was used to determine the distribution of magnesium stearate, a lubricant, on the surface of tablets. The lubrication was carried out via a punch-face lubrication system with different spraying rates applied on placebo and active-containing tablets. Principal component analysis was used for decomposing the matrix of Raman mapping spectra. Some of the loadings associated with minuscule variation in the data significantly overlap with the Raman spectrum of magnesium stearate in placebo tablets and allow for imaging the domains of magnesium stearate via corresponding scores. Despite the negligible variation accounted for by respective principal components, the score images seem reliable as demonstrated through thresholding the one-dimensional representation and the spectra of the hot pixels that show a weak but perceivable magnesium stearate band at 1295 cm(-1). The same approach was applied on the active formulation, but no magnesium stearate was identified, presumably due to overwhelming concentration and spectral contribution of the active pharmaceutical ingredient.

Application of SERS spectroscopy to the identification of (3,4-methylenedioxy)amphetamine in forensic samples utilizing matrix stabilized silver halides.

PubMed

Sägmüller, B; Schwarze, B; Brehm, G; Schneider, S

2001-11-01

A method based on surface-enhanced Raman scattering (SERS) spectroscopy was developed to meet the need for the reliable and rapid identification of illicit drugs such as the 'designer drug' XTC, preferably to increase the security of legal certificates. A matrix stabilized silver halide dispersion on a microtiter plate is used as the SERS-active substrate, providing an easy to use system for sample preparation and probing by means of a Raman microscope. The potential of the method is demonstrated by applying it to the identification of the psychoactive ingredients of drug containing tablets which were confiscated by the local police at techno-music events. The samples of interest were 26 different brands of XTC tablets and several pieces of evidence (powders) containing amphetamine. For reference, we show SERS and Raman spectra of pristine amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethamphetamine.

Floating treatment wetlands for domestic wastewater treatment.

PubMed

Faulwetter, J L; Burr, M D; Cunningham, A B; Stewart, F M; Camper, A K; Stein, O R

2011-01-01

Floating islands are a form of treatment wetland characterized by a mat of synthetic matrix at the water surface into which macrophytes can be planted and through which water passes. We evaluated two matrix materials for treating domestic wastewater, recycled plastic and recycled carpet fibers, for chemical oxygen demand (COD) and nitrogen removal. These materials were compared to pea gravel or open water (control). Experiments were conducted in laboratory scale columns fed with synthetic wastewater containing COD, organic and inorganic nitrogen, and mineral salts. Columns were unplanted, naturally inoculated, and operated in batch mode with continuous recirculation and aeration. COD was efficiently removed in all systems examined (>90% removal). Ammonia was efficiently removed by nitrification. Removal of total dissolved N was ∼50% by day 28, by which time most remaining nitrogen was present as NO(3)-N. Complete removal of NO(3)-N by denitrification was accomplished by dosing columns with molasses. Microbial communities of interest were visualized with denaturing gradient gel electrophoresis (DGGE) by targeting specific functional genes. Shifts in the denitrifying community were observed post-molasses addition, when nitrate levels decreased. The conditioning time for reliable nitrification was determined to be approximately three months. These results suggest that floating treatment wetlands are a viable alternative for domestic wastewater treatment.

Effects of added surfactant on swelling and molecular transport in drug-loaded tablets based on hydrophobically modified poly(acrylic acid).

PubMed

Knöös, Patrik; Wahlgren, Marie; Topgaard, Daniel; Ulvenlund, Stefan; Piculell, Lennart

2014-08-14

A combination of NMR chemical shift imaging and self-diffusion experiments is shown to give a detailed molecular picture of the events that occur when tablets of hydrophobically modified poly(acrylic acid) loaded with a drug (griseofulvin) swell in water in the presence or absence of surfactant (sodium octylbenzenesulfonate). The hydrophobic substituents on the polymer bind and trap the surfactant molecules in mixed micelles, leading to a slow effective surfactant transport that occurs via a small fraction of individually dissolved surfactant molecules in the water domain. Because of the efficient binding of surfactant, the penetrating water is found to diffuse past the penetrating surfactant into the polymer matrix, pushing the surfactant front outward as the matrix swells. The added surfactant has little effect on the transport of drug because both undissolved solid drug and surfactant-solubilized drug function as reservoirs that essentially follow the polymer as it swells. However, the added surfactant nevertheless has a strong indirect effect on the release of griseofulvin, through the effect of the surfactant on the solubility and erosion of the polymer matrix. The surfactant effectively solubilizes the hydrophobically modified polymer, making it fully miscible with water, leading to a more pronounced swelling and a slower erosion of the polymer matrix.

A new amoxicillin/clavulanate therapeutic system: preparation, in vitro and pharmacokinetic evaluation.

PubMed

Kerc, Janez; Opara, Jerneja

2007-04-20

A new peroral amoxicillin/clavulanate therapeutic system composed of immediate release tablet and controlled release floating capsule was developed and evaluated by in vivo bioavailability study. Pharmacokinetic (PK) parameters for amoxicillin and clavulanic acid of the new therapeutic systems: AUCt, AUCi, (AUCt/AUCi), Cmax, Tmax, kel, T(1/2) and additionally for amoxicillin T(4) and T(2) were calculated from the plasma levels. The study confirmed enhanced pharmacokinetic parameters of a newly developed therapeutic system containing 1500 mg of amoxicillin and 125 mg of clavulanic acid. Prolonged time over MIC of amoxicillin in relation to a regular immediate release amoxicillin/clavulanate formulation was confirmed.

Using NMR chemical shift imaging to monitor swelling and molecular transport in drug-loaded tablets of hydrophobically modified poly(acrylic acid): methodology and effects of polymer (in)solubility.

PubMed

Knöös, Patrik; Topgaard, Daniel; Wahlgren, Marie; Ulvenlund, Stefan; Piculell, Lennart

2013-11-12

A new technique has been developed using NMR chemical shift imaging (CSI) to monitor water penetration and molecular transport in initially dry polymer tablets that also contain small low-molecular weight compounds to be released from the tablets. Concentration profiles of components contained in the swelling tablets could be extracted via the intensities and chemical shift changes of peaks corresponding to protons of the components. The studied tablets contained hydrophobically modified poly(acrylic acid) (HMPAA) as the polymer component and griseofulvin and ethanol as hydrophobic and hydrophilic, respectively, low-molecular weight model compounds. The water solubility of HMPAA could be altered by titration with NaOH. In the pure acid form, HMPAA tablets only underwent a finite swelling until the maximum water content of the polymer-rich phase, as confirmed by independent phase studies, had been reached. By contrast, after partial neutralization with NaOH, the polyacid became fully miscible with water. The solubility of the polymer affected the water penetration, the polymer release, and the releases of both ethanol and griseofulvin. The detailed NMR CSI concentration profiles obtained highlighted the clear differences in the disintegration/dissolution/release behavior for the two types of tablet and provided insights into their molecular origin. The study illustrates the potential of the NMR CSI technique to give information of importance for the development of pharmaceutical tablets and, more broadly, for the general understanding of any operation that involves the immersion and ultimate disintegration of a dry polymer matrix in a solvent.

Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies.

PubMed

Hiremath, Praveen S; Saha, Ranendra N

2008-01-01

The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using Korsmeyer-Peppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f (2) metric values. The release profiles found to follow Higuchi's square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.

Development of a new generation of high-temperature composite materials

NASA Technical Reports Server (NTRS)

Brindley, P. K.

1990-01-01

Intermetallic matrix composites proposed to meet advanced aeropropulsion requirements are discussed. The powder metallurgy fabrication process currently being used to produce these intermetallic matrix composites will be presented, as will properties of one such composite, SiC/Ti3Al+Nb. In addition, the direction of future research will be outlined, including plans for enhanced fabrication of intermetallic composites by the arc-spray technique and fiber development by the floating-zone process.

Development and evaluation of Ca(+ 2) ion cross-linked carboxymethyl xanthan gum tablet prepared by wet granulation technique.

PubMed

Maity, Siddhartha; Sa, Biswanath

2014-08-01

The objective of this work was to study the release behavior of prednisolone from calcium-cross-linked carboxymethyl xanthan gum (CMXG) tablets in dissolution medium having different pH values prevailing in the gastrointestinal lumen. Xanthan gum (XG) was derivatized to CMXG which was then cross-linked in situ with Ca(+2) ion during wet massing step of tablet preparation. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry studies did not show any drug-polymer interaction although the drug underwent solid-state transformation during compression as evident from X-ray diffraction analysis. In vitro release study demonstrated that increase in the amount of Ca(+2) ion decreased the drug release, and beyond a certain amount, the drug release increased. While increase in both drug load and tablet crushing strength decreased the drug release, increase in exposure time in acid solution of pH 1.2 increased the overall release of the drug. The mechanism of drug release was non-Fickian/anomalous. The results indicated that variation in the amount of Ca(+2) ion can modulate the drug release from CMXG matrix tablets as needed.

Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

PubMed Central

Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

2012-01-01

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

Tablet potency of Tianeptine in coated tablets by near infrared spectroscopy: model optimisation, calibration transfer and confidence intervals.

PubMed

Boiret, Mathieu; Meunier, Loïc; Ginot, Yves-Michel

2011-02-20

A near infrared (NIR) method was developed for determination of tablet potency of active pharmaceutical ingredient (API) in a complex coated tablet matrix. The calibration set contained samples from laboratory and production scale batches. The reference values were obtained by high performance liquid chromatography (HPLC) and partial least squares (PLS) regression was used to establish a model. The model was challenged by calculating tablet potency of two external test sets. Root mean square errors of prediction were respectively equal to 2.0% and 2.7%. To use this model with a second spectrometer from the production field, a calibration transfer method called piecewise direct standardisation (PDS) was used. After the transfer, the root mean square error of prediction of the first test set was 2.4% compared to 4.0% without transferring the spectra. A statistical technique using bootstrap of PLS residuals was used to estimate confidence intervals of tablet potency calculations. This method requires an optimised PLS model, selection of the bootstrap number and determination of the risk. In the case of a chemical analysis, the tablet potency value will be included within the confidence interval calculated by the bootstrap method. An easy to use graphical interface was developed to easily determine if the predictions, surrounded by minimum and maximum values, are within the specifications defined by the regulatory organisation. Copyright © 2010 Elsevier B.V. All rights reserved.

Magnetic resonance imaging and image analysis for assessment of HPMC matrix tablets structural evolution in USP Apparatus 4.

PubMed

Kulinowski, Piotr; Dorożyński, Przemysław; Młynarczyk, Anna; Węglarz, Władysław P

2011-05-01

The purpose of the study was to present a methodology for the processing of Magnetic Resonance Imaging (MRI) data for the quantification of the dosage form matrix evolution during drug dissolution. The results of the study were verified by comparison with other approaches presented in literature. A commercially available, HPMC-based quetiapine fumarate tablet was studied with a 4.7T MR system. Imaging was performed inside an MRI probe-head coupled with a flow-through cell for 12 h in circulating water. The images were segmented into three regions using threshold-based segmentation algorithms due to trimodal structure of the image intensity histograms. Temporal evolution of dry glassy, swollen glassy and gel regions was monitored. The characteristic features were observed: initial high expansion rate of the swollen glassy and gel layers due to initial water uptake, dry glassy core disappearance and maximum area of swollen glassy region at 4 h, and subsequent gel layer thickness increase at the expense of swollen glassy layer. The temporal evolution of an HPMC-based tablet by means of noninvasive MRI integrated with USP Apparatus 4 was found to be consistent with both the theoretical model based on polymer disentanglement concentration and experimental VIS/FTIR studies.

Simultaneous chemometric determination of pyridoxine hydrochloride and isoniazid in tablets by multivariate regression methods.

PubMed

Dinç, Erdal; Ustündağ, Ozgür; Baleanu, Dumitru

2010-08-01

The sole use of pyridoxine hydrochloride during treatment of tuberculosis gives rise to pyridoxine deficiency. Therefore, a combination of pyridoxine hydrochloride and isoniazid is used in pharmaceutical dosage form in tuberculosis treatment to reduce this side effect. In this study, two chemometric methods, partial least squares (PLS) and principal component regression (PCR), were applied to the simultaneous determination of pyridoxine (PYR) and isoniazid (ISO) in their tablets. A concentration training set comprising binary mixtures of PYR and ISO consisting of 20 different combinations were randomly prepared in 0.1 M HCl. Both multivariate calibration models were constructed using the relationships between the concentration data set (concentration data matrix) and absorbance data matrix in the spectral region 200-330 nm. The accuracy and the precision of the proposed chemometric methods were validated by analyzing synthetic mixtures containing the investigated drugs. The recovery results obtained by applying PCR and PLS calibrations to the artificial mixtures were found between 100.0 and 100.7%. Satisfactory results obtained by applying the PLS and PCR methods to both artificial and commercial samples were obtained. The results obtained in this manuscript strongly encourage us to use them for the quality control and the routine analysis of the marketing tablets containing PYR and ISO drugs. Copyright © 2010 John Wiley & Sons, Ltd.

Multiple response optimization of processing and formulation parameters of Eudragit RL/RS-based matrix tablets for sustained delivery of diclofenac.

PubMed

Elzayat, Ehab M; Abdel-Rahman, Ali A; Ahmed, Sayed M; Alanazi, Fars K; Habib, Walid A; Sakr, Adel

2017-11-01

Multiple response optimization is an efficient technique to develop sustained release formulation while decreasing the number of experiments based on trial and error approach. Diclofenac matrix tablets were optimized to achieve a release profile conforming to USP monograph, matching Voltaren ® SR and withstand formulation variables. The percent of drug released at predetermined multiple time points were the response variables in the design. Statistical models were obtained with relative contour diagrams being overlaid to predict process and formulation parameters expected to produce the target release profile. Tablets were prepared by wet granulation using mixture of equivalent quantities of Eudragit RL/RS at overall polymer concentration of 10-30%w/w and compressed at 5-15KN. Drug release from the optimized formulation E4 (15%w/w, 15KN) was similar to Voltaren, conformed to USP monograph and found to be stable. Substituting lactose with mannitol, reversing the ratio between lactose and microcrystalline cellulose or increasing drug load showed no significant difference in drug release. Using dextromethorphan hydrobromide as a model soluble drug showed burst release due to higher solubility and formation of micro cavities. A numerical optimization technique was employed to develop a stable consistent promising formulation for sustained delivery of diclofenac.

A statistical-textural-features based approach for classification of solid drugs using surface microscopic images.

PubMed

Tahir, Fahima; Fahiem, Muhammad Abuzar

2014-01-01

The quality of pharmaceutical products plays an important role in pharmaceutical industry as well as in our lives. Usage of defective tablets can be harmful for patients. In this research we proposed a nondestructive method to identify defective and nondefective tablets using their surface morphology. Three different environmental factors temperature, humidity and moisture are analyzed to evaluate the performance of the proposed method. Multiple textural features are extracted from the surface of the defective and nondefective tablets. These textural features are gray level cooccurrence matrix, run length matrix, histogram, autoregressive model and HAAR wavelet. Total textural features extracted from images are 281. We performed an analysis on all those 281, top 15, and top 2 features. Top 15 features are extracted using three different feature reduction techniques: chi-square, gain ratio and relief-F. In this research we have used three different classifiers: support vector machine, K-nearest neighbors and naïve Bayes to calculate the accuracies against proposed method using two experiments, that is, leave-one-out cross-validation technique and train test models. We tested each classifier against all selected features and then performed the comparison of their results. The experimental work resulted in that in most of the cases SVM performed better than the other two classifiers.

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethylcellulose matrix tablets in situ-is it possible to detect phenomena related to drug dissolution within the hydrated matrices?

PubMed

Kulinowski, Piotr; Młynarczyk, Anna; Jasiński, Krzysztof; Talik, Przemysław; Gruwel, Marco L H; Tomanek, Bogusław; Węglarz, Władysław P; Dorożyński, Przemysław

2014-09-01

So far, the hydrated part of the HPMC matrix has commonly been denoted as a "gel" or "pseudogel" layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena. Multiparametric, spatially and temporally resolved T2 MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T2 signals. Two components in the T2 decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T2 values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external "gel-like" layer. We have introduced a new paradigm in the characterization of hydrating matrices using (1)H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods.

Influence of the components of Kollicoat SR film on mechanical properties of floating pellets from the point of view of tableting.

PubMed

Lunio, R; Sawicki, W

2008-10-01

The influence of pellet core ingredients on pellet behaviour, e.g. during compression, is well known. In this study the influence of components of a Kollicoat SR polymer film on mechanical properties was investigated. The aim of this study was to evaluate the influence of polymer film components on the mechanical properties of the pellet as a whole, from the point of view of tableting. Tablets should disintegrate into undeformed pellets floating in this environment for 5-6 h, releasing the model drug--verapamil hydrochloride--if possible in a controlled way. The usefulness of texture analysis and work of compression measurement was also evaluated. Kollicoat SR in the form of a 30D aqueous dispersion was chosen as the main component of the polymer film. Polyvinyl pyrrolidone K-30 as a pore former, and propylene glycol, triethyl citrate and dibutyl sebacate plasticisers were selected as typical additives. The influence of different thickness of polymer film on behaviour during stress was also evaluated. After coating the cores with a 20 microm Kollicoat SR dispersion film, an increase in mechanical strength, in comparison to the pellet core, was observed (2.74 to 3.34 mJ). Addition of porophor increased the work of compression by 50% to 5.1 mJ. The investigation of the influence of plasticiser on film properties proved that the kind of plasticiser used in the polymer film had no effect on the mechanical properties of the film or pellets. Only in the case of the film with triethyl citrate was no distinct of the pellet core found. Pellets coated both with films with triethyl citrate and with dibutyl sebacate, in contrast to pellets with a film coating with propylene glycol, showed a significant decrease of the dissolution rate of verapamil hydrochloride (20, 10 and 40% at 6 hours, respectively). It is possible to compress pellets with a 50 microm polymer film without affecting the dissolution rate, as was confirmed during release studies. When using Kollicoat SR the most appropriate plasticizer seems to be triethyl citrate, and in this case a change of behavior during compression analysis by texture analyzer was observed. But so relationship was found between the type of plasticizer and the work needed to obtain a given deformation.

Preparation and characterization of cross-linked excipient of coprocessed xanthan gum-acacia gum as matrix for sustained release tablets

NASA Astrophysics Data System (ADS)

Surini, Silvia; Wati, Dina Risma; Syahdi, Rezi Riadhi

2018-02-01

Sustained release tablet is solid dosage form which is designed to release drugs slowly in the body. This research was intended to prepare and characterize the cross-linked excipients of co-processed xanthan gum-acacia gum (CL-Co-XGGA) as matrices for sustained release tablets with gliclazide as a model drug. CL-Co-XGGA excipients were cross-linked materials of co-processed excipients of xanthan gum-acacia gum (Co-XGGA) using sodium trimetaphosphate. Co-processed excipients of xanthan gum-acacia gum were prepared in the ratio of each excipient 1:2, 1:1 and 2:1. Co-XGGA and CL-Co-XGGA excipients were characterized physically, chemically and functionally. Then, the sustained release (SR) tablets were formulated by wet granulation method using CL-Co-XGGA excipients as matrices. Also, the dissolution study of the gliclazide SR tablets was carried out in phosphate buffer medium pH 7,4 containing sodium lauryl sulphate 0.2% for 12 hours. The results showed that the degree of substitution (DS) of CL-Co-XGGA 1:2, 1:1, 2:1 excipients were respectively 0.067, 0.082 and 0.08. Besides that, the excipients gel strengths were 14.03, 17.27 and 20,70 gF, respectively. The cross-linked excipients had improved flow properties and swelling capability compared to the Co-XGGA excipients. The results of the gliclazide SR tablets evaluations showed that all tablets were passed all tablet requirements. Moreover, the gliclazide release from SR tablets F1 - F6 revealed the sustained release profile, which was following zero order kinetics (F1, F2, F3, F6) and Higuchi kinetics (F4 and F5). It could be concluded that the obtained CL-Co-XGGA excipients might be used as matrices for sustained release tablets and could retard drug release up to 8 until 32 hours.

Diffusion and Swelling Measurements in Pharmaceutical Powder Compacts Using Terahertz Pulsed Imaging

PubMed Central

Yassin, Samy; Su, Ke; Lin, Hungyen; Gladden, Lynn F; Zeitler, J Axel

2015-01-01

Tablet dissolution is strongly affected by swelling and solvent penetration into its matrix. A terahertz-pulsed imaging (TPI) technique, in reflection mode, is introduced as a new tool to measure one-dimensional swelling and solvent ingress in flat-faced pharmaceutical compacts exposed to dissolution medium from one face of the tablet. The technique was demonstrated on three tableting excipients: hydroxypropylmethyl cellulose (HPMC), Eudragit RSPO, and lactose. Upon contact with water, HPMC initially shrinks to up to 13% of its original thickness before undergoing expansion. HPMC and lactose were shown to expand to up to 20% and 47% of their original size in 24 h and 13 min, respectively, whereas Eudragit does not undergo dimensional change. The TPI technique was used to measure the ingress of water into HPMC tablets over a period of 24 h and it was observed that water penetrates into the tablet by anomalous diffusion. X-ray microtomography was used to measure tablet porosity alongside helium pycnometry and was linked to the results obtained by TPI. Our results highlight a new application area of TPI in the pharmaceutical sciences that could be of interest in the development and quality testing of advanced drug delivery systems as well as immediate release formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1658–1667, 2015 PMID:25645509

Formulation and Evaluation of Fixed-Dose Combination of Bilayer Gastroretentive Matrix Tablet Containing Atorvastatin as Fast-Release and Atenolol as Sustained-Release

PubMed Central

Dey, Sanjay; Chattopadhyay, Sankha; Mazumder, Bhaskar

2014-01-01

The objective of the present study was to develop bilayer tablets of atorvastatin and atenolol that are characterized by initial fast-release of atorvastatin in the stomach and comply with the release requirements of sustained-release of atenolol. An amorphous, solvent evaporation inclusion complex of atorvastatin with β-cyclodextrin, present in 1 : 3 (drug/cyclodextrin) molar ratio, was employed in the fast-release layer to enhance the dissolution of atorvastatin. Xanthan gum and guar gum were integrated in the sustained-release layer. Bilayer tablets composed of sustained-release layer (10% w/w of xanthan gum and guar gum) and fast-release layer [1 : 3 (drug/cyclodextrin)] showed the desired release profile. The atorvastatin contained in the fast-release layer showed an initial fast-release of more than 60% of its drug content within 2 h, followed by sustained release of the atenolol for a period of 12 h. The pharmacokinetic study illustrated that the fast absorption and increased oral bioavailability of atorvastatin as well as therapeutic concentration of atenolol in blood were made available through adoption of formulation strategy of bilayer tablets. It can be concluded that the bilayer tablets of atorvastatin and atenolol can be successfully employed for the treatment of hypertension and hypercholesterolemia together through oral administration of single tablet. PMID:24527446

Diffusion and swelling measurements in pharmaceutical powder compacts using terahertz pulsed imaging.

PubMed

Yassin, Samy; Su, Ke; Lin, Hungyen; Gladden, Lynn F; Zeitler, J Axel

2015-05-01

Tablet dissolution is strongly affected by swelling and solvent penetration into its matrix. A terahertz-pulsed imaging (TPI) technique, in reflection mode, is introduced as a new tool to measure one-dimensional swelling and solvent ingress in flat-faced pharmaceutical compacts exposed to dissolution medium from one face of the tablet. The technique was demonstrated on three tableting excipients: hydroxypropylmethyl cellulose (HPMC), Eudragit RSPO, and lactose. Upon contact with water, HPMC initially shrinks to up to 13% of its original thickness before undergoing expansion. HPMC and lactose were shown to expand to up to 20% and 47% of their original size in 24 h and 13 min, respectively, whereas Eudragit does not undergo dimensional change. The TPI technique was used to measure the ingress of water into HPMC tablets over a period of 24 h and it was observed that water penetrates into the tablet by anomalous diffusion. X-ray microtomography was used to measure tablet porosity alongside helium pycnometry and was linked to the results obtained by TPI. Our results highlight a new application area of TPI in the pharmaceutical sciences that could be of interest in the development and quality testing of advanced drug delivery systems as well as immediate release formulations. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association.

Simulating Matrix Crack and Delamination Interaction in a Clamped Tapered Beam

NASA Technical Reports Server (NTRS)

De Carvalho, N. V.; Seshadri, B. R.; Ratcliffe, J. G.; Mabson, G. E.; Deobald, L. R.

2017-01-01

Blind predictions were conducted to validate a discrete crack methodology based on the Floating Node Method to simulate matrix-crack/delamination interaction. The main novel aspects of the approach are: (1) the implementation of the floating node method via an 'extended interface element' to represent delaminations, matrix-cracks and their interaction, (2) application of directional cohesive elements to infer overall delamination direction, and (3) use of delamination direction and stress state at the delamination front to determine migration onset. Overall, good agreement was obtained between simulations and experiments. However, the validation exercise revealed the strong dependence of the simulation of matrix-crack/delamination interaction on the strength data (in this case transverse interlaminar strength, YT) used within the cohesive zone approach applied in this work. This strength value, YT, is itself dependent on the test geometry from which the strength measurement is taken. Thus, choosing an appropriate strength value becomes an ad-hoc step. As a consequence, further work is needed to adequately characterize and assess the accuracy and adequacy of cohesive zone approaches to model small crack growth and crack onset. Additionally, often when simulating damage progression with cohesive zone elements, the strength is lowered while keeping the fracture toughness constant to enable the use of coarser meshes. Results from the present study suggest that this approach is not recommended for any problem involving crack initiation, small crack growth or multiple crack interaction.

AN ADA LINEAR ALGEBRA PACKAGE MODELED AFTER HAL/S

NASA Technical Reports Server (NTRS)

Klumpp, A. R.

1994-01-01

This package extends the Ada programming language to include linear algebra capabilities similar to those of the HAL/S programming language. The package is designed for avionics applications such as Space Station flight software. In addition to the HAL/S built-in functions, the package incorporates the quaternion functions used in the Shuttle and Galileo projects, and routines from LINPAK that solve systems of equations involving general square matrices. Language conventions in this package follow those of HAL/S to the maximum extent practical and minimize the effort required for writing new avionics software and translating existent software into Ada. Valid numeric types in this package include scalar, vector, matrix, and quaternion declarations. (Quaternions are fourcomponent vectors used in representing motion between two coordinate frames). Single precision and double precision floating point arithmetic is available in addition to the standard double precision integer manipulation. Infix operators are used instead of function calls to define dot products, cross products, quaternion products, and mixed scalar-vector, scalar-matrix, and vector-matrix products. The package contains two generic programs: one for floating point, and one for integer. The actual component type is passed as a formal parameter to the generic linear algebra package. The procedures for solving systems of linear equations defined by general matrices include GEFA, GECO, GESL, and GIDI. The HAL/S functions include ABVAL, UNIT, TRACE, DET, INVERSE, TRANSPOSE, GET, PUT, FETCH, PLACE, and IDENTITY. This package is written in Ada (Version 1.2) for batch execution and is machine independent. The linear algebra software depends on nothing outside the Ada language except for a call to a square root function for floating point scalars (such as SQRT in the DEC VAX MATHLIB library). This program was developed in 1989, and is a copyrighted work with all copyright vested in NASA.

Matrix tablets based on thiolated poly(acrylic acid): pH-dependent variation in disintegration and mucoadhesion.

PubMed

Guggi, Davide; Marschütz, Michaela K; Bernkop-Schnürch, Andreas

2004-04-15

This study examined the influence of the pH on the mucoadhesive and cohesive properties of polyarcylic acid (PAA) and thiolated PAA. The pH of PAA (molecular mass: 450 kDa) and of a corresponding PAA-cysteine conjugate was adjusted to 3, 4, 5, 6, 7 and 8. The amount of immobilised thiol groups and disulfide bonds was determined via Ellman's reagent. Tablets were compressed out of each pH-batch of both thiolated and unmodified PAA and the swelling behaviour, the disintegration time and the mucoadhesiveness were evaluated. The amount of thiol/disulfide groups per gram thiolated PAA of pH 3 and pH 8 was determined to be 332 +/- 94 micromol and 162 +/- 46 micromol, respectively. The thiolated PAA tablets displayed a minimum four-fold higher water uptake compared to unmodified PAA tablets. A faster and higher water uptake of both polymer types was observed above pH 5. Thiolated polymer tablets showed a 3-20-fold more prolonged disintegration time than unmodified PAA tablets. The cohesiveness of PAA-cysteine conjugate increased at higher pH, whereas the unmodified PAA behaved inversely. A 3-7-fold stronger mucoadhesiveness was observed for the PAA-cysteine conjugate tablets compared to unmodified PAA tablets. For both thiolated and unmodified polymer the mucoadhesiveness was 2-4-fold enhanced below pH 5. The difference in mucoadhesion between the two polymer types was most pronounced at these lower pH values. In this study substantial information regarding the pH-dependence of mucoadhesion and cohesion of unmodified polyacrylates and of thiolated polyacrylates is provided, representing helpful basic information for an ameliorated deployment of these polymers.

Fabricating a Shell-Core Delayed Release Tablet Using Dual FDM 3D Printing for Patient-Centred Therapy.

PubMed

Okwuosa, Tochukwu C; Pereira, Beatriz C; Arafat, Basel; Cieszynska, Milena; Isreb, Abdullah; Alhnan, Mohamed A

2017-02-01

Individualizing gastric-resistant tablets is associated with major challenges for clinical staff in hospitals and healthcare centres. This work aims to fabricate gastric-resistant 3D printed tablets using dual FDM 3D printing. The gastric-resistant tablets were engineered by employing a range of shell-core designs using polyvinylpyrrolidone (PVP) and methacrylic acid co-polymer for core and shell structures respectively. Filaments for both core and shell were compounded using a twin-screw hot-melt extruder (HME). CAD software was utilized to design a capsule-shaped core with a complementary shell of increasing thicknesses (0.17, 0.35, 0.52, 0.70 or 0.87 mm). The physical form of the drug and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. A shell thickness ≥0.52 mm was deemed necessary in order to achieve sufficient core protection in the acid medium. The technology proved viable for incorporating different drug candidates; theophylline, budesonide and diclofenac sodium. XRPD indicated the presence of theophylline crystals whilst budesonide and diclofenac sodium remained amorphous in the PVP matrix of the filaments and 3D printed tablets. Fabricated tablets demonstrated gastric resistant properties and a pH responsive drug release pattern in both phosphate and bicarbonate buffers. Despite its relatively limited resolution, FDM 3D printing proved to be a suitable platform for a single-process fabrication of delayed release tablets. This work reveals the potential of dual FDM 3D printing as a unique platform for personalising delayed release tablets to suit an individual patient's needs.

Floating lipid beads for the improvement of bioavailability of poorly soluble basic drugs: in-vitro optimization and in-vivo performance in humans.

PubMed

Abouelatta, Samar M; Aboelwafa, Ahmed A; Khalil, Rawia M; ElGazayerly, Omaima N

2015-01-01

The challenge in developing oral drug delivery systems of poorly soluble basic drugs is primarily due to their pH dependent solubility. Cinnarizine (CNZ), a model for a poorly soluble basic drug, has pH dependent solubility; where it dissolves readily at low pH in the stomach and exhibits a very low solubility at pH values greater than 4. It is also characterized by a short half life of 3-6h, which requires frequent daily administration resulting in poor patient compliance. In an attempt to solve these problems, extended release floating lipid beads were formulated. A 2(4) full factorial design was utilized for optimization of the effects of various independent variables; lipid:drug ratio, % Pluronic F-127, % Sterotex, and Gelucire 43/01:Gelucire 50/13 ratio, on the loading efficiency and release of CNZ from the lipid beads. In-vivo pharmacokinetic study of the optimized CNZ-lipid beads compared to Stugeron® (reference standard) was performed in healthy human volunteers. A promising approach for enhancing the bioavailability of the poorly soluble basic drug, CNZ, utilizing novel and simple floating lipid beads was successfully developed. Zero order release profile of CNZ was achieved for 12h. Mean AUC0-24 and AUC0-∞ of the optimized CNZ-loaded lipid beads were 4.23 and 6.04 times that of Stugeron® tablets respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison Between Terrestrial Explosion Crater Morphology in Floating Ice and Europan Chaos

NASA Technical Reports Server (NTRS)

Billings, S. E.; Kattenhorn, S. A.

2003-01-01

Craters created by explosives have been found to serve as valuable analogs to impact craters, within limits. Explosion craters have been created in floating terrestrial ice in experiments related to clearing ice from waterways. Features called chaos occur on the surface of Europa s floating ice shell. Chaos is defined as a region in which the background plains have been disrupted. Common features of chaos include rafted blocks of pre-existing terrain suspended in a matrix of smooth or hummocky material; low surface albedo; and structural control on chaos outline shape by pre-existing lineaments. All published models of chaos formation call on endogenic processes whereby chaos forms through thermal processes. Nonetheless, we note morphological similarities between terrestrial explosion craters and Europan chaos at a range of scales and consider whether some chaos may have formed by impact. We explore these similarities through geologic and morphologic mapping.

Resilience of Floating Treatment Wetlands to Repeated Freeze-Thaw Cycles

NASA Astrophysics Data System (ADS)

Ortega, K.; Marchetto, P.; Magner, J.

2017-12-01

Floating treatment wetlands (FTWs), made of a matrix of recycled polyethylene terephthalate (PET) fibers, are currently being used as a method to reduce nutrient loading in lakes. The matrix encourages growth of biofilms, which uptake nutrients from the water. However, the usefulness of FTWs has only been assessed in areas where the lakes do not freeze over in the winter. Repeated freeze-thaw cycles were run on sections of the FTWs in a laboratory setting in order to test the resilience of the PET fibers over the FTWs' advertised fifteen-year lifespan. Preliminary findings suggest that the stresses caused by freezing and thawing of the surrounding water contribute to deterioration of the PET fibers, leading to production of microplastics. Estimations indicate that approximately 0.063% of a FTW's mass could be lost as microplastics over the course of its lifespan. Production of microplastics contributes to plastic pollution in the treatment water, possibly offsetting any nutrient remediation the FTWs perform.

The Unified Floating Point Vector Coprocessor for Reconfigurable Hardware

NASA Astrophysics Data System (ADS)

Kathiara, Jainik

There has been an increased interest recently in using embedded cores on FPGAs. Many of the applications that make use of these cores have floating point operations. Due to the complexity and expense of floating point hardware, these algorithms are usually converted to fixed point operations or implemented using floating-point emulation in software. As the technology advances, more and more homogeneous computational resources and fixed function embedded blocks are added to FPGAs and hence implementation of floating point hardware becomes a feasible option. In this research we have implemented a high performance, autonomous floating point vector Coprocessor (FPVC) that works independently within an embedded processor system. We have presented a unified approach to vector and scalar computation, using a single register file for both scalar operands and vector elements. The Hybrid vector/SIMD computational model of FPVC results in greater overall performance for most applications along with improved peak performance compared to other approaches. By parameterizing vector length and the number of vector lanes, we can design an application specific FPVC and take optimal advantage of the FPGA fabric. For this research we have also initiated designing a software library for various computational kernels, each of which adapts FPVC's configuration and provide maximal performance. The kernels implemented are from the area of linear algebra and include matrix multiplication and QR and Cholesky decomposition. We have demonstrated the operation of FPVC on a Xilinx Virtex 5 using the embedded PowerPC.

Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations.

PubMed

Hiremath, Praveen S; Saha, Ranendra N

2008-10-01

The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.

Formulation and Evaluation of a Novel Matrix-Type Orally Disintegrating Ibuprofen Tablet

PubMed Central

Tayebi, Hoda; Mortazavi, Seyed Alireza

2011-01-01

Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation. PMID:24250378

3D printing of tablets using inkjet with UV photoinitiation.

PubMed

Clark, Elizabeth A; Alexander, Morgan R; Irvine, Derek J; Roberts, Clive J; Wallace, Martin J; Sharpe, Sonja; Yoo, Jae; Hague, Richard J M; Tuck, Chris J; Wildman, Ricky D

2017-08-30

Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform. This work hypothesizes that suitable solvent based ink formulations can be developed that allow the production of solid dosage forms that meet the standards required for pharmaceutical tablets, whilst offering a platform for flexible and personalized manufacture. We demonstrate this using piezo-activated inkjetting to 3D print ropinirole hydrochloride. The tablets produced consist of a cross-linked poly(ethylene glycol diacrylate) (PEGDA) hydrogel matrix containing the drug, photoinitiated in a low oxygen environment using an aqueous solution of Irgacure 2959. At a Ropinirole HCl loading of 0.41mg, drug release from the tablet is shown to be Fickian. Raman and IR spectroscopy indicate a high degree of cross-linking and formation of an amorphous solid dispersion. This is the first publication of a UV inkjet 3D printed tablet. Consequently, this work opens the possibility for the translation of scalable, high precision and bespoke ink-jet based additive manufacturing to the pharmaceutical sector. Copyright © 2017. Published by Elsevier B.V.

Determinant Computation on the GPU using the Condensation Method

NASA Astrophysics Data System (ADS)

Anisul Haque, Sardar; Moreno Maza, Marc

2012-02-01

We report on a GPU implementation of the condensation method designed by Abdelmalek Salem and Kouachi Said for computing the determinant of a matrix. We consider two types of coefficients: modular integers and floating point numbers. We evaluate the performance of our code by measuring its effective bandwidth and argue that it is numerical stable in the floating point number case. In addition, we compare our code with serial implementation of determinant computation from well-known mathematical packages. Our results suggest that a GPU implementation of the condensation method has a large potential for improving those packages in terms of running time and numerical stability.

Development and in vitro evaluation of carboxymethyl chitosan based drug delivery system for the controlled release of propranolol hydrochloride

NASA Astrophysics Data System (ADS)

Hernawan; Nur Hayati, Septi; Nisa, Khoirun; Wheni Indrianingsih, Anastasia; Darsih, Cici; Kismurtono, Muhammad

2017-12-01

Propranolol hydrochloride is a nonselective β-adrenergic drug and has been used as angina pectoris, antihypertensive, and that of many other cardiovascular disorders. It has a relatively short plasma half-life and duration of action are considered too short in certain circumstances. Thus, it’s fascinating to elongate the action. The tablet formula was based on extended-release by a propranolol hydrochloride based carboxymethyl chitosan matrix. Here we used direct compression technique with internal wet granulation to prepare the tablets. The tablets were evaluated for physical properties (hardness, weight variation test, friability) and in vitro release studies. There was no interaction observed between propranolol hydrochloride and excipients. Dissolution profiles of each formulation were followed zero order model. In conclusion, these results strongly suggest that in appropriate proportions carboxymethyl chitosan with internal granulation is suitable for formulating propranolol hydrochloride controlled release.

Polymer mobilization and drug release during tablet swelling. A 1H NMR and NMR microimaging study.

PubMed

Dahlberg, Carina; Fureby, Anna; Schuleit, Michael; Dvinskikh, Sergey V; Furó, István

2007-09-26

The objective of this study was to investigate the swelling characteristics of a hydroxypropyl methylcellulose (HPMC) matrix incorporating the hydrophilic drug antipyrine. We have used this matrix to introduce a novel analytical method, which allows us to obtain within one experimental setup information about the molecular processes of the polymer carrier and its impact on drug release. Nuclear magnetic resonance (NMR) imaging revealed in situ the swelling behavior of tablets when exposed to water. By using deuterated water, the spatial distribution and molecular dynamics of HPMC and their kinetics during swelling could be observed selectively. In parallel, NMR spectroscopy provided the concentration of the drug released into the aqueous phase. We find that both swelling and release are diffusion controlled. The ability of monitoring those two processes using the same experimental setup enables mapping their interconnection, which points on the importance and potential of this analytical technique for further application in other drug delivery forms.

In-vitro characterization of 5-aminosalicylic acid release from MMX mesalamine tablets and determination of tablet coating thickness.

PubMed

Tenjarla, Srini; Abinusawa, Adeyinka

2011-01-01

Substantial variability in gastrointestinal pH is observed in patients with ulcerative colitis (UC). We characterized the effect of pH on 5-aminosalicylic acid (5-ASA) release from MMX mesalamine tablets (Shire Pharmaceuticals Inc., Wayne, PA, USA), examined thickness/uniformity of tablet film coatings, and explored the influence of simulating altered gastrointestinal motility. Nondestructive, three-dimensional, terahertz pulse imaging (TPI) was used to characterize the film coating of three lots of MMX mesalamine tablets (n=36). Thereafter, 5-ASA release from these tablets was evaluated using United States Pharmacopeia (USP) apparatus II at pH 6.8 and 7.2. Onset of tablet film-coat breach and mean dissolution time were determined for each lot. 5-ASA release was also assessed at three different paddle rotation speeds (50, 75, and 100 rpm) at pH 7.2. The mean ± SD film-coating thickness of the three lots of MMX mesalamine tablets were 109.2 ± 16.8, 113.1 ± 19.5, and 113.8 ± 19.8 μM, respectively. At pH 6.8 (100 rpm), the onset of film-coat breach was 10-30 minutes, whereas at pH 7.2 this was observed within 10 minutes. 5-ASA release was uniform at both pH conditions, with minimal lot-to-lot variability. Complete drug release was achieved within 6 hours under both pH conditions. 5-ASA release increased in proportion with paddle speed, but remained prolonged at all speeds. 5-ASA release from MMX mesalamine is unaffected by normal variations in simulated intracolonic pH. The dissolution profile of 5-ASA from MMX mesalamine tablets may be attributed to consistent outer film coatings and the hydrogel-forming matrix that controls the drug release after dissolution of the film coating.

Quantifying Thin Mat Floating Marsh Strength and Interaction with Hydrodynamic Conditions

NASA Astrophysics Data System (ADS)

Collins, J. H., III; Sasser, C.; Willson, C. S.

2016-12-01

Louisiana possesses over 350,000 acres of unique floating vegetated systems known as floating marshes or flotants. Floating marshes make up 70% of the Terrebonne and Barataria basin wetlands and exist in several forms, mainly thick mat or thin mat. Salt-water intrusion, nutria grazing, and high-energy wave events are believed to be some contributing factors to the degradation of floating marshes; however, there has been little investigation into the hydrodynamic effects on their structural integrity. Due to their unique nature, floating marshes could be susceptible to changes in the hydrodynamic environment that may result from proposed river freshwater and sediment diversion projects introducing flow to areas that are typically somewhat isolated. This study aims to improve the understanding of how thin mat floating marshes respond to increased hydrodynamic stresses and, more specifically, how higher water velocities might increase the washout probability of this vegetation type. There are two major components of this research: 1) A thorough measurement of the material properties of the vegetative mats as a root-soil matrix composite material; and 2) An accurate numerical simulation of the hydrodynamics and forces imposed on the floating marsh mats by the flow. To achieve these goals, laboratory and field experiments were conducted using a customized device to measure the bulk properties of typical floating marshes. Additionally, Delft-3D FLOW and ANSYS FLUENT were used to simulate the flow around a series of simplified mat structures in order to estimate the hydrodynamic forcings on the mats. The hydrodynamic forcings are coupled with a material analysis, allowing for a thorough analysis of their interaction under various conditions. The 2-way Fluid Structure Interaction (F.S.I.) between the flow and the mat is achieved by coupling a Finite Element Analysis (F.E.A.) solver in ANSYS with FLUENT. The flow conditions necessary for the structural failure of the floating marshes are determined for a multitude of mat shapes and sizes, leading to a quantifiable critical velocity required for washout. Ultimately, through dimensional analysis, an equation for washout potential will be developed from the results, which could be used as a design guideline.

Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets.

PubMed

Ullah, Majeed; Ullah, Hanif; Murtaza, Ghulam; Mahmood, Qaisar; Hussain, Izhar

2015-01-01

The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted.

Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

PubMed Central

Ullah, Majeed; Ullah, Hanif; Mahmood, Qaisar; Hussain, Izhar

2015-01-01

The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted. PMID:26380301

Formulation of Indomethacin Colon Targeted Delivery Systems Using Polysaccharides as Carriers by Applying Liquisolid Technique

PubMed Central

Elkhodairy, Kadria A.; Elsaghir, Hanna A.; Al-Subayiel, Amal M.

2014-01-01

The present study aimed at the formulation of matrix tablets for colon-specific drug delivery (CSDD) system of indomethacin (IDM) by applying liquisolid (LS) technique. A CSDD system based on time-dependent polymethacrylates and enzyme degradable polysaccharides was established. Eudragit RL 100 (E-RL 100) was employed as time-dependent polymer, whereas bacterial degradable polysaccharides were presented as LS systems loaded with the drug. Indomethacin-loaded LS systems were prepared using different polysaccharides, namely, guar gum (GG), pectin (PEC), and chitosan (CH), as carriers separately or in mixtures of different ratios of 1 : 3, 1 : 1, and 3 : 1. Liquisolid systems that displayed promising results concerning drug release rate in both pH 1.2 and pH 6.8 were compressed into tablets after the addition of the calculated amount of E-RL 100 and lubrication with magnesium stearate and talc in the ratio of 1 : 9. It was found that E-RL 100 improved the flowability and compressibility of all LS formulations. The release data revealed that all formulations succeeded to sustain drug release over a period of 24 hours. Stability study indicated that PEC-based LS system as well as its matrix tablets was stable over the period of storage (one year) and could provide a minimum shelf life of two years. PMID:24971345

Chosen interval methods for solving linear interval systems with special type of matrix

NASA Astrophysics Data System (ADS)

Szyszka, Barbara

2013-10-01

The paper is devoted to chosen direct interval methods for solving linear interval systems with special type of matrix. This kind of matrix: band matrix with a parameter, from finite difference problem is obtained. Such linear systems occur while solving one dimensional wave equation (Partial Differential Equations of hyperbolic type) by using the central difference interval method of the second order. Interval methods are constructed so as the errors of method are enclosed in obtained results, therefore presented linear interval systems contain elements that determining the errors of difference method. The chosen direct algorithms have been applied for solving linear systems because they have no errors of method. All calculations were performed in floating-point interval arithmetic.

Indirect spectrophotometric determination of ultra trace amounts of selenium based on dispersive liquid-liquid microextraction-solidified floating organic drop.

PubMed

Haji Shabani, Ali Mohammad; Dadfarnia, Shayessteh; Nozohor, Mahnaz

2013-12-01

A novel dispersive liquid-liquid microextraction-solidified floating organic drop (DLLME-SFOD) method combined with fiber optic-linear array detection spectrophotometry has been developed for the indirect determination of selenium. The method is based on the oxidation of the I(-) to iodine by inorganic Se(IV). The produced I2 reacts with the excess of I(-) ions in acidic media to give triiodide ions. The I3(-) is then extracted into 1-undecanol by DLLME-SFOD upon the formation of an ion pair with cetyltrimethylammonium cation. The extracted ion pair is determined by measuring its absorption at 360 nm. The absorbance signal is proportional to the selenium concentration in the aqueous phase. Under optimum conditions, the method provided an enrichment factor of 250 with a detection limit of 16.0 μg L(-1) and a linear dynamic range of 40.0-1000.0 μg L(-1). The relative standard deviation was found to be 2.1% (n=7) at 100.0 μg L(-1) concentration level. The method was successfully applied to th e determination of selenium in water samples and selenium plus tablet. Copyright © 2013 Elsevier B.V. All rights reserved.

Amorphous Formulation and in Vitro Performance Testing of Instantly Disintegrating Buccal Tablets for the Emergency Delivery of Naloxone.

PubMed

Alqurshi, Abdulmalik; Kumar, Zahrae; McDonald, Rebecca; Strang, John; Buanz, Asma; Ahmed, Shagufta; Allen, Elizabeth; Cameron, Peter; Rickard, James A; Sandhu, Verity; Holt, Chris; Stansfield, Rebecca; Taylor, David; Forbes, Ben; Royall, Paul G

2016-05-02

The aim of this study was to develop a freeze-dried buccal tablet for the rapid delivery of naloxone in opioid overdose. The tablet composition was optimized to produce an amorphous matrix, which was confirmed by the absence of peaks associated with crystallinity observed by differential scanning calorimetry and powder X-ray diffraction. Tablets with high gelatin content lacked adequate porosity. Mannitol was added to the formulation to bridge and intercalate gelatin's tight polymer aggregates, however sodium bicarbonate was also required to prevent crystallization within the tablets. A linear reduction in mannitol's recrystallization enthalpy was observed with increasing sodium bicarbonate concentration (ΔrecryH = -20.3[NaHCO3] + 220.9; r(2) = 0.9, n = 18). The minimum sodium bicarbonate concentration for full inhibition of mannitol crystallization was 10.9% w/w. Freeze-dried tablets with lower amounts of sodium bicarbonate possessed a crystalline fraction that PXRD identified as mannitol hemihydrate from the unique peak at 9.7° 2θ. Mannitol's greater affinity for both ions and residual water rather than its affinity for self-association was the mechanism for the inhibition of crystallization observed here. The optimized tablet (composition mannitol 24% w/w (4.26 mg), gelatin 65% w/w (11.7 mg), sodium bicarbonate 11% w/w (1.98 mg), and naloxone 800 μg) formed predominantly amorphous tablets that disintegrated in less than 10 s. Optimized tablets were chemically and physically stable over 9 months storage at 25 °C. As speed of drug liberation is the critical performance attribute for a solid dosage form designed to deliver drug in an emergency, a novel imaging based in vitro disintegration assay for buccal tablets was developed. The assay was optimized with regard to conditions in the buccal cavity: i.e., temperature 33-37 °C, volume of medium (0.1-0.7 mL), and use of mucin-containing biorelevant medium. The disintegration assay was sensitive to temperature, medium volume, and medium composition; naloxone tablet disintegration was extremely rapid, with full disintegration ranging from 5 to 20 s. In conclusion, rapidly disintegrating tablets have been developed which are suitable for proof-of-concept clinical trial in humans to determine the pharmacokinetics of naloxone delivered via the buccal route.

Lipid tethering of breast tumor cells enables real-time imaging of free-floating cell dynamics and drug response

PubMed Central

Whipple, Rebecca A.; Zhang, Peipei; Sooklal, Elisabeth L.; Martin, Stuart S.; Jewell, Christopher M.

2016-01-01

Free-floating tumor cells located in the blood of cancer patients, known as circulating tumor cells (CTCs), have become key targets for studying metastasis. However, effective strategies to study the free-floating behavior of tumor cells in vitro have been a major barrier limiting the understanding of the functional properties of CTCs. Upon extracellular-matrix (ECM) detachment, breast tumor cells form tubulin-based protrusions known as microtentacles (McTNs) that play a role in the aggregation and re-attachment of tumor cells to increase their metastatic efficiency. In this study, we have designed a strategy to spatially immobilize ECM-detached tumor cells while maintaining their free-floating character. We use polyelectrolyte multilayers deposited on microfluidic substrates to prevent tumor cell adhesion and the addition of lipid moieties to tether tumor cells to these surfaces through interactions with the cell membranes. This coating remains optically clear, allowing capture of high-resolution images and videos of McTNs on viable free-floating cells. In addition, we show that tethering allows for the real-time analysis of McTN dynamics on individual tumor cells and in response to tubulin-targeting drugs. The ability to image detached tumor cells can vastly enhance our understanding of CTCs under conditions that better recapitulate the microenvironments they encounter during metastasis. PMID:26871289

Floating Ice-Algal Aggregates below Melting Arctic Sea Ice

PubMed Central

Assmy, Philipp; Ehn, Jens K.; Fernández-Méndez, Mar; Hop, Haakon; Katlein, Christian; Sundfjord, Arild; Bluhm, Katrin; Daase, Malin; Engel, Anja; Fransson, Agneta; Granskog, Mats A.; Hudson, Stephen R.; Kristiansen, Svein; Nicolaus, Marcel; Peeken, Ilka; Renner, Angelika H. H.; Spreen, Gunnar; Tatarek, Agnieszka; Wiktor, Jozef

2013-01-01

During two consecutive cruises to the Eastern Central Arctic in late summer 2012, we observed floating algal aggregates in the melt-water layer below and between melting ice floes of first-year pack ice. The macroscopic (1-15 cm in diameter) aggregates had a mucous consistency and were dominated by typical ice-associated pennate diatoms embedded within the mucous matrix. Aggregates maintained buoyancy and accumulated just above a strong pycnocline that separated meltwater and seawater layers. We were able, for the first time, to obtain quantitative abundance and biomass estimates of these aggregates. Although their biomass and production on a square metre basis was small compared to ice-algal blooms, the floating ice-algal aggregates supported high levels of biological activity on the scale of the individual aggregate. In addition they constituted a food source for the ice-associated fauna as revealed by pigments indicative of zooplankton grazing, high abundance of naked ciliates, and ice amphipods associated with them. During the Arctic melt season, these floating aggregates likely play an important ecological role in an otherwise impoverished near-surface sea ice environment. Our findings provide important observations and measurements of a unique aggregate-based habitat during the 2012 record sea ice minimum year. PMID:24204642

Floating ice-algal aggregates below melting arctic sea ice.

PubMed

Assmy, Philipp; Ehn, Jens K; Fernández-Méndez, Mar; Hop, Haakon; Katlein, Christian; Sundfjord, Arild; Bluhm, Katrin; Daase, Malin; Engel, Anja; Fransson, Agneta; Granskog, Mats A; Hudson, Stephen R; Kristiansen, Svein; Nicolaus, Marcel; Peeken, Ilka; Renner, Angelika H H; Spreen, Gunnar; Tatarek, Agnieszka; Wiktor, Jozef

2013-01-01

During two consecutive cruises to the Eastern Central Arctic in late summer 2012, we observed floating algal aggregates in the melt-water layer below and between melting ice floes of first-year pack ice. The macroscopic (1-15 cm in diameter) aggregates had a mucous consistency and were dominated by typical ice-associated pennate diatoms embedded within the mucous matrix. Aggregates maintained buoyancy and accumulated just above a strong pycnocline that separated meltwater and seawater layers. We were able, for the first time, to obtain quantitative abundance and biomass estimates of these aggregates. Although their biomass and production on a square metre basis was small compared to ice-algal blooms, the floating ice-algal aggregates supported high levels of biological activity on the scale of the individual aggregate. In addition they constituted a food source for the ice-associated fauna as revealed by pigments indicative of zooplankton grazing, high abundance of naked ciliates, and ice amphipods associated with them. During the Arctic melt season, these floating aggregates likely play an important ecological role in an otherwise impoverished near-surface sea ice environment. Our findings provide important observations and measurements of a unique aggregate-based habitat during the 2012 record sea ice minimum year.

Testing lyoequivalency for three commercially sustained-release tablets containing diltiazem hydrochloride.

PubMed

Maswadeh, Hamzah A; Al-Hanbali, Othman A; Kanaan, Reem A; Shakya, Ashok K; Maraqa, Anwar

2010-01-01

In vitro release kinetics of three commercially available sustained release tablets (SR) diltiazem hydrochloride were studied at pH 1.1 for 2 h and for another 6 h at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process was studied by analyzing the dissolution data using five kinetic equations: the zero-order equation, the first-order equation, the Higuchi square root equation, the Hixson-Crowell cube root law and the Peppas equation. Analyses of the dissolution kinetic data for diltiazem hydrochloride commercial SR tablets showed that both Dilzacard and Dilzem SR tablets released drug by Non-Fickian (Anomalous transport) release with release exponent (n) equal to 0.59 and 0.54, respectively, which indicate the summation of both diffusion and dissolution controlled drug release. Bi-Tildiem SR tablets released drug by super case II (n = 1.29) which indicate zero-order release due to the dissolution of polymeric matrix and relaxation of the polymer chain. This finding was also in agreement with results obtained from application of zero-order and Hixson-Crowell equations. A dissolution profile comparative study was done to test the lyoequivelancy of the three products by using the mean dissolution time (MDT), dissimilarity factor f1 and similarity factor f2. Results showed that the three products are different and not lyoequivalent.

Evaluation of the viability of Lactobacillus spp. after the production of different solid dosage forms.

PubMed

Brachkova, Mariya I; Duarte, Aida; Pinto, João F

2009-09-01

The work aims to provide evidence on the viability of Lactobacillus spp. and a spore form of Bacillus subtilis from nonprocessed bacteria to coated dosage forms (i.e., mini-tablets, pellets, and their coated forms). Lactobacillus spp. were cultivated overnight in MRS broth (10(9) cfu/mL) and B. subtilis spores were produced on plate count agar (10(7) cfu/mL) for 2 weeks. Bacteria and spores were freeze-dried in skim milk enriched with glycerol. The cakes were further processed into tablets (2.5 mm diameter) by direct compression with or without microcrystalline cellulose and inulin. Pellets (1-1.4 mm diameter) were produced by extrusion-spheronization of bacterial and spore suspensions with microcrystalline cellulose, lactose, inulin, and skim milk. Both tablets and pellets were film coated. The properties of the dosage forms, particularly the bacterial viability, were evaluated immediately after production and throughout storage for 6 months at 4 degrees C. The study has shown that for an adequate stabilization of the bacteria a protective matrix (e.g., skim milk) and cryoprotectors (e.g., glycerol) must be present at early stages of bacterial de-hydration. Tabletting had a less deleterious effect (<2 log units) on bacteria when compared to pelletization (in some cases 3 log units). Enteric coating (15%, w/w) of either tablets or pellets did not affect the viability of the bacteria.

Mucoadhesive Microparticles in a Rapidly Dissolving Tablet for Sustained Drug Delivery to the Eye

PubMed Central

Choy, Young Bin; Patel, Samirkumar R.; Park, Jung-Hwan; McCarey, Bernard E.; Edelhauser, Henry F.

2011-01-01

Purpose. To test the hypothesis that mucoadhesive microparticles formulated in a rapidly dissolving tablet can achieve sustained drug delivery to the eye. Methods. Mucoadhesive microparticles, smaller than 5 μm were fabricated with poly(lactic-co-glycolic acid) and poly(ethylene glycol) as a core material and mucoadhesion promoter, respectively, and encapsulated pilocarpine as a model drug. These microparticles were embedded in a poly(vinyl alcohol) matrix to form a dry tablet designed to reduce rapid clearance of the microparticles on initial application to the eye. Results. This in vitro drug release study exhibited that for all formulations, approximately 90% of pilocarpine was released during the first 10 minutes, and the remaining 10% was released slowly for 3 hours. In vivo mucoadhesion test on the rabbit eye indicated that mucoadhesive microparticles adhered significantly better to the preocular surface than other formulations. To assess the pharmacodynamics, the most prolonged pilocarpine-induced pupil constriction was observed in rabbit eyes in vivo using a tablet with mucoadhesive microparticles; it lasted up to 330 minutes. Conclusions. The authors conclude that mucoadhesive microparticles formulated into a dry dosage form is a promising system for sustained drug delivery to the eye. PMID:21245405

Escherichia coli biofilms have an organized and complex extracellular matrix structure.

PubMed

Hung, Chia; Zhou, Yizhou; Pinkner, Jerome S; Dodson, Karen W; Crowley, Jan R; Heuser, John; Chapman, Matthew R; Hadjifrangiskou, Maria; Henderson, Jeffrey P; Hultgren, Scott J

2013-09-10

Bacterial biofilms are ubiquitous in nature, and their resilience is derived in part from a complex extracellular matrix that can be tailored to meet environmental demands. Although common developmental stages leading to biofilm formation have been described, how the extracellular components are organized to allow three-dimensional biofilm development is not well understood. Here we show that uropathogenic Escherichia coli (UPEC) strains produce a biofilm with a highly ordered and complex extracellular matrix (ECM). We used electron microscopy (EM) techniques to image floating biofilms (pellicles) formed by UPEC. EM revealed intricately constructed substructures within the ECM that encase individual, spatially segregated bacteria with a distinctive morphology. Mutational and biochemical analyses of these biofilms confirmed curli as a major matrix component and revealed important roles for cellulose, flagella, and type 1 pili in pellicle integrity and ECM infrastructure. Collectively, the findings of this study elucidated that UPEC pellicles have a highly organized ultrastructure that varies spatially across the multicellular community. Bacteria can form biofilms in diverse niches, including abiotic surfaces, living cells, and at the air-liquid interface of liquid media. Encasing these cellular communities is a self-produced extracellular matrix (ECM) that can be composed of proteins, polysaccharides, and nucleic acids. The ECM protects biofilm bacteria from environmental insults and also makes the dissolution of biofilms very challenging. As a result, formation of biofilms within humans (during infection) or on industrial material (such as water pipes) has detrimental and costly effects. In order to combat bacterial biofilms, a better understanding of components required for biofilm formation and the ECM is required. This study defined the ECM composition and architecture of floating pellicle biofilms formed by Escherichia coli.

Downstream processing from hot-melt extrusion towards tablets: A quality by design approach.

PubMed

Grymonpré, W; Bostijn, N; Herck, S Van; Verstraete, G; Vanhoorne, V; Nuhn, L; Rombouts, P; Beer, T De; Remon, J P; Vervaet, C

2017-10-05

Since the concept of continuous processing is gaining momentum in pharmaceutical manufacturing, a thorough understanding on how process and formulation parameters can impact the critical quality attributes (CQA) of the end product is more than ever required. This study was designed to screen the influence of process parameters and drug load during HME on both extrudate properties and tableting behaviour of an amorphous solid dispersion formulation using a quality-by-design (QbD) approach. A full factorial experimental design with 19 experiments was used to evaluate the effect of several process variables (barrel temperature: 160-200°C, screw speed: 50-200rpm, throughput: 0.2-0.5kg/h) and drug load (0-20%) as formulation parameter on the hot-melt extrusion (HME) process, extrudate and tablet quality of Soluplus ® -Celecoxib amorphous solid dispersions. A prominent impact of the formulation parameter on the CQA of the extrudates (i.e. solid state properties, moisture content, particle size distribution) and tablets (i.e. tabletability, compactibility, fragmentary behaviour, elastic recovery) was discovered. The resistance of the polymer matrix to thermo-mechanical stress during HME was confirmed throughout the experimental design space. In addition, the suitability of Raman spectroscopy as verification method for the active pharmaceutical ingredient (API) concentration in solid dispersions was evaluated. Incorporation of the Raman spectroscopy data in a PLS model enabled API quantification in the extrudate powders with none of the DOE-experiments resulting in extrudates with a CEL content deviating>3% of the label claim. This research paper emphasized that HME is a robust process throughout the experimental design space for obtaining amorphous glassy solutions and for tabletting of such formulations since only minimal impact of the process parameters was detected on the extrudate and tablet properties. However, the quality of extrudates and tablets can be optimized by adjusting specific formulations parameters (e.g. drug load). Copyright © 2017 Elsevier B.V. All rights reserved.

Application of ethyl cellulose, microcrystalline cellulose and octadecanol for wax based floating solid dispersion pellets.

PubMed

Yan, Hong-Xiang; Zhang, Shuang-Shuang; He, Jian-Hua; Liu, Jian-Ping

2016-09-05

The present study aimed to develop and optimize the wax based floating sustained-release dispersion pellets for a weakly acidic hydrophilic drug protocatechuic acid to achieve prolonged gastric residence time and improved bioavailability. This low-density drug delivery system consisted of octadecanol/microcrystalline cellulose mixture matrix pellet cores prepared by extrusion-spheronization technique, coated with drug/ethyl cellulose 100cp solid dispersion using single-step fluid-bed coating method. The formulation-optimized pellets could maintain excellent floating state without lag time and sustain the drug release efficiently for 12h based on non-Fickian transport mechanism. Observed by SEM, the optimized pellet was the dispersion-layered spherical structure containing a compact inner core. DSC, XRD and FTIR analysis revealed drug was uniformly dispersed in the amorphous molecule form and had no significant physicochemical interactions with the polymer dispersion carrier. The stability study of the resultant pellets further proved the rationality and integrity of the developed formulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modeling Fatigue Damage Onset and Progression in Composites Using an Element-Based Virtual Crack Closure Technique Combined With the Floating Node Method

NASA Technical Reports Server (NTRS)

De Carvalho, Nelson V.; Krueger, Ronald

2016-01-01

A new methodology is proposed to model the onset and propagation of matrix cracks and delaminations in carbon-epoxy composites subject to fatigue loading. An extended interface element, based on the Floating Node Method, is developed to represent delaminations and matrix cracks explicitly in a mesh independent fashion. Crack propagation is determined using an element-based Virtual Crack Closure Technique approach to determine mixed-mode energy release rates, and the Paris-Law relationship to obtain crack growth rate. Crack onset is determined using a stressbased onset criterion coupled with a stress vs. cycle curve and Palmgren-Miner rule to account for fatigue damage accumulation. The approach is implemented in Abaqus/Standard® via the user subroutine functionality. Verification exercises are performed to assess the accuracy and correct implementation of the approach. Finally, it was demonstrated that this approach captured the differences in failure morphology in fatigue for two laminates of identical stiffness, but with layups containing ?deg plies that were either stacked in a single group, or distributed through the laminate thickness.

Alternative antiretroviral therapy formulations for patients unable to swallow solid oral dosage forms.

PubMed

Duggan, Joan M; Akpanudo, Barbara; Shukla, Vipul; Gutterson, Glen; Eitniear, Lindsey; Sahloff, Eric G

2015-09-15

Evidence-based guidance is presented to assist clinicians in selecting alternative formulations of antiretroviral (ARV) agents for patients with human immunodeficiency virus (HIV) infection who are unable to swallow tablets or capsules. The inability to take medications in standard oral dosage forms can be associated with nonadherence or the use of alternative administration strategies such as capsule or tablet breaking, crushing, or chewing. Patients with HIV infection require long-term ARV therapy to maintain viral suppression; ARV agents are predominately available as tablets and capsules that may pose swallowing difficulties for some patients. Using a variety of sources (the primary literature, pharmaceutical package inserts, and requests for unpublished data from drug manufacturers), available evidence on the bioavailability of ARV medications after disruption of the capsule or tablet matrix was reviewed; information on alternative formulations of ARV agents was also assessed. With several ARV agents, disruption of the solid oral dosage form by crushing, chewing, or breaking tablets or opening capsules prior to ingestion has been shown to result in altered bioavailability or pharmacokinetics and thus the potential for incomplete virological suppression, increased adverse effects, and suboptimal health outcomes. Of the 33 single-agent ARV medications and combination ARV products in five classes available at the time of review, approximately half exist as powders, liquids, injectables, or chewable or dissolvable tablets. If alternative ARV formulations or administration methods are used, close monitoring for achievement of virological and immunologic success and potential toxicities is recommended. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Synchrotron Radiation Microcomputed Tomography Guided Chromatographic Analysis for Displaying the Material Distribution in Tablets.

PubMed

Zhang, Liu; Wu, Li; Wang, Caifen; Zhang, Guoqing; Yu, Lin; Li, Haiyan; Maharjan, Abi; Tang, Yan; He, Dunwei; York, Peter; Sun, Huimin; Yin, Xianzhen; Zhang, Jiwen; Sun, Lixin

2018-03-06

One unusual and challenging scientific field that has received only cursory attention to date is the three-dimensional (3D) microstructure and spatial distribution of drug(s) and formulation materials in solid dosage forms. This study aims to provide deeper insight into the relationships between the microstructure of multiple-unit pellet system (MUPS) tablets and the spatial distribution of the active pharmaceutical ingredient (API) and excipients to facilitate the design of quantitative models for drug delivery systems. Synchrotron radiation X-ray microcomputed tomography (SR-μCT) was established as a 3D structure elucidation technique, which, in conjunction with liquid chromatography coupled to mass spectrometry (LC-MS) or liquid chromatography with evaporative light-scattering detector (LC-ELSD) enables chemical analysis of tablets. On the basis of the specific interior construction of theophylline MUPS tablets, the spatial distribution of materials was acquired by quantifying microregion samples that had been validated by SR-μCT for their locations in the MUPS tablets. The 3D structure of the MUPS tablets was catalogued as three structural domains: a matrix layer (ML), a protective cushion layer (PCL), and pellets (PL). Compared with the components in the ML, components in the PL had a larger proportion of theophylline, sucrose, and diethyl phthalate and a smaller proportion of lactose and sodium lauryl sulfate, whereas glyceryl monostearate was found to account for a large portion of the PCL. Microstructural characterization-guided zonal chemical determination represents a new approach for quality assessment and the development of drug delivery systems with in-depth insight into their constituent layers on a new scale.

Physicochemical characterization and mechanisms of release of theophylline from melt-extruded dosage forms based on a methacrylic acid copolymer.

PubMed

Young, Christopher R; Dietzsch, Caroline; Cerea, Matteo; Farrell, Thomas; Fegely, Kurt A; Rajabi-Siahboomi, Ali; McGinity, James W

2005-09-14

The purpose of the current study was to investigate the physicochemical properties of melt-extruded dosage forms based on Acryl-EZE and to determine the influence of gelling agents on the mechanisms and kinetics of drug release from thermally processed matrices. Acryl-EZE is a pre-mixed excipient blend based on a methacrylic acid copolymer that is optimized for film-coating applications. Powder blends containing theophylline, Acryl-EZE, triethyl citrate and an optional gelling agent, Methocel K4M Premium (hydroxypropyl methylcellulose, HPMC, hypromellose 2208) or Carbopol 974P (carbomer), were thermally processed using a Randcastle single-screw extruder. The physical and chemical stability of materials during processing was determined using thermal gravimetric analysis and HPLC. The mechanism of drug release was determined using the Korsmeyer-Peppas model and the hydration and erosion of tablets during the dissolution studies were investigated. The excipient blends were physically and chemically stable during processing, and the resulting dosage forms exhibited pH-dependent dissolution properties. Extrusion of blends containing HPMC or carbomer changed the mechanism and kinetics of drug release from the thermally processed dosage forms. At concentrations of 5% or below, carbomer was more effective than HPMC at extending the duration of theophylline release from matrix tablets. Furthermore, carbomer containing tablets were stable upon storage for 3 months at 40 degrees C/75% RH. Thus, hot-melt extrusion was an effective process for the preparation of controlled release matrix systems based on Acryl-EZE.

Determination of fat-soluble vitamins and carotenoids in standard reference material 3280 multivitamin/multielement tablets by liquid chromatography with absorbance detection.

PubMed

Thomas, Jeanice B; Sharpless, Katherine E; Yen, James H; Rimmer, Catherine A

2011-01-01

The concentrations of selected fat-soluble vitamins and carotenoids in Standard Reference Material (SRM) 3280 Multivitamin/Multielement Tablets have been determined by two independent LC methods, with measurements performed by the National Institute of Standards and Technology (NIST). This SRM has been prepared as part of a collaborative effort between NIST and the National Institutes of Health Office of Dietary Supplements. The SRM is also intended to support the Dietary Supplement Ingredient Database that is being established by the U.S. Department of Agriculture. The methods used at NIST to determine the concentration levels of vitamins A and E, and beta-carotene in the SRM used RPLC with absorbance detection. The relative precision of these methods ranged from 2 to 8% for the analytes measured. SRM 3280 is primarily intended for use in validating analytical methods for the determination of selected vitamins, carotenoids, and elements in multivitamin/multielement tablets and similar matrixes.

In vitro release kinetics of Tolmetin from tabletted Eudragit microparticles.

PubMed

Pignatello, R; Consoli, P; Puglisi, G

2000-01-01

In a previous paper the preparation has been described, by three different techniques, of microparticles made of Eudragit RS 100 and RL 100 containing a NSAI agent, Tolmetin. Freely flowing microparticles failed to affect significantly the in vitro drug release, which displayed a similar dissolution profile after micro-encapsulation to the free drug powder. Microparticles were then converted into tablets and the effect of compression on drug delivery, as well as that of the presence of co-additives, was studied in the present work. Furthermore, microparticles were also prepared by adding MgO to the polymer matrix, to reduce the sensitivity of the drug to pH changes during its dissolution. Similarly, magnesium stearate was also used for microparticle formation as a droplet stabilizer, in order to reduce particle size and hinder rapid drug release. A mathematical evaluation, by using two semi-empirical equations, was applied to evaluate the influence of dissolution and diffusion phenomena upon drug release from microparticle tablets.

Structural modifications of polymethacrylates: impact on thermal behavior and release characteristics of glassy solid solutions.

PubMed

Claeys, Bart; De Coen, Ruben; De Geest, Bruno G; de la Rosa, Victor R; Hoogenboom, Richard; Carleer, Robert; Adriaensens, Peter; Remon, Jean Paul; Vervaet, Chris

2013-11-01

Polymethacrylates such as Eudragit® polymers are well established as drug delivery matrix. Here, we synthesize several Eudragit E PO (n-butyl-, dimethylaminoethyl-, methyl-methacrylate-terpolymer) analogues via free radical polymerization. These polymers are processed via hot melt extrusion, followed by injection molding and evaluated as carriers to produce immediate release solid solution tablets. Three chemical modifications increased the glass transition temperature of the polymer: (a) substitution of n-butyl by t-butyl groups, (b) reduction of the dimethylaminoethyl methacrylate (DMAEMA) content, and (c) incorporation of a bulky isobornyl repeating unit. These structural modifications revealed the possibility to increase the mechanical stability of the tablets via altering the polymer Tg without influencing the drug release characteristics and glassy solid solution forming properties. The presence of DMAEMA units proved to be crucial with respect to API/polymer interaction (essential in creating glassy solid solutions) and drug release characteristics. Moreover, these chemical modifications accentuate the need for a more rational design of (methacrylate) polymer matrix excipients for drug formulation via hot melt extrusion and injection molding. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of pore CaCO3 form agencies on dissolution mechanisms of amoxicillin drugs encapsulated in hydrogels full-IPN chitosan N-vinyl caprolactam

NASA Astrophysics Data System (ADS)

Budianto, Emil; Fauzia, Maghfira

2018-04-01

The administration of amoxicillin trihydrate in Helicobacter pylori infection is not effective enough because the conventional preparations used have a short retention time in the stomach. To overcome this problem, amoxicillin trihydrate was encapsulated into the floating drug delivery matrix-matrix. In this study, the full-ipn acetaldehyde crosslinked hydrogel (N-vinyl caprolactam) was synthesized with a 10% CaCO3 pore forming agent and then encapsulated on amoxicillin trihydrate and studied the mechanism of drug dissolution with its kinetic kinetics approach. The K-PNVCL Hydrogel produces optimal properties which are then loaded with amoxicillin trihydrate in situ and post loading. In this research, we have got the percentage of swelling, floating time, the efficiency of in situ and post loading 873%; 3.15 minutes; 99.8% and 99.4%. The dissolution test was performed on amoxicillin trihydrate which had been encapsulated K-PNVCL hydrogel in vitro at pH 1.2 resulting in 94.5% for in situ loading and 98.5% for post loading. Results of the kinetics of drug release for post loading and in situ loading methods tend to follow the Higuchi model kinetics. The drug release mechanism occurs by Fickian diffusion. Proof of drug release mechanism from K-PNVCL hydrogel matrix is further done by Scanning Electron Microscope (SEM) instrument.

A novel double-layer mucoadhesive tablet containing probiotic strain for vaginal administration: Design, development and technological evaluation.

PubMed

Sánchez, María Teresa; Ruiz, María Adolfina; Castán, Herminia; Morales, María Encarnación

2018-01-15

Vulvovaginal candidosis caused by Candida spp. is the most prevalent vaginal infection in Europe and the second one in EE.UU, so it has become a major female concern. Probiotics bacteria have been proposed as an alternative treatment with the aim of avoiding the adverse effects associated with conventional therapies including antibiotics and other aggressive drugs for the vaginal mucosa and microbiota. The purpose of this work was to design and develop a novel vaginal tablet that contained Lactobacillus spp. bacteria as a treatment against vulvovaginal infections. A total of 21 two-layers vaginal tablets, which contained different polymeric ratios, were proposed. However, formulation F4 (20mg Na-CMC; 50mg Carbopol® 934; 20mg chitosan) was selected as optimal according to its swelling index and dissolution/erosion capability. F4 tablets showed suitable technological properties for vaginal administration as well as mucoadhesion time (24.36±0.88h) and force (0.0941N). Disintegration assay in simulated vaginal fluid (SVF, pH5.5) showed that effervescent layer disappeared in 27.48±0.05s whilst matrix layer was totally gelled in 1h. Two different release profiles were achieved; on the one hand, a promptly release due to the dissolution of both effervescent layer and matrix layer's surface (1.10×10 8 CFU/g), on the second hand, a prolonged released of the remaining bacteria until 24h (5.48×10 7 CFU/g). For stability and storage study, it was found that bacteria viability was constant until 90days in both ways of storage, in a desiccator and at room temperature, with a final dosage of 10 8 CFU/g which was considered appropriate for vaginal therapy (10 8 -10 10 CFU/g). Copyright © 2017 Elsevier B.V. All rights reserved.

Gum Ghatti--a pharmaceutical excipient: development, evaluation and optimization of sustained release mucoadhesive matrix tablets of domperidone.

PubMed

Gurpreetarora; Malik, Karan; Rana, Vikas; Singh, Inderbir

2012-01-01

The objective of this study was to extend the GI residence time of the dosage form and to control the release of domperidone using directly compressible sustained release mucoadhesive matrix (SRMM) tablets. A 2-factor centre composite design (CCD) was employed to study the influence of independent variables like gum ghatti (GG) (X1) and hydroxylpropylmethyl cellulose K 15M (HPMC K 15M) (X2) on dependent variable like mucoadhesive strength, tensile strength, release exponent (n), t50 (time for 50% drug release), rel(10 h) (release after 10 h) and rel(18 h) (release after 18 h). Tablets were prepared by direct compression technology and evaluated for tablet parametric test (drug assay, diameter, thickness, hardness and tensile strength), mucoadhesive strength (using texture analyzer) and in vitro drug release studies. The tensile strength and mucoadhesive strength were found to be increased from 0.665 +/- 0.1 to 1.591 +/- 0.1 MN/cm2 (Z1 to Z9) and 10.789 +/- 0.985 to 50.924 +/- 1.150 N (Z1 to Z9), respectively. The release kinetics follows first order and Hixson Crowell equation indicating drug release following combination of diffusion and erosion. The n varies between 0.834 and 1.273, indicating release mechanism shifts from non fickian (anomalous release) to super case II, which depict that drug follows multiple drug release mechanism. The t50 time was found to increase from 5 +/- 0.12 to 11.4 +/- 0.14 h (Z1 to Z9) and release after 10 and 18 h decreases with increasing concentration of both polymers concluding with release controlling potential of polymers. The accelerated stability studies were performed on optimized formulation as per ICH guideline and the result showed that there was no significant change in tensile strength, mucoadhesive strength and drug assay.

Designing nacre-like materials for simultaneous stiffness, strength and toughness: Optimum materials, composition, microstructure and size

NASA Astrophysics Data System (ADS)

Barthelat, Francois

2014-12-01

Nacre, bone and spider silk are staggered composites where inclusions of high aspect ratio reinforce a softer matrix. Such staggered composites have emerged through natural selection as the best configuration to produce stiffness, strength and toughness simultaneously. As a result, these remarkable materials are increasingly serving as model for synthetic composites with unusual and attractive performance. While several models have been developed to predict basic properties for biological and bio-inspired staggered composites, the designer is still left to struggle with finding optimum parameters. Unresolved issues include choosing optimum properties for inclusions and matrix, and resolving the contradictory effects of certain design variables. Here we overcome these difficulties with a multi-objective optimization for simultaneous high stiffness, strength and energy absorption in staggered composites. Our optimization scheme includes material properties for inclusions and matrix as design variables. This process reveals new guidelines, for example the staggered microstructure is only advantageous if the tablets are at least five times stronger than the interfaces, and only if high volume concentrations of tablets are used. We finally compile the results into a step-by-step optimization procedure which can be applied for the design of any type of high-performance staggered composite and at any length scale. The procedure produces optimum designs which are consistent with the materials and microstructure of natural nacre, confirming that this natural material is indeed optimized for mechanical performance.

Formation of chocolate-tablet boudins: Results from scaled analogue models

NASA Astrophysics Data System (ADS)

Zulauf, J.; Zulauf, G.; Göttlich, J.; Peinl, M.

2014-11-01

We used power-law viscous plasticine as a rock analogue to simulate chocolate tablet boudinage of rocks undergoing dislocation creep. A competent plasticine layer, oriented perpendicular to the main shortening direction, Z, underwent two phases of plane strain in a weaker plasticine matrix, with the principal stretching axis, X, and the axis of no-change, Y, replacing each other from the first to the second phase. In each phase of plane strain, boudinage was controlled by an initial phase of viscous necking followed by extension fracture along the neck domain. Increase in the magnitude of finite strain (e) and decrease in layer thickness (Hi) result in a decrease in the boudin width (Wa) and an increase in the number of boudins (N). Given the viscosity ratio between layer and matrix (m) is higher than ca. 5, the number of boudins decreases and the boudin width increases with increasing values of m. An unexpected result of the present study is that in each experiment, the number of boudins was significantly higher during the second phase of plane strain. This difference should be related to additional drag of the matrix plasticine on the stiff layer in the neck domains formed during the first phase of boudinage. The aspect ratio of the second generation of boudins (Wd = Wa/Hi) is compatible with aspect ratios of natural boudins and with aspect ratios calculated using analytical solutions.

Formulation and development of pH-independent/dependent sustained release matrix tablets of ondansetron HCl by a continuous twin-screw melt granulation process.

PubMed

Patil, Hemlata; Tiwari, Roshan V; Upadhye, Sampada B; Vladyka, Ronald S; Repka, Michael A

2015-12-30

The objective of the present study was to develop pH-independent/dependent sustained release (SR) tablets of ondansetron HCl dihydrate (OND), a selective 5-HT3 receptor antagonist that is used for prevention of nausea and vomiting caused by chemotherapy, radiotherapy and postoperative treatment. The challenge with the OND API is its pH-dependent solubility and relatively short elimination half-life. Therefore, investigations were made to solve these problems in the current study. Formulations were prepared using stearic acid as a binding agent via a melt granulation process in a twin-screw extruder. The micro-environmental pH of the tablet was manipulated by the addition of fumaric acid to enhance the solubility and release of OND from the tablet. The in vitro release study demonstrated sustained release for 24h with 90% of drug release in formulations using stearic acid in combination with ethyl cellulose, whereas 100% drug release in 8h for stearic acid-hydroxypropylcellulose matrices. The formulation release kinetics was correlated to the Higuchi diffusion model and a non-Fickian drug release mechanism. The results of the present study demonstrated for the first time the pH dependent release from hydrophilic-lipid matrices as well as pH independent release from hydrophobic-lipid matrices for OND SR tablets manufactured by means of a continuous melt granulation technique utilizing a twin-screw extruder. Copyright © 2015 Elsevier B.V. All rights reserved.

Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

PubMed

Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

2016-07-01

Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Sea Peoples, from Cuneiform Tablets to Carbon Dating

PubMed Central

Kaniewski, David; Van Campo, Elise; Van Lerberghe, Karel; Boiy, Tom; Vansteenhuyse, Klaas; Jans, Greta; Nys, Karin; Weiss, Harvey; Morhange, Christophe; Otto, Thierry; Bretschneider, Joachim

2011-01-01

The 13th century BC witnessed the zenith of the Aegean and Eastern Mediterranean civilizations which declined at the end of the Bronze Age, ∼3200 years ago. Weakening of this ancient flourishing Mediterranean world shifted the political and economic centres of gravity away from the Levant towards Classical Greece and Rome, and led, in the long term, to the emergence of the modern western civilizations. Textual evidence from cuneiform tablets and Egyptian reliefs from the New Kingdom relate that seafaring tribes, the Sea Peoples, were the final catalyst that put the fall of cities and states in motion. However, the lack of a stratified radiocarbon-based archaeology for the Sea People event has led to a floating historical chronology derived from a variety of sources spanning dispersed areas. Here, we report a stratified radiocarbon-based archaeology with anchor points in ancient epigraphic-literary sources, Hittite-Levantine-Egyptian kings and astronomical observations to precisely date the Sea People event. By confronting historical and science-based archaeology, we establish an absolute age range of 1192–1190 BC for terminal destructions and cultural collapse in the northern Levant. This radiocarbon-based archaeology has far-reaching implications for the wider Mediterranean, where an elaborate network of international relations and commercial activities are intertwined with the history of civilizations. PMID:21687714

Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

PubMed

Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal

2016-01-01

The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

A comparison of companion matrix methods to find roots of a trigonometric polynomial

NASA Astrophysics Data System (ADS)

Boyd, John P.

2013-08-01

A trigonometric polynomial is a truncated Fourier series of the form fN(t)≡∑j=0Naj cos(jt)+∑j=1N bj sin(jt). It has been previously shown by the author that zeros of such a polynomial can be computed as the eigenvalues of a companion matrix with elements which are complex valued combinations of the Fourier coefficients, the "CCM" method. However, previous work provided no examples, so one goal of this new work is to experimentally test the CCM method. A second goal is introduce a new alternative, the elimination/Chebyshev algorithm, and experimentally compare it with the CCM scheme. The elimination/Chebyshev matrix (ECM) algorithm yields a companion matrix with real-valued elements, albeit at the price of usefulness only for real roots. The new elimination scheme first converts the trigonometric rootfinding problem to a pair of polynomial equations in the variables (c,s) where c≡cos(t) and s≡sin(t). The elimination method next reduces the system to a single univariate polynomial P(c). We show that this same polynomial is the resultant of the system and is also a generator of the Groebner basis with lexicographic ordering for the system. Both methods give very high numerical accuracy for real-valued roots, typically at least 11 decimal places in Matlab/IEEE 754 16 digit floating point arithmetic. The CCM algorithm is typically one or two decimal places more accurate, though these differences disappear if the roots are "Newton-polished" by a single Newton's iteration. The complex-valued matrix is accurate for complex-valued roots, too, though accuracy decreases with the magnitude of the imaginary part of the root. The cost of both methods scales as O(N3) floating point operations. In spite of intimate connections of the elimination/Chebyshev scheme to two well-established technologies for solving systems of equations, resultants and Groebner bases, and the advantages of using only real-valued arithmetic to obtain a companion matrix with real-valued elements, the ECM algorithm is noticeably inferior to the complex-valued companion matrix in simplicity, ease of programming, and accuracy.

Direct analysis of 18 flavonol glycosides, aglycones and terpene trilactones in Ginkgo biloba tablets by matrix solid phase dispersion coupled with ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry.

PubMed

Liu, Xin-Guang; Yang, Hua; Cheng, Xiao-Lan; Liu, Lei; Qin, Yong; Wang, Qi; Qi, Lian-Wen; Li, Ping

2014-08-01

Analysis and quality control of Ginkgo biloba have been comprehensively studied. However, little attention has been devoted to the simultaneous extraction and analysis of flavonols and terpene trilactones, especially for direct quantification of flavonol glycosides. This work described a rapid strategy for one-step extraction and quantification of the components. A matrix solid phase dispersion (MSPD) method was designed for the extraction of ginkgo ingredients and compared with the heat-reflux and ultrasonic extraction methods. An ultra-high performance liquid chromatography (UHPLC)-tandem-triple-quadrupole-mass spectrometry (QQQ-MS) method was developed for detection of the 18 components, including 10 original flavonol glycosides, 3 aglycones, and 5 lactones. Subsequently, the proposed strategy was used for the analysis of 12 G. biloba tablets. Results showed that MSPD produced comparable extraction efficiency but consumed less time and required lower solvent volumes compared with conventional methods. Without hydrolysis, the concentration detected was much closer to the original in the sample. The total flavonol glycoside contents in ginkgo tablets ranged from 3.59 to 125.21μgmg(-1), and the terpene trilactone varied from 3.45 to 57.8μgmg(-1) among different manufacturers. In conclusion, the proposed MSPD and UHPLC-QQQ-MS is rapid and sensitive in providing comprehensive profile of chemical constituents especially the genuine flavonol glycosides for improved quality control of ginkgo products. Copyright © 2014 Elsevier B.V. All rights reserved.

Collective cell behavior on basement membranes floating in space

NASA Astrophysics Data System (ADS)

Ellison, Sarah; Bhattacharjee, Tapomoy; Morley, Cameron; Sawyer, W.; Angelini, Thomas

The basement membrane is an essential part of the polarity of endothelial and epithelial tissues. In tissue culture and organ-on-chip devices, monolayer polarity can be established by coating flat surfaces with extracellular matrix proteins and tuning the trans-substrate permeability. In epithelial 3D culture, spheroids spontaneously establish inside-out polarity, morphing into hollow shell-like structures called acini, generating their own basement membrane on the inner radius of the shell. However, 3D culture approaches generally lack the high degree of control provided by the 2D culture plate or organ-on-chip devices, making it difficult to create more faithful in vitro tissue models with complex surface curvature and morphology. Here we present a method for 3D printing complex basement membranes covered in cells. We 3D print collagen-I and Matrigel into a 3D growth medium made from jammed microgels. This soft, yielding material allows extracellular matrix to be formed as complex surfaces and shapes, floating in space. We then distribute MCF10A epithelial cells across the polymerized surface. We envision employing this strategy to study 3D collective cell behavior in numerous model tissue layers, beyond this simple epithelial model.

Evaluation of hydrophobic materials as matrices for controlled-release drug delivery.

PubMed

Quadir, Mohiuddin Abdul; Rahman, M Sharifur; Karim, M Ziaul; Akter, Sanjida; Awkat, M Talat Bin; Reza, Md Selim

2003-07-01

The present study was undertaken to evaluate the effect of different insoluble and erodable wax-lipid based materials and their content level on the release profile of drug from matrix systems. Matrix tablets of theophylline were prepared using carnauba wax, bees wax, stearic acid, cetyl alcohol, cetostearyl alcohol and glyceryl monostearate as rate-retarding agents by direct compression process. The release of theophylline from these hydrophobic matrices was studied over 8-hours in buffer media of pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The release kinetics was found to be governed by the type and content of hydrophobic materials in the matrix. At lower level of wax matrices (25%), a potential burst release was observed with all the materials being studied. Bees wax could not exert any sustaining action while an extensive burst release was found with carnauba wax at this hydrophobic load. Increasing the concentration of fat-wax materials significantly decreased the burst effect of drug from the matrix. At higher hydrophobic level (50% of the matrix), the rate and extent of drug release was significantly reduced due to increased tortuosity and reduced porosity of the matrix. Cetostearyl alcohol imparted the strongest retardation of drug release irrespective of fat-wax level. Numerical fits indicate that the Higuchi square root of time model was the most appropriate one for describing the release profile of theophylline from hydrophobic matrices. The release mechanism was also explored and explained with biexponential equation. Application of this model indicates that Fickian or case I kinetics is the predominant mechanism of drug release from these wax-lipid matrices. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with cetostearyl matrix. The greater sustaining activity of cetostearyl alcohol can be attributed to some level of swelling and erosion within this matrix at lower fat-wax level which is also supported by release exponent values and Fickian fraction release against time profile of this agent. The results generated in this study showed that proper selection of these hydrophobic materials based on their physico-chemical properties is important in designing wax matrix tablets with desired dissolution profile.

Sparse matrix-vector multiplication on network-on-chip

NASA Astrophysics Data System (ADS)

Sun, C.-C.; Götze, J.; Jheng, H.-Y.; Ruan, S.-J.

2010-12-01

In this paper, we present an idea for performing matrix-vector multiplication by using Network-on-Chip (NoC) architecture. In traditional IC design on-chip communications have been designed with dedicated point-to-point interconnections. Therefore, regular local data transfer is the major concept of many parallel implementations. However, when dealing with the parallel implementation of sparse matrix-vector multiplication (SMVM), which is the main step of all iterative algorithms for solving systems of linear equation, the required data transfers depend on the sparsity structure of the matrix and can be extremely irregular. Using the NoC architecture makes it possible to deal with arbitrary structure of the data transfers; i.e. with the irregular structure of the sparse matrices. So far, we have already implemented the proposed SMVM-NoC architecture with the size 4×4 and 5×5 in IEEE 754 single float point precision using FPGA.

Preparation of directionally solidified BaTi2O5-Ba6Ti17O40 eutectic by the floating zone method

NASA Astrophysics Data System (ADS)

Shiga, K.; Katsui, H.; Goto, T.

2017-02-01

The BaTi2O5-Ba6Ti17O40 eutectic (BaO-68.7 mol% TiO2) was directionally solidified by the floating zone (FZ) method and crystalline phases, microstructures and orientation were investigated. Ba6Ti17O40 with faceted rod-like shape was dispersed in the BaTi2O5 matrix. The growth directions of BaTi2O5 and Ba6Ti17O40 were parallel to the b and a axis, respectively, and the orientation relations were BaTi2O5 (010)//Ba6Ti17O40(60 2 ̅) and BaTi2O5 (001)//Ba6Ti17O40 (001).

Effect of drug loading method against the dissolution mechanism of encapsulated amoxicillin trihidrate drug in matrix of semi-IPN chitosan-poly (N-vinyl pyrrolidone) hydrogel with pore forming agent CaCO3

NASA Astrophysics Data System (ADS)

Nurjannah, Yanah; Budianto, Emil

2018-04-01

Heliobacter pylori (H.pylori) is a type of bacteria that causes inflammation in the lining of the stomach. The treatment of the bacterial infection by using conventional medicine which is amoxicillin trihidrate has a very short retention time in the stomach which is about 1-1,5 hours. Floating drug delivery system is expected to have a long retention time in the stomach so the efficiency of drug can be achieved. In this study, has been synthesized matrix of semi-IPN chitosan-Poly(N-vinil pyrrolidone) hydrogel with a pore-forming agent of CaCO3 under optimum conditions. Amoxicillin is encapsulated in a matrix hydrogel to be applied as a floating drug delivery system by in situ loading and post loading methods. The encapsulation efficiency and dissolution of in situ loading and post loading hydrogels are performed in vitro on gastric pH. In situ loading hydrogel shows higer percentage of encapsulation efficiency and dissolution compared to post loading hydrogel. The encapsulation efficiency of in situ and post loading hydrogels were 92,1% and 89,4%, respectively. The aim of drug dissolution by mathematical equation model is to know kinetics and the mecanism of dissolution. The kinetics release of in situ hydrogel tends to follow first order kinetics, while the post loading hydrogel follow the Higuchi model. The dissolution mecanism of hydrogels is erosion.

Dispersive liquid-liquid microextraction based on solidification of floating organic droplet for the determination of triazine and triazoles in mineral water samples.

PubMed

Bolzan, Cátia M; Caldas, Sergiane S; Guimarães, Bruno S; Primel, Ednei G

2016-09-01

A simple, rapid, and sensitive method for the determination of atrazine, simazine, cyproconazole, tebuconazole, and epoxiconazole in mineral water employing the dispersive liquid-liquid microextraction with solidification of a floating organic drop with determination by liquid chromatography tandem mass spectrometry has been developed. A mixed solution of 250 μL 1-dodecanol and 1250 μL methanol was injected rapidly into 10 mL aqueous solution (pH 7.0) with 2% w/v NaCl. After centrifugation for 5 min at 2000 rpm, the organic solvent droplets floated on the surface of the aqueous solution and the floating solvent solidified. The method limits of detection were between 3.75 and 37.5 ng/L and limits of quantification were between 12.5 and 125 ng/L. The recoveries ranged from 70 to 118% for repeatability and between 76 and 95% for intermediate precision with a relative standard deviation from 2 to 18% for all compounds. Low matrix effect was observed. The proposed method can be successfully applied in routine analysis for determination of pesticide residues in mineral water samples, allowing for monitoring of triazine and triazoles at levels below the regulatory limits set by international and national legislations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interactive wire-frame ship hullform generation and display

NASA Technical Reports Server (NTRS)

Calkins, D. E.; Garbini, J. L.; Ishimaru, J.

1984-01-01

An interactive automated procedure to generate a wire frame graphic image of a ship hullform, which uses a digitizing tablet in conjunction with the hullform lines drawing, was developed. The geometric image created is displayed on an Evans & Sutherland PS-300 graphics terminal for real time interactive viewing or is output as hard copy on an inexpensive dot matrix printer.

Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

PubMed

Campiñez, María Dolores; Caraballo, Isidoro; Puchkov, Maxim; Kuentz, Martin

2017-07-01

The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

Intestinal Targeting of Ganciclovir Release Employing a Novel HEC-PAA Blended Lyomatrix.

PubMed

Mabrouk, Mostafa; Mulla, Jameel A S; Kumar, Pradeep; Chejara, Dharmesh R; Badhe, Ravindra V; Choonara, Yahya E; du Toit, Lisa C; Pillay, Viness

2016-10-01

A hydroxyethylcellulose-poly(acrylic acid) (HEC-PAA) lyomatrix was developed for ganciclovir (GCV) intestine targeting to overcome its undesirable degradation in the stomach. GCV was encapsulated within the HEC-PAA lyomatrix prepared by lyophilization. Conventional tablets were also prepared with identical GCV concentrations in order to compare the GCV release behavior from the lyomatrix and tablets. GCV incorporation (75.12%) was confirmed using FTIR, DSC, and TGA. The effect of GCV loading on the microstructure properties of the lyomatrix was evaluated by SEM, AFM, and BET surface area measurements. The in vitro drug release study showed steady and rapid release profiles from the GCV-loaded lyomatrix compared with the tablet formulation at identical pH values. Minimum GCV release was observed at acidic pH (≤40%) and maximum release occurred at intestinal pH values (≥90%) proving the intestinal targeting ability of the lyomatrix. Kinetic modeling revealed that the GCV-loaded lyomatrix exhibited zero-order release kinetics (n = 1), while the tablets were best described via the Peppas model. Textural analysis highlighted enhanced matrix resilience and rigidity gradient (12.5%, 20 Pa) for the GCV-loaded lyomatrix compared to the pure (7%, 9.5 Pa) HEC-PAA lyomatrix. Bench-top MRI imaging was used to confirm the mechanism of GCV release behavior by monitoring the swelling and erosion rates. The swelling and erosion rate of the tablets was not sufficient to achieve rapid zero-order GCV release as with the lyomatrix. These combined results suggest that the HEC-PAA lyomatrix may be suitable for GCV intestinal targeting after oral administration.

Native and microwave-modified Terminalia mantaly gums as sustained-release and bioadhesive excipients in naproxen matrix tablet formulations.

PubMed

Odeniyi, Michael Ayodele; Oyedokun, Babatunde Mukhtar; Bamiro, Oluyemisi Adebowale

2017-01-01

Hydrophilic polymers provide a means of sustaining drug delivery. Native gums may be limited in function, but modification may improve their activity. The aim of the study was to evaluate native and modified forms of Terminalia mantaly gum for their sustained-release and bioadhesive properties. The native gum (NTM) was modified by microwave irradiation for 20 seconds (MTM20) and 60 seconds (MTM60) and characterized using microscopy, Fourier transform infrared spectroscopy (FTIR) and packing properties. The effects of the thermally induced molecular reorientation were determined. Tablet formulations of naproxen were produced by direct compression. The mechanical, bioadhesive and release properties of the formulations were determined. Irradiation of NTM improved the gum's flow properties, resulting in Carr's Index and Hausner's ratios lower than 16% and 1.25, respectively. Swelling studies showed that MTM20 and MTM60 had lower water absorption capacity and swelling index values, while packing properties improved upon irradiation, as depicted by lower tapped density values. FTIR spectra of samples showed that the irradiated gums were distinct from the native gums and did not interact with naproxen sodium. The gum's mechanical properties improved with MTM20 and MTM60 and sustained-release action of up 12 h was obtained. Inclusion of hydroxypropyl methylcellulose (HPMC) in the tablet formulations proved critical for bioadhesion. Microwave irradiation of native Terminalia mantaly gum improved the flow, mechanical and sustained-release properties of Naproxen tablets, and the addition of HPMC increased bioadhesion properties. The tablet properties of the native gum were significantly improved after 20 s of microwave irradiation.

Preparation and evaluation of enteric coated tablets of hot melt extruded lansoprazole

PubMed Central

Alsulays, Bader B.; Kulkarni, Vijay; Alshehri, Sultan M.; Almutairy, Bjad K.; Ashour, Eman A.; Morott, Joseph T.; Alshetaili, Abdullah S.; Park, Jun-Bom; Tiwari, Roshan V.; Repka, Michael A.

2017-01-01

The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon® 12 PF (K12) polymeric matrix. Lutrol® F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug. Inclusion of MgO improved LNS extrudability and release and resulted in over 80% drug release in the buffer stage. Hot-melt extruded LNS was physically and chemically stable after 12 months of storage. Both formulations were studied for compatibility with Eudragit® L 100-55. The optimized formulation was compressed into a tablet followed by coating process utilizing a pan coater using L 100-55 as an enteric coating polymer. In a two-step dissolution study, the release profile of the enteric coated LNS tablets in the acidic stage was less than 10% of the LNS, while that in the buffer stage was more than 80%. Drug content analysis revealed the LNS content to be 97%, indicating the chemical stability of the enteric coated tablet after storage for 6 months. HME, which has not been previously used for LNS, is a valuable technique to reduce processing time in the manufacture of enteric coated formulations of an acid-sensitive active pharmaceutical ingredient as compared to the existing methods. PMID:27486807

Highly sensitive and selective spectrofluorimetric determination of metoclopramide hydrochloride in pharmaceutical tablets and serum samples using Eu3+ ion doped in sol-gel matrix.

PubMed

Attia, M S; Aboaly, M M

2010-06-30

A simple, sensitive and selective spectrofluorimetric method for the determination of Metoclopramide hydrochloride (MCP) is developed. The MCP can remarkably enhances the luminescence intensity of the Eu(3+) ion doped in sol-gel matrix at lambda(ex)=380 nm in DMSO at pH 8.7. The intensity of the emission band of Eu(3+) ion doped in sol-gel matrix increases due to energy transfer from MCP to Eu(3+) in the excited state. The enhancement of the emission band of Eu(3+) ion doped in sol-gel matrix at 617 nm was found to be directly proportional to the concentration of MCP with a dynamic range of 5 x 10(-9) - 1.0 x 10(-6) mol L(-1) and detection limit of 2.2 x10(-11) mol L(-1). Copyright 2010 Elsevier B.V. All rights reserved.

Enhancing tablet disintegration characteristics of a highly water-soluble high-drug-loading formulation by granulation process.

PubMed

Pandey, Preetanshu; Levins, Christopher; Pafiakis, Steve; Zacour, Brian; Bindra, Dilbir S; Trinh, Jade; Buckley, David; Gour, Shruti; Sharif, Shasad; Stamato, Howard

2018-07-01

The objective of this study was to improve the disintegration and dissolution characteristics of a highly water-soluble tablet matrix by altering the manufacturing process. A high disintegration time along with high dependence of the disintegration time on tablet hardness was observed for a high drug loading (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process. Keeping the formulation composition mostly constant, a fluid-bed granulation (FBG) process was explored as an alternate granulation method using a 2 (4-1) fractional factorial design with two center points. FBG batches (10 batches) were manufactured using varying disingtegrant amount, spray rate, inlet temperature (T) and atomization air pressure. The resultant final blend particle size was affected significantly by spray rate (p = .0009), inlet T (p = .0062), atomization air pressure (p = .0134) and the interaction effect between inlet T*spray rate (p = .0241). The compactibility of the final blend was affected significantly by disintegrant amount (p < .0001), atomization air pressure (p = .0013) and spray rate (p = .05). It was observed that the fluid-bed batches gave significantly lower disintegration times than the HSWG batches, and mercury intrusion porosimetry data revealed that this was caused by the higher internal pore structure of tablets manufactured using the FBG batches.

Characterisation of pore structures of pharmaceutical tablets: A review.

PubMed

Markl, Daniel; Strobel, Alexa; Schlossnikl, Rüdiger; Bøtker, Johan; Bawuah, Prince; Ridgway, Cathy; Rantanen, Jukka; Rades, Thomas; Gane, Patrick; Peiponen, Kai-Erik; Zeitler, J Axel

2018-03-01

Traditionally, the development of a new solid dosage form is formulation-driven and less focus is put on the design of a specific microstructure for the drug delivery system. However, the compaction process particularly impacts the microstructure, or more precisely, the pore architecture in a pharmaceutical tablet. Besides the formulation, the pore structure is a major contributor to the overall performance of oral solid dosage forms as it directly affects the liquid uptake rate, which is the very first step of the dissolution process. In future, additive manufacturing is a potential game changer to design the inner structures and realise a tailor-made pore structure. In pharmaceutical development the pore structure is most commonly only described by the total porosity of the tablet matrix. Yet it is of great importance to consider other parameters to fully resolve the interplay between microstructure and dosage form performance. Specifically, tortuosity, connectivity, as well as pore shape, size and orientation all impact the flow paths and play an important role in describing the fluid flow in a pharmaceutical tablet. This review presents the key properties of the pore structures in solid dosage forms and it discusses how to measure these properties. In particular, the principles, advantages and limitations of helium pycnometry, mercury porosimetry, terahertz time-domain spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Sustained release of diltiazem HCl tableted after co-spray drying and physical mixing with PVAc and PVP.

PubMed

Al-Zoubi, Nizar; Al-Obaidi, Ghada; Tashtoush, Bassam; Malamataris, Stavros

2016-01-01

In this work, aqueous diltiazem HCl and polyvinyl-pyrrolidone (PVP) solutions were mixed with Kollicoat SR 30D and spray dried to microparticles of different drug:excipient ratio and PVP content. Co-spray dried products and physical mixtures of drug, Kollidon SR and PVP were tableted. Spray drying process, co-spray dried products and compressibility/compactability of co-spray dried and physical mixtures, as well as drug release and water uptake of matrix-tablets was evaluated. Simple power equation fitted drug release and water uptake (R(2) > 0.909 and 0.938, respectively) and correlations between them were examined. Co-spray dried products with PVP content lower than in physical mixtures result in slower release, while at equal PVP content (19 and 29% w/w of excipient) in similar release (f2 > 50). Increase of PVP content increases release rate and co-spray drying might be an alternative, when physical mixing is inadequate. Co-spray dried products show better compressibility/compatibility but higher stickiness to the die-wall compared to physical mixtures. SEM observations and comparison of release and swelling showed that distribution of tableted component affects only the swelling, while PVP content for both co-spray dried and physical mixes is major reason for release alterations and an aid for drug release control.

Role of cellulose ether polymers on ibuprofen release from matrix tablets.

PubMed

Vueba, M L; Batista de Carvalho, L A E; Veiga, F; Sousa, J J; Pina, Maria Eugénia

2005-08-01

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and beta-cyclodextrin (beta-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE(20 h)), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models-Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.

Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets.

PubMed

Shahiwala, Aliasgar; Zarar, Aisha

2018-01-01

In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Risk based approach for design and optimization of stomach specific delivery of rifampicin.

PubMed

Vora, Chintan; Patadia, Riddhish; Mittal, Karan; Mashru, Rajashree

2013-10-15

The research envisaged focuses on risk management approach for better recognizing the risks, ways to mitigate them and propose a control strategy for the development of rifampicin gastroretentive tablets. Risk assessment using failure mode and effects analysis (FMEA) was done to depict the effects of specific failure modes related to respective formulation/process variable. A Box-Behnken design was used to investigate the effect of amount of sodium bicarbonate (X1), pore former HPMC (X2) and glyceryl behenate (X3) on percent drug release at 1st hour (Q1), 4th hour (Q4), 8th hour (Q8) and floating lag time (min). Main effects and interaction plots were generated to study effects of variables. Selection of the optimized formulation was done using desirability function and overlay contour plots. The optimized formulation exhibited Q1 of 20.9%, Q4 of 59.1%, Q8 of 94.8% and floating lag time of 4.0 min. Akaike information criteria and Model selection criteria revealed that the model was best described by Korsmeyer-Peppas power law. The residual plots demonstrated no existence of non-normality, skewness or outliers. The composite desirability for optimized formulation computed using equations and software were 0.84 and 0.86 respectively. FTIR, DSC and PXRD studies ruled out drug polymer interaction due to thermal treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Implementation of kernels on the Maestro processor

NASA Astrophysics Data System (ADS)

Suh, Jinwoo; Kang, D. I. D.; Crago, S. P.

Currently, most microprocessors use multiple cores to increase performance while limiting power usage. Some processors use not just a few cores, but tens of cores or even 100 cores. One such many-core microprocessor is the Maestro processor, which is based on Tilera's TILE64 processor. The Maestro chip is a 49-core, general-purpose, radiation-hardened processor designed for space applications. The Maestro processor, unlike the TILE64, has a floating point unit (FPU) in each core for improved floating point performance. The Maestro processor runs at 342 MHz clock frequency. On the Maestro processor, we implemented several widely used kernels: matrix multiplication, vector add, FIR filter, and FFT. We measured and analyzed the performance of these kernels. The achieved performance was up to 5.7 GFLOPS, and the speedup compared to single tile was up to 49 using 49 tiles.

Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance.

PubMed

Nnamani, Petra Obioma; Ugwu, Agatha Adaora; Ibezim, Emmanuel Chinedu; Kenechukwu, Franklin Chimaobi; Akpa, Paul Achile; Ogbonna, John-Dike Nwabueze; Obitte, Nicholas Chinedu; Odo, Amelia Ngozi; Windbergs, Maike; Lehr, Claus-Michael; Attama, Anthony Amaechi

The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether-lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol ® ATO 5/Transcutol ® HP and tallow fat/Transcutol ® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol ® ATO 5/Transcutol ® HP batch, then 81% and 95% for tallow fat/Transcutol ® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol ® ATO 5/Transcutol ® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol ® HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem ® tablets (86%) and chloroquine phosphate tablets (66%). No significant difference ( P <0.05) in parasite reduction between double (4/24 mg/kg) and single (2/12 mg/kg) strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg), for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms.

Sustained-release liquisolid compact tablets containing artemether–lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

PubMed Central

Nnamani, Petra Obioma; Ugwu, Agatha Adaora; Ibezim, Emmanuel Chinedu; Kenechukwu, Franklin Chimaobi; Akpa, Paul Achile; Ogbonna, John-Dike Nwabueze; Obitte, Nicholas Chinedu; Odo, Amelia Ngozi; Windbergs, Maike; Lehr, Claus-Michael; Attama, Anthony Amaechi

2016-01-01

The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether–lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol® ATO 5/Transcutol® HP and tallow fat/Transcutol® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol® ATO 5/Transcutol® HP batch, then 81% and 95% for tallow fat/Transcutol® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol® ATO 5/Transcutol® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol® HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem® tablets (86%) and chloroquine phosphate tablets (66%). No significant difference (P<0.05) in parasite reduction between double (4/24 mg/kg) and single (2/12 mg/kg) strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg), for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms. PMID:27932882

Mechanical properties and drug release of venlafaxine HCl solid mini matrices prepared by hot-melt extrusion and hot or ambient compression.

PubMed

Avgerinos, Theodoros; Kantiranis, Nikolaos; Panagopoulou, Athanasia; Malamataris, Stavros; Kachrimanis, Kyriakos; Nikolakakis, Ioannis

2018-02-01

Objective/significance: To elucidate the role of plasticizers in different mini matrices and correlate mechanical properties with drug release. Cylindrical pellets were prepared by hot-melt extrusion (HME) and mini tablets by hot (HC) and ambient compression (AC). Venlafaxine HCl was the model drug, Eudragit ® RSPO the matrix former and citric acid or Lutrol ® F127 the plasticizers. The matrices were characterized for morphology, crystallinity, and mechanical properties. The influence of plasticizer's type and content on the extrusion pressure (P e ) during HME and ejection during tableting was examined and the mechanical properties were correlated with drug release parameters. Resistance to extrusion and tablet ejection force were reduced by Lutrol ® F127 which also produced softer and weaker pellets with faster release, but harder and stronger HC tablets with slower release. HME pellets showed greater tensile strength (T) and 100 times slower release than tablets. P e correlated with T and resistance to deformation of the corresponding pellets (r 2  = 0.963 and 0.945). For both HME and HC matrices the decrease of drug release with T followed a single straight line (r 2  = 0.990) and for HME the diffusion coefficient (D e ) and retreat rate constant (k b ) decreased linearly with T (r 2  = 0.934 and 0.972). Lutrol ® F127 and citric acid are efficient plasticizers and Lutrol ® F127 is a thermal binder/lubricant in HC compression. The different bonding mechanisms of the matrices were reflected in the mechanical strength and drug release. Relationships established between T and drug release parameters for HME and HC matrices may be useful during formulation work.

Development of a controlled release formulation by continuous twin screw granulation: Influence of process and formulation parameters.

PubMed

Vanhoorne, V; Vanbillemont, B; Vercruysse, J; De Leersnyder, F; Gomes, P; Beer, T De; Remon, J P; Vervaet, C

2016-05-30

The aim of this study was to evaluate the potential of twin screw granulation for the continuous production of controlled release formulations with hydroxypropylmethylcellulose as hydrophilic matrix former. Metoprolol tartrate was included in the formulation as very water soluble model drug. A premix of metoprolol tartrate, hydroxypropylmethylcellulose and filler (ratio 20/20/60, w/w) was granulated with demineralized water via twin screw granulation. After oven drying and milling, tablets were produced on a rotary Modul™ P tablet press. A D-optimal design (29 experiments) was used to assess the influence of process (screw speed, throughput, barrel temperature and screw design) and formulation parameters (starch content of the filler) on the process (torque), granule (size distribution, shape, friability, density) and tablet (hardness, friability and dissolution) critical quality attributes. The torque was dominated by the number of kneading elements and throughput, whereas screw speed and filling degree only showed a minor influence on torque. Addition of screw mixing elements after a block of kneading elements improved the yield of the process before milling as it resulted in less oversized granules and also after milling as less fines were present. Temperature was also an important parameter to optimize as a higher temperature yielded less fines and positively influenced the aspect ratio. The shape of hydroxypropylmethylcellulose granules was comparable to that of immediate release formulations. Tensile strength and friability of tablets were not dependent on the process parameters. The use of starch as filler was not beneficial with regard to granule and tablet properties. Complete drug release was obtained after 16-20h and was independent of the design's parameters. Copyright © 2016 Elsevier B.V. All rights reserved.

Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design.

PubMed

Morovati, Amirhosein; Ghaffari, Alireza; Erfani Jabarian, Lale; Mehramizi, Ali

2017-01-01

Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug. Owing to its poor flowability and compressibility, formulating tablets especially high-dose one, may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of Mucinex ® was purposed. A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent variables (Release "%" in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent one (X 1 : Cetyl alcohol, X 2 : Starch 1500 ® , X 3 : HPMC K100M amounts). Two granule portions were prepared using melt and wet granulations, blended together prior to compression. An optimum formulation was obtained (X 1 : 37.10, X 2 : 2, X 3 : 42.49 mg). Desirability function was 0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74 and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500 ® modulated guaifenesin release from HPMC K100M matrices, while due to their binding properties, improved its poor flowability and compressibility, too.

Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design

PubMed Central

Morovati, Amirhosein; Ghaffari, Alireza; Erfani jabarian, Lale; Mehramizi, Ali

2017-01-01

Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug. Owing to its poor flowability and compressibility, formulating tablets especially high-dose one, may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of Mucinex® was purposed. A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent variables (Release “%” in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent one (X1: Cetyl alcohol, X2: Starch 1500®, X3: HPMC K100M amounts). Two granule portions were prepared using melt and wet granulations, blended together prior to compression. An optimum formulation was obtained (X1: 37.10, X2: 2, X3: 42.49 mg). Desirability function was 0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74 and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500® modulated guaifenesin release from HPMC K100M matrices, while due to their binding properties, improved its poor flowability and compressibility, too. PMID:29552045

Synthesis of Thiolated Alginate and Evaluation of Mucoadhesiveness, Cytotoxicity and Release Retardant Properties

PubMed Central

Jindal, A. B.; Wasnik, M. N.; Nair, Hema A.

2010-01-01

Modification of polymers by covalent attachment of thiol bearing pendant groups is reported to impart many beneficial properties to them. Hence in the present study, sodium alginate–cysteine conjugate was synthesized by carbodiimide mediated coupling under varying reaction conditions and the derivatives characterized for thiol content. The thiolated alginate species synthesized had bound thiol content ranging from 247.8±11.03–324.54±10.107 ΅mol/g of polymer depending on the reaction conditions. Matrix tablets based on sodium alginate-cysteine conjugate and native sodium alginate containing tramadol hydrochloride as a model drug were prepared and mucoadhesive strength and in vitro drug release from the tablets were compared. Tablets containing 75 mg sodium alginate-cysteine conjugate could sustain release of 10 mg of model drug for 3 h, whereas 90% of the drug was released within 1 h from corresponding tablets prepared using native sodium alginate. An approximately 2-fold increase in the minimal detachment force of the tablets from an artificial mucin film was observed for sodium alginate–cysteine conjugate as compared to native sodium alginate. In vitro cytotoxicity studies in L-929 mouse fibroblast cells studied using an MTT assay revealed that at low concentrations of polymer, sodium alginate–cysteine conjugate was less toxic to L-929 mouse fibroblast cell line when compared to native sodium alginate. Hence, thiolation is found to be a simple route to improving polymer performance. The combination of improved controlled drug release and mucoadhesive properties coupled with the low toxicity of these new excipients builds up immense scope for the use of thiolated polymers in mucoadhesive drug delivery systems. PMID:21969750

Gauss Elimination: Workhorse of Linear Algebra.

DTIC Science & Technology

1995-08-05

linear algebra computation for solving systems, computing determinants and determining the rank of matrix. All of these are discussed in varying contexts. These include different arithmetic or algebraic setting such as integer arithmetic or polynomial rings as well as conventional real (floating-point) arithmetic. These have effects on both accuracy and complexity analyses of the algorithm. These, too, are covered here. The impact of modern parallel computer architecture on GE is also

Cellulose nanofiber aerogel as a promising biomaterial for customized oral drug delivery

PubMed Central

Bhandari, Jyoti; Mishra, Harshita; Mishra, Pawan Kumar; Wimmer, Rupert; Ahmad, Farhan J; Talegaonkar, Sushama

2017-01-01

Cellulose nanofiber (CNF) aerogels with favorable floatability and mucoadhesive properties prepared by the freeze-drying method have been introduced as new possible carriers for oral controlled drug delivery system. Bendamustine hydrochloride is considered as the model drug. Drug loading was carried out by the physical adsorption method, and optimization of drug-loaded formulation was done using central composite design. A very lightweight-aerogel-with-matrix system was produced with drug loading of 18.98%±1.57%. The produced aerogel was characterized for morphology, tensile strength, swelling tendency in media with different pH values, floating behavior, mucoadhesive detachment force and drug release profiles under different pH conditions. The results showed that the type of matrix was porous and woven with excellent mechanical properties. The drug release was assessed by dialysis, which was fitted with suitable mathematical models. Approximately 69.205%±2.5% of the drug was released in 24 hours in medium of pH 1.2, whereas ~78%±2.28% of drug was released in medium of pH 7.4, with floating behavior for ~7.5 hours. The results of in vivo study showed a 3.25-fold increase in bioavailability. Thus, we concluded that CNF aerogels offer a great possibility for a gastroretentive drug delivery system with improved bioavailability. PMID:28352172

Poly(2-ethyl-2-oxazoline) as matrix excipient for drug formulation by hot melt extrusion and injection molding.

PubMed

Claeys, Bart; Vervaeck, Anouk; Vervaet, Chris; Remon, Jean Paul; Hoogenboom, Richard; De Geest, Bruno G

2012-10-15

Here we evaluate poly(2-ethyl-2-oxazoline)s (PEtOx) as a matrix excipient for the production of oral solid dosage forms by hot melt extrusion (HME) followed by injection molding (IM). Using metoprolol tartrate as a good water-soluble model drug we demonstrate that drug release can be delayed by HME/IM, with the release rate controlled by the molecular weight of the PEtOx. Using fenofibrate as a lipophilic model drug we demonstrate that relative to the pure drug the dissolution rate is strongly enhanced by formulation in HME/IM tablets. For both drug molecules we find that solid solutions, i.e. molecularly dissolved drug in a polymeric matrix, are obtained by HME/IM. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A sparse matrix algorithm on the Boolean vector machine

NASA Technical Reports Server (NTRS)

Wagner, Robert A.; Patrick, Merrell L.

1988-01-01

VLSI technology is being used to implement a prototype Boolean Vector Machine (BVM), which is a large network of very small processors with equally small memories that operate in SIMD mode; these use bit-serial arithmetic, and communicate via cube-connected cycles network. The BVM's bit-serial arithmetic and the small memories of individual processors are noted to compromise the system's effectiveness in large numerical problem applications. Attention is presently given to the implementation of a basic matrix-vector iteration algorithm for space matrices of the BVM, in order to generate over 1 billion useful floating-point operations/sec for this iteration algorithm. The algorithm is expressed in a novel language designated 'BVM'.

Development of a new generation of high-temperature composite materials

NASA Technical Reports Server (NTRS)

Brindley, Pamela K.

1987-01-01

There are ever-increasing demands to develop low-density materials that maintain high strength and stiffness properties at elevated temperatures. Such materials are essential if the requirements for advanced aircraft, space power generation, and space station plans are to be realized. Metal matrix composites and intermetallic matrix composites are currently being investigated at NASA Lewis for such applications because they offer potential increases in strength, stiffness, and use temperature at a lower density than the most advanced single-crystal superalloys presently available. Today's discussion centers around the intermetallic matrix composites proposed by Lewis for meeting advanced aeropropulsion requirements. The fabrication process currently being used at Lewis to produce intermetallic matrix composites will be reviewed, and the properties of one such composite, SiC/Ti3Al+Nb, will be presented. In addition, the direction of future research will be outlined, including plans for enhanced fabrication of aluminide composites by the arc spray technique and fiber development by the floating-zone process.

Escherichia coli Biofilms Have an Organized and Complex Extracellular Matrix Structure

PubMed Central

Hung, Chia; Zhou, Yizhou; Pinkner, Jerome S.; Dodson, Karen W.; Crowley, Jan R.; Heuser, John; Chapman, Matthew R.; Hadjifrangiskou, Maria; Henderson, Jeffrey P.; Hultgren, Scott J.

2013-01-01

ABSTRACT Bacterial biofilms are ubiquitous in nature, and their resilience is derived in part from a complex extracellular matrix that can be tailored to meet environmental demands. Although common developmental stages leading to biofilm formation have been described, how the extracellular components are organized to allow three-dimensional biofilm development is not well understood. Here we show that uropathogenic Escherichia coli (UPEC) strains produce a biofilm with a highly ordered and complex extracellular matrix (ECM). We used electron microscopy (EM) techniques to image floating biofilms (pellicles) formed by UPEC. EM revealed intricately constructed substructures within the ECM that encase individual, spatially segregated bacteria with a distinctive morphology. Mutational and biochemical analyses of these biofilms confirmed curli as a major matrix component and revealed important roles for cellulose, flagella, and type 1 pili in pellicle integrity and ECM infrastructure. Collectively, the findings of this study elucidated that UPEC pellicles have a highly organized ultrastructure that varies spatially across the multicellular community. PMID:24023384

Formulation and process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant.

PubMed

Leane, Michael M; Sinclair, Wayne; Qian, Feng; Haddadin, Raja; Brown, Alan; Tobyn, Mike; Dennis, Andrew B

2013-01-01

Amorphous forms of poorly soluble drugs are more frequently being incorporated into solid dispersions for administration and extensive research has led to a reasonable understanding of how these dispersions, although still kinetically unstable, improve stability relative to the pure amorphous form. There remains however a paucity of literature describing the effects on such solid dispersions of subsequent processing into solid dosage forms such as tablets. This paper addresses this area by looking at the effects of the addition of common excipients and different manufacturing routes on the stability of a spray-dried dispersion (SDD) of the cannabinoid CB-1 antagonist, ibipinabant. A marked difference in physical stability of tablets was seen with the different fillers with microcrystalline cellulose (MCC) giving the best stability profile. It was found that minimising the number of compression steps led to improved formulation stability with a direct compression process giving the best results. Increased levels of crystallinity were seen in coated tablets most likely due to the exposure of the amorphous matrix to moisture and heat during the coating process. DSIMS analysis of the SDD particles indicated increased levels of polymer on the surface.

The Influence of High Drug Loading in Xanthan Tablets and Media with Different Physiological pH and Ionic Strength on Swelling and Release.

PubMed

Mikac, Urša; Sepe, Ana; Baumgartner, Saša; Kristl, Julijana

2016-03-07

The formation of a gel coat around xanthan (Xan) tablets, empty or loaded with pentoxifylline (PF), and its release in media differing in pH and ionic strength by NMR, MR imaging, and two release methods were studied. The T1 and T2 NMR relaxation times in gels depend predominantly on Xan concentration; the presence of PF has negligible influence on them. It is interesting that the matrix swelling is primarily regulated by Xan despite high drug loading (25%, 50%). The gastric pH and high ionic strength of the media do not influence the position of the penetration and swelling fronts but do affect the erosion front and gel thickness. The different release profiles obtained in mixing and nonmixing in vitro methods are the consequence of matrix hydration level and erosion at the surface. In water and in diluted acid medium with low ionic strength, the main release mechanism is erosion, whereas in other media (pH 1.2, μ ≥ 0.20 M), anomalous transport dominates as was found out by fitting of measured data with theoretical model. Besides the in vitro investigation that mimics gastric conditions, mathematical modeling makes the product development more successful.

Effects of coformers on phase transformation and release profiles of carbamazepine cocrystals in hydroxypropyl methylcellulose based matrix tablets.

PubMed

Qiu, Shi; Li, Mingzhong

2015-02-01

The aim of this study was to investigate the effects of coformers on phase transformation and release profiles of carbamazepine (CBZ) cocrystals in hydroxypropyl methylcellulose (HPMC) based matrix tablets. It has been found that selection of different coformers of saccharin (SAC) and cinnamic acid (CIN) can affect the stability of CBZ cocrystals in solution, resulting in significant differences in the apparent solubility of CBZ. The dissolution advantage of CBZ-SAC cocrystals can only be shown for a short period during dissolution because of the fast conversion to its dihydrate form (DH). HPMC can partially inhibit the crystallisation of CBZ DH during dissolution of CBZ-SAC cocrystal. However, the increased viscosity of HPMC dissolution medium reduced the dissolution rate of CBZ-SAC cocrystals. Therefore the CBZ-SAC cocrystal formulation did not show any significant advantage in CBZ release rate. In contrast the improved CBZ dissolution rate of CBZ-CIN cocrystal can be realised in both solution and formulation due to its high stability. In conclusion, exploring and understanding the mechanisms of the phase transformation of pharmaceutical cocrystals in aqueous medium for selection of lead cocrystals is the key for success of product development. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and in vivo evaluation of an oral delivery system for low molecular weight heparin based on thiolated polycarbophil.

PubMed

Kast, Constantia E; Guggi, Davide; Langoth, Nina; Bernkop-Schnürch, Andreas

2003-06-01

It was the purpose of this study to develop a new oral drug delivery system for low molecular weight heparin (LMWH) providing an improved bioavailability and a prolonged therapeutic effect. The permeation enhancing polycarbophil-cysteine conjugate (PCP-Cys) used in this study displayed 111.4 +/- 6.4 microM thiol groups per gram polymer. Permeation studies on freshly excised intestinal mucosa were performed in Ussing chambers demonstrating a 2-fold improved uptake of heparin as a result of the addition of 0.5% (w/v) PCP-Cys and the permeation mediator glutathione (GSH). Tablets containing PCP-Cys, GSH, and 279 IU of LMWH showed a sustained drug release over 4 h. To guarantee the swelling of the polymeric carrier matrix in the small intestine tablets were enteric coated. They were orally given to rats. For tablets being based on the thiomer/GSH system an absolute bioavailability of 19.9 +/- 9.3% (means +/- SD; n = 5) vs. intravenous injection could be achieved. whereas tablets comprising unmodified PCP did not lead to a significant (p < 0.01) heparin concentration in plasma. The permeation enhancing effect and subsequently a therapeutic heparin level was maintained for 24 h after a single dose. Because of the strong and prolonged lasting permeation enhancing effect of the thiomer/GSH system, the oral bioavailability of LMWH could be significantly improved. This new delivery system represents therefore a promising tool for the oral administration of heparin.

Fluorescent quantification of terazosin hydrochloride content in human plasma and tablets using second-order calibration based on both parallel factor analysis and alternating penalty trilinear decomposition.

PubMed

Zou, Hong-Yan; Wu, Hai-Long; OuYang, Li-Qun; Zhang, Yan; Nie, Jin-Fang; Fu, Hai-Yan; Yu, Ru-Qin

2009-09-14

Two second-order calibration methods based on the parallel factor analysis (PARAFAC) and the alternating penalty trilinear decomposition (APTLD) method, have been utilized for the direct determination of terazosin hydrochloride (THD) in human plasma samples, coupled with the excitation-emission matrix fluorescence spectroscopy. Meanwhile, the two algorithms combing with the standard addition procedures have been applied for the determination of terazosin hydrochloride in tablets and the results were validated by the high-performance liquid chromatography with fluorescence detection. These second-order calibrations all adequately exploited the second-order advantages. For human plasma samples, the average recoveries by the PARAFAC and APTLD algorithms with the factor number of 2 (N=2) were 100.4+/-2.7% and 99.2+/-2.4%, respectively. The accuracy of two algorithms was also evaluated through elliptical joint confidence region (EJCR) tests and t-test. It was found that both algorithms could give accurate results, and only the performance of APTLD was slightly better than that of PARAFAC. Figures of merit, such as sensitivity (SEN), selectivity (SEL) and limit of detection (LOD) were also calculated to compare the performances of the two strategies. For tablets, the average concentrations of THD in tablet were 63.5 and 63.2 ng mL(-1) by using the PARAFAC and APTLD algorithms, respectively. The accuracy was evaluated by t-test and both algorithms could give accurate results, too.

Fibrinogen inhibits fibroblast-mediated contraction of collagen

PubMed Central

Nien, Yih-Dar; Han, Yuan-Ping; Tawil, Bill; Chan, Linda S.; Tuan, Tai-Lan; Garner, Warren L.

2008-01-01

Extracellular matrix changes in composition and organization as it transitions from the provisional matrix of the fibrin/platelet plug to collagen scar in healed wounds. The manner in which individual matrix proteins affect these activities is not well established. In this article we describe the interactions of two important extracellular matrix components, fibrin and collagen, using an in vitro model of wound contraction, the fibroblast-populated collagen lattice. We utilized different fibrinogen sources and measured tissue reorganization in floating and tensioned collagen lattices. Our results showed that both fibrin and fibrinogen decreased the contraction of fibroblast populated collagen lattices in a dose-dependent manner. Polymerization of fibrinogen to fibrin using thrombin had no effect on this inhibition. Further, there was no effect due to changes in protein concentration, alternate components of the fibrin sealant, or the enzymatic action of thrombin. These results suggest that the initial stability of the fibrin provisional matrix is due to the fibrin, because this protein appears to inhibit contraction of the matrix. This may be important in the early phases of wound healing when clot stability is vital for hemostasis. Later, as fibrin is replaced by collagen, wound contraction can occur. PMID:12950643

Presolar silicates in the matrix and fine-grained rims around chondrules in primitive CO3.0 chondrites: Evidence for pre-accretionary aqueous alteration of the rims in the solar nebula

NASA Astrophysics Data System (ADS)

Haenecour, Pierre; Floss, Christine; Zega, Thomas J.; Croat, Thomas K.; Wang, Alian; Jolliff, Bradley L.; Carpenter, Paul

2018-01-01

To investigate the origin of fine-grained rims around chondrules (FGRs), we compared presolar grain abundances, elemental compositions and mineralogies in fine-grained interstitial matrix material and individual FGRs in the primitive CO3.0 chondrites Allan Hills A77307, LaPaz Icefield 031117 and Dominion Range 08006. The observation of similar overall O-anomalous (∼155 ppm) and C-anomalous grain abundances (∼40 ppm) in all three CO3.0 chondrites suggests that they all accreted from a nebular reservoir with similar presolar grain abundances. The presence of presolar silicate grains in FGRs combined with the observation of similar estimated porosity between interstitial matrix regions and FGRs in LAP 031117 and ALHA77307, as well as the identification of a composite FGR (a small rimmed chondrule within a larger chondrule rim) in ALHA77307, all provide evidence for a formation of FGRs by accretion of dust grains onto freely-floating chondrules in the solar nebula before their aggregation into their parent body asteroids. Our study also shows systematically lower abundances of presolar silicate grains in the FGRs than in the matrix regions of CO3 chondrites, while the abundances of SiC grains are the same in all areas, within errors. This trend differs from CR2 chondrites in which the presolar silicate abundances are higher in the FGRs than in the matrix, but similar to each other within 2σ errors. This observation combined with the identification of localized (micrometer-scaled) aqueous alteration in a FGR of LAP 031117 suggests that the lower abundance of presolar silicates in FGRs reflects pre-accretionary aqueous alteration of the fine-grained material in the FGRs. This pre-accretionary alteration could be due to either hydration and heating of freely floating rimmed chondrules in icy regions of the solar nebula or melted water ice associated with 26Al-related heating inside precursor planetesimals, followed by aggregation of FGRs into the CO chondrite parent-body.

Parallel Preconditioning for CFD Problems on the CM-5

NASA Technical Reports Server (NTRS)

Simon, Horst D.; Kremenetsky, Mark D.; Richardson, John; Lasinski, T. A. (Technical Monitor)

1994-01-01

Up to today, preconditioning methods on massively parallel systems have faced a major difficulty. The most successful preconditioning methods in terms of accelerating the convergence of the iterative solver such as incomplete LU factorizations are notoriously difficult to implement on parallel machines for two reasons: (1) the actual computation of the preconditioner is not very floating-point intensive, but requires a large amount of unstructured communication, and (2) the application of the preconditioning matrix in the iteration phase (i.e. triangular solves) are difficult to parallelize because of the recursive nature of the computation. Here we present a new approach to preconditioning for very large, sparse, unsymmetric, linear systems, which avoids both difficulties. We explicitly compute an approximate inverse to our original matrix. This new preconditioning matrix can be applied most efficiently for iterative methods on massively parallel machines, since the preconditioning phase involves only a matrix-vector multiplication, with possibly a dense matrix. Furthermore the actual computation of the preconditioning matrix has natural parallelism. For a problem of size n, the preconditioning matrix can be computed by solving n independent small least squares problems. The algorithm and its implementation on the Connection Machine CM-5 are discussed in detail and supported by extensive timings obtained from real problem data.

Simultaneous separation of water- and fat-soluble vitamins in isocratic pressure-assisted capillary electrochromatography using a methacrylate-based monolithic column.

PubMed

Yamada, Hiroki; Kitagawa, Shinya; Ohtani, Hajime

2013-06-01

A method of simultaneous separation of water- and fat-soluble vitamins using pressure-assisted CEC with a methacrylate-based capillary monolithic column was developed. In the proposed method, water-soluble vitamins were mainly separated electrophoretically, while fat soluble-ones were separated chromatographically by the interaction with a methacrylate-based monolith. A mixture of six water-soluble and four fat-soluble vitamins was separated simultaneously within 20 min with an isocratic elution using 1 M formic acid (pH 1.9)/acetonitrile (30:70, v/v) containing 10 mM ammonium formate as a mobile phase. When the method was applied to a commercial multivitamin tablet and a spiked one, the vitamins were successfully analyzed, and no influence of the matrix contained in the tablet was observed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development and evaluation of a monolithic floating dosage form for furosemide.

PubMed

Menon, A; Ritschel, W A; Sakr, A

1994-02-01

The poor bioavailability of orally dosed furosemide (60%), a weakly acidic drug, is due to the presence of a biological window comprised of the upper gastrointestinal tract. The purpose of the present study was to develop and optimize in vitro a monolithic modified-release dosage form (MMR) for furosemide with increased gastric residence time and to evaluate the in vivo performance of the dosage form. The principle of floatation was used to restrict the MMR to the stomach. A two-factor three-level full factorial experimental design was employed for formulation development. A flow-through cell was designed to evaluate in vitro dissolution parameters. Quadratic regression models indicated the polymer viscosity and polymer:drug ratio to be significant (p < 0.05) formulation factors in determining the duration of buoyancy and the release profile. Statistical optimization using response surface methodology with certain physiological constraints relating to gastric emptying time predicted an optimal MMR. In vivo evaluation of the optimized MMR in beagle dogs resulted in a significant increase (p < 0.05) in the absolute bioavailability for the MMR dosage form (42.9%) as compared to the commercially available tablet (33.4%) and enteric product (29.5%). Significant in vitro/in vivo correlations (p < 0.05) were obtained for the MMR using deconvolution analysis normalized for bioavailability. The floating dosage form was found to be a feasible approach in delivering furosemide to the upper gastrointestinal tract to maximize drug absorption.

Multi-unit dosage formulations of theophylline for controlled release applications.

PubMed

Uhumwangho, Michael U; Okor, Roland S

2007-01-01

The study was carried out to investigate the drug release profiles of multi-unit dosage formulations of theophylline consisting of both the fast and slow release components in a unit dose. The fast release component consisted of conventional granules of theophylline formed by mixing the drug powder with starch mucilage (20% w/v) while the slow release component consisted of wax granulations of theophylline formed by triturating the drug powder with a melted Carnauba wax (drug:wax ratio, 4:1). The granules were either filled into capsules or tabletted. In the study design, the drug release characteristics of the individual fast or slow release particles were first determined separately and then mixed in various proportions for the purpose of optimizing the drug release profiles. The evaluating parameters were the prompt release in the first 1 h (mp), the maximum release (m infinity) and the time to attain it (t infinity). Total drug content in each capsule or tablet was 300 mg and two of such were used in dissolution studies. The release kinetics and hence the release mechanism was confirmed by measuring the linear regression coefficient (R2 values) of the release data. The release kinetics was generally most consistent with the Higuchi square root of time relationship (R2 = 0.95). indicating a diffusion-controlled mechanism. The mp (mg) and t infinity (h) values for capsules and tablets of the conventional granules were (420 mg, 3 h) and (348 mg, 5 h), respectively, while for the capsules and tablets of the wax granulations mp and t infinity values were (228 mg, 9 h) and (156 mg, 12 h), respectively, indicating that a combination of wax granulation and tableting markedly retarded drug release. In the multi-unit dose formulations where the conventional and wax granulations were mixed in the ratios 2:1, 1:1 and 1:2 (conventional: matrix), the m infinity and t infinity values for the capsules were (378 mg, 6 h), (326 mg, 6 h) and (272 mg, 7 h), reSpectively. The corresponding values of m infinity and t infinity for the tablets were (240 mg, 9 h), (180 mg, 11 h) and (128 mg, 12 h) against the set target (200 mg, 12 h). The indication is that tableting rather than encapsulation can more effectively control drug release from the systems.

Charge retention characteristics of silicide-induced crystallized polycrystalline silicon floating gate thin-film transistors for active matrix organic light-emitting diode.

PubMed

Park, Jae Hyo; Son, Se Wan; Byun, Chang Woo; Kim, Hyung Yoon; Joo, So Na; Lee, Yong Woo; Yun, Seung Jae; Joo, Seung Ki

2013-10-01

In this work, non-volatile memory thin-film transistor (NVM-TFT) was fabricated by nickel silicide-induced laterally crystallized (SILC) polycrystalline silicon (poly-Si) as the active layer. The nickel seed silicide-induced crystallized (SIC) poly-Si was used as storage layer which is embedded in the gate insulator. The novel unit pixel of active matrix organic light-emitting diode (AMOLED) using NVM-TFT is proposed and investigated the electrical and optical performance. The threshold voltage shift showed 17.2 V and the high reliability of retention characteristic was demonstrated until 10 years. The retention time can modulate the recharge refresh time of the unit pixel of AMOLED up to 5000 sec.

Development of two step liquid-liquid extraction tandem UHPLC-MS/MS method for the simultaneous determination of Ginkgo flavonoids, terpene lactones and nimodipine in rat plasma: Application to the pharmacokinetic study of the combination of Ginkgo biloba dispersible tablets and Nimodipine tablets.

PubMed

Xiao, Jie; Wang, Tianyang; Li, Pei; Liu, Ran; Li, Qing; Bi, Kaishun

2016-08-15

A sensitive, reliable and accurate UHPLC-MS/MS method has been firstly established and validated for the simultaneous quantification of ginkgo flavonoids, terpene lactones and nimodipine in rat plasma after oral administration of Ginkgo biloba dispersible tablets, Nimodipine tablets and the combination of the both, respectively. The plasma samples were extracted by two step liquid-liquid extraction, nimodipine was extracted by hexane-ether (3:1, v/v) at the first step, after that ginkgo flavonoids and terpene lactones were extracted by ethyl acetate. Then the analytes were successfully separated by running gradient elution with the mobile phase consisting of 0.1% formic acid in water and methanol at a flow rate of 0.6mL/min. The detection of the analytes was performed on a UHPLC-MS/MS system with turbo ion spray source in the negative ion and multiple reaction monitoring (MRM) mode. The calibration curves for the determination of all the analytes showed good linearity (R(2)>0.99), and the lower limits of quantification were 0.50-4.00ng/mL. Intra-day and inter-day precisions were in the range of 3.6%-9.2% and 3.2%-13.1% for all the analytes. The mean extraction recoveries of the analytes were within 69.82%-103.5% and the matrix were within 82.8%-110.0%. The validated method had been successfully applied to compare the pharmacokinetic parameters of ginkgo flavonoids, terpene lactones and nimodipine in rat plasma after oral administration of Ginkgo biloba dispersible tablets, Nimodipine tablets with the combination of the both. There were no statistically significant differences on the pharmacokinetic behaviors of all the analytes between the combined and single administration groups. Results showed that the combination of the two agents may avoid dosage adjustments in clinic and the combination is more convenient as well as efficient on different pathogenesis of cerebral ischemia. Copyright © 2016 Elsevier B.V. All rights reserved.

Abuse-deterrent features of an extended-release morphine drug product developed using a novel injection-molding technology for oral drug delivery.

PubMed

Skak, Nikolaj; Elhauge, Torben; Dayno, Jeffrey M; Lindhardt, Karsten

A novel technology platform (Guardian™ Technology, Egalet Corporation, Wayne, PA) was used to manufacture morphine abuse-deterrent (AD), extended-release (ER), injection-molded tablets (morphine-ADER-IMT; ARYMO® ER [morphine sulfate] ER tablets; Egalet Corporation), a recently approved morphine product with AD labeling. The aim of this article is to highlight how the features of Guardian™ Technology are linked to the ER profile and AD characteristics of morphine-ADER-IMT. The ER profile of morphine-ADER-IMT is attributed to the precise release of morphine from the polymer matrix. The approved dosage strengths of morphine-ADER-IMT are bioequivalent to corresponding dosage strengths of morphine ER (MS Contin®; Purdue Pharma LP, Stamford, CT). Morphine-ADER-IMT was very resistant to physical manipulations intended to reduce particle size, with <10 percent of particles being reduced to <500µm, regarded by the US Food and Drug Administration as a relevant cutoff for potential insufflation in their generic solid oral AD opioid guidance. Furthermore, morphine was not readily extracted from the polymer matrix of morphine-ADER-IMT in small- or large-volume solvent extraction studies that evaluated the potential for intravenous and oral abuse. The ER profile and AD characteristics of morphine-ADER-IMT are a result of Guardian™ Technology. The combination of the polyethylene oxide matrix and the use of injection molding differentiate morphine-ADER-IMT from other approved AD opioids that deter abuse using physical and chemical barriers. The high degree of flexibility of the Guardian™ Technology enables the development of products that can be tailored to almost any desired release profile; as such, it is a technology platform that may be useful for the development of a wide range of pharmaceutical products.

Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets.

PubMed

Sadia, Muzna; Sośnicka, Agata; Arafat, Basel; Isreb, Abdullah; Ahmed, Waqar; Kelarakis, Antonios; Alhnan, Mohamed A

2016-11-20

This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

Hydration induced material transfer in membranes of osmotic pump tablets measured by synchrotron radiation based FTIR.

PubMed

Wu, Li; Yin, Xianzhen; Guo, Zhen; Tong, Yajun; Feng, Jing; York, Peter; Xiao, Tiqiao; Chen, Min; Gu, Jingkai; Zhang, Jiwen

2016-03-10

Osmotic pump tablets are reliable oral controlled drug delivery systems based on their semipermeable membrane coating. This research used synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy and imaging to investigate the hydration induced material transfer in the membranes of osmotic pump tablets. SR-FTIR was applied to record and map the chemical information of a micro-region of the membranes, composed of cellulose acetate (CA, as the water insoluble matrix) and polyethylene glycol (PEG, as the soluble pore forming agent and plasticizing agent). The microstructure and chemical change of membranes hydrated for 0, 5, 10 and 30min were measured using SR-FTIR, combined with scanning electronic microscopy and atom force microscopy. The SR-FTIR microspectroscopy results indicated that there was a major change at the absorption range of 2700-3100cm(-1) in the membranes after different periods of hydration time. The absorption bands at 2870-2880cm(-1) and 2950-2960cm(-1) were assigned to represent CA and PEG, respectively. The chemical group signal distribution illustrated by the ratio of PEG to CA demonstrated that the trigger of drug release in the preliminary stage was due to the rapid transfer of PEG into liquid medium with a sharp decrease of PEG in the membranes. The SR-FTIR mapping results have demonstrated the hydration induced material transfer in the membranes of osmotic pump tablets and enabled reassessment of the drug release mechanism of membrane controlled osmotic pump systems. Copyright © 2016 Elsevier B.V. All rights reserved.

A sensitive and rapid assay for 4-aminophenol in paracetamol drug and tablet formulation, by flow injection analysis with spectrophotometric detection.

PubMed

Bloomfield, M S

2002-12-06

4-Aminophenol (4AP) is the primary degradation product of paracetamol which is limited at a low level (50 ppm or 0.005% w/w) in the drug substance by the European, United States, British and German Pharmacopoeias, employing a manual colourimetric limit test. The 4AP limit is widened to 1000 ppm or 0.1% w/w for the tablet product monographs, which quote the use of a less sensitive automated HPLC method. The lower drug substance specification limit is applied to our products, (50 ppm, equivalent to 25 mug 4AP in a tablet containing 500-mg paracetamol) and the pharmacopoeial HPLC assay was not suitable at this low level due to matrix interference. For routine analysis a rapid, automated assay was required. This paper presents a highly sensitive, precise and automated method employing the technique of Flow Injection (FI) analysis to quantitatively assay low levels of this degradant. A solution of the drug substance, or an extract of the tablets, containing 4AP and paracetamol is injected into a solvent carrier stream and merged on-line with alkaline sodium nitroprusside reagent, to form a specific blue derivative which is detected spectrophotometrically at 710 nm. Standard HPLC equipment is used throughout. The procedure is fully quantitative and has been optimised for sensitivity and robustness using a multivariate experimental design (multi-level 'Central Composite' response surface) model. The method has been fully validated and is linear down to 0.01 mug ml(-1). The approach should be applicable to a range of paracetamol products.

Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms.

PubMed

Gioumouxouzis, Christos I; Chatzitaki, Aikaterini-Theodora; Karavasili, Christina; Katsamenis, Orestis L; Tzetzis, Dimitrios; Mystiridou, Emmanouela; Bouropoulos, Nikolaos; Fatouros, Dimitrios G

2018-06-14

Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (μCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.

Continuous twin screw granulation of controlled release formulations with various HPMC grades.

PubMed

Vanhoorne, V; Janssens, L; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

2016-09-25

HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation. The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24h with release profiles close to zero-order. The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC. Copyright © 2016 Elsevier B.V. All rights reserved.

Application of maltodextrin as chiral selector in capillary electrophoresis for quantification of amlodipine enantiomers in commercial tablets.

PubMed

Nojavan, Saeed; Pourmoslemi, Shabnam; Behdad, Hamideh; Fakhari, Ali Reza; Mohammadi, Ali

2014-08-01

Maltodextrin was investigated as a chiral selector in capillary electrophoresis (CE) analysis of amlodipine (AM) enantiomers. For development of a stereoselective CE method, various effective parameters on the enantioseparation were optimized. The best results were achieved on an uncoated fused silica capillary at 20 °C using phosphate buffer (100 mM, pH 4) containing 10% w/v maltodextrin (dextrose equivalent value 4-7). The UV detector was set at 214 nm and a constant voltage of 20 kV was applied. The range of quantitation was 2.5-250 µg/mL (R(2)  > 0.999) for both enantiomers. Intra- (n = 5) and interday (n = 3) relative standard deviation (RSD) values were less than 7%. The limits of quantitation and detection were 1.7 µg/mL and 0.52 µg/mL, respectively. Recoveries of R(+) and S(-) enantiomers from tablet matrix were 97.2% and 97.8%, respectively. The method was applied for the quantification of AM enantiomers in commercial tablets. Also, the enantioseparation capability of heparin was evaluated and the results showed that heparin did not have any chiral selector activity in this study. Copyright © 2014 Wiley Periodicals, Inc.

In vivo evaluation of an oral drug delivery system for peptides based on S-protected thiolated chitosan.

PubMed

Dünnhaupt, Sarah; Barthelmes, Jan; Iqbal, Javed; Perera, Glen; Thurner, Clemens C; Friedl, Heike; Bernkop-Schnürch, Andreas

2012-06-28

The aim of the present study was the development and evaluation in vitro as well as in vivo of an oral delivery system based on a novel type of thiolated chitosan, so-called S-protected thiolated chitosan, for the peptide drug antide. The sulfhydryl ligand thioglycolic acid (TGA) was covalently attached to chitosan (CS) in the first step of modification. In the second step, these thiol groups of thiolated chitosan were protected by disulfide bond formation with the thiolated aromatic residue 6-mercaptonicotinamide (6-MNA). Absorptive transport studies of antide were evaluated ex vivo using rat intestinal mucosa. Matrix tablets of each polymer sample were prepared and their effect on the absorption of antide evaluated in vivo in male Sprague-Dawley rats. In addition, tablets were examined in terms of their disintegration, swelling and drug release behavior. The resulting S-protected thiomer (TGA-MNA) exhibited 840μmol of covalently linked 6-MNA per gram thiomer. Based on the implementation of this hydrophobic ligand on the thiolated backbone, the disintegration behavior was reduced greatly and a controlled release of the peptide could be achieved. Furthermore, permeation studies with TGA-MNA on rat intestine revealed a 4.5-fold enhanced absorptive transport of the peptide in comparison to antide in solution. Additional in vivo studies confirmed the potential of this novel conjugate. Oral administration of antide in solution led to only very small detectable quantities in plasma with an absolute and relative bioavailability (BA) of 0.003 and 0.03%, only. In contrast, with antide incorporated in TGA-MNA matrix tablets an absolute and relative BA of 1.4 and 10.9% could be reached, resulting in a 421-fold increased area under the plasma concentration time curve (AUC) compared to the antide solution. According to these results, S-protected thiolated chitosan as oral drug delivery system might be a valuable tool for improving the bioavailability of peptides. Copyright © 2012 Elsevier B.V. All rights reserved.

An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

PubMed

Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

2015-04-30

Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Biocompatible interpolymer complex matrix tablets - an oral sustained release class-III antidiabetic drug

NASA Astrophysics Data System (ADS)

Ershadul Haque, S. K.; Sheela, A.

2017-11-01

Development of sustained release formulations of Metformin hydrochloride (Met) having low bioavailability and short half-life is one of the frontier areas of research towards achieving novel drug delivery systems. Towards the same, we have prepared interpolymer complexes (IPCs) of chitosan (CH) and two different viscosity grades of hydroxypropyl methylcellulose - HPMC (K4M and K100M) in various ratios, say, 4:6, 2:8, 1:9, respectively. The IPCs are characterized by Fourier transform infrared spectroscopy (FT-IR) and Thermo gravimetric analysis (TGA) techniques. Drug compatibility study is carried out by FT-IR and powder X-ray diffraction (XRD) techniques. The physical properties and drug content of formulated tablets are evaluated and found to be optimum. In addition, in vitro drug release kinetics is carried out at two different pH, say, 1.2 and 6.8. The release pattern from different polymeric matrices is shown in figure below: a) Chitosan, HPMC K4M and HPMC K100M b) IPCs of CH/HPMC K4M in [2:3, 1:4 and 1:9 ratios] c) IPCs of CH/HPMC K100M in [2:3, 1:4 and 1:9 ratios]. From the study, it has been observed that the drug release is sustained for a period of 12h in 1:9 ratio of CH: K100M IPC due to the formation of complex network matrix.

Evaluation of the resistance of a geopolymer-based drug delivery system to tampering.

PubMed

Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne

2014-04-25

Tamper-resistance is an important property of controlled-release formulations of opioid drugs. Tamper-resistant formulations aim to increase the degree of effort required to override the controlled release of the drug molecules from extended-release formulations for the purpose of non-medical use. In this study, the resistance of a geopolymer-based formulation to tampering was evaluated by comparing it with a commercial controlled-release tablet using several methods commonly used by drug abusers. Because of its high compressive strength and resistance to heat, much more effort and time was required to extract the drug from the geopolymer-based formulation. Moreover, in the drug-release test, the geopolymer-based formulation maintained its controlled-release characteristics after milling, while the drug was released immediately from the milled commercial tablets, potentially resulting in dose dumping. Although the tampering methods used in this study does not cover all methods that abuser could access, the results obtained by the described methods showed that the geopolymer matrix increased the degree of effort required to override the controlled release of the drug, suggesting that the formulation has improved resistance to some common drug-abuse tampering methods. The geopolymer matrix has the potential to make the opioid product less accessible and attractive to non-medical users. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of beta-cyclodextrin complexation on glipizide release from hydroxypropyl methylcellulose matrix tablets.

PubMed

Shivakumar, H N; Desai, B G; Pandya, Saumyak; Karki, S S

2007-01-01

Glipizide was complexed with beta-cyclodextrin in an attempt to enhance the drug solubility. The phase solubility diagram was classified as A(L) type, which was characterized by an apparent 1:1 stability constant that had a value of 413.82 M(-1). Fourier transform infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry and proton nuclear magnetic resonance spectral analysis indicated considerable interaction between the drug and beta-cyclodextrin. A 2(3) factorial design was employed to prepare hydroxypropyl methylcellulose (HPMC) matrix tablets containing the drug or its complex. The effect of the total polymer loads (X1), levels of HPMC K100LV (X9), and complexation (X3) on release at first hour (Y1), 24 h (Y2), time taken for 50% release (Y3), and diffusion exponent (Y4) was systematically analyzed using the F test. Mathematical models containing only the significant terms (P < 0.05) were generated for each parameter by multiple linear regression analysis and analysis of variance. Complexation was found to exert a significant effect on Y1, Y2, and Y3, whereas total polymer loads significantly influenced all the responses. The models generated were validated by developing two new formulations with a combination of factors within the experimental domain. The experimental values of the response parameters were in close agreement with the predicted values, thereby proving-the validity of the generated mathematical models.

Robust stability of second-order systems

NASA Technical Reports Server (NTRS)

Chuang, C.-H.

1993-01-01

A feedback linearization technique is used in conjunction with passivity concepts to design robust controllers for space robots. It is assumed that bounded modeling uncertainties exist in the inertia matrix and the vector representing the coriolis, centripetal, and friction forces. Under these assumptions, the controller guarantees asymptotic tracking of the joint variables. A Lagrangian approach is used to develop a dynamic model for space robots. Closed-loop simulation results are illustrated for a simple case of a single link planar manipulator with freely floating base.

Solidification of floating organic droplet in dispersive liquid-liquid microextraction as a green analytical tool.

PubMed

Mansour, Fotouh R; Danielson, Neil D

2017-08-01

Dispersive liquid-liquid microextraction (DLLME) is a special type of microextraction in which a mixture of two solvents (an extracting solvent and a disperser) is injected into the sample. The extraction solvent is then dispersed as fine droplets in the cloudy sample through manual or mechanical agitation. Hence, the sample is centrifuged to break the formed emulsion and the extracting solvent is manually separated. The organic solvents commonly used in DLLME are halogenated hydrocarbons that are highly toxic. These solvents are heavier than water, so they sink to the bottom of the centrifugation tube which makes the separation step difficult. By using solvents of low density, the organic extractant floats on the sample surface. If the selected solvent such as undecanol has a freezing point in the range 10-25°C, the floating droplet can be solidified using a simple ice-bath, and then transferred out of the sample matrix; this step is known as solidification of floating organic droplet (SFOD). Coupling DLLME to SFOD combines the advantages of both approaches together. The DLLME-SFOD process is controlled by the same variables of conventional liquid-liquid extraction. The organic solvents used as extractants in DLLME-SFOD must be immiscible with water, of lower density, low volatility, high partition coefficient and low melting and freezing points. The extraction efficiency of DLLME-SFOD is affected by types and volumes of organic extractant and disperser, salt addition, pH, temperature, stirring rate and extraction time. This review discusses the principle, optimization variables, advantages and disadvantages and some selected applications of DLLME-SFOD in water, food and biomedical analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Floating-Point Modules Targeted for Use with RC Compilation Tools

NASA Technical Reports Server (NTRS)

Sahin, Ibrahin; Gloster, Clay S.

2000-01-01

Reconfigurable Computing (RC) has emerged as a viable computing solution for computationally intensive applications. Several applications have been mapped to RC system and in most cases, they provided the smallest published execution time. Although RC systems offer significant performance advantages over general-purpose processors, they require more application development time than general-purpose processors. This increased development time of RC systems provides the motivation to develop an optimized module library with an assembly language instruction format interface for use with future RC system that will reduce development time significantly. In this paper, we present area/performance metrics for several different types of floating point (FP) modules that can be utilized to develop complex FP applications. These modules are highly pipelined and optimized for both speed and area. Using these modules, and example application, FP matrix multiplication, is also presented. Our results and experiences show, that with these modules, 8-10X speedup over general-purpose processors can be achieved.

Correcting for surface topography in X-ray fluorescence imaging

PubMed Central

Geil, E. C.; Thorne, R. E.

2014-01-01

Samples with non-planar surfaces present challenges for X-ray fluorescence imaging analysis. Here, approximations are derived to describe the modulation of fluorescence signals by surface angles and topography, and suggestions are made for reducing this effect. A correction procedure is developed that is effective for trace element analysis of samples having a uniform matrix, and requires only a fluorescence map from a single detector. This procedure is applied to fluorescence maps from an incised gypsum tablet. PMID:25343805

Effect drug loading process on dissolution mechanism of encapsulated amoxicillin trihydrate in hydrogel semi-IPN chitosan methyl cellulose with pore forming agent KHCO3 as a floating drug delivery system

NASA Astrophysics Data System (ADS)

Fithawati, Garnis; Budianto, Emil

2018-04-01

Common treatment for Helicobacter pylori by repeated oral consumption of amoxicillin trihydrate is not effective. Amoxicillin trihydrate has a very short residence time in stomach which leads into its ineffectiveness. Residence time of amoxicillin trihydrate can be improved by encapsulating amoxicillin trihydrate into a floating drug delivery system. In this study, amoxicillin trihydrate is encapsulated into hydrogel semi-IPN chitosan methyl cellulose matrix as a floating drug delivery system and then treated with 20% KHCO3 as pore forming agent. Drug loading process used are in-situ loading and post loading. In-situ loading process has higher efficiency percentage and dissolution percentage than post loading process. In-situ loading process resulted 100% efficiency with 92,70% dissolution percentage. Post loading process resulted 98,7% efficiency with 90,42% dissolution percentage. Mechanism of drug dissolution study by kinetics approach showed both in-situ loading process and post loading process are diffusion and degradation process (n=0,4913) and (n=0,4602) respectively. These results are supported by characterization data from optical microscope and scanning electron microscopy (SEM). Data from optical microscope showed both loading process resulted in coarser hydrogel surface. Characterization using SEM showed elongated pores in both loading process after dissolution test.

A comparative pharmacokinetic study of three flavonoids and three anthraquinones in normal and gastrointestinal motility disorders rat plasma after the oral administration of Wei-Chang-Shu tablet using high-performance liquid chromatography-tandem mass spectrometry.

PubMed

Ren, Yan; Zhao, Weiwei; Zhao, Juanjuan; Chen, Xiangming; Yu, Chen; Liu, Mengan

2017-11-01

A simple, fast and reliable high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent Zorbax SB-C 18 column (4.6 × 150 mm, 5 μm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity (r > 0.99), intra-/inter-day precision (1.0-10.1%), accuracy (relative error, <7.6%), stability (0.6-13.2%), extract recovery (74.9-91.9%) and matrix effect (89.1-109%). The lower limits of quantification of the six analytes varied from 0.92 to 10.4 ng/mL. The validated method was successfully applied to compare the pharmacokinetic properties of Wei-Chang-Shu tablet in normal rats and in rats with gastrointestinal motility disorders. The results indicated that there were obvious differences in the pharmacokinetic behavior between normal and model rats. This study will be helpful in the clinical application of Wei-Chang-Shu tablet. Copyright © 2017 John Wiley & Sons, Ltd.

Detection of Lipitor counterfeits: a comparison of NIR and Raman spectroscopy in combination with chemometrics.

PubMed

de Peinder, P; Vredenbregt, M J; Visser, T; de Kaste, D

2008-08-05

Research has been carried on the feasibility of near infrared (NIR) and Raman spectroscopy as rapid screening methods to discriminate between genuine and counterfeits of the cholesterol-lowering medicine Lipitor. Classification, based on partial least squares discriminant analysis (PLS-DA) models, appears to be successful for both spectroscopic techniques, irrespective of whether atorvastatine or lovastatine has been used as the active pharmaceutical ingredient (API). The discriminative power of the NIR model, in particular, largely relies on the spectral differences of the tablet matrix. This is due to the relative large sample volume that is probed with NIR and the strong spectroscopic activity of the excipients. PLS-DA models based on NIR or Raman spectra can also be applied to distinguish between atorvastatine and lovastatine as the API used in the counterfeits tested in this study. A disadvantage of Raman microscopy for this type of analysis is that it is primarily a surface technique. As a consequence spectra of the coating and the tablet core might differ. Besides, spectra may change with the position of the laser in case the sample is inhomogeneous. However, the robustness of the PLS-DA models turned out to be sufficiently large to allow a reliable discrimination. Principal component analysis (PCA) of the spectra revealed that the conditions, at which tablets have been stored, affect the NIR data. This effect is attributed to the adsorption of water from the atmosphere after unpacking from the blister. It implies that storage conditions should be taken into account when the NIR technique is used for discriminating purposes. However, in this study both models based on NIR spectra and Raman data enabled reliable discrimination between genuine and counterfeited Lipitor tablets, regardless of their storage conditions.

In vitro dissolution kinetic study of theophylline from hydrophilic and hydrophobic matrices.

PubMed

Maswadeh, Hamzah M; Semreen, Mohammad H; Abdulhalim, Abdulatif A

2006-01-01

Oral dosage forms containing 300 mg theophylline in matrix type tablets, were prepared by direct compression method using two kinds of matrices, glycerylbehenate (hydrophobic), and (hydroxypropyl)methyl cellulose (hydrophilic). The in vitro release kinetics of these formulations were studied at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process were studied by analyzing the dissolution data using four kinetic equations, the zero-order equation, the first-order equation, the Higuchi square root equation and the Hixson-Crowell cube root law. The analysis of the dissolution kinetic data for the theophylline preparations in this study shows that it follows the first order kinetics and the release process involves erosion / diffusion and an alteration in the surface area and diameter of the matrix system, as well as in the diffusion path length from the matrix drug load during the dissolution process. This relation is best described by the use of both the first-order equation and the Hixson-Crowell cube root law.

Effect of hydrophobic inclusions on polymer swelling kinetics studied by magnetic resonance imaging.

PubMed

Gajdošová, Michaela; Pěček, Daniel; Sarvašová, Nina; Grof, Zdeněk; Štěpánek, František

2016-03-16

The rate of drug release from polymer matrix-based sustained release formulations is often controlled by the thickness of a gel layer that forms upon contact with dissolution medium. The effect of formulation parameters on the kinetics of elementary rate processes that contribute to gel layer formation, such as water ingress, polymer swelling and erosion, is therefore of interest. In the present work, gel layer formation has been investigated by magnetic resonance imaging (MRI), which is a non-destructive method allowing direct visualization of effective water concentration inside the tablet and its surrounding. Using formulations with Levetiracetam as the active ingredient, HPMC as a hydrophilic matrix former and carnauba wax (CW) as a hydrophobic component in the matrix system, the effect of different ratios of these two ingredients on the kinetics of gel formation (MRI) and drug release (USP 4 like dissolution test) has been investigated and interpreted using a mathematical model. Copyright © 2016 Elsevier B.V. All rights reserved.

Dual-mechanism gastroretentive drug delivery system loaded with an amorphous solid dispersion prepared by hot-melt extrusion.

PubMed

Vo, Anh Q; Feng, Xin; Pimparade, Manjeet; Ye, Xinyou; Kim, Dong Wuk; Martin, Scott T; Repka, Michael A

2017-05-01

In the present study, we aimed to prepare a gastroretentive drug delivery system that would be both highly resistant to gastric emptying via multiple mechanisms and would also potentially induce in situ supersaturation. The bioadhesive floating pellets, loaded with an amorphous solid dispersion, were prepared in a single step of hot-melt extrusion technology. Hydroxypropyl cellulose (Klucel™ MF) and hypromellose (Benecel™ K15M) were used as matrix-forming polymers, and felodipine was used as the model drug. The foam pellets were fabricated based on the expansion of CO 2 , which was generated from sodium bicarbonate during the melt-extrusion process. A 2 n full factorial experimental design was utilized to investigate the effects of formulation compositions to the pellet properties. The melt-extrusion process transformed the crystalline felodipine into an amorphous state that was dispersed and "frozen" in the polymer matrix. All formulations showed high porosity and were able to float immediately, without lag time, on top of gastric fluid, and maintained their buoyancy over 12h. The pellet-specific floating force, which could be as high as 4800μN/g, increased significantly during the first hour, and was relatively stable until 9h. The sodium bicarbonate percentage was found to be most significantly effect to the floating force. The ex vivo bioadhesion force of the pellets to porcine stomach mucosa was approximately 5mN/pellet, which was more than five times higher than the gravitation force of the pellet saturated with water. Drug release was well controlled up to 12h in the sink condition of 0.5% sodium lauryl sulphate in 0.1N HCl. The dissolution at 1, 3, 5, and 8h were 5-12%, 25-45%, 55-80%, and ≥75% respectively for all 11 formulations. In biorelevant dissolution medium, a supersaturated solution was formed, and the concentration was maintained at around 2μg/mL, approximately 10-folds higher than that of the pure felodipine. All input factors significantly affected dissolution in the first 3h, but afterwards, only drug load and hypromellose (HPMC) content had significant effects. The prepared drug delivery system has great potential in overcoming low and fluctuating bioavailability of poorly soluble drugs. Felodipine (PubChem CID: 3333); hypromellose (PubChem CID: 57503849), hydroxypropyl cellulose (PubChem CID: 71306830), sodium bicarbonate (PubChem CID: 516892); sodium carbonate (PubChem CID: 10340). Copyright © 2017 Elsevier B.V. All rights reserved.

Electro-hydrodynamic printing of drugs onto edible substrates

NASA Astrophysics Data System (ADS)

Shen, Yueyang; Elele, Ezinwa; Palle, Prashanth; Khusid, Boris; Basaran, Osman; McGough, Patrick T.; Collins, Robert T.

2009-11-01

While most existing drugs are manufactured as tablets using powder processing techniques, there is growing interest in printing drops containing pharmaceutical actives on edible substrates. We have developed a drop-on-demand (DOD) printing method appropriate for either replacing existing manufacturing platforms or enabling personalized medicine that overcomes the various critical challenges facing current DOD technologies. To eliminate adverse effects of electro-chemical reactions at the fluid-electrode interface, the fluid is infused into an electrically insulating nozzle to form a pendant drop that serves as a floating electrode capacitively coupled to external electrodes. A liquid bridge is formed and broken as the voltage applied at the electrode is varied in time. This gentle method for drop deposition has been demonstrated to operate with fluids spanning over three orders of magnitude in viscosity and conductivity. The proposed method has the potential for the evolving field of pharmaceutical and biomedical applications requiring the deposition of fluids at the exact locations with high volume accuracy.

The use of thiolated polymers as carrier matrix in oral peptide delivery--proof of concept.

PubMed

Bernkop-Schnürch, Andreas; Pinter, Yvonne; Guggi, Davide; Kahlbacher, Hermann; Schöffmann, Gudrun; Schuh, Maximilian; Schmerold, Ivo; Del Curto, Maria Dorly; D'Antonio, Mauro; Esposito, Pierandrea; Huck, Christian

2005-08-18

It was the aim of this study to develop an oral delivery system for the peptide drug antide. The stability of the therapeutic peptide towards gastrointestinal peptidases was evaluated. The therapeutic agent and the permeation mediator glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) and compressed to tablets. Drug release studies were performed in the dissolution test apparatus according to the Pharmacopoeia Europea using the paddle method and demineralized water as release medium. In order to avoid mucoadhesion of these delivery systems already in the oral cavity and oesophagus tablets were coated with a triglyceride. These tablets were orally given to pigs (weight: 50+/-2 kg; Edelschwein Pietrain). Moreover, antide was administered intravenously, subcutaneously and orally in solution. Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In contrast, antide was rapidly degraded by elastase. Consequently a stomach-targeted delivery system was designed. Drug release studies demonstrated an almost zero-order controlled release of antide over 8 h. In vivo studies demonstrated a relative bioavailability of 34.4% for the subcutaneous administration. Oral administration of antide in solution led to no detectable concentrations of the drug in plasma at all. In contrast, administering antide being incorporated in the thiolated polymer resulted in a significant uptake of the peptide. The absolute and relative bioavailability was determined to be 1.1% and 3.2%, respectively.

Development of buccal drug delivery systems based on a thiolated polymer.

PubMed

Langoth, Nina; Kalbe, Jochen; Bernkop-Schnürch, Andreas

2003-02-18

The purpose of the present study was to investigate the benefit of thiolated polymers (thiomers) for the development of buccal drug delivery systems. L-Cysteine was thereby covalently attached to polycarbophil (PCP) mediated by a carbodiimide. The resulting conjugate displayed 140.5+/-8.4 microM thiol groups per gram polymer. Disintegration studies were carried out with tablets based on unmodified polymer and conjugated polymer, respectively. Due to the formation of disulfide bonds within the thiolated polymer, the stability of matrix-tablets based on this polymer was strongly improved. Additionally tensile studies were carried out, which were in good correlation with further results obtained by mucoadhesion studies, using the rotating cylinder method. These results showed that tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding control. Moreover, the enzyme inhibitory properties of polymers were evaluated as well. Thiolated PCP increased the stability of the synthetic substrate for aminopeptidase N-leu-p-nitroanilide (N-leu-pNA) and the model drug leucin-enkephalin (leu-enkephalin) against enzymatic degradation on buccal mucosa. Due to the use of thiolated polymers also a controlled drug release for leu-enkephalin was guaranteed over a time period for more than 24 h. Results of the present studies suggest that thiolated polymers represent a very useful tool for buccal delivery of peptide drugs.

The influence of granulation on super disintegrant performance.

PubMed

Zhao, Na; Augsburger, Larry L

2006-02-01

The purpose of this study is to identify the causes of efficiency loss of super disintegrants following granulation or reworking. Two processes, precompression and prewetting, were proposed to simulate the processes during dry and wet granulation, respectively. The disintegration efficiency of the resulting disintegrant granules was tested in model formulations composed of dicalcium phosphate and lactose with the unprocessed disintegrants as controls. No significant difference was shown in the intrinsic swelling and the water uptake abilities of all super disintegrants following dry granulation. However, a significant decrease was observed for both Primojel and Polyplasdone XL10 in the rate of water being absorbed into the tablet matrix following wet granulation, but not for Ac-Di-Sol. United States Pharmacopeia (USP) disintegration testing without disc revealed a significant increase in disintegration time for tablets formulated with dry granulated Primojel and Polyplasdone XL10 and all wet granulated disintegrants. The increase in particle size following granulation appears to be the cause of the loss in disintegration efficiency. In conclusion, Ac-Di-Sol is less affected by both precompression and prewetting. The efficiency of Primojel and Polyplasdone XL10 is highly dependent on their particle size. Descreasing the particle size tends to increase their efficiency. Due to the size increase following granulation, a higher addition level of super disintegrant is required to ensure fast and uniform disintegration of tablets prepared by granulation.

The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets.

PubMed

Kulinowski, Piotr; Hudy, Wiktor; Mendyk, Aleksander; Juszczyk, Ewelina; Węglarz, Władysław P; Jachowicz, Renata; Dorożyński, Przemysław

2016-06-01

In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.

Efficient algorithms for computing a strong rank-revealing QR factorization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu, M.; Eisenstat, S.C.

1996-07-01

Given an m x n matrix M with m {ge} n, it is shown that there exists a permutation {Pi} and an integer k such that the QR factorization given by equation (1) reveals the numerical rank of M: the k x k upper-triangular matrix A{sub k} is well conditioned, norm of (C{sub k}){sub 2} is small, and B{sub k} is linearly dependent on A{sub k} with coefficients bounded by a low-degree polynomial in n. Existing rank-revealing QR (RRQR) algorithms are related to such factorizations and two algorithms are presented for computing them. The new algorithms are nearly as efficientmore » as QR with column pivoting for most problems and take O(mn{sup 2}) floating-point operations in the worst case.« less

A Novel Acidic Matrix Protein, PfN44, Stabilizes Magnesium Calcite to Inhibit the Crystallization of Aragonite*

PubMed Central

Pan, Cong; Fang, Dong; Xu, Guangrui; Liang, Jian; Zhang, Guiyou; Wang, Hongzhong; Xie, Liping; Zhang, Rongqing

2014-01-01

Magnesium is widely used to control calcium carbonate deposition in the shell of pearl oysters. Matrix proteins in the shell are responsible for nucleation and growth of calcium carbonate crystals. However, there is no direct evidence supporting a connection between matrix proteins and magnesium. Here, we identified a novel acidic matrix protein named PfN44 that affected aragonite formation in the shell of the pearl oyster Pinctada fucata. Using immunogold labeling assays, we found PfN44 in both the nacreous and prismatic layers. In shell repair, PfN44 was repressed, whereas other matrix proteins were up-regulated. Disturbing the function of PfN44 by RNAi led to the deposition of porous nacreous tablets with overgrowth of crystals in the nacreous layer. By in vitro circular dichroism spectra and fluorescence quenching, we found that PfN44 bound to both calcium and magnesium with a stronger affinity for magnesium. During in vitro calcium carbonate crystallization and calcification of amorphous calcium carbonate, PfN44 regulated the magnesium content of crystalline carbonate polymorphs and stabilized magnesium calcite to inhibit aragonite deposition. Taken together, our results suggested that by stabilizing magnesium calcite to inhibit aragonite deposition, PfN44 participated in P. fucata shell formation. These observations extend our understanding of the connections between matrix proteins and magnesium. PMID:24302723

What is the difference in organic matrix of aragonite vs. vaterite polymorph in natural shell and pearl? Study of the pearl-forming freshwater bivalve mollusc Hyriopsis cumingii.

PubMed

Ma, Yufei; Berland, Sophie; Andrieu, Jean-Pierre; Feng, Qingling; Bédouet, Laurent

2013-04-01

Aragonite pearl, vaterite pearl and shell nacre of the freshwater mollusc Hyriopsis cumingii (Zhejiang province, China) were chosen to analyze microstructure and organic composition in the different habits of calcium carbonate. SEM and TEM were used to reveal the microstructure and mineralogical phase. We found that tablets in vaterite exhibited more irregular texture and were packaged with more organic matrices than in aragonite forms. Then a peculiar method was introduced to extract water soluble matrix (WSM), acid soluble matrix (ASM) and acid insoluble matrix (AIM) from the three samples, and biochemical analysis of these organic matrixes involved in crystal formation and polymorph selection was carried out. High performance liquid chromatography (HPLC) confirms the hydrophobic pattern of the organic matrix intermingled with mineral, the opposite of the early mobilizable water soluble fraction. Amino acid composition confirms hydrophobic residues as major components of all the extracts, but it reveals an imbalance in acidic residues rates in WSM vs. ASM and in aragonite vs. vaterite. Electrophoresis gives evidence for signatures in proteins with a 140 kDa material specific for aragonite in WSM. Conversely all ASM extracts reveal the presence of about 55 kDa components, including a discrete band in vaterite extract. Copyright © 2012 Elsevier B.V. All rights reserved.

Modeling Quasi-Static and Fatigue-Driven Delamination Migration

NASA Technical Reports Server (NTRS)

De Carvalho, N. V.; Ratcliffe, J. G.; Chen, B. Y.; Pinho, S. T.; Baiz, P. M.; Tay, T. E.

2014-01-01

An approach was proposed and assessed for the high-fidelity modeling of progressive damage and failure in composite materials. It combines the Floating Node Method (FNM) and the Virtual Crack Closure Technique (VCCT) to represent multiple interacting failure mechanisms in a mesh-independent fashion. Delamination, matrix cracking, and migration were captured failure and migration criteria based on fracture mechanics. Quasi-static and fatigue loading were modeled within the same overall framework. The methodology proposed was illustrated by simulating the delamination migration test, showing good agreement with the available experimental data.

Bit-parallel arithmetic in a massively-parallel associative processor

NASA Technical Reports Server (NTRS)

Scherson, Isaac D.; Kramer, David A.; Alleyne, Brian D.

1992-01-01

A simple but powerful new architecture based on a classical associative processor model is presented. Algorithms for performing the four basic arithmetic operations both for integer and floating point operands are described. For m-bit operands, the proposed architecture makes it possible to execute complex operations in O(m) cycles as opposed to O(m exp 2) for bit-serial machines. A word-parallel, bit-parallel, massively-parallel computing system can be constructed using this architecture with VLSI technology. The operation of this system is demonstrated for the fast Fourier transform and matrix multiplication.

Application of the combinative particle size reduction technology H 42 to produce fast dissolving glibenclamide tablets.

PubMed

Salazar, Jaime; Müller, Rainer H; Möschwitzer, Jan P

2013-07-16

Standard particle size reduction techniques such as high pressure homogenization or wet bead milling are frequently used in the production of nanosuspensions. The need for micronized starting material and long process times are their evident disadvantages. Combinative particle size reduction technologies have been developed to overcome the drawbacks of the standard techniques. The H 42 combinative technology consists of a drug pre-treatment by means of spray-drying followed by standard high pressure homogenization. In the present paper, spray-drying process parameters influencing the diminution effectiveness, such as drug and surfactant concentration, were systematically analyzed. Subsequently, the untreated and pre-treated drug powders were homogenized for 20 cycles at 1500 bar. For untreated, micronized glibenclamide, the particle size analysis revealed a mean particle size of 772 nm and volume-based size distribution values of 2.686 μm (d50%) and 14.423 μm (d90%). The use of pre-treated material (10:1 glibenclamide/docusate sodium salt ratio spray-dried as ethanolic solution) resulted in a mean particle size of 236 nm and volume-based size distribution values of 0.131 μm (d50%) and 0.285 μm (d90%). These results were markedly improved compared to the standard process. The nanosuspensions were further transferred into tablet formulations. Wet granulation, freeze-drying and spray-drying were investigated as downstream methods to produce dry intermediates. Regarding the dissolution rate, the rank order of the downstream processes was as follows: Spray-drying>freeze-drying>wet granulation. The best drug release (90% within 10 min) was obtained for tablets produced with spray-dried nanosuspension containing 2% mannitol as matrix former. In comparison, the tablets processed with micronized glibenclamide showed a drug release of only 26% after 10 min. The H 42 combinative technology could be successfully applied in the production of small drug nanocrystals. A nanosuspension transfer to tablets that maintained the fast dissolution properties of the drug nanocrystals was successfully achieved. Copyright © 2013 Elsevier B.V. All rights reserved.

Crystal growth formation in melt extrudates.

PubMed

Bruce, Caroline; Fegely, Kurt A; Rajabi-Siahboomi, Ali R; McGinity, James W

2007-08-16

The purpose of the study was to investigate the physical state of hot-melt extruded guaifenesin tablets containing either Acryl-EZE or Eudragit L100-55 and to study the physicochemical factors influencing crystal growth of guaifenesin on the surface of the extrudates. The powder mixtures containing Acryl-EZE were extruded on a single-screw Randcastle Microtruder at 20rpm and at temperatures of 90, 95, 110 degrees C (zones 1, 2, 3, respectively) and 115 degrees C (die), before being manually cut into tablets (250+/-5mg). Extrudates containing Eudragit L100-55, TEC and guaifenesin were extruded at temperatures ranging from 60 to 115 degrees C. Modulated differential calorimetry (DSC) was used to demonstrate the plasticizing effect of guaifenesin on Eudragit L100-55. Powder X-ray diffraction (PXRD) showed that while the drug powder is crystalline, extrudates containing up to 25% drug exhibited an amorphous diffraction profile. Extrudates containing higher drug concentrations showed an amorphous profile with some crystalline peaks corresponding to guaifenesin, indicating that the limit of solubility of drug in the matrix had been exceeded. Scanning electron microscopy was used to demonstrate that drug crystallization was a surface phenomenon and dependent on the drug concentration. In vitro dissolution testing showed no effect of surface crystallization of guaifenesin on drug release rates of extruded matrix tablets. The influence of hydrophilic polymeric additives including PVP K25, polycarbophil, PEG 3,350, poloxamer 188 or poly(ethylene oxide) as crystal growth inhibitors was investigated at a level of 10% based on the drug content. The extent of crystal growth was reduced for all additives. Complete drug release in pH 6.8 phosphate buffer was prolonged from 4h in extrudates containing Acryl-EZE and guaifenesin to 8h in extrudates containing Eudragit L100-55, TEC and guaifenesin. Drug release in extrudates containing Eudragit L100-55 and guaifenesin was not affected by the presence of hydrophilic additives present at 10% based on the drug content. In vitro drug release studies showed no significant change during storage for up to 6 months at 25 degrees C/60% relative humidity and 40 degrees C/75% relative humidity.

In vitro quantitative ((1))H and ((19))F nuclear magnetic resonance spectroscopy and imaging studies of fluvastatin™ in Lescol® XL tablets in a USP-IV dissolution cell.

PubMed

Zhang, Qilei; Gladden, Lynn; Avalle, Paolo; Mantle, Michael

2011-12-20

Swellable polymeric matrices are key systems in the controlled drug release area. Currently, the vast majority of research is still focused on polymer swelling dynamics. This study represents the first quantitative multi-nuclear (((1))H and ((19))F) fast magnetic resonance imaging study of the complete dissolution process of a commercial (Lescol® XL) tablet, whose formulation is based on the hydroxypropyl methylcellulose (HPMC) polymer under in vitro conditions in a standard USP-IV (United States Pharmacopeia apparatus IV) flow-through cell that is incorporated into high field superconducting magnetic resonance spectrometer. Quantitative RARE ((1))H magnetic resonance imaging (MRI) and ((19))F nuclear magnetic resonance (NMR) spectroscopy and imaging methods have been used to give information on: (i) dissolution media uptake and hydrodynamics; (ii) active pharmaceutical ingredient (API) mobilisation and dissolution; (iii) matrix swelling and dissolution and (iv) media activity within the swelling matrix. In order to better reflect the in vivo conditions, the bio-relevant media Simulated Gastric Fluid (SGF) and Fasted State Simulated Intestinal Fluid (FaSSIF) were used. A newly developed quantitative ultra-fast MRI technique was applied and the results clearly show the transport dynamics of media penetration and hydrodynamics along with the polymer swelling processes. The drug dissolution and mobility inside the gel matrix was characterised, in parallel to the ((1))H measurements, by ((19))F NMR spectroscopy and MRI, and the drug release profile in the bulk solution was recorded offline by UV spectrometer. We found that NMR spectroscopy and 1D-MRI can be uniquely used to monitor the drug dissolution/mobilisation process within the gel layer, and the results from ((19))F NMR spectra indicate that in the gel layer, the physical mobility of the drug changes from "dissolved immobilised drug" to "dissolved mobilised drug". Copyright © 2011 Elsevier B.V. All rights reserved.

Distribution of a low dose compound within pharmaceutical tablet by using multivariate curve resolution on Raman hyperspectral images.

PubMed

Boiret, Mathieu; de Juan, Anna; Gorretta, Nathalie; Ginot, Yves-Michel; Roger, Jean-Michel

2015-01-25

In this work, Raman hyperspectral images and multivariate curve resolution-alternating least squares (MCR-ALS) are used to study the distribution of actives and excipients within a pharmaceutical drug product. This article is mainly focused on the distribution of a low dose constituent. Different approaches are compared, using initially filtered or non-filtered data, or using a column-wise augmented dataset before starting the MCR-ALS iterative process including appended information on the low dose component. In the studied formulation, magnesium stearate is used as a lubricant to improve powder flowability. With a theoretical concentration of 0.5% (w/w) in the drug product, the spectral variance contained in the data is weak. By using a principal component analysis (PCA) filtered dataset as a first step of the MCR-ALS approach, the lubricant information is lost in the non-explained variance and its associated distribution in the tablet cannot be highlighted. A sufficient number of components to generate the PCA noise-filtered matrix has to be used in order to keep the lubricant variability within the data set analyzed or, otherwise, work with the raw non-filtered data. Different models are built using an increasing number of components to perform the PCA reduction. It is shown that the magnesium stearate information can be extracted from a PCA model using a minimum of 20 components. In the last part, a column-wise augmented matrix, including a reference spectrum of the lubricant, is used before starting MCR-ALS process. PCA reduction is performed on the augmented matrix, so the magnesium stearate contribution is included within the MCR-ALS calculations. By using an appropriate PCA reduction, with a sufficient number of components, or by using an augmented dataset including appended information on the low dose component, the distribution of the two actives, the two main excipients and the low dose lubricant are correctly recovered. Copyright © 2014 Elsevier B.V. All rights reserved.

A sparse matrix-vector multiplication based algorithm for accurate density matrix computations on systems of millions of atoms

NASA Astrophysics Data System (ADS)

Ghale, Purnima; Johnson, Harley T.

2018-06-01

We present an efficient sparse matrix-vector (SpMV) based method to compute the density matrix P from a given Hamiltonian in electronic structure computations. Our method is a hybrid approach based on Chebyshev-Jackson approximation theory and matrix purification methods like the second order spectral projection purification (SP2). Recent methods to compute the density matrix scale as O(N) in the number of floating point operations but are accompanied by large memory and communication overhead, and they are based on iterative use of the sparse matrix-matrix multiplication kernel (SpGEMM), which is known to be computationally irregular. In addition to irregularity in the sparse Hamiltonian H, the nonzero structure of intermediate estimates of P depends on products of H and evolves over the course of computation. On the other hand, an expansion of the density matrix P in terms of Chebyshev polynomials is straightforward and SpMV based; however, the resulting density matrix may not satisfy the required constraints exactly. In this paper, we analyze the strengths and weaknesses of the Chebyshev-Jackson polynomials and the second order spectral projection purification (SP2) method, and propose to combine them so that the accurate density matrix can be computed using the SpMV computational kernel only, and without having to store the density matrix P. Our method accomplishes these objectives by using the Chebyshev polynomial estimate as the initial guess for SP2, which is followed by using sparse matrix-vector multiplications (SpMVs) to replicate the behavior of the SP2 algorithm for purification. We demonstrate the method on a tight-binding model system of an oxide material containing more than 3 million atoms. In addition, we also present the predicted behavior of our method when applied to near-metallic Hamiltonians with a wide energy spectrum.

Effects of pore forming agents of potassium bicarbonate and drug loading method against dissolution mechanisms of amoxicillin drugs encapsulated in hydrogel full-Ipn chitosan-poly(N-vinylcaprolactam) as a floating drug delivery system

NASA Astrophysics Data System (ADS)

Aini, Nurul; Rahayu, Dyah Utami Cahyaning; Budianto, Emil

2018-04-01

The limitation of amoxicillin trihydrate in the treatment of H. pylori bacteria is relatively short retention time in the stomach. The FDDS (Floating Drug Delivery System) amoxicillin trihydrate into a chitosan-poly(N-vinylcaprolactam) full-Ipn hydrogel matrix using a pore-forming agent KHCO3 is expected to overcome these limitations. The pore-forming agent to be used is 15% KHCO3 compound. Chemical kinetics approach is performed to determine the dissolution mechanism of amoxicillin trihydrate from K-PNVCL hydrogel in vitro on gastric pH and characterization using SEM performed to confirm the dissolution mechanism. Hydrogels with the addition of pore-forming agents will be loading in situ loading and post loading. Fourier Transform Infra Red (FTIR) spectroscopy was used to characterize K-PNVCL and UV-Vis hydrogels used to calculate the efficiency of encapsulation and drug dissolution rate in K-PNVCL hydrogel. Hydrogel K-PNVCL / KHCO3 that encapsulated by in situ loading method resulted in an encapsulation efficiency of 93.5% and dissolution of 93.4%. While the Hydrogel K-PNVCL / KHCO3 which is drug encapsulation resulted in an encapsulation efficiency of 87.2% with dissolution of 81.5%. Chemical kinetics approach to in situ encapsulation of loading and post loading shows the dissolution mechanism occurring in the K-PNVCL / KHCO3 hydrogel matrix occurs by diffusion. Observation using optical microscope and SEM showed the mechanism of drug dissolution in Hydrogel K-PNVCL occurred by diffusion.

Sensitive determination of cadmium using solidified floating organic drop microextraction-slotted quartz tube-flame atomic absorption spectroscopy.

PubMed

Akkaya, Erhan; Chormey, Dotse Selali; Bakırdere, Sezgin

2017-09-20

In this study, solidified floating organic drop microextraction (SFODME) by 1-undecanol was combined with slotted quartz tube flame atomic absorption spectrometry (SQT-FAAS) for the determination of cadmium at trace levels. Formation of a complex with 4,4'-dimethyl-2,2'-bipyridine facilitated the extraction of cadmium from aqueous solutions. Several chemical variables were optimized in order to obtain high extraction outputs. Parameters such as concentration of the ligand, pH, and amount of buffer solution were optimized to enhance the formation of cadmium complex. The SFODME method was assisted by dispersion of extractor solvent into aqueous solutions using 2-propanol. Under the optimum extraction and instrumental conditions, the limit of detection and limit of quantitation values obtained for cadmium using the combined methods (SFODME-SQT-FAAS) were found to be 0.4 and 1.3 μg L -1 , respectively. Matrix effects on the method were also examined for tap water and wastewater, and spiked recovery results were found to be very satisfactory. Graphical Abstract SFODME-SQT-FAAS system for sensitive determination of cadmium.

Neural dynamics in reconfigurable silicon.

PubMed

Basu, A; Ramakrishnan, S; Petre, C; Koziol, S; Brink, S; Hasler, P E

2010-10-01

A neuromorphic analog chip is presented that is capable of implementing massively parallel neural computations while retaining the programmability of digital systems. We show measurements from neurons with Hopf bifurcations and integrate and fire neurons, excitatory and inhibitory synapses, passive dendrite cables, coupled spiking neurons, and central pattern generators implemented on the chip. This chip provides a platform for not only simulating detailed neuron dynamics but also uses the same to interface with actual cells in applications such as a dynamic clamp. There are 28 computational analog blocks (CAB), each consisting of ion channels with tunable parameters, synapses, winner-take-all elements, current sources, transconductance amplifiers, and capacitors. There are four other CABs which have programmable bias generators. The programmability is achieved using floating gate transistors with on-chip programming control. The switch matrix for interconnecting the components in CABs also consists of floating-gate transistors. Emphasis is placed on replicating the detailed dynamics of computational neural models. Massive computational area efficiency is obtained by using the reconfigurable interconnect as synaptic weights, resulting in more than 50 000 possible 9-b accurate synapses in 9 mm(2).

Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy.

PubMed

Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Fadaeinasab, Mehran; Khaing, Si Lay; Chung, Lip Yong; Mohamad Haron, Didi Erwandi B; Noordin, Mohamed Ibrahim

2017-01-01

This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. 153 Sm 2 O 3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time ( T max ) at which the maximum concentration of metformin HCl in the blood ( C max ) was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. C max and the half-life were found to be within an acceptable range. It is therefore concluded that MKP3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region.

Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy

PubMed Central

Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Fadaeinasab, Mehran; Khaing, Si Lay; Chung, Lip Yong; Mohamad Haron, Didi Erwandi B; Noordin, Mohamed Ibrahim

2017-01-01

This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. 153Sm2O3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time (Tmax) at which the maximum concentration of metformin HCl in the blood (Cmax) was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. Cmax and the half-life were found to be within an acceptable range. It is therefore concluded that MKP3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region. PMID:28031701

Bioadhesive tablets containing cyclodextrin complex of itraconazole for the treatment of vaginal candidiasis.

PubMed

Cevher, Erdal; Açma, Ayşe; Sinani, Genada; Aksu, Buket; Zloh, Mire; Mülazımoğlu, Lütfiye

2014-08-01

Itraconazole (ITR) is commonly used in the treatment of Candida infections. It has a nephrotoxic effect and low bioavailability in patients who suffer from renal insufficiency, and its poor solubility in water makes ITR largely unavailable. Cyclodextrins (CyDs) are used to form inclusion complexes with drugs to improve their aqueous solubility and to reduce their side effects. In this study, ITR was complexed with γ-cyclodextrin (γ-CyD), hydroxypropyl-β-cyclodextrin (HP-β-CyD), methyl-β-cyclodextrin (Met-β-CyD) and sulphobutyl ether-β-cyclodextrin (SBE7-β-CyD) to increase its water solubility and to reduce the side effects of the drug without decreasing antifungal activity. Complex formation between ITR and CyDs was evaluated using SEM, (1)H NMR and XRD studies. The antifungal activity of the complexes was analyzed on Candida albicans strains, and the susceptibility of the strains was found to be higher for the ITR-SBE7-β-CyD complex than for the complexes that were prepared with other CyDs. Vaginal bioadhesive sustained release tablet formulations were developed using the ITR-SBE7-β-CyD inclusion complex to increase the residence time of ITR in the vagina, thereby boosting the efficacy of the treatment. The swelling, matrix erosion and bioadhesion properties of formulations and the drug release rate of these tablets were analyzed, and the most therapeutically effective vaginal formulation was determined. Copyright © 2014 Elsevier B.V. All rights reserved.

Thiomers for oral delivery of hydrophilic macromolecular drugs.

PubMed

Bernkop-Schnürch, Andreas; Hoffer, Martin H; Kafedjiiski, Krum

2004-11-01

In recent years thiolated polymers (thiomers) have appeared as a promising new tool in oral drug delivery. Thiomers are obtained by the immobilisation of thio-bearing ligands to mucoadhesive polymeric excipients. By the formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of thiomers are up to 130-fold improved compared with the corresponding unmodified polymers. Owing to the formation of inter- and intramolecular disulfide bonds within the thiomer itself, matrix tablets and particulate delivery systems show strong cohesive properties, resulting in comparatively higher stability, prolonged disintegration times and a more controlled drug release. The permeation of hydrophilic macromolecular drugs through the gastrointestinal (GI) mucosa can be improved by the use of thiomers. Furthermore, some thiomers exhibit improved inhibitory properties towards GI peptidases. The efficacy of thiomers in oral drug delivery has been demonstrated by various in vivo studies. A pharmacological efficacy of 1%, for example, was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Furthermore, tablets comprising a thiomer and pegylated insulin resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Low-molecular-weight heparin embedded in thiolated polycarbophil led to an absolute bioavailability of > or = 20% after oral administration to rats. In these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. These results indicate drug carrier systems based on thiomers appear to be a promising tool for oral delivery of hydrophilic macromolecular drugs.

Mechanistic modelling of drug release from a polymer matrix using magnetic resonance microimaging.

PubMed

Kaunisto, Erik; Tajarobi, Farhad; Abrahmsen-Alami, Susanna; Larsson, Anette; Nilsson, Bernt; Axelsson, Anders

2013-03-12

In this paper a new model describing drug release from a polymer matrix tablet is presented. The utilization of the model is described as a two step process where, initially, polymer parameters are obtained from a previously published pure polymer dissolution model. The results are then combined with drug parameters obtained from literature data in the new model to predict solvent and drug concentration profiles and polymer and drug release profiles. The modelling approach was applied to the case of a HPMC matrix highly loaded with mannitol (model drug). The results showed that the drug release rate can be successfully predicted, using the suggested modelling approach. However, the model was not able to accurately predict the polymer release profile, possibly due to the sparse amount of usable pure polymer dissolution data. In addition to the case study, a sensitivity analysis of model parameters relevant to drug release was performed. The analysis revealed important information that can be useful in the drug formulation process. Copyright © 2013 Elsevier B.V. All rights reserved.

Determination of arsenic in traditional Chinese medicine by microwave digestion with flow injection-inductively coupled plasma mass spectrometry (FI-ICP-MS).

PubMed

Ong, E S; Yong, Y L; Woo, S O

1999-01-01

A simple, rapid, and sensitive method with high sample throughput was developed for determining arsenic in traditional Chinese medicine (TCM) in the form of uncoated tablets, sugar-coated tablets, black pills, capsules, powders, and syrups. The method involves microwave digestion with flow injection-inductively coupled plasma mass spectrometry (FI-ICP-MS). Method precision was 2.7-10.1% (relative standard deviation, n = 6) for different concentrations of arsenic in different TCM samples analyzed by different analysts on different days. Method accuracy was checked with a certified reference material (sea lettuce, Ulva lactuca, BCR CRM 279) for external calibration and by spiking arsenic standard into different TCMs. Recoveries of 89-92% were obtained for the certified reference material and higher than 95% for spiked TCMs. Matrix interference was insignificant for samples analyzed by the method of standard addition. Hence, no correction equation was used in the analysis of arsenic in the samples studied. Sample preparation using microwave digestion gave results that were very similar to those obtained by conventional wet acid digestion using nitric acid.

Formulation and characterization of a compacted multiparticulate system for modified release of water-soluble drugs--part 1--acetaminophen.

PubMed

Cantor, Stuart L; Hoag, Stephen W; Augsburger, Larry L

2009-03-01

The aim of this study was to characterize and evaluate a modified release, multiparticulate tablet formulation consisting of placebo beads and drug-loaded beads. Acetaminophen (APAP) bead formulations containing ethylcellulose (EC) from 40-60% and placebo beads containing 30% calcium silicate and prepared using 0-20% alcohol were developed using extrusion-spheronization and studied using a central composite experimental design. Particle size and true density of beads were measured. Segregation testing was performed using the novel ASTM D6940-04 method on a 50:50 blend of uncoated APAP beads (60%EC) : calcium silicate placebo beads (10% alcohol). Tablets were prepared using an instrumented Stokes-B2 rotary tablet press and evaluated for crushing strength and dissolution rate. Compared with drug beads (60%EC), placebo beads (10% alcohol) were smaller but had higher true densities: 864.8 mum and 1.27 g/cm(3), and 787.1 mum and 1.73 g/cm(3), respectively. Segregation testing revealed that there was approximately a 20% difference in drug content (as measured by the coefficient of variation) between initial and final blend samples. Although calcium silicate-based placebo beads were shown to be ineffective cushioning agents in blends with Surelease(R)-coated APAP beads, they were found to be very compactibile when used alone and gave tablet crushing strength values between 14 and 17 kP. The EC in the APAP bead matrix minimally suppressed the drug release from uncoated beads (t(100%) = 2 h). However, while tablets containing placebo beads reformulated with glycerol monostearate (GMS) showed a slower release rate (t(60%)= 5 h) compared with calcium silicate-based placebos, some coating damage ( approximately 30%) still occurred on compression as release was faster than coated APAP beads alone. While tablets containing coated drug beads can be produced with practical crushing strengths (>8 kP) and low compression pressures (10-35 MPa), dissolution studies revealed that calcium silicate-based placebos are ineffective as cushioning agents. Blend segregation was likely observed due to the particle size and the density differences between APAP beads and calcium silicate-based placebo beads; placebo bead percolation can perhaps be minimized by increasing their size during the extrusion-spheronization process. The GMS- based placebos offer greater promise as cushioning agents for compacted, coated drug beads; however, this requires an optimized compression pressure range and drug bead : placebo bead ratio (i.e., 50:50).

Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice.

PubMed

Tahaineh, Linda M; Gharaibeh, Shadi F

2012-08-01

Tablet splitting is a common practice for multiple reasons including cost savings; however, it does not necessarily result in weight-uniform half-tablets. To determine weight uniformity of half-tablets resulting from splitting 4 products available in the Jordanian market and investigate the effect of tablet characteristics on weight uniformity of half-tablets. Ten random tablets each of warfarin 5 mg, digoxin 0.25 mg, phenobarbital 30 mg, and prednisolone 5 mg were weighed and split by 6 PharmD students using a knife. The resulting half-tablets were weighed and evaluated for weight uniformity. Other relevant physical characteristics of the 4 products were measured. The average tablet hardness of the sampled tablets ranged from 40.3 N to 68.9 N. Digoxin, phenobarbital, and prednisolone half-tablets failed the weight uniformity test; however, warfarin half-tablets passed. Digoxin, warfarin, and phenobarbital tablets had a score line and warfarin tablets had the deepest score line of 0.81 mm. Splitting warfarin tablets produces weight-uniform half-tablets that may possibly be attributed to the hardness and the presence of a deep score line. Digoxin, phenobarbital, and prednisolone tablet splitting produces highly weight variable half-tablets. This can be of clinical significance in the case of the narrow therapeutic index medication digoxin.

El Hierro's floating stones as messengers of crust-magma interaction at depth

NASA Astrophysics Data System (ADS)

Burchardt, S.; Troll, V. R.; Schmeling, H.; Koyi, H.; Blythe, L. S.; Longpré, M. A.; Deegan, F. M.

2012-04-01

During the early stages of the submarine eruption that started on October 10 2011 south of El Hierro, Canary Islands, Spain, peculiar eruption products were found floating on the sea surface. These centimetre- to decimetre-sized "bombs" have been termed "restingolites" after the nearby village La Restinga and consist of a basaltic rind and a white to light grey core that resembles pumice in texture. According to Troll et al. (2011; see also Troll et al. EGU 2012 Abstracts), this material consists of a glassy matrix hosting extensive vesicle networks, which results in extremely low densities allowing these rocks to float on sea water. Mineralogical and geochemical analyses reveal that the "restingolites" originate from the sedimentary rocks (sand-, silt-, and mudstones) that form layer 1 of the oceanic crust beneath El Hierro. During the onset and early stages of the eruption, magma ponded at the base of this sedimentary sequence, breaking its way through the sedimentary rocks to the ocean floor. The textures of the "restingolites" reveal that crust-magma interaction during fragmentation and transport of the xenoliths involved rapid partial melting and volatile exsolution. Xenoliths strikingly similar to those from El Hierro are known from eruptions on other Canary Islands (e.g. La Palma, Gran Canaria, and Lanzarote). In fact, they resemble in texture xenoliths of various protoliths from volcanic areas worldwide (e.g. Krakatao, Indonesia, Cerro Quemado, Guatemala, Laacher See, Germany). This indicates that the process of partial melting and volatile exsolution, which the "restingolites" bear witness of, is probably occurring frequently during shallow crustal magma emplacement. Thermomechanical numerical models of the effect of the density decrease associated with the formation of vesicle networks in partially molten xenoliths show that xenoliths of crustal rocks initially sink in a magma chamber, but may start to float to the chamber roof once they start to heat up and vesiculate. The "floating stones" from El Hierro thus represent the products of crust-magma interaction beneath the Canary Islands, but is probably relevant in most volcanic areas and tectonic settings. In addition, xenolith devolatilisation has important general implications for the mechanics of crustal recycling, magma emplacement into the upper crust and volatile release from active volcanic systems.

Dose uniformity of scored and unscored tablets: Application of the FDA Tablet Scoring Guidance for Industry.

PubMed

Ciavarella, Anthony; Khan, Mansoor; Gupta, Abhay; Faustino, Patrick

2016-06-20

This FDA laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5-2.1 standard deviation (SD) of the % label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3-9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting "can affect how much drug is present in the split tablet and available for absorption" as stated in the guidance (1). Copyright © 2016, Parenteral Drug Association.

Microstructure of Tablet-Pharmaceutical Significance, Assessment, and Engineering.

PubMed

Sun, Changquan Calvin

2017-05-01

To summarize the microstructure - property relationship of pharmaceutical tablets and approaches to improve tablet properties through tablet microstructure engineering. The main topics reviewed here include: 1) influence of material properties and manufacturing process parameters on the evolution of tablet microstructure; 2) impact of tablet structure on tablet properties; 3) assessment of tablet microstructure; 4) development and engineering of tablet microstructure. Microstructure plays a decisive role on important pharmaceutical properties of a tablet, such as disintegration, drug release, and mechanical strength. Useful information on mechanical properties of a powder can be obtained from analyzing tablet porosity-pressure data. When helium pycnometry fails to accurately measure true density of a water-containing powder, non-linear regression of tablet density-pressure data is a useful alternative method. A component that is more uniformly distributed in a tablet generally exerts more influence on the overall tablet properties. During formulation development, it is highly recommended to examine the relationship between any property of interest and tablet porosity when possible. Tablet microstructure can be engineered by judicious selection of formulation composition, including the use of the optimum solid form of the drug and appropriate type and amount of excipients, and controlling manufacturing process.

Systematic evaluation of common lubricants for optimal use in tablet formulation.

PubMed

Paul, Shubhajit; Sun, Changquan Calvin

2018-05-30

As an essential formulation component for large-scale tablet manufacturing, the lubricant preserves tooling by reducing die-wall friction. Unfortunately, lubrication also often results in adverse effects on tablet characteristics, such as prolonged disintegration, slowed dissolution, and reduced mechanical strength. Therefore, the choice of lubricant and its optimal concentration in a tablet formulation is a critical decision in tablet formulation development to attain low die-wall friction while minimizing negative impact on other tablet properties. Three commercially available tablet lubricants, i.e., magnesium stearate, sodium stearyl fumerate, and stearic acid, were systematically investigated in both plastic and brittle matrices to elucidate their effects on reducing die-wall friction, tablet strength, tablet hardness, tablet friability, and tablet disintegration kinetics. Clear understanding of the lubrication efficiency of commonly used lubricants as well as their impact on tablet characteristics would help future tablet formulation efforts. Copyright © 2018 Elsevier B.V. All rights reserved.

Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

PubMed

Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the world. Tablets are often split to modify dose strength, make swallowing easier, and reduce cost to the consumer. To better address product quality for this widely used practice, the U.S. Food and Drug Administration (FDA) published a Guidance for Industry that addresses tablet splitting. The guidance provides testing criteria for scored tablets, which is a part of the FDA review process for drugs. The model drugs selected for this study were amlodipine and gabapentin, which have different sizes, shapes, and tablet scores. Whole and split amlodipine tablets were tested for drug content because of a concern that the low-dose strength may cause greater variability. Whole and split gabapentin tablets were tested for weight variation because of their higher dosage strength of 600 mg. All whole tablets met the acceptance criteria for the Uniformity of Dosage Units based on the guidance recommendations. When unscored amlodipine tablets were split by a splitter, all formulations did not meet the acceptance criteria. When fully scored gabapentin tablets were split by hand and by splitter, they met the acceptance criteria. The findings of this FDA study indicated physical characteristics such as size, shape, and tablet score can affect the uniformity of split tablets. © PDA, Inc. 2016.

Investigating the effect of processing parameters on pharmaceutical tablet disintegration using a real-time particle imaging approach.

PubMed

Rajkumar, Arthi D; Reynolds, Gavin K; Wilson, David; Wren, Stephen; Hounslow, Michael J; Salman, Agba D

2016-09-01

Tablet disintegration is a fundamental parameter that is tested in vitro before a product is released to the market, to give confidence that the tablet will break up in vivo and that active drug will be available for absorption. Variations in tablet properties cause variation in disintegration behaviour. While the standardised pharmacopeial disintegration test can show differences in the speed of disintegration of different tablets, it does not give any mechanistic information about the underlying cause of the difference. With quantifiable disintegration data, and consequently an improved understanding into tablet disintegration, a more knowledge-based approach could be applied to the research and development of future tablet formulations. The aim of the present research was to introduce an alternative method which will enable a better understanding of tablet disintegration using a particle imaging approach. A purpose-built flow cell was employed capable of online observation of tablet disintegration, which can provide information about the changing tablet dimensions and the particles released with time. This additional information can improve the understanding of how different materials and process parameters affect tablet disintegration. Standard USP analysis was also carried out to evaluate and determine whether the flow cell method can suitably differentiate the disintegration behaviour of tablets produced using different processing parameters. Placebo tablets were produced with varying ratios of insoluble and soluble filler (mannitol and MCC, respectively) so that the effect of variation in the formulation can be investigated. To determine the effect of the stress applied during granulation and tableting on tablet disintegration behaviour, analysis was carried out on tablets produced using granular material compressed at 20 or 50bar, where a tableting load of either 15 or 25kN was used. By doing this the tablet disintegration was examined in terms of the tablet porosity by monitoring the tablet area and particle release. It was found that when 20 and 50bar roller compaction pressure was used the USP analysis showed almost identical disintegration times for the consequent tablets. With the flow cell method a greater tablet swelling was observed for the lower pressure followed by steady tablet erosion. Additionally, more particles were released during disintegration due to the smaller granule size distribution within the tablet. When a higher tableting pressure was applied the tablet exhibited a delay in the time taken to reach the maximum swelling area, and slower tablet erosion and particle release were also observed, largely due to the tablet being much denser causing slower water uptake. This was in agreement with the USP analysis data. Overall it was confirmed by using both the standard USP analysis and flow cell method that the tablet porosity affects the tablet disintegration, whereby a more porous tablet disintegrates more slowly. But a more in-depth understanding was obtained using the flow cell method as it was determined that tablets will swell to varying degrees and release particles at different rates depending on the roller compaction and tableting pressure used. Copyright © 2016 Elsevier B.V. All rights reserved.

14 CFR 27.753 - Main float design.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Main float design. 27.753 Section 27.753... STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Floats and Hulls § 27.753 Main float design. (a) Bag floats. Each bag float must be designed to withstand— (1) The maximum pressure differential...

14 CFR 29.753 - Main float design.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Main float design. 29.753 Section 29.753... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Floats and Hulls § 29.753 Main float design. (a) Bag floats. Each bag float must be designed to withstand— (1) The maximum pressure differential...

[Influence of polymer type on the physical properties and the release study of papaverine hydrochloride from tablets].

PubMed

Kasperek, Regina; Polski, Andrzej; Sobótka-Polska, Karolina; Poleszak, Ewa

2014-01-01

Polymers are widely used in drug manufacturing. Researchers studied their impact on the bioavailability of active substances or on physical properties of tablets for many years. To study the influence of polymer excipients, such as microcrystalline cellulose (Avicel PH 101, Avicel PH 102), croscarmellose sodium, crospovidone or polyvinylpyrrolidone, on the release profile of papaverine hydrochloride from tablets and on the physical properties of tablets. Six series of uncoated tablets were prepared by indirect method, with previous wet granulation. Tablets contained papaverine hydrochloride and various excipients. The physical properties of the prepared granules, tablets and the release profile of papaverine hydrochloride from tablets were examined. The content of papaverine hydrochloride from the release study were determined spectrophotometrically. All tablets met the pharmacopoeia requirements during following tests: the disintegration time of tablets, uncoated tablets resistance to abrasion, the weight uniformity and dose formulations, their dimensions, the resistance to crushing of tablets and the drug substance content in the tablet. In four cases more than 80% of papaverine was released up to 2 min, in one formula it was up to 5 min, and in last one up to 10 min. Tablets containing crospovidone disintegrated faster than tablets with croscarmellose sodium. Adding gelatinized starch to the tablet composition increased the disintegration time, hardness and delayed the release of papaverine. During the wet granulation process, granules containing polyvinylpyrrolidone were characterized by a suitable flow properties and slightly prolonged disintegration time. Tablets containing Avicel PH 102 compared to tablets with Avicel PH 101 had less weight loss during the test of mechanical resistance, improved hardness and faster release profile of papaverine from tablets.

Tableting Properties and Compression Models of Labisia pumila Tablets.

PubMed

Etti, C J; Yusof, Y A; Chin, N L; Mohd Tahir, S

2017-03-04

The tableting properties of Labisia pumila herbal powder, which is well known for its therapeutic benefits was investigated. The herbal powder was compressed into tablets using a stainless steel cylindrical uniaxial die of 13-mm- diameter with compaction pressures ranging from 7 to 25 MPa. Two feed weights, 0.5 and 1.0 g were used to form tablets. Some empirical models were used to describe the compressibility behavior of Labisia pumila tablets. The strength and density of tablets increased with increase in compaction pressure and resulted in reduction in porosity of the tablets. Smaller feeds, higher forces and increase in compaction pressure, contributed to more coherent tablets. These findings can be used to enhance the approach and understanding of tableting properties of Labisia pumila herbal powder tablets.

Monitoring of internal pH gradients within multi-layer tablets by optical methods and EPR imaging.

PubMed

Eisenächer, Friederike; Schädlich, Andreas; Mäder, Karsten

2011-09-30

The high variability of gastrointestinal pH is a general challenge regarding constant release from oral drug delivery systems, especially for ionisable drugs. These drugs often show a pH-dependent solubility and therewith associated intra- and inter-individual variability of emerging drug plasma levels. Several strategies have been investigated with the intention to influence the microenvironmental pH (pH(M)) within solid formulations and therefore achieve pH-independent release profiles. Because of the heterogeneity of solid systems, a precise prediction of the occurring pH(M) is rather difficult. It is therefore important to monitor the pH(M) within the formulations to achieve requested release as well as to minimise pH-dependent degradation processes of the active compound. The purpose of the current study was the analysis of pH(M) gradients within 2- and 3-layer tablets during hydration using 3 different techniques for comparison intensions, in particular a pH indicator dye, fluorescence imaging and EPR imaging. The influence of the presence or absence of pH modifying substances and of an additional lipophilic inter layer on the pH(M) was investigated as well as the variation of matrix forming excipient and buffer pH. The influence of the pH(M) on drug release was analysed as well. In addition, benchtop MRI was accomplished to gain a deeper insight on the hydration and erosion behaviour of 2- and 3-layer tablets. Copyright © 2010 Elsevier B.V. All rights reserved.

Magnetic effervescent tablet-assisted ionic liquid dispersive liquid-liquid microextraction of selenium for speciation in foods and beverages.

PubMed

Wang, Xiaojun; Wu, Long; Cao, Jiaqi; Hong, Xincheng; Ye, Rui; Chen, Weiji; Yuan, Ting

2016-07-01

A novel, simple and rapid method based on magnetic effervescent tablet-assisted ionic liquid dispersive liquid-liquid microextraction (MEA-IL-DLLME) followed by graphite furnace atomic absorption spectrometry (GFAAS) determination was established for the speciation of selenium in various food and beverage samples. In the procedure, a special magnetic effervescent tablet containing CO2 sources (sodium carbonate and sodium dihydrogenphosphate), ionic liquids and Fe3O4 magnetic nanoparticles (MNPs) was used to combine extractant dispersion and magnetic recovery procedures into a single step. The parameters influencing the microextraction efficiency, such as pH of the sample solution, volume of ionic liquid, amount of MNPs, concentration of the chelating agent, salt effect and matrix effect were investigated and optimised. Under the optimised conditions, the limits of detection (LODs) for Se(IV) were 0.021 μg l(-)(1) and the linear dynamic range was 0.05-5.0 μg l(-)(1). The relative standard deviation for seven replicate measurements of 1.0 μg l(-)(1) of Se(IV) was 2.9%. The accuracy of the developed method was evaluated by analysis of the standard reference materials (GBW10016 tea, GBW10017 milk powder, GBW10043 Liaoning rice, GBW10046 Henan wheat, GBW10048 celery). The proposed method was successfully applied to food and beverage samples including black tea, milk powder, mushroom, soybean, bamboo shoots, energy drink, bottled water, carbonated drink and mineral water for the speciation of Se(IV) and Se(VI) with satisfactory relative recoveries (92.0-108.1%).

3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery.

PubMed

Siyawamwaya, Margaret; du Toit, Lisa C; Kumar, Pradeep; Choonara, Yahya E; Kondiah, Pierre P P D; Pillay, Viness

2018-04-12

A 3D-Bioplotter® was employed to 3D print (3DP) a humic acid-polyquaternium 10 (HA-PQ10) controlled release fixed dose combination (FDC) tablet comprising of the anti-HIV-1 drugs, efavirenz (EFV), tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Chemical interactions, surface morphology and mechanical strength of the FDC were ascertained. In vitro drug release studies were conducted in biorelevant media followed by in vivo study in the large white pigs, in comparison with a market formulation, Atripla®. In vitro-in vivo correlation of results was undertaken. EFV, TDF and FTC were successfully entrapped in the 24-layered rectangular prism-shaped 3DP FDC with a loading of ∼12.5 mg/6.3 mg/4 mg of EFV/TDF/FTC respectively per printed layer. Hydrogen bonding between the EFV/TDF/FTC and HA-PQ10 was detected which was indicative of possible drug solubility enhancement. The overall surface of the tablet exhibited a fibrilla structure and the 90° inner pattern was determined to be optimal for 3DP of the FDC. In vitro and in vivo drug release profiles from the 3DP FDC demonstrated that intestinal-targeted and controlled drug release was achieved. A 3DP FDC was successfully manufactured with the aid of a 3D-Bioplotter in a single step process. The versatile HA-PQ10 entrapped all drugs and achieved an enhanced relative bioavailability of EFV, TDF, and FTC compared to the market formulation for potentially enhanced HIV treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

40 CFR 65.45 - External floating roof converted into an internal floating roof.

Code of Federal Regulations, 2010 CFR

2010-07-01

... External floating roof converted into an internal floating roof. The owner or operator who elects to... 40 Protection of Environment 15 2010-07-01 2010-07-01 false External floating roof converted into an internal floating roof. 65.45 Section 65.45 Protection of Environment ENVIRONMENTAL PROTECTION...

Nystatin

MedlinePlus

Mycostatin® Oral Tablets ... Mycostatin® Vaginal Tablets ... Nilstat® Oral Tablets ... Nilstat® Vaginal Tablets ... Nystatin® Vaginal Tablets ... Nystatin comes as a tablet, capsule, and a liquid to take by mouth; a soft lozenge (pastille) to be dissolved slowly in the mouth; a ...

Preconcentration of lead using solidification of floating organic drop and its determination by electrothermal atomic absorption spectrometry

PubMed Central

Chamsaz, Mahmoud; Akhoundzadeh, Jeiran; Arbab-zavar, Mohammad Hossein

2012-01-01

A simple microextraction method based on solidification of a floating organic drop (SFOD) was developed for preconcentration of lead prior to its determination by electrothermal atomic absorption spectrometry (ETAAS). Ammonium pyrolidinedithiocarbamate (APDC) was used as complexing agent, and the formed complex was extracted into a 20 μL of 1-undecanol. The extracted complex was diluted with ethanol and injected into a graphite furnace. An orthogonal array design (OAD) with OA16 (45) matrix was employed to study the effects of different parameters such as pH, APDC concentration, stirring rate, sample solution temperature and the exposure time on the extraction efficiency. Under the optimized experimental conditions the limit of detection (based on 3 s) and the enhancement factor were 0.058 μg L−1 and 113, respectively. The relative standard deviation (RSD) for 8 replicate determinations of 1 μg L−1 of Pb was 8.8%. The developed method was validated by the analysis of certified reference materials and was successfully applied to the determination of lead in water and infant formula base powder samples. PMID:25685441

Effective correlator for RadioAstron project

NASA Astrophysics Data System (ADS)

Sergeev, Sergey

This paper presents the implementation of programme FX-correlator for Very Long Baseline Interferometry, adapted for the project "RadioAstron". Software correlator implemented for heterogeneous computing systems using graphics accelerators. It is shown that for the task interferometry implementation of the graphics hardware has a high efficiency. The host processor of heterogeneous computing system, performs the function of forming the data flow for graphics accelerators, the number of which corresponds to the number of frequency channels. So, for the Radioastron project, such channels is seven. Each accelerator is perform correlation matrix for all bases for a single frequency channel. Initial data is converted to the floating-point format, is correction for the corresponding delay function and computes the entire correlation matrix simultaneously. Calculation of the correlation matrix is performed using the sliding Fourier transform. Thus, thanks to the compliance of a solved problem for architecture graphics accelerators, managed to get a performance for one processor platform Kepler, which corresponds to the performance of this task, the computing cluster platforms Intel on four nodes. This task successfully scaled not only on a large number of graphics accelerators, but also on a large number of nodes with multiple accelerators.

Human dermal and gingival fibroblasts in a three-dimensional culture: a comparative study on matrix remodeling.

PubMed

Chaussain Miller, C; Septier, D; Bonnefoix, M; Lecolle, S; Lebreton-Decoster, C; Coulomb, B; Pellat, B; Godeau, G

2002-03-01

Free-floating collagen lattice is considered a useful tool for assessing wound healing in vitro. This work compared extracellular matrix remodeling in collagen lattices populated by gingival or dermal fibroblasts. For 21 days we followed gel contraction and changes in cell number of collagen lattices seeded with l.5 x 10(5) fibroblasts of each tissue. We also used indirect immunodetection to study extracellular matrix components, metalloproteinases (MMPs), and their tissues inhibitors (TIMPs). In addition, the presence of MMPs and TIMPs in the culture media was analyzed by zymography and western blotting. No significant difference was found concerning gel contraction and changes in cell number. We observed the early expression of fibrillin I and collagen type III, apparently codistributed and at the end of the gel contraction their disappearance. Concomitantly we demonstrated the expression of MMPs and TIMPs, initially localized in cellular cytoplasm, then spreading in the extracellular compartment, and even found in the culture medium. This remodeling was more rapid and intense with gingival fibroblasts than dermal fibroblasts. In conclusion, gingival fibroblasts seem more efficient at remodeling the connective tissue than dermal fibroblasts and could lead to the better wound healing observed in vivo.

System-on-chip architecture and validation for real-time transceiver optimization: APC implementation on FPGA

NASA Astrophysics Data System (ADS)

Suarez, Hernan; Zhang, Yan R.

2015-05-01

New radar applications need to perform complex algorithms and process large quantity of data to generate useful information for the users. This situation has motivated the search for better processing solutions that include low power high-performance processors, efficient algorithms, and high-speed interfaces. In this work, hardware implementation of adaptive pulse compression for real-time transceiver optimization are presented, they are based on a System-on-Chip architecture for Xilinx devices. This study also evaluates the performance of dedicated coprocessor as hardware accelerator units to speed up and improve the computation of computing-intensive tasks such matrix multiplication and matrix inversion which are essential units to solve the covariance matrix. The tradeoffs between latency and hardware utilization are also presented. Moreover, the system architecture takes advantage of the embedded processor, which is interconnected with the logic resources through the high performance AXI buses, to perform floating-point operations, control the processing blocks, and communicate with external PC through a customized software interface. The overall system functionality is demonstrated and tested for real-time operations using a Ku-band tested together with a low-cost channel emulator for different types of waveforms.

How do tablet properties influence swallowing behaviours?

PubMed

Yamamoto, Shinya; Taniguchi, Hiroshige; Hayashi, Hirokazu; Hori, Kazuhiro; Tsujimura, Takanori; Nakamura, Yuki; Sato, Hideaki; Inoue, Makoto

2014-01-01

Behavioural performance of tablet swallowing was evaluated with different tablet conditions in terms of size, number and surface coating. Four different types of tablets were prepared: small or large, and with or without a surface coating. Fourteen normal male adults were instructed to swallow the prepared tablets with 15 ml of water. The number of tablets in one trial was changed from one to three. To evaluate swallowing and tablet transport, electromyographic activity was recorded in the left suprahyoid muscles, and videofluorographic images were examined. All tablet conditions (size, number and surface coating) affected the swallowing performance in terms of total number of swallows, electromyographic burst patterns and location of remaining tablets. Increases in the size and number of tablets increased the number of swallows and electromyographic burst area and duration. In addition, all of these parameters increased while swallowing tablets without a coating compared with tablets with a coating. Location of the remaining tablets was mainly within the mouth. This study only clarified the normal pattern of tablet swallowing under several conditions in healthy subjects, but the results may facilitate comprehensive evaluation and treatment planning in terms of administering medication to dysphagic patients. © 2013 Royal Pharmaceutical Society.

Analysis of drug content and weight uniformity for half-tablets of 6 commonly split medications.

PubMed

Hill, Shaynan W; Varker, Andrew S; Karlage, Kelly; Myrdal, Paul B

2009-04-01

Cost savings can be achieved with the practice of tablet splitting. Previous research has shown weight nonuniformity within tablet halves. However, limited research to date has found that the potential dose inaccuracy resulting from splitting tablets does not significantly affect clinical outcomes. To determine the drug content and weight in split half-tablets of 6 commonly split medications using drug assay analysis. This study was performed by 2 fourth-year pharmacy students using 30 randomly selected tablets of each of the following 6 medications: warfarin sodium 5 milligrams (mg), simvastatin 80 mg, metoprolol succinate 200 mg, metoprolol tartrate 25 mg, citalopram 40 mg, and lisinopril 40 mg. A randomly selected half of the tablets were split by a single pharmacy student using a tablet cutter, and the remaining tablets were kept whole. Drug content was analyzed for 15 whole tablets and 30 half-tablets for each of the 6 drugs using high performance liquid chromatography, an analytical tool used to identify and quantify substances in solution. Drug content uniformity was assessed by comparing drug content within half-tablets with one-half of the drug content mean found for all whole tablets in the sample. Weight uniformity was assessed by comparing half-tablet weights, as determined by a Mettler analytical balance, with one-half of the mean weight for whole tablets in the sample. The percentages by which each whole tablet's or half-tablet's drug content and weight differed from sample mean values were compared with proxy United States Pharmacopeia (USP) specification ranges for drug content (95%-105% for warfarin sodium and 90%-110% for the other 5 drugs). Additionally, these outcomes were compared for nonscored versus scored tablets. The percent relative standard deviation (%RSD, ratio of the standard deviation to the mean), a commonly used measure of the repeatability and precision of assays used to analyze drug content, was also calculated in order to determine whether the drugs met proxy USP specification for %RSD (less than 6% for all drugs studied). A total of 43 of 180 half-tablets (23.9%) differed from sample mean values by a percentage that fell outside of proxy USP specification for drug content; warfarin sodium (11 of 30 half-tablets, 36.7%), simvastatin (3 of 30 half-tablets, 10.0%) metoprolol succinate (10 of 30 half-tablets, 33.3%), metoprolol tartrate (4 of 30 half-tablets, 13.3%), citalopram (5 of 30 half-tablets, 16.7%), and lisinopril (10 of 30 half-tablets, 33.3%). Half-tablets outside of proxy USP specification for weight included warfarin sodium (10 of 30 half-tablets, 33.3%), metoprolol succinate (6 of 30 half-tablets, 20%), and lisinopril (7 of 30 half-tablets, 23.3%). The %RSDs for drug content and weight fell outside of the proxy USP specification for %RSD for metoprolol succinate (drug content = 8.98%, weight = 7.70%) and lisinopril (drug content = 10.41%, weight = 8.13%). Mean percent weight loss after splitting was less than 1% for all drugs except lisinopril, which had an average weight loss of 1.25%. The total numbers of scored (nonscored) tablet halves that fell outside of proxy USP specification were 20 (23) for drug content and 10 (13) for weight. When measuring drug content, the numbers of out-of-range half-tablets for scored (nonscored) drugs were 36 (44) at 95%-105%, 9 (23) at 90%-110%, 0 (10) at 85%-115%, and 0 (1) at 75%-125%. When measuring weight, the numbers of out-of-range half-tablets for scored (nonscored) drugs were 28 (38) at 95%-105%, 0 (14) at 90%-110%, 0 (3) at 85%-115%, and 0 (0) at 75%-125%. Dose variation exceeded a proxy USP specification for more than one-third of sampled half-tablets of warfarin sodium, metoprolol succinate, and lisinopril and appeared to be greater for nonscored tablets as compared with scored tablets. Drug content variation in half-tablets appeared to be attributable primarily to weight variation occurring when tablets powder or fragment during the splitting process. Therefore, equal daily doses will be determined by the ability of patients to split tablets perfectly in half.

Acceleration of Radiance for Lighting Simulation by Using Parallel Computing with OpenCL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zuo, Wangda; McNeil, Andrew; Wetter, Michael

2011-09-06

We report on the acceleration of annual daylighting simulations for fenestration systems in the Radiance ray-tracing program. The algorithm was optimized to reduce both the redundant data input/output operations and the floating-point operations. To further accelerate the simulation speed, the calculation for matrix multiplications was implemented using parallel computing on a graphics processing unit. We used OpenCL, which is a cross-platform parallel programming language. Numerical experiments show that the combination of the above measures can speed up the annual daylighting simulations 101.7 times or 28.6 times when the sky vector has 146 or 2306 elements, respectively.

Zolpidem

MedlinePlus

Zolpidem comes as a tablet (Ambien) and an extended-release (long-acting) tablet (Ambien CR) to take ... the tongue. If you are taking the tablets, extended-release tablets, sublingual tablets (Edluar), or oral spray, ...

Spectrofluorimetric assessment of chlorzoxazone and ibuprofen in pharmaceutical formulations by using Eu-tetracycline HCl optical sensor doped in sol-gel matrix.

PubMed

Attia, M S; Ramsis, M N; Khalil, L H; Hashem, S G

2012-03-01

A novel, simple, sensitive and selective spectrofluorimetric method was developed for the determination of trace amounts of chlorzoxazone and Ibuprofen in pharmaceutical tablets using optical sensor Eu-Tetracycline HCl doped in sol-gel matrix. The chlorzoxazone or Ibuprofen can remarkably enhance the luminescence intensity of Eu-Tetracycline HCl complex doped in a sol-gel matrix in dimethylformamide (DMF) at pH 9.7 and 6.3, respectively, λ(ex) = 400 nm. The enhancing of luminescence intensity peak of Eu-Tetracycline HCl complex at 617 nm is proportional to the concentration of chlorzoxazone or Ibuprofen a result that suggested profitable application as a simple optical sensor for chlorzoxazone or Ibuprofen assessment. The dynamic ranges found for the determination of chlorzoxazone and Ibuprofen concentration are 5 × 10(-9)-1 × 10(-4) and 1 × 10(-8)-7 × 10(-5) mol L(-1), and the limit of detection (LOD) and quantitation limit of detection (LOQ) are 3.1 × 10(-10), 9.6 × 10(-10) and 5.6 × 10(-10), 1.7 × 10(-9) mol L(-1), respectively.

21 CFR 520.1872 - Praziquantel, pyrantel pamoate, and febantel tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... tablets. 520.1872 Section 520.1872 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1872 Praziquantel, pyrantel pamoate, and febantel tablets. (a) Specifications. Each tablet or chewable tablet contains either: (1) Tablet No. 1: 22.7 milligrams praziquantel, 22.7 milligrams pyrantel...

A new tablet brittleness index.

PubMed

Gong, Xingchu; Sun, Changquan Calvin

2015-06-01

Brittleness is one of the important material properties that influences the success or failure of powder compaction. We have discovered that the reciprocal of diametrical elastic strain at fracture is the most suitable tablet brittleness indices (TBIs) for quantifying brittleness of pharmaceutical tablets. The new strain based TBI is supported by both theoretical considerations and a systematic statistical analysis of friability data. It is sufficiently sensitive to changes in both tablet compositions and compaction parameters. For all tested materials, it correctly shows that tablet brittleness increases with increasing tablet porosity for the same powder. In addition, TBI increases with increasing content of a brittle excipient, lactose monohydrate, in the mixtures with a plastic excipient, microcrystalline cellulose. A probability map for achieving less than 1% tablet friability at various combinations of tablet tensile strength and TBI was constructed. Data from marketed tablets validate this probability map and a TBI value of 150 is recommended as the upper limit for pharmaceutical tablets. This TBI can be calculated from the data routinely obtained during tablet diametrical breaking test, which is commonly performed for assessing tablet mechanical strength. Therefore, it is ready for adoption for quantifying tablet brittleness to guide tablet formulation development since it does not require additional experimental work. Copyright © 2015 Elsevier B.V. All rights reserved.

First order coupled dynamic model of flexible space structures with time-varying configurations

NASA Astrophysics Data System (ADS)

Wang, Jie; Li, Dongxu; Jiang, Jianping

2017-03-01

This paper proposes a first order coupled dynamic modeling method for flexible space structures with time-varying configurations for the purpose of deriving the characteristics of the system. The model considers the first time derivative of the coordinate transformation matrix between the platform's body frame and the appendage's floating frame. As a result it can accurately predict characteristics of the system even if flexible appendages rotate with complex trajectory relative to the rigid part. In general, flexible appendages are fixed on the rigid platform or forced to rotate with a slow angular velocity. So only the zero order of the transformation matrix is considered in conventional models. However, due to neglecting of time-varying terms of the transformation matrix, these models introduce severe error when appendages, like antennas, for example, rotate with a fast speed relative to the platform. The first order coupled dynamic model for flexible space structures proposed in this paper resolve this problem by introducing the first time derivative of the transformation matrix. As a numerical example, a central core with a rotating solar panel is considered and the results are compared with those given by the conventional model. It has been shown that the first order terms are of great importance on the attitude of the rigid body and dynamic response of the flexible appendage.

Evaluation of cellulose II powders as a potential multifunctional excipient in tablet formulations.

PubMed

de la Luz Reus Medina, Maria; Kumar, Vijay

2006-09-28

The use of UICEL-A/102 and UICEL-XL, the cellulose II powders, as a multifunctional direct compression excipient in the design of tablets containing hydrochlorothiazide (HCTZ) or ibuprofen (IBU), the model low and high dose drugs, respectively, has been reported. Commercial Oretic and Advil tablets containing HCTZ and IBU, respectively, and tablets made using Avicel PH-102 - the most commonly and widely used commercial direct compression excipient, were used in the study for comparison purposes. Tablets were made by first blending drug with the excipient and then with stearic acid, a lubricant, in a V-blender, followed by compressing into a tablet on a hydraulic press using 105 MPa of compression pressure and a dwell time of 30 s. The crushing strengths of HCTZ tablets decreased in the order Avicel PH-102>UICEL-XL, UICEL-A/102>Oretic and of IBU tablets in the order Avicel PH-102 > or = UICEL-XL approximately UICEL-A/102>Advil. The friability values for all tablets were well below the maximum 1% USP tolerance limit. UICEL-A/102 and UICEL-XL tablets containing HCTZ disintegrated rapidly (<25 s). Oretic tablets disintegrated in about 60 s, while Avicel PH-102 tablets remained intact during 1 h test period. The IBU tablets made using UICEL-A/102 disintegrated the fastest, UICEL-XL and Advil tablets the next, and Avicel PH-102 tablets remained intact. All tablets, except for those of Avicel PH-102, conformed to the USP drug release requirements. These results conclusively show that UICEL-A/102 and UICEL-XL have the potential to be used as filler, binder, and disintegrant, all-in-one, in the design of tablets containing either a low dose or high dose drug by the direct compression method.

Evaluation of the tablets' surface flow velocities in pan coaters.

PubMed

Dreu, Rok; Toschkoff, Gregor; Funke, Adrian; Altmeyer, Andreas; Knop, Klaus; Khinast, Johannes; Kleinebudde, Peter

2016-09-01

The tablet pan coating process involves various types of transverse tablet bed motions, ranging from rolling to cascading. To preserve satisfactory results in terms of coating quality after scale-up, understanding the dynamics of pan coating process should be achieved. The aim of this study was to establish a methodology of estimating translational surface velocities of the tablets in a pan coater and to assess their dependence on the drum's filling degree, the pan speed, the presence of baffles and the selected tablet properties in a dry bed system and during coating while varying the drum's filling degree and the pan speed. Experiments were conducted on the laboratory scale and on the pilot scale in side-vented pan coaters. Surface movement of biconvex two-layer tablets was assessed before, during and after the process of active coating. In order to determine the tablets' surface flow velocities, a high-speed video of the tablet surface flow was recorded via a borescope inserted into the coating drum and analysed via a cross-correlation algorithm. The obtained tablet velocity data were arranged in a linear fashion as a function of the coating drum's radius and frequency. Velocity data obtained during coating were close to those of dry tablets after coating. The filling degree had little influence on the tablet velocity profile in a coating drum with baffles but clearly affected it in a coating drum without baffles. In most but not all cases, tablets with a lower static angle of repose had tablet velocity profiles with lower slopes than tablets with higher inter-tablet friction. This particular tablet velocity response can be explained by case specific values of tablet bed's dynamic angle of repose. Copyright © 2016 Elsevier B.V. All rights reserved.

Accuracy of tablet splitting and liquid measurements: an examination of who, what and how.

PubMed

Abu-Geras, Dana; Hadziomerovic, Dunja; Leau, Andrew; Khan, Ramzan Nazim; Gudka, Sajni; Locher, Cornelia; Razaghikashani, Maryam; Lim, Lee Yong

2017-05-01

To examine factors that might affect the ability of patients to accurately halve tablets or measure a 5-ml liquid dose. Eighty-eight participants split four different placebo tablets by hand and using a tablet splitter, while 85 participants measured 5 ml of water, 0.5% methylcellulose (MC) and 1% MC using a syringe and dosing cup. Accuracy of manipulation was determined by mass measurements. The general population was less able than pharmacy students to break tablets into equal parts, although age, gender and prior experience were insignificant factors. Greater accuracy of tablet halving was observed with tablet splitter, with scored tablets split more equally than unscored tablets. Tablet size did not affect the accuracy of splitting. However, >25% of small scored tablets failed to be split by hand, and 41% of large unscored tablets were split into >2 portions in the tablet splitter. In liquid measurement, the syringe provided more accurate volume measurements than the dosing cup, with higher accuracy observed for the more viscous MC solutions than water. Formulation characteristics and manipulation technique have greater influences on the accuracy of medication modification and should be considered in off-label drug use in vulnerable populations. © 2016 Royal Pharmaceutical Society.

Axial strength test for round flat faced versus capsule shaped bilayer tablets.

PubMed

Franck, Jason; Abebe, Admassu; Keluskar, Rekha; Martin, Kyle; Majumdar, Antara; Kottala, Niranjan; Stamato, Howard

2015-03-01

There has been increasing interest in fixed dose combination (FDC) therapy. Multi-layer tablets are a popular choice among various technologies to deliver FDCs. In most cases, round flat faced tooling is used in testing tablets as they have the simplest geometry. However, shaped tooling is more common for commercial products and may have an effect on bilayer tablet strength. Capsule shaped bilayer tablets, similar to a commercial image, and holders conforming to the tablet topology, were compared with similar round flat faced bilayer tablets and their corresponding holders. Bilayer tablets were subjected to an axial test device, until fracture and the quantitative breaking force value was recorded. As the second layer compression force increases, regardless of holder design, an increase in breaking force occurs as expected. This consistent trend provides insight regarding the breaking force of capsule shaped bilayer tablets. The results of this study show that at lower second layer compression forces, tablet geometry does not significantly impact the results. However, at higher compression forces, a significant difference in breaking force between tablet geometries exists. Therefore, using a test geometry close to the final commercial tablet image is recommended to have the most accurate prediction for tablet breakage.

[Tablets and tablet production - with special reference to Icelandic conditions].

PubMed

Skaftason, Jóhannes F; Jóhannesson, Thorkell

2013-04-01

Modern tablet compression was instituted in England in 1844 by William Brockedon (1787-1854). The first tablets made according to Brockedon´s procedures contained watersoluble salts and were most likely compressed without expedients. In USA a watershed occurred around 1887 when starch (amylum maydis) was introduced to disperse tablets in aqueous milieu in order to corroborate bioavailability of drugs in the almentary canal. About the same time great advances in tablet production were introduced by the British firm Burroughs Wellcome and Co. In Denmark on the other hand tablet production remained on low scale until after 1920. As Icelandic pharmacies and drug firms modelled themselves mostly upon Danish firms tablet production was first instituted in Iceland around 1930. The first tablet machines in Iceland were hand-driven. More efficent machines came after 1945. Around 1960 three sizeable tablet producers were in Iceland; now there is only one. Numbers of individual tablet species (generic and proprietary) on the market rose from less than 10 in 1913 to 500 in 1965, with wide variations in numbers in between. Tablets have not wiped out other medicinal forms for peroral use but most new peroral drugs have been marketed in the form of tablets during the last decades.

Accelerating scientific computations with mixed precision algorithms

NASA Astrophysics Data System (ADS)

Baboulin, Marc; Buttari, Alfredo; Dongarra, Jack; Kurzak, Jakub; Langou, Julie; Langou, Julien; Luszczek, Piotr; Tomov, Stanimire

2009-12-01

On modern architectures, the performance of 32-bit operations is often at least twice as fast as the performance of 64-bit operations. By using a combination of 32-bit and 64-bit floating point arithmetic, the performance of many dense and sparse linear algebra algorithms can be significantly enhanced while maintaining the 64-bit accuracy of the resulting solution. The approach presented here can apply not only to conventional processors but also to other technologies such as Field Programmable Gate Arrays (FPGA), Graphical Processing Units (GPU), and the STI Cell BE processor. Results on modern processor architectures and the STI Cell BE are presented. Program summaryProgram title: ITER-REF Catalogue identifier: AECO_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AECO_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 7211 No. of bytes in distributed program, including test data, etc.: 41 862 Distribution format: tar.gz Programming language: FORTRAN 77 Computer: desktop, server Operating system: Unix/Linux RAM: 512 Mbytes Classification: 4.8 External routines: BLAS (optional) Nature of problem: On modern architectures, the performance of 32-bit operations is often at least twice as fast as the performance of 64-bit operations. By using a combination of 32-bit and 64-bit floating point arithmetic, the performance of many dense and sparse linear algebra algorithms can be significantly enhanced while maintaining the 64-bit accuracy of the resulting solution. Solution method: Mixed precision algorithms stem from the observation that, in many cases, a single precision solution of a problem can be refined to the point where double precision accuracy is achieved. A common approach to the solution of linear systems, either dense or sparse, is to perform the LU factorization of the coefficient matrix using Gaussian elimination. First, the coefficient matrix A is factored into the product of a lower triangular matrix L and an upper triangular matrix U. Partial row pivoting is in general used to improve numerical stability resulting in a factorization PA=LU, where P is a permutation matrix. The solution for the system is achieved by first solving Ly=Pb (forward substitution) and then solving Ux=y (backward substitution). Due to round-off errors, the computed solution, x, carries a numerical error magnified by the condition number of the coefficient matrix A. In order to improve the computed solution, an iterative process can be applied, which produces a correction to the computed solution at each iteration, which then yields the method that is commonly known as the iterative refinement algorithm. Provided that the system is not too ill-conditioned, the algorithm produces a solution correct to the working precision. Running time: seconds/minutes

Relationship between Age and the Ability to Break Scored Tablets

PubMed Central

Notenboom, Kim; Vromans, Herman; Schipper, Maarten; Leufkens, Hubert G. M.; Bouvy, Marcel L.

2016-01-01

Background: Practical problems with the use of medicines, such as difficulties with breaking tablets, are an often overlooked cause for non-adherence. Tablets frequently break in uneven parts and loss of product can occur due to crumbling and powdering. Health characteristics, such as the presence of peripheral neuropathy, decreased grip strength and manual dexterity, can affect a patient's ability to break tablets. As these impairments are associated with aging and age-related diseases, such as Parkinson's disease and arthritis, difficulties with breaking tablets could be more prevalent among older adults. The objective of this study was to investigate the relationship between age and the ability to break scored tablets. Methods: A comparative study design was chosen. Thirty-six older adults and 36 young adults were systematically observed with breaking scored tablets. Twelve different tablets were included. All participants were asked to break each tablet by three techniques: in between the fingers with the use of nails, in between the fingers without the use of nails and pushing the tablet downward with one finger on a solid surface. It was established whether a tablet was broken or not, and if broken, whether the tablet was broken accurately or not. Results: The older adults experienced more difficulties to break tablets compared to the young adults. On average, the older persons broke 38.1% of the tablets, of which 71.0% was broken accurately. The young adults broke 78.2% of the tablets, of which 77.4% was broken accurately. Further analysis by mixed effects logistic regression revealed that age was associated with the ability to break tablets, but not with the accuracy of breaking. Conclusions: Breaking scored tablets by hand is less successful in an elderly population compared to a group of young adults. Health care providers should be aware that tablet breaking is not appropriate for all patients and for all drugs. In case tablet breaking is unavoidable, a patient's ability to break tablets should be assessed by health care providers and instructions on the appropriate method of breaking should be provided. PMID:27507946

Suberin Fatty Acids from Outer Birch Bark: Isolation and Physical Material Characterization.

PubMed

Heinämäki, Jyrki; Pirttimaa, Minni M; Alakurtti, Sami; Pitkänen, H Pauliina; Kanerva, Heimo; Hulkko, Janne; Paaver, Urve; Aruväli, Jaan; Yliruusi, Jouko; Kogermann, Karin

2017-04-28

The isolation and physical material properties of suberin fatty acids (SFAs) were investigated with special reference to their potential applications as novel pharmaceutical excipients. SFAs were isolated from outer birch bark (OBB) with a new extractive hydrolysis method. The present simplified isolation process resulted in a moderate batch yield and chemical purity of SFAs, but further development is needed for establishing batch-to-batch variation. Cryogenic milling was the method of choice for the particle size reduction of SFAs powder. The cryogenically milled SFAs powder exhibited a semicrystalline structure with apparent microcrystalline domains within an amorphous fatty acids matrix. The thermogravimetric analysis (TGA) of SFAs samples showed a good thermal stability up to 200 °C, followed by a progressive weight loss, reaching a plateau at about 95% volatilization at about 470 °C. The binary blends of SFAs and microcrystalline cellulose (MCC; Avicel PH 101) in a ratio of 25:75 (w/w) displayed good powder flow and tablet compression properties. The corresponding theophylline-containing tablets showed sustained or prolonged-release characteristics. The physicochemical and bulk powder properties of SFAs isolated from OBB are auspicious in terms of potential pharmaceutical excipient applications.

Testing the performance of pure spectrum resolution from Raman hyperspectral images of differently manufactured pharmaceutical tablets.

PubMed

Vajna, Balázs; Farkas, Attila; Pataki, Hajnalka; Zsigmond, Zsolt; Igricz, Tamás; Marosi, György

2012-01-27

Chemical imaging is a rapidly emerging analytical method in pharmaceutical technology. Due to the numerous chemometric solutions available, characterization of pharmaceutical samples with unknown components present has also become possible. This study compares the performance of current state-of-the-art curve resolution methods (multivariate curve resolution-alternating least squares, positive matrix factorization, simplex identification via split augmented Lagrangian and self-modelling mixture analysis) in the estimation of pure component spectra from Raman maps of differently manufactured pharmaceutical tablets. The batches of different technologies differ in the homogeneity level of the active ingredient, thus, the curve resolution methods are tested under different conditions. An empirical approach is shown to determine the number of components present in a sample. The chemometric algorithms are compared regarding the number of detected components, the quality of the resolved spectra and the accuracy of scores (spectral concentrations) compared to those calculated with classical least squares, using the true pure component (reference) spectra. It is demonstrated that using appropriate multivariate methods, Raman chemical imaging can be a useful tool in the non-invasive characterization of unknown (e.g. illegal or counterfeit) pharmaceutical products. Copyright © 2011 Elsevier B.V. All rights reserved.

Variability in the 3,4-methylenedioxymethamphetamine content of 'ecstasy' tablets in the UK.

PubMed

Wood, David Michael; Stribley, Vasoulla; Dargan, Paul Ivor; Davies, Susannah; Holt, David W; Ramsey, John

2011-09-01

Toxicity, such as hyperpyrexia, associated with the use of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') appears to be related to serum MDMA concentrations. However, there does not appear to be a similar association with the number of tablets ingested, suggesting variation in the tablet content of MDMA. Although work has shown this variation in other areas of the world, no studies have reported on the variation of MDMA content in UK ecstasy tablets. Ecstasy tablets seized from individuals attending nightclubs were analysed qualitatively to determine if they contained MDMA and quantitatively to determine the MDMA content per tablet. The mean amount of MDMA hydrochloride in 101 seized ecstasy tablets was 58.7±22.9 mg per tablet, with a range of 20 mg to 131 mg per tablet. The majority (96.0%) of tablets contained less than 100 mg MDMA per tablet. There appeared to be a bimodal distribution of MDMA content at approximately 20-40 mg per tablet and 60-80 mg per tablet. There is variability in the MDMA content of ecstasy tablets in the UK. This variability could potentially put users at increased risk of acute harm due to inadvertent excess ingestion of MDMA, as they are unaware of the differences in the MDMA content. Repeat sampling and quantification of MDMA content of ecstasy tablets in the UK will allow better education of users about the potential harms associated with the variability in the MDMA content. In addition, it will provide information to allow the monitoring of changes in not only the MDMA content, but also other adulterants, in ecstasy tablets.

Exploiting data representation for fault tolerance

DOE PAGES

Hoemmen, Mark Frederick; Elliott, J.; Sandia National Lab.; ...

2015-01-06

Incorrect computer hardware behavior may corrupt intermediate computations in numerical algorithms, possibly resulting in incorrect answers. Prior work models misbehaving hardware by randomly flipping bits in memory. We start by accepting this premise, and present an analytic model for the error introduced by a bit flip in an IEEE 754 floating-point number. We then relate this finding to the linear algebra concepts of normalization and matrix equilibration. In particular, we present a case study illustrating that normalizing both vector inputs of a dot product minimizes the probability of a single bit flip causing a large error in the dot product'smore » result. Moreover, the absolute error is either less than one or very large, which allows detection of large errors. Then, we apply this to the GMRES iterative solver. We count all possible errors that can be introduced through faults in arithmetic in the computationally intensive orthogonalization phase of GMRES, and show that when the matrix is equilibrated, the absolute error is bounded above by one.« less

Mouse embryonic stem cell culture for generation of three-dimensional retinal and cortical tissues.

PubMed

Eiraku, Mototsugu; Sasai, Yoshiki

2011-12-15

Generation of compound tissues with complex structures is a major challenge in cell biology. In this article, we describe a protocol for mouse embryonic stem cell (ESC) culture for in vitro generation of three-dimensional retinal tissue, comparing it with the culture protocol for cortical tissue generation. Dissociated ESCs are reaggregated in a 96-well plate with reduced cell-plate adhesion and cultured as floating aggregates. Retinal epithelium is efficiently generated when ESC aggregates are cultured in serum-free medium containing extracellular matrix proteins, spontaneously forming hemispherical vesicles and then progressively transforming into a shape reminiscent of the embryonic optic cup in 9-10 d. In long-term culture, the ESC-derived optic cup generates a fully stratified retinal tissue consisting of all major neural retinal components. In contrast, the cortical differentiation culture can be started without exogenous extracellular matrix proteins, and it generates stratified cortical epithelia consisting of four distinct layers in 13 d.

Performance and Accuracy of LAPACK's Symmetric TridiagonalEigensolvers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demmel, Jim W.; Marques, Osni A.; Parlett, Beresford N.

2007-04-19

We compare four algorithms from the latest LAPACK 3.1 release for computing eigenpairs of a symmetric tridiagonal matrix. These include QR iteration, bisection and inverse iteration (BI), the Divide-and-Conquer method (DC), and the method of Multiple Relatively Robust Representations (MR). Our evaluation considers speed and accuracy when computing all eigenpairs, and additionally subset computations. Using a variety of carefully selected test problems, our study includes a variety of today's computer architectures. Our conclusions can be summarized as follows. (1) DC and MR are generally much faster than QR and BI on large matrices. (2) MR almost always does the fewestmore » floating point operations, but at a lower MFlop rate than all the other algorithms. (3) The exact performance of MR and DC strongly depends on the matrix at hand. (4) DC and QR are the most accurate algorithms with observed accuracy O({radical}ne). The accuracy of BI and MR is generally O(ne). (5) MR is preferable to BI for subset computations.« less

Design space construction of multiple dose-strength tablets utilizing bayesian estimation based on one set of design-of-experiments.

PubMed

Maeda, Jin; Suzuki, Tatsuya; Takayama, Kozo

2012-01-01

Design spaces for multiple dose strengths of tablets were constructed using a Bayesian estimation method with one set of design of experiments (DoE) of only the highest dose-strength tablet. The lubricant blending process for theophylline tablets with dose strengths of 100, 50, and 25 mg is used as a model manufacturing process in order to construct design spaces. The DoE was conducted using various Froude numbers (X(1)) and blending times (X(2)) for theophylline 100-mg tablet. The response surfaces, design space, and their reliability of the compression rate of the powder mixture (Y(1)), tablet hardness (Y(2)), and dissolution rate (Y(3)) of the 100-mg tablet were calculated using multivariate spline interpolation, a bootstrap resampling technique, and self-organizing map clustering. Three experiments under an optimal condition and two experiments under other conditions were performed using 50- and 25-mg tablets, respectively. The response surfaces of the highest-strength tablet were corrected to those of the lower-strength tablets by Bayesian estimation using the manufacturing data of the lower-strength tablets. Experiments under three additional sets of conditions of lower-strength tablets showed that the corrected design space made it possible to predict the quality of lower-strength tablets more precisely than the design space of the highest-strength tablet. This approach is useful for constructing design spaces of tablets with multiple strengths.

Bioavailability, pharmacokinetics, and safety of riociguat given as an oral suspension or crushed tablet with and without food

PubMed Central

Frey, Reiner; Becker, Corina; Unger, Sigrun; Wensing, Georg; Mück, Wolfgang

2016-01-01

Abstract Riociguat is approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Some patients have difficulty swallowing tablets; therefore, 2 randomized, nonblinded, crossover studies compared the relative bioavailability of riociguat oral suspensions and immediate-release (IR) tablet and of crushed-tablet preparations versus whole IR tablet. In study 1, 30 healthy subjects received 5 single riociguat doses: 0.3 and 2.4 mg (0.15 mg/mL suspensions), 0.15 mg (0.03 mg/mL), and 1.0 mg (whole IR tablet) under fasted conditions and 2.4 mg (0.15 mg/mL) after a high-fat, high-calorie American-style breakfast. In study 2, 25 healthy men received 4 single 2.5-mg doses: whole IR tablet and crushed IR tablet suspended in applesauce and water, respectively, under fasted conditions, and whole IR tablet after a continental breakfast. In study 1, dose-normalized pharmacokinetics of riociguat oral suspensions and 1.0-mg whole IR tablet were similar in fasted conditions; 90% confidence intervals for riociguat area under the curve (AUC) to dose and mean maximum concentration (Cmax) to dose were within bioequivalence criteria. After food, dose-normalized AUC and Cmax decreased by 15% and 38%, respectively. In study 2, riociguat exposure was similar for all preparations; AUC ratios for crushed-IR-tablet preparations to whole IR tablet were within bioequivalence criteria. The Cmax increased by 17% for crushed IR tablet in water versus whole IR tablet. Food intake decreased Cmax of the whole tablet by 16%, with unaltered AUC versus fasted conditions. Riociguat bioavailability was similar between the oral suspensions and the whole IR tablet; exposure was similar between whole IR tablet and crushed-IR-tablet preparations. Minor food effects were observed. Results suggest that riociguat formulations are interchangeable. PMID:27162630

Bioavailability, pharmacokinetics, and safety of riociguat given as an oral suspension or crushed tablet with and without food.

PubMed

Saleh, Soundos; Frey, Reiner; Becker, Corina; Unger, Sigrun; Wensing, Georg; Mück, Wolfgang

2016-03-01

Riociguat is approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Some patients have difficulty swallowing tablets; therefore, 2 randomized, nonblinded, crossover studies compared the relative bioavailability of riociguat oral suspensions and immediate-release (IR) tablet and of crushed-tablet preparations versus whole IR tablet. In study 1, 30 healthy subjects received 5 single riociguat doses: 0.3 and 2.4 mg (0.15 mg/mL suspensions), 0.15 mg (0.03 mg/mL), and 1.0 mg (whole IR tablet) under fasted conditions and 2.4 mg (0.15 mg/mL) after a high-fat, high-calorie American-style breakfast. In study 2, 25 healthy men received 4 single 2.5-mg doses: whole IR tablet and crushed IR tablet suspended in applesauce and water, respectively, under fasted conditions, and whole IR tablet after a continental breakfast. In study 1, dose-normalized pharmacokinetics of riociguat oral suspensions and 1.0-mg whole IR tablet were similar in fasted conditions; 90% confidence intervals for riociguat area under the curve (AUC) to dose and mean maximum concentration (C max) to dose were within bioequivalence criteria. After food, dose-normalized AUC and C max decreased by 15% and 38%, respectively. In study 2, riociguat exposure was similar for all preparations; AUC ratios for crushed-IR-tablet preparations to whole IR tablet were within bioequivalence criteria. The C max increased by 17% for crushed IR tablet in water versus whole IR tablet. Food intake decreased C max of the whole tablet by 16%, with unaltered AUC versus fasted conditions. Riociguat bioavailability was similar between the oral suspensions and the whole IR tablet; exposure was similar between whole IR tablet and crushed-IR-tablet preparations. Minor food effects were observed. Results suggest that riociguat formulations are interchangeable.

Tablet splitting: is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting.

PubMed

Helmy, Sally A

2015-01-01

Tablet splitting is a well-established medical practice in clinical settings for multiple reasons, including cost savings and ease of swallowing. However, it does not necessarily result in weight-uniform half tablets. To (a) investigate the effect of tablet characteristics on weight and content uniformity of half tablets, resulting from splitting 16 commonly used medications in the outpatient setting and (b) provide recommendations for safe tablet-splitting prescribing practices. Ten random tablets from each of the selected medications were weighed and split by 5 volunteers (2 men and 3 women aged 25-44 years) using a knife. The selected medications were mirtazapine 30 mg, bromazepam 3 mg, oxcarbazepin 150 mg, sertraline 50 mg, carvedilol 25 mg, bisoprolol fumarate 10 mg, losartan 50 mg, digoxin 0.25 mg, amiodarone HCl 200 mg, metformin HCl 1,000 mg, glimepiride 4 mg, montelukast 10 mg, ibuprofen 600 mg, celecoxib 200 mg, meloxicam 15 mg, and sildenafil citrate 50 mg. The resulting half tablets were evaluated for weight and drug content uniformity in accordance with proxy United States Pharmacopeia (USP) specification (95%-105% for digoxin and 90%-110% for the other 15 drugs). Weight and drug content uniformity were assessed by comparing weight or drug content of the half tablets with one-half of the mean weight or drug content for all whole tablets in the sample. The percentages by which the weight and drug content of each whole tablet or half tablet differed from sample mean values were calculated. Other relevant physical characteristics of the 16 products were measured. A total of 52 of 320 half tablets (16.2%) and 48 of 320 half tablets (15.0%) fell outside of the proxy USP specification for weight and drug content, respectively. Bromazepam, carvedilol, bisoprolol, losartan, digoxin, and meloxicam half tablets failed the weight and content uniformity test; however, the half tablets for the rest of the medications passed the test. Mean percent weight loss after splitting was less than 1.5% for all drugs. Bromazepam, carvedilol, and digoxin showed the highest powdering loss during the tablet-splitting process. Tablet splitting could be safer and easier when drug- and patient-specific criteria have been met. Tablet size, shape, and hardness may also play a role in the decision to split a tablet or not. Tablets containing drugs with a wide therapeutic index and long half-life might be more suitable candidates for division. Dose variation exceeded a proxy USP specification for more than one-third of sampled half tablets of bromazepam, carvedilol, bisoprolol, and digoxin. Drug content variation in half tablets appeared to be attributed to weight variation due to fragment or powder loss during the splitting process.

Bosentan

MedlinePlus

Bosentan comes as a tablet and as a dispersible tablet (tablet that can be dissolved in liquid) to take by mouth. It is usually taken ... your doctor.If you are taking the dispersible tablet, place the tablet in a small amount of ...

21 CFR 520.82b - Aminopropazine fumarate, neomycin sulfate tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aminopropazine fumarate, neomycin sulfate tablets... Aminopropazine fumarate, neomycin sulfate tablets. (a) Specifications. The drug is in tablet form. Each tablet... administered at a dosage level of one to two tablets per 10 pounds of body weight twice daily for 3 days.1 (3...

[Production and assessing release of imipramine and magnesium from tablets].

PubMed

Kasperek, Regina; Zimmer, Łukasz; Szalast-Pietrzak, Agnieszka; Marzec, Zbigniew; Poleszak, Ewa

2014-01-01

In the pharmaceutical technology there is a trend to produce tablets composed of several medicinal substances to increase therapeutic effect and reduce the frequency of drug administration. In the literature there are reports concerning pharmacological studies in which a potentiation of the effects has been observed after a co-administration of antidepressant imipramine and magnesium. Currently, there is no formulation on the market comprising imipramine and magnesium, therefore, it was decided to produce uncoated tablets. In order to prepare the tablets by direct compression, it was necessary to select suitable excipients. The aim of the study was to elaborate the composition and to prepare the tablets with imipramine and magnesium, as well as to assess the quality of the tablets by physical characteristics and by the release study of the active substances. In order to prepare the tablets, compositions of different polymers and other excipients were added. The tablets were produced by direct compression method in a tablet press. Physical properties of the obtained tablets and the release of the active substances into an acidic medium in a paddle apparatus were tested. The contents of imipramine and magnesium were determined by different methods: spectrophotometrically and atomic absorption spectrometry, respectively. The composition of excipients necessary to produce tablets comprising imipramine and magnesium was established. All of prepared tablets were in compliance with the pharmacopoeial requirements. The release tests showed that above 80% of imipramine was released within 20-35 min and 80-76% of magnesium up to 45 min from the composed tablets and one-ingredient tablets, respectively. The compositions of excipients for tablets consisting of imipramine and magnesium were presented. The active substances were released within 45 min in the acidic medium, and the administration of these substances in the composed tablets did not affect pharmaceutical availability.

Exploration of the associations of touch-screen tablet computer usage and musculoskeletal discomfort.

PubMed

Chiang, Hsin-Yu Ariel; Liu, Chien-Hsiou

2016-03-10

Tablet users may be at high risk of developing physical discomfort because of their usage behaviors and tablet design. Investigate the usage of tablets, variations in head and neck posture associated with different tablet tilt angles, and the association of tablet use with users' musculoskeletal discomfort. A survey of users' subjective perceptions conducted by questionnaire and measurements of users' postures by a 3D Motion analysis system was used to explore the effects of tablet use. The questionnaire results indicated that over half of the participants reported physical discomfort after using tablets, with the most prevalent discomfort in the neck and shoulders, and more intensity of discomfort for the back although only few participants experienced it. Chi-squared tests indicated that significantly more participants who tended to use tablet computers to play games reported having musculoskeletal discomfort after using a tablet. In addition, preferences for tablet tilt angles varied across tasks (reading and game playing). The results from the 3D motion analysis revealed that head and neck flexion angles were significantly reduced when the tablets were positioned at relatively steep tilt angles. Neck flexion angle was significantly higher in game playing. These data add information regarding to the usage of tablet and its associations with physical discomfort (significantly more participants who tended to use tablet computers to play games reported having musculoskeletal discomfort after using a tablet). Steep tilt angles (such as 60°) may cause tablet users to decrease their head and neck flexion angles, which could lead to a more neutral, effortless, and ergonomically correct posture. Maintaining proper neck posture during active activities such as game playing is recommended to avoid neck discomfort.

Understanding the Delamination Risk of a Trilayer Tablet Using Minipiloting Tools.

PubMed

Tao, Jing; Robertson-Lavalle, Sophia; Pandey, Preetanshu; Badawy, Sherif

2017-11-01

A multilayer tablet is one of the formulation options used to mitigate chemical and physical incompatibility between different drug substances. Feasibility studies of multilayer tablets are often conducted using round flat-faced punch tooling. However, the link between different tooling designs and multilayer tablet performance is not well established. This study uses a prototype trilayer tablet and examines tooling design considerations when conducting small-scale studies to gauge the risk of interfacial defects. The impact of tablet weight and dimensions was evaluated to gain understanding of the effect of scale-up/down of tablet size. The factors in tooling selection, including tablet shape, cup depth, and size of embossing were evaluated to gain insight on the impact of tooling design on the interfacial strength of the trilayer tablet. It was found that tablet weight and dimensions can significantly affect the interfacial strength due to their impact on force transmission during compression and the retardation force from the die wall during ejection. Round flat-faced tooling generated trilayer tablets of the strongest interfacial strength compared to typical commercial tablets-oval shaped with concave surfaces. These factors should be accounted for when using round flat compacts to assess the interface risks of a multilayer tablet. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Non-contact weight measurement of flat-faced pharmaceutical tablets using terahertz transmission pulse delay measurements.

PubMed

Bawuah, Prince; Silfsten, Pertti; Ervasti, Tuomas; Ketolainen, Jarkko; Zeitler, J Axel; Peiponen, Kai-Erik

2014-12-10

By measuring the time delay of a terahertz pulse traversing a tablet, and hence its effective refractive index, it is possible to non-invasively and non-destructively detect the weight of tablets made of microcrystalline cellulose (MCC). Two sets of MCC tablets were used in the study: Set A (training set) consisted of 13 tablets with nominally constant height but varying porosities, whereas Set B (test set) comprised of 21 tablets with nominally constant porosity but different heights. A linear correlation between the estimated absolute weight based on the terahertz measurement and the measured weight of both sets of MCC tablets was found. In addition, it was possible to estimate the height of the tablets by utilizing the estimated absolute weight and calculating the relative change of height of each tablet with respect to an ideal tablet. A good agreement between the experimental and the calculated results was found highlighting the potential of this technique for in-line sensing of the weight, porosity and the relative change in height of the tablets compared to a reference/ideal tablet. In this context, we propose a quantitative quality control method to assess the deviations in porosity of tablets immediately after compaction. Copyright © 2014 Elsevier B.V. All rights reserved.

33 CFR 144.01-1 - Life floats.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Life floats. 144.01-1 Section 144... CONTINENTAL SHELF ACTIVITIES LIFESAVING APPLIANCES Manned Platforms § 144.01-1 Life floats. Each manned platform shall be provided with at least two approved life floats. The life floats shall have sufficient...

46 CFR 160.027-3 - Additional requirements for life floats.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 6 2010-10-01 2010-10-01 false Additional requirements for life floats. 160.027-3..., CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Life Floats for Merchant Vessels § 160.027-3 Additional requirements for life floats. (a) Each life float must have a platform designed...

46 CFR 160.027-3 - Additional requirements for life floats.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 6 2011-10-01 2011-10-01 false Additional requirements for life floats. 160.027-3..., CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Life Floats for Merchant Vessels § 160.027-3 Additional requirements for life floats. (a) Each life float must have a platform designed...

33 CFR 144.01-1 - Life floats.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Life floats. 144.01-1 Section 144... CONTINENTAL SHELF ACTIVITIES LIFESAVING APPLIANCES Manned Platforms § 144.01-1 Life floats. Each manned platform shall be provided with at least two approved life floats. The life floats shall have sufficient...

14 CFR 29.757 - Hull and auxiliary float strength.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Hull and auxiliary float strength. 29.757... AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Floats and Hulls § 29.757 Hull and auxiliary float strength. The hull, and auxiliary floats if used, must withstand the...

33 CFR 144.01-1 - Life floats.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Life floats. 144.01-1 Section 144... CONTINENTAL SHELF ACTIVITIES LIFESAVING APPLIANCES Manned Platforms § 144.01-1 Life floats. Each manned platform shall be provided with at least two approved life floats. The life floats shall have sufficient...

33 CFR 144.01-1 - Life floats.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Life floats. 144.01-1 Section 144... CONTINENTAL SHELF ACTIVITIES LIFESAVING APPLIANCES Manned Platforms § 144.01-1 Life floats. Each manned platform shall be provided with at least two approved life floats. The life floats shall have sufficient...

33 CFR 144.01-1 - Life floats.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Life floats. 144.01-1 Section 144... CONTINENTAL SHELF ACTIVITIES LIFESAVING APPLIANCES Manned Platforms § 144.01-1 Life floats. Each manned platform shall be provided with at least two approved life floats. The life floats shall have sufficient...

46 CFR 160.027-3 - Additional requirements for life floats.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Additional requirements for life floats. 160.027-3..., CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Life Floats for Merchant Vessels § 160.027-3 Additional requirements for life floats. (a) Each life float must have a platform designed...

46 CFR 160.027-3 - Additional requirements for life floats.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Additional requirements for life floats. 160.027-3..., CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Life Floats for Merchant Vessels § 160.027-3 Additional requirements for life floats. (a) Each life float must have a platform designed...

46 CFR 160.027-3 - Additional requirements for life floats.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 6 2012-10-01 2012-10-01 false Additional requirements for life floats. 160.027-3..., CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Life Floats for Merchant Vessels § 160.027-3 Additional requirements for life floats. (a) Each life float must have a platform designed...