Formulation studies for mirtazapine orally disintegrating tablets.

PubMed

Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

2016-01-01

Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab). Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium. Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media. Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles. Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

Application of a novel automatic disintegration apparatus for the development and evaluation of a direct compression rapidly disintegrating tablet.

PubMed

Jung, Huijeong Ashley; Augsburger, Larry L

2012-07-01

An automatic disintegration tester was developed and used to explore disintegration mechanism and times of rapidly disintegrating tablets. DT50, the time required for a tablet to decrease in its thickness by half, allowed an unbiased determination of disintegration time. Calcium silicate concentration, Explotab® concentration, DiPac®/Xylitab® ratio as fillers, and compression pressure were evaluated using a central composite model design analysis for their DT50, tensile strength, and friability. Tablets that could reasonably be handled (friability <10%) could be produced. The expansion coefficient (n) and the exponential rate constant (k) for disintegrating tablets, originally measured by Caramella et al. using force kinetics, could be determined from axial displacement data measured directly without the need to assume that disintegration force generation was indicative of changes in tablet volume. The n values of tablets containing calcium silicate, Ditab® and/or Xylitab®, magnesium stearate, and Explotab® suggested that the amount of Explotab® was not a significant factor in determining the disintegration mechanism; however, the type of disintegrant used did alter the n value. Primojel® and Explotab®, which are in the same class of disintegrants, exhibited similar DT50, n, and k. Polyplasdone® XL exhibited a much higher n, while yielding faster DT50, suggesting that its performance is more dependent on facilitating the interfacial separation of particles. AcDiSol® showed no apparent moisture sensitivity in regards to disintegration efficiency. The use of the novel apparatus proved to be useful in measuring disintegration efficiency of rapidly disintegrating tablets and in providing valuable information on the disintegration phenomena.

Evaluation of the disintegration time of rapidly disintegrating tablets via a novel method utilizing a CCD camera.

PubMed

Morita, Yutaka; Tsushima, Yuki; Yasui, Masanobu; Termoz, Ryoji; Ajioka, Junko; Takayama, Kozo

2002-09-01

Many kinds of rapidly disintegrating or oral disintegrating tablets (RDT) have been developed to improve the ease of tablet administration, especially for elderly and pediatric patients. In these cases, knowledge regarding disintegration behavior appears important with respect to the development of such a novel tablet. Ordinary disintegration testing, such as the Japanese Pharmacopoeia (JP) method, faces limitations with respect to the evaluation of rapid disintegration due to strong agitation. Therefore, we have developed a novel apparatus and method to determine the dissolution of the RDT. The novel device consists of a disintegrating bath and CCD camera interfaced with a personal computer equipped with motion capture and image analysis software. A newly developed RDT containing various types of binder was evaluated with this protocol. In this method, disintegration occurs in a mildly agitated medium, which allows differentiation of minor distinctions among RDTs of different formulations. Simultaneously, we were also able to detect qualitative information, i.e., morphological changes in the tablet during disintegration. This method is useful for the evaluation of the disintegration of RDT during pharmaceutical development, and also for quality control during production.

Varying efficacy of superdisintegrants in orally disintegrating tablets among different manufacturers.

PubMed

Mittapalli, R K; Qhattal, H S Sha; Lockman, P R; Yamsani, M R

2010-11-01

The main objective of the present study was to develop an orally disintegrating tablet formulation of domperidone and to study the functionality differences of superdisintegrants each obtained from two different sources on the tablet properties. Domperidone tablets were formulated with different superdisintegrants by direct compression. The effect of the type of superdisintegrant, its concentration and source was studied by measuring the in-vitro disintegration time, wetting time, water absorption ratios, drug release by dissolution and in-vivo oral disintegration time. Tablets prepared with crospovidone had lower disintegration times than tablets prepared from sodium starchglycolate and croscarmellose sodium. Formulations prepared with Polyplasdone XL, Ac-Di-Sol, and Explotab (D series) were better than formulations prepared with superdisintegrants obtained from other sources (DL series) which had longer disintegration times and lower water uptake ratios. The in-vivo disintegration time of formulation D-106 containing polyplasdone XL was significantly lower than that of the marketed formulation Domel-MT. The results from this study suggest that disintegration of orally disintegrating tablets is dependent on the nature of superdisintegrant, concentration in the formulation and its source. Even though a superdisintegrant meets USP standards there can be a variance among manufacturers in terms of performance. This is not only limited to in-vitro studies but carries over to disintegration times in the human population.

Disintegration of chemotherapy tablets for oral administration in patients with swallowing difficulties.

PubMed

Siden, Rivka; Wolf, Matthew

2013-06-01

The administration of oral chemotherapeutic drugs can be problematic in patients with swallowing difficulties. Inability to swallow solid dosage forms can compromise compliance and may lead to poor clinical outcome. The current technique of tablet crushing to aid in administration is considered an unsafe practice. By developing a technique to disintegrate tablets in an oral syringe, the risk associated with tablet crushing can be avoided. The purpose of this study was to determine the feasibility of using disintegration in an oral syringe for the administration of oral chemotherapeutic tablets. Eight commonly used oral chemotherapeutic drugs were tested. Tablets were placed in an oral syringe and allowed to disintegrate in tap water. Various volumes and temperatures were tested to identify which combination allows for complete disintegration of the tablet in the shortest amount of time. The oral syringe disintegration method was considered feasible if disintegration occurred in ≤15 min and in ≤20 mL of water and the dispersion passed through an oral syringe tip. The following tablets were shown to disintegrate within 15 min and in <20 mL of water: busulfan, cyclophosphamide 50 mg, dasatinib, imatinib, methotrexate, and thioguanine. For these drugs, drug-specific information pamphlets can be prepared for patient or caregiver use. Mercaptopurine, cyclophosphamide 25 mg, and mitotane tablets did not pass the disintegration test. Disintegrating oral chemotherapeutic tablets in a syringe provides a closed system to administer hazardous drugs and allows for the safe administration of oral chemotherapeutic drugs in a tablet form to patients with swallowing difficulties.

A new modified wetting test and an alternative disintegration test for orally disintegrating tablets.

PubMed

Hooper, Patrick; Lasher, Jason; Alexander, Kenneth S; Baki, Gabriella

2016-02-20

Industrial manufacturing of solid oral dosage forms require quality tests, such as friability, hardness, and disintegration. The United States Pharmacopeia (USP) disintegration test uses 900mL of water. However, recent studies of orally disintegrating tablets (ODTs) have shown that this volume does not accurately portray the oral environment. In our study, various tests were conducted with a more moderate amount of water that accurately resembles the oral environment. A simulated wetting test was performed to calculate the water absorption ratio. Results showed that wetting was comparable to disintegration. Although the wetting test worked for most types of ODTs, it had limitations that produced inaccurate results. This led to the use of a modified shaking water bath test. This test was found to work for all types of ODT products and was not subject to the limitations of the wetting test. The shake test could provide disintegration times rather than water permeation times; however, it could not be used to calculate the water absorption ratio. A strong correlation was observed between the standardized shake test and the USP disintegration times for the tablets. This shake test could be used during the development stages and quality tests for ODTs with relative ease. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro disintegration studies of weekly generic alendronate sodium tablets (70 mg) available in the US.

PubMed

Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

2009-02-01

Bisphosphonates as a class have the potential to cause upper gastrointestinal irritation. Although the generic alendronate sodium tablets are bioequivalent to the branded product, a potential concern is that the pharmaceutical attributes of the various generic formulations my affect the potential for local irritation and tolerability. The in vitro disintegration times were determined using the method described in the US Pharmacopeia 30 (USP 30). The disintegration of three generic alendronate sodium tablets 70 mg available in the United States was compared to that of the branded product. The mean disintegration times of the generic alendronate sodium tablets ranged from 9 to 10 s for the Barr lots to 108 s for the Watson lot. The disintegration time of the branded product (Fosamax) was 53 s. The three Barr lots and one Teva lot had rapid disintegration times which were similar to the disintegration standards (< 30 s) for orally disintegrating tablets. Since there is no established disintegration time for alendronate sodium tablets there can be no assurance that the generic tablets are equivalent to the branded product in terms of esophageal exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration performance. Copies of generic alendronate sodium tablets are approved based on the results of single-dose bioavailability studies in healthy subjects and this is not considered adequate to establish similar disintegration characteristics.

Correlation of dissolution and disintegration results for an immediate-release tablet.

PubMed

Nickerson, Beverly; Kong, Angela; Gerst, Paul; Kao, Shangming

2018-02-20

The drug release rate of a rapidly dissolving immediate-release tablet formulation with a highly soluble drug is proposed to be controlled by the disintegration rate of the tablet. Disintegration and dissolution test methods used to evaluate the tablets were shown to discriminate manufacturing process differences and compositionally variant tablets. In addition, a correlation was established between disintegration and dissolution. In accordance with ICH Q6A, this work demonstrates that disintegration in lieu of dissolution is suitable as the drug product quality control method for evaluating this drug product. Copyright © 2017 Elsevier B.V. All rights reserved.

[Preparation and quality control of pyridostigmine bromide orally disintegrating tablet].

PubMed

Zhang, Li; Tan, Qun-you; Cheng, Xun-guan; Wang, Hong; Hu, Ni-ni; Zhang, Jing-qing

2012-05-01

To prepare orally disintegrating tablets containing pyridostigmine bromide and optimize formulations. Solid dispersion was prepared using solvent evaporation-deposition method. The formulation was optimized by central composite design-response surface methodology (RSM plus CCD) with disintegration time as a reference parameter. The orally disintegrating tablets showed integrity and were smooth with desirable taste and feel in mouth. The disintegration time was less than 30 s. The cumulative drug dissolution was around 8.5% (around 2.5 mg which was less than bitterness threshold of pyridostigmine bromide of 3 mg) within 5 min in water while the cumulative drug dissolution was higher than 95% within 2 min in 0.1 N HCl. The orally disintegrating tablets are reasonable in formulation, feasible in technology and patient-friendly.

Functionality of disintegrants and their mixtures in enabling fast disintegration of tablets by a quality by design approach.

PubMed

Desai, Parind Mahendrakumar; Er, Patrick Xuan Hua; Liew, Celine Valeria; Heng, Paul Wan Sia

2014-10-01

Investigation of the effect of disintegrants on the disintegration time and hardness of rapidly disintegrating tablets (RDTs) was carried out using a quality by design (QbD) paradigm. Ascorbic acid, aspirin, and ibuprofen, which have different water solubilities, were chosen as the drug models. Disintegration time and hardness of RDTs were determined and modeled by executing combined optimal design. The generated models were validated and used for further analysis. Sodium starch glycolate, croscarmellose sodium, and crospovidone were found to lengthen disintegration time when utilized at high concentrations. Sodium starch glycolate and crospovidone worked synergistically in aspirin RDTs to decrease disintegration time. Sodium starch glycolate-crospovidone mixtures, as well as croscarmellose sodium-crospovidone mixtures, also decreased disintegration time in ibuprofen RDTs at high compression pressures as compared to the disintegrants used alone. The use of sodium starch glycolate in RDTs with highly water soluble active ingredients like ascorbic acid slowed disintegration, while microcrystalline cellulose and crospovidone drew water into the tablet rapidly and quickened disintegration. Graphical optimization analysis demonstrated that the RDTs with desired disintegration times and hardness can be formulated with a larger area of design space by combining disintegrants at difference compression pressures. QbD was an efficient and effective paradigm in understanding formulation and process parameters and building quality in to RDT formulated systems.

Fabrication and optimization of fast disintegrating tablets employing interpolymeric chitosan-alginate complex and chitin as novel superdisintegrants.

PubMed

Goel, Honey; Tiwary, Ashok K; Rana, Vikas

2011-01-01

The objective of the present work was to optimize the formulation of fast disintegrating tablets (FDTs) of ondansetron HCl containing novel superdisintegrants, possessing sufficient mechanical strength and disintegration time comparable to those containing crospovidone or croscarmellose sodium. The FDTs were formulated using a novel superdisintegrant (chitosan-alginate (1:1) interpolymer complex and chitin) to achieve a sweet tasting disintegrating system. The results revealed that chitin (5-20%) increased the porosity and decreased the DT of tablets. At higher concentrations chitin maintained tablet porosity even at 5.5 kg crushing strength. Ondansetron HCl was found to antagonize the wicking action of glycine. Further, evaluation of the mechanism of disintegration revealed that glycine transported the aqueous medium to different parts of the tablets while the chitosan-alginate complex swelled up due to transfer of moisture from glycine. This phenomenon resulted in breakage of the tablet within seconds. For preparing optimized FDTs, the reduced model equations generated from Box-Behnken design (BBD) were solved after substituting the known disintegration time of FDTs containing superdisintegrants in the reduced model equations. The results suggested that excipient system under investigation not only improved the disintegration time but also made it possible to prepare FDTs with higher crushing strength as compared to tablets containing known superdisintegrants.

A new formulation for orally disintegrating tablets using a suspension spray-coating method.

PubMed

Okuda, Y; Irisawa, Y; Okimoto, K; Osawa, T; Yamashita, S

2009-12-01

The aim of this study was to design a new orally disintegrating tablet (ODT) that has high tablet hardness and a fast oral disintegration rate using a new preparation method. To obtain rapid disintegration granules (RDGs), a saccharide, such as trehalose, mannitol, or lactose, was spray-coated with a suspension of corn starch using a fluidized-bed granulator (suspension method). As an additional disintegrant, crospovidone, light anhydrous silicic acid, or hydroxypropyl starch was also included in the suspension. The RDGs obtained possessed extremely large surface areas, narrow particle size distribution, and numerous micro-pores. When tabletting these RDGs, it was found that the RDGs increased tablet hardness by decreasing plastic deformation and increasing the contact frequency between granules. In all tablets, a linear relationship was observed between tablet hardness and oral disintegration time. From each linear correlation line, a slope (D/H value) and an intercept (D/H(0) value) were calculated. Tablets with small D/H and D/H(0) values could disintegrate immediately in the oral cavity regardless of the tablet hardness and were considered to be appropriate for ODTs. Therefore, these values were used as key parameters to select better ODTs. Of all the RDGs prepared in this study, mannitol spray-coated with a suspension of corn starch and crospovidone (2.5:1 w/w ratio) showed most appropriate properties for ODTs; fast in vivo oral disintegration time, and high tablet hardness. In conclusion, this simple method to prepare superior formulations for new ODTs was established by spray-coating mannitol with a suspension of appropriate disintegrants.

Disintegration of sublingual tablets: proposal for a validated test method and acceptance criterion.

PubMed

Weda, M; van Riet-Nales, D A; van Aalst, P; de Kaste, D; Lekkerkerker, J F F

2006-12-01

In the Netherlands the market share of isosorbide dinitrate 5 mg sublingual tablets is dominated by 2 products (A and B). In the last few years complaints have been received from health care professionals on product B. During patient use the disintegration of the tablet was reported to be slow and/or incomplete, and ineffectiveness was experienced. In the European Pharmacopoeia (Ph. Eur.) no requirement is present for the disintegration time of sublingual tablets. The purpose of this study was to compare the in vitro disintegration time of products A and B, and to establish a suitable test method and acceptance criterion. A and B were tested with the Ph. Eur. method described in the monograph on disintegration of tablets and capsules as well as with 3 modified tests using the same Ph. Eur. apparatus, but without movement of the basket-rack assembly. In modified test 1 and modified test 2 water was used as medium (900 ml and 50 ml respectively), whereas in modified test 3 artificial saliva was used (50 ml). In addition, disintegration was tested in Nessler tubes with 0.5 and 2 ml of water. Finally, the Ph. Eur. method was also applied to other sublingual tablets with other drug substances on the Dutch market. With modified test 3 no disintegration could be achieved within 20 min. With the Ph. Eur. method and modified tests 1 and 2 product A and B differed significantly (p < 0. 001), with product B having longer disintegration times. These 3 methods were capable of discriminating between products and between batches. The time measured with the Ph. Eur. method was significantly lower compared to modified tests 1 and 2 (p < 0.001) and correlated well with the Nessler tube results. It is concluded that the in vivo complaints on product B could be related to the in vitro data. Furthermore, it is proposed that for immediate release of sublingual tablets the disintegration time should be tested. The Ph. Eur. method is considered suitable for this test. In view of the

Clinical disintegration time of orally disintegrating tablets clinically available in Japan in healthy volunteers.

PubMed

Yoshita, Tomohiro; Uchida, Shinya; Namiki, Noriyuki

2013-01-01

Disintegration time is an important characteristic of orally disintegrating tablets (ODTs), and evaluation of disintegration time is a key step in formulation development, manufacturing, and clinical practice. In this study, we aimed to clarify the clinical disintegration time of ODTs that are currently used clinically, and to evaluate its correlation with the in vitro disintegration time of ODTs which was measured using Tricorptester, a newly developed disintegration testing apparatus. The clinical disintegration time of 17 ODT products was measured in healthy volunteers (n=9-10; age range, 21-28 years). A randomized single-blind trial was performed; each tablet was placed on the tongues of the participants, and it disintegrated in their oral cavities. No significant difference was observed in the clinical disintegration time of each ODT among the 3 groups to which the subjects were randomly assigned. The clinical disintegration time of the 17 ODT products was between 17.6 s and 33.8 s. The in vitro disintegration time of 26 clinically used ODT products measured using Tricorptester ranged between 4.40 s and 30.4 s. A significant positive correlation was observed between in vitro and clinical disintegration times (r=0.79; p<0.001). This study shows that all the tested products, which are clinically available in Japan, showed good disintegration and that the disintegration time varied according to the product. In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity.

Taste masking of ondansetron hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets.

PubMed

Khan, Shagufta; Kataria, Prashant; Nakhat, Premchand; Yeole, Pramod

2007-06-22

The purpose of this research was to mask the intensely bitter taste of ondansetron HCl and to formulate a rapid-disintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by complexing ondansetron HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratios by the precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.2, and molecular property. Complex that did not release drug in SSF was considered taste-masked and selected for formulation RDTs. The complex with drug-polymer ratio of 8:2 did not show drug release in SSF; therefore, it was selected. The properties of tablets such as tensile strength, wetting time, water absorption ratio, in vitro disintegration time, and disintegration in the oral cavity were investigated to elucidate the wetting and disintegration characteristics of tablets. Polyplasdone XL-10 7% wt/wt gave the minimum disintegration time. Tablets of batch F4 containing spray-dried mannitol and microcrystalline cellulose in the ratio 1:1 and 7% wt/wt Polyplasdone XL-10 showed faster disintegration, within 12.5 seconds, than the marketed tablet (112 seconds). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Taste evaluation of RDT in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) ultimately reaching to 0 within 15 minutes, whereas ondansetron HCl was rated intensely bitter with a score of 3 for 10 minutes. Tablets of batch F4 also revealed rapid drug release (t(90), 60 seconds) in SGF compared with marketed formulation (t(90), 240 seconds; P < .01). Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets in the oral cavity.

Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics.

PubMed

El-Say, Khalid M; Ahmed, Tarek A; Abdelbary, Maged F; Ali, Bahaa E; Aljaeid, Bader M; Zidan, Ahmed S

2015-12-01

This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets) as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1), swelling pressure of the superdisintegrant (X2), and the surface area of Aerosil as a glidant (X3). Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for pre- and post-compression characteristics. The prepared OD-mini-tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2) and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use.

An in vitro analysis of disintegration times of different formulations of olanzapine orodispersible tablet: a preliminary report.

PubMed

Hobbs, David; Karagianis, Jamie; Treuer, Tamas; Raskin, Joel

2013-12-01

Orodispersible tablets (ODTs) are tablet or wafer forms of medication that disintegrate in the mouth, aided only by saliva. ODTs rely on different fast dissolve/disintegration manufacturing technologies. Disintegration time differences for several olanzapine ODT forms were investigated. Risperdal M-Tab(®) was included as a non-olanzapine ODT comparator. Eleven olanzapine ODT examples and orodispersible risperidone strengths were evaluated in vitro for formulation composition, manufacturing method, disintegration and dissolution characteristics, and formulation differences in comparison with freeze dried Zydis(®) ODT. Automated dissolution test equipment captured ODT dissolution rates by measuring real-time release of active ingredient. A high-speed video camera was used to capture tablet disintegration times in warm simulated saliva. The main outcome measure was the disintegration and dissolution characteristics of the ODT formulations. The ODT manufacturing method was associated with time to disintegrate; the fastest were freeze dried tablets, followed by soft compressed tablets and then hard/dense tablets. Olanzapine Zydis(®) was the only ODT that completely disintegrated in less than 4 s for all strengths (5, 10, 15, and 20 mg), followed by 5-mg Prolanz FAST(®) (12 s) and then risperidone ODT 4 mg (40 s). Reasons for slow dissolution of the olanzapine generics may include low product potency, excipient binding, excipient solubility, active ingredient particle size and incomplete disintegration. Differences in the formulation and manufacturing process of olanzapine ODTs appear to have a strong influence on the disintegration time of the active compound; differences that may potentially impact their use in clinical practice.

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

In vitro disintegration and dissolution studies of once-weekly copies of alendronate sodium tablets (70 mg) and in vivo implications.

PubMed

Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

2008-04-01

The aim of this study was to evaluate the in vitro disintegration and dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada, Germany, the Netherlands, and the United Kingdom compared to the branded product (Fosamax). The disintegration and dissolution times were determined using the methods described in the United States Pharmacopeia 30 (USP 30). The disintegration of four orally disintegrating tablets (non-bisphosphonates) and branded film-coated risedronate sodium tablets were included for comparison. The mean disintegration times of the alendronic acid tablets ranged from 14 s for Pharmachemie (Netherlands) to 342 s (5.7 min) for Betapharm (Germany). The mean disintegration time of the branded product tablets ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets with very rapid disintegration times which are similar to those of orally disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with very rapid mean disintegration times are as follows: Pharmachemie (Netherlands), 14 s; Novopharm (Canada), 13-24 s; GRY-Pharma (Germany), 21 s; Juta Pharma (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14-29 s. Since there is no established disintegration time for alendronic acid tablets there can be no assurance that the copy tablets are equivalent to the branded product in terms of esophageal drug exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration and performance. The dissolution of all the bisphosphonate tablets was rapid with greater than 80% dissolved in 15 min and all products conformed to the USP 30 specification. The dissolution of all alendronic acid tablets was rapid and complete and conformed to the established USP 30 specifications which should ensure adequate drug absorption from the copy products. However, copies of alendronic acid tablets are approved based on the results of single-dose bioavailability studies in

Oral Disintegration Tablets of Stavudine for HIV Management: A New Technological Approach.

PubMed

Sankar, V; Ramakrishna, B; Devi, P Shalini; Karthik, S

2012-11-01

Stavudine oral disintegration tablets were formulated to minimize the bitter taste and to reduce the first-pass hepatic metabolism. The various precompression parameters like the angle of repose, bulk density, compressibility index and Hausner's ratio were determined for the powder blend. In this study, 14 formulations of stavudine oral disintegration tablet were prepared by direct compression method. The tablets were evaluated for weight variation, percentage friability, disintegration time, hardness, wetting time and water absorption ratio. The in vitro dissolution study results of the batch S1 (stavudine+crospovidone+sodium starch glycollate) are encouraging as highest dissolution rate (99.2% in 100 min) and lowest time of disintegration (56 s) was achieved. The in vivo drug release studies were carried out in rabbits and the relative bioavailability of formulation S1 was found to be 2.83 times greater than that of conventional tablets.

Rapidly disintegrating tablets containing taste masked metoclopramide hydrochloride prepared by extrusion-precipitation method.

PubMed

Randale, Shivsagar Ashok; Dabhi, Chandu Somatbhai; Tekade, Avinash Ramrao; Belgamwar, Veena Shailendra; Gattani, Surendra Ganeshlal; Surana, Sanjay Javarilal

2010-04-01

The purpose of this study was to mask the intensely bitter taste of metoclopramide HCl and to formulate a rapid disintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by complexing metoclopramide HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratio by the extrusion-precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.8, taste evaluation in oral cavity and molecular property. The complex having drug-polymer ratio of 1 : 2 shows significant taste masking, confirmed by drug release in SSF and in-vivo taste evaluation; therefore, it was selected for further study. Taste evaluation of DPCs in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) within 10 s, whereas, metoclopramide HCl was rated intensely bitter with a score of +3 for 10 s. Tablets were evaluated for various parameters like tensile strength, wetting time, water absorption ratio, in-vitro disintegration time, and disintegration in oral cavity. The effect of diluents, lubricants and sweetening agent (Xylisorb) on the disintegration time was also evaluated. Tablets of batch F3 containing mannitol and microcrystalline cellulose in the ratio 1 : 1 and 8% w/w crosspovidone showed faster disintegration (within 20 s) than the marketed formulation (180 s). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Tablets of batch F3 also revealed rapid drug release (t(90), 90 s) in SGF compared with marketed formulation (t(90), 600 s).

Formulation Development and Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate for Respiratory Disorders

PubMed Central

Sharma, Deepak

2013-01-01

Recent developments in fast disintegrating tablets have brought convenience in dosing to pediatric and elderly patients who have trouble in swallowing tablets. The objective of the present study was to prepare the fast disintegrating tablet of salbutamol sulphate for respiratory disorders for pediatrics. As precision of dosing and patient's compliance become important prerequisites for a long-term treatment, there is a need to develop a formulation for this drug which overcomes problems such as difficulty in swallowing, inconvenience in administration while travelling, and patient's acceptability. Hence, the present investigation were undertaken with a view to develop a fast disintegrating tablet of salbutamol sulphate which offers a new range of products having desired characteristics and intended benefits. Superdisintegrants such as sodium starch glycolate was optimized. Different binders were optimized along with optimized superdisintegrant concentration. The tablets were prepared by direct compression technique. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and uniformity of content. Optimized formulation was evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. It was concluded that fast disintegrating tablets of salbutamol sulphate were formulated successfully with desired characteristics which disintegrated rapidly; provided rapid onset of action; and enhanced the patient convenience and compliance. PMID:23956881

Oral Disintegration Tablets of Stavudine for HIV Management: A New Technological Approach

PubMed Central

Sankar, V.; Ramakrishna, B.; Devi, P. Shalini; Karthik, S.

2012-01-01

Stavudine oral disintegration tablets were formulated to minimize the bitter taste and to reduce the first-pass hepatic metabolism. The various precompression parameters like the angle of repose, bulk density, compressibility index and Hausner's ratio were determined for the powder blend. In this study, 14 formulations of stavudine oral disintegration tablet were prepared by direct compression method. The tablets were evaluated for weight variation, percentage friability, disintegration time, hardness, wetting time and water absorption ratio. The in vitro dissolution study results of the batch S1 (stavudine+crospovidone+sodium starch glycollate) are encouraging as highest dissolution rate (99.2% in 100 min) and lowest time of disintegration (56 s) was achieved. The in vivo drug release studies were carried out in rabbits and the relative bioavailability of formulation S1 was found to be 2.83 times greater than that of conventional tablets. PMID:23798782

[Oral disintegrating tablets. A new, modern, solid dosage form].

PubMed

Popa, Graţiela; Gafiţanu, Eliza

2003-01-01

The pharmaceutical market shows lately an increasing interest in orally disintegrating tablets, due to their good acceptability among certain age categories (ex. elderly, children), and other patients with difficulties in swallowing classic solid dosage forms. Some of the methods of preparing such tablets have gained industrial applicability: molding, lyophilization, direct compression with highly soluble excipients, super disintegrants and/or effervescent systems. Some of the patients have had a good impact on the pharmaceutical market and more improvements are expected in the next few years, with new drugs to be formulated as fast dissolving dosage formulations.

Formulation of multiparticulate systems as lyophilised orally disintegrating tablets.

PubMed

Alhusban, Farhan; Perrie, Yvonne; Mohammed, Afzal R

2011-11-01

The current study aimed to exploit the electrostatic associative interaction between carrageenan and gelatin to optimise a formulation of lyophilised orally disintegrating tablets (ODTs) suitable for multiparticulate delivery. A central composite face centred (CCF) design was applied to study the influence of formulation variables (gelatin, carrageenan and alanine concentrations) on the crucial responses of the formulation (disintegration time, hardness, viscosity and pH). The disintegration time and viscosity were controlled by the associative interaction between gelatin and carrageenan upon hydration which forms a strong complex that increases the viscosity of the stock solution and forms tablet with higher resistant to disintegration in aqueous medium. Therefore, the levels of carrageenan, gelatin and their interaction in the formulation were the significant factors. In terms of hardness, increasing gelatin and alanine concentration was the most effective way to improve tablet hardness. Accordingly, optimum concentrations of these excipients were needed to find the best balance that fulfilled all formulation requirements. The revised model showed high degree of predictability and optimisation reliability and therefore was successful in developing an ODT formulation with optimised properties that were able deliver enteric coated multiparticulates of omeprazole without compromising their functionality. Copyright © 2011 Elsevier B.V. All rights reserved.

Sucralose as co-crystal co-former for hydrochlorothiazide: development of oral disintegrating tablets.

PubMed

Arafa, Mona F; El-Gizawy, Sanaa A; Osman, Mohamed A; El Maghraby, Gamal M

2016-08-01

Development of oral disintegrating tablets requires enhancement of drug dissolution and selection of sweetener. Co-crystallization of drugs with inert co-former is an emerging technique for enhancing dissolution rate. The benefit of this technique will become even greater if one of the sweeteners can act as co-crystal co-former to enhance dissolution and mask the taste. Accordingly, the objective of this work was to investigate the efficacy of sucralose as a potential co-crystal co-former for enhancing the dissolution rate of hydrochlorothiazide. This was extended to prepare oral disintegrating tablets. Co-crystallization was achieved after dissolving hydrochlorothiazide with increasing molar ratios of sucralose in the least amount of acetone. The co-crystallization products were characterized using Fourier transform infrared spectroscopy, differential thermal analysis and powder X-ray diffraction. These measurements indicated that co-crystallization process started at a drug sucralose molar ratio of 1:1 and completed at 1:2. The developed co-crystals exhibited faster drug dissolution compared with the control, with co-crystal containing the drug with sucralose at 1:2 molar ratio being optimum. The later was used to prepare fast disintegrating tablets. These tablets had acceptable physical characteristics and showed fast disintegration with subsequent rapid dissolution. The study introduced sucralose as co-crystal co-former for enhanced dissolution and masking the taste.

Dissolution testing of orally disintegrating tablets.

PubMed

Kraemer, Johannes; Gajendran, Jayachandar; Guillot, Alexis; Schichtel, Julian; Tuereli, Akif

2012-07-01

For industrially manufactured pharmaceutical dosage forms, product quality tests and performance tests are required to ascertain the quality of the final product. Current compendial requirements specify a disintegration and/or a dissolution test to check the quality of oral solid dosage forms. These requirements led to a number of compendial monographs for individual products and, at times, the results obtained may not be reflective of the dosage form performance. Although a general product performance test is desirable for orally disintegrating tablets (ODTs), the complexity of the release controlling mechanisms and short time-frame of release make such tests difficult to establish. For conventional oral solid dosage forms (COSDFs), disintegration is often considered to be the prerequisite for subsequent dissolution. Hence, disintegration testing is usually insufficient to judge product performance of COSDFs. Given the very fast disintegration of ODTs, the relationship between disintegration and dissolution is worthy of closer scrutiny. This article reviews the current status of dissolution testing of ODTs to establish the product quality standards. Based on experimental results, it appears that it may be feasible to rely on the dissolution test without a need for disintegration studies for selected ODTs on the market. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

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.

PREPARATION AND CHARACTERIZATION OF ORALLY DISINTEGRATING LORATADINE TABLETS MANUFACTURED WITH CO-PROCESSED MIXTURES.

PubMed

Amelian, Aleksandra; Szekalska, Marta; Wilczewska, Agnieszka Zofia; Basa, Anna; Winnicka, Katarzyna

2016-01-01

The aim of this study was to develop orally disintegrated tablets (ODT) with loratadine using Parteck ODT and Ludiflash--new commercially available tableting excipients based on co-processed mannitol. ODT containing loratadine were prepared with 3% addition of various superdisintegrants (AcDiSol, Kollidon CL-F and Kollidon CL-SF) by direct compression method. Obtained tablets were characterized for friability, pore structure, and wetting and disintegration time measured by four independents methods. In order to identify possible interactions between loratadine and the excipients, differential scanning calorimetry was used. The results showed that all formulated ODT were characterized by appropriate mechanical properties (friability < 1%), the uniform content of the drug substance and pleasant mouth feeling. Disintegration time below 30 s was observed in formulations with crospovidones as disintegrant.

High-Throughput Synthetic Chemistry Enabled by Organic Solvent Disintegrating Tablet.

PubMed

Li, Tingting; Xu, Lei; Xing, Yanjun; Xu, Bo

2017-01-17

Synthetic chemistry remains a time- and labor-intensive process of inherent hazardous nature. Our organic solvent disintegrating tablet (O-Tab) technology has shown potential to make industrial/synthetic chemistry more efficient. As is the case with pharmaceutical tablets, our reagent-containing O-Tabs are mechanically strong, but disintegrate rapidly when in contact with reaction media (organic solvents). For O-Tabs containing sensitive chemicals, they can be further coated to insulate them from air and moisture. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of a novel and simple method to evaluate disintegration of rapidly disintegrating tablets.

PubMed

Hoashi, Yohei; Tozuka, Yuichi; Takeuchi, Hirofumi

2013-01-01

The purpose of this study was to develop and test a novel and simple method for evaluating the disintegration time of rapidly disintegrating tablets (RDTs) in vitro, since the conventional disintegration test described in the pharmacopoeia produces poor results due to the difference of its environmental conditions from those of an actual oral cavity. Six RDTs prepared in our laboratory and 5 types of commercial RDTs were used as model formulations. Using our original apparatus, a good correlation was observed between in vivo and in vitro disintegration times by adjusting the height from which the solution was dropped to 8 cm and the weight of the load to 10 or 20 g. Properties of RDTs, such as the pattern of their disintegrating process, can be assessed by verifying the load. These findings confirmed that our proposed method for an in vitro disintegration test apparatus is an excellent one for estimating disintegration time and the disintegration profile of RDTs.

Impact of chitosan as a disintegrant on the bioavailability of furosemide tablets: in vitro evaluation and in vivo simulation of novel formulations.

PubMed

Rasool, Bazigha Kadhim Abdul; Fahmy, Sahar Abdelsattar; Galeel, Omar Waleed Abdul

2012-10-01

To determine the effect of chitosan, starch powder, polyvinylpyrrolidone (PVP), Avicel PH 101 powder, Avicel PH 102 granules as a function of different concentrations on the solubility, disintegration and hence dissolution of furosemide from immediate release tablet dosage forms. The tablets were prepared by the wet granulation method and evaluated for hardness, friability, disintegration and in vitro dissolution. Chitosan 7% w/w showed the fastest disintegration of furosemide tablets among the other disintegrants studied. This was attributed to its highest swelling properties and velocity constant of water uptake. The step of adding chitosan during tablet preparation had a great effect on the physical properties and dissolution profiles of the prepared tablets with external addition of chitosan showed best results compared to best results comparing to internal-external or internal addition. The most appropriate force of compression was 4ton/cm(2). The selected formula F15 containing 7% w/w chitosan was successful and showed a high significant (p<0.001) enhancement in disintegration and dissolution behaviors of furosemide tablets in comparison with the commercially available Furosemide ® tablets. These results were supported by the simulated data where F15 formula showed the highest plasma concentration C-max 1.89mcg/mL after 0.5 hr compared to C-max 1.05mcg/mL after 1hr for the reference. The present study demonstrated that chitosan is a very good candidate to be used as a tablet disintegrant and was able to enhance the dissolution of poorly absorbable drugs.

Evaluation of the Disintegrant Properties of Native Starches of Five New Cassava Varieties in Paracetamol Tablet Formulations

PubMed Central

Adjei, Frank Kumah; Osei, Yaa Asantewaa; Kuntworbe, Noble

2017-01-01

The disintegrant potential of native starches of five new cassava (Manihot esculenta Crantz.) varieties developed by the Crops Research Institute of Ghana (CRIG) was studied in paracetamol tablet formulations. The yield of the starches ranged from 8.0 to 26.7%. The starches were basic (pH: 8.1–9.9), with satisfactory moisture content (≤15%), swelling capacity (≥20%), ash values (<1%), flow properties, and negligible toxic metal ion content, and compatible with the drug. The tensile strength (Ts), crushing strength (Cs), and friability (Ft) of tablets containing 5–10% w/w of the cassava starches were similar (p > 0.05) to those containing maize starch BP. The disintegration times of the tablets decreased with increase in concentration of the cassava starches. The tablets passed the disintegration test (DT ≤ 15 min) and exhibited faster disintegration times (p > 0.05) than those containing maize starch BP. The disintegration efficiency ratio (DER) and the disintegration parameter DERc of the tablets showed that cassava starches V20, V40, and V50 had better disintegrant activity than maize starch BP. The tablets passed the dissolution test for immediate release tablets (≥70% release in 45 min) with dissolution rates similar to those containing maize starch BP. PMID:28781909

Role of Water Sorption in Tablet Crushing Strength, Disintegration, and Dissolution.

PubMed

Sacchetti, M; Teerakapibal, R; Kim, K; Elder, E J

2017-08-01

Drugs formulated as tablets are subjected to accelerated stability conditions with the goal of identifying a stable formulation that will exhibit a sufficiently long shelf life. Water sorption at a condition such as 40°C/75% RH can result in significant changes in tablet properties such as a decrease in dissolution rate, the cause of which may be difficult to interpret, given the complex nature of ingredients and their interactions in a tablet. In this research, three drugs, displaying a wide range of physicochemical properties, were formulated with commonly used diluents, disintegrants, and binders, using a design of experiments approach. The tablets were stored at accelerated conditions and assessed for content, dissolution, disintegration, and crushing strength, as well as other properties. The research demonstrated many water-induced effects in tablet properties. Due to the experimental design approach that revealed many interactions, it was possible to interpret all of the changes observed in tablet crushing strength, disintegration, and dissolution for the drugs using a common set of physical principles. Specifically, the relevant factors considered were (1) mechanical properties of materials, (2) water sorption surface effects in surface diffusion and capillary condensation, (3) water sorption bulk effects for amorphous materials such as viscous flow/spreading, and (4) water-induced stress on interparticle bonding arising from volume expansion. These physical principles enable a comprehensive interpretation of the complex changes observed in tablet properties, which should be valuable in the design of tablet formulations that will be stable to accelerated storage conditions.

Bio-predictive tablet disintegration: effect of water diffusivity, fluid flow, food composition and test conditions.

PubMed

Radwan, Asma; Wagner, Manfred; Amidon, Gordon L; Langguth, Peter

2014-06-16

Food intake may delay tablet disintegration. Current in vitro methods have little predictive potential to account for such effects. The effect of a variety of factors on the disintegration of immediate release tablets in the gastrointestinal tract has been identified. They include viscosity of the media, precipitation of food constituents on the surface of the tablet and reduction of water diffusivity in the media as well as changes in the hydrodynamics in the surrounding media of the solid dosage form. In order to improve the predictability of food affecting the disintegration of a dosage form, tablet disintegration in various types of a liquefied meal has been studied under static vs. dynamic (agitative) conditions. Viscosity, water diffusivity, osmolality and Reynolds numbers for the different media were characterized. A quantitative model is introduced which predicts the influence of the Reynolds number in the tablet disintegration apparatus on the disintegration time. Viscosity, water diffusivity and media flow velocity are shown to be important factors affecting dosage form disintegration. The results suggest the necessity of considering these parameters when designing a predictive model for simulating the in vivo conditions. Based on these experiments and knowledge on in vivo hydrodynamics in the GI tract, it is concluded that the disintegration tester under current pharmacopoeial conditions is operated in an unphysiological mode and no bioprediction may be derived. Recommendations regarding alternative mode of operation are made. Copyright © 2013 Elsevier B.V. All rights reserved.

Influence of disintegrants in different substrate physical form on dimensional recovery of multi-component tablet.

PubMed

Sarkar, Srimanta; Ooi, Shing Ming; Liew, Celine Valeria; Tan, Bing Xun; Heng, Paul Wan Sia

2014-11-20

This study investigated the influence of different disintegrants, present in different substrate physical forms, on dimensional recovery of multi-component tablets prepared at different compression pressures. Formulations containing model drug, metformin, (10%, w/w), different disintegrants (10%, w/w), and lactose (80%, w/w) were compressed directly or after granulation using polyvinyl pyrrolidone (1%, w/w) as binder, into tablets (350 mg, 10mm diameter) at 150, 200, and 250 N/mm(2) compression pressures. Tablets were characterized for immediate dimensional recovery (IR) after ejection from the die, latent dimensional recovery (LR) over 24 h, tensile strength, and disintegration. The IR was predominantly contributed by crystalline components whereas LR was brought about by polymeric materials. With increased compression pressure, higher degree of plastic deformation of the polymeric disintegrants resulted in tablet with lower LR and higher tensile strength. Presence of polyvinyl pyrrolidone in the granules contributed considerably to plastic deformation, and the tablets produced had lower LR, higher tensile strength, and longer disintegration time. This study indicated that use of granules as the feed substrate physical form and a prudent selection of components may enable the coating of resultant tablets immediately after compression without the risk of coat damage due to LR. Copyright © 2014 Elsevier B.V. All rights reserved.

Food-dependent disintegration of immediate release fosamprenavir tablets: in vitro evaluation using magnetic resonance imaging and a dynamic gastrointestinal system.

PubMed

Brouwers, Joachim; Anneveld, Bart; Goudappel, Gert-Jan; Duchateau, Guus; Annaert, Pieter; Augustijns, Patrick; Zeijdner, Evelijn

2011-02-01

In the present study, we demonstrated the value of two advanced tools, the TNO gastric and small Intestinal Model (TIM-1) and magnetic resonance imaging (MRI), for the in vitro evaluation of food-dependent disintegration of immediate release fosamprenavir tablets. Upon introduction of a tablet with the nutritional drink Scandishake Mix® in the stomach compartment of TIM-1, simulating the fed state, disintegration and fosamprenavir dissolution were significantly postponed compared to the fasted state (lag time 80 ± 23 min). This resulted in a lag in the appearance of bioaccessible fosamprenavir (<5% during the first 2h), even though the nutritional state did not significantly alter the cumulative bioaccessibility after 5h. These results were in agreement with the previously observed postprandial delay in gastric fosamprenavir tablet disintegration and subsequent amprenavir absorption in healthy volunteers. Therefore, TIM-1 can be used in tablet development to identify food-induced disintegration issues causing unexpected clinical behavior. From a mechanistic perspective, we applied MRI to illustrate impaired water ingress in fosamprenavir tablets immersed in the nutritional drink compared to simulated gastric fluid. This effect may be attributed to both competition between nutritional components and the tablet for the available water (indicated by reduced rotational and translational diffusion) as well as the possible formation of a food-dependent precipitation layer on the HPMC-coated tablet. Copyright © 2010 Elsevier B.V. All rights reserved.

Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements.

PubMed

Markl, Daniel; Sauerwein, Johanna; Goodwin, Daniel J; van den Ban, Sander; Zeitler, J Axel

2017-05-01

The aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale. Samples of 18 batches of biconvex tablets from a production-scale design of experiments study into exploring the design space of a commercial tablet manufacturing process were used. The tablet production involved the process steps of high-shear wet granulation, fluid-bed drying and subsequent compaction. The 18 batches were produced using a 4 factor split plot design to study the effects of process changes on the disintegration time. Non-destructive and contactless terahertz transmission measurements of the whole tablets without prior sample preparation were performed to measure the effective refractive index and absorption coefficient of 6 tablets per batch. The disintegration time (R 2  = 0.86) and API dissolved after 15 min (R 2  = 0.96) linearly correlates with the effective refractive index, n eff , measured at terahertz frequencies. In contrast, no such correlation could be established from conventional hardness measurements. The magnitude of n eff represents the optical density of the sample and thus it reflects both changes in tablet porosity as well as granule density. For the absorption coefficient, α eff , we observed a better correlation with dissolution after 20 min (R 2  = 0.96) and a weaker correlation with disintegration (R 2  = 0.83) compared to n eff . The measurements of n eff and α eff provide promising predictors for the disintegration and dissolution time of tablets. The high penetration power of terahertz radiation makes it possible to sample a significant volume proportion of a tablet without any prior sample preparation. Together with the short measurement time (seconds), the potential to

The Influence of Formulation and Manufacturing Process Parameters on the Characteristics of Lyophilized Orally Disintegrating Tablets

PubMed Central

Jones, Rhys J.; Rajabi-Siahboomi, Ali; Levina, Marina; Perrie, Yvonne; Mohammed, Afzal R.

2011-01-01

Gelatin is a principal excipient used as a binder in the formulation of lyophilized orally disintegrating tablets. The current study focuses on exploiting the physicochemical properties of gelatin by varying formulation parameters to determine their influence on orally disintegrating tablet (ODT) characteristics. Process parameters, namely pH and ionic strength of the formulations, and ball milling were investigated to observe their effects on excipient characteristics and tablet formation. The properties and characteristics of the formulations and tablets which were investigated included: glass transition temperature, wettability, porosity, mechanical properties, disintegration time, morphology of the internal structure of the freeze-dried tablets, and drug dissolution. The results from the pH study revealed that adjusting the pH of the formulation away from the isoelectric point of gelatin, resulted in an improvement in tablet disintegration time possibly due to increase in gelatin swelling resulting in greater tablet porosity. The results from the ionic strength study revealed that the inclusion of sodium chloride influenced tablet porosity, tablet morphology and the glass transition temperature of the formulations. Data from the milling study showed that milling the excipients influenced formulation characteristics, namely wettability and powder porosity. The study concludes that alterations of simple parameters such as pH and salt concentration have a significant influence on formulation of ODT. PMID:24310589

Formulation and Evaluation of Fast-Disintegrating Sublingual Tablets of Atropine Sulfate: the Effect of Tablet Dimensions and Drug Load on Tablet Characteristics.

PubMed

Aodah, Alhussain; Bafail, Rawan S; Rawas-Qalaji, Mutasem

2017-07-01

In this study, we formulated and evaluated the effects of tablet dimensions and drug load on the characteristics of atropine sulfate (AS) fast-disintegrating sublingual tablets (FDSTs). We aim to develop AS FDSTs as an alternative non-invasive and portable dosage form for the emergency treatment of organophosphate (OP) toxicity. AS autoinjector, AtroPen®, is the only self-administered dosage form available as an antidote for-out-of-hospital emergency use, but it is associated with several limitations and drawbacks. Seven FDST formulations of two tablet sizes, 150 mg (A) and 50 mg (B), and of several AS loads, 0 mg (A1, B1), 2 mg (A2, B2), 4 mg (B3), and 8 mg (B4a, B4b), were formulated and manufactured by direct compression. AS FDST characteristics were evaluated using USP and non-USP tests. Results were statistically compared at p < 0.05. All FDSTs passed the USP content uniformity and friability tests, disintegrated and released AS in ≤30 and 60 s. B1 and B2 were significantly harder than A1 and A2. Water uptake of A1 was significantly the highest. However, B1 and B2 had shorter disintegration and wetting times and higher amounts of AS dissolved than did A1 and A2 (p < 0.05). Increasing AS negatively affected FDST tensile strength (p < 0.05 for B4a) and water uptake (p < 0.05 for B3, B4a and B4b), however, without affecting AS dissolution. Formulation of AS up to 16% into smaller FDSTs was successful. Smaller FDSTs were harder and disintegrated more quickly. These AS FDSTS have the potential for further in vivo testing to evaluate their OP antidote potential.

The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs).

PubMed

Brniak, Witold; Jachowicz, Renata; Pelka, Przemyslaw

2015-09-01

Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20 years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800-900 mL of distilled water. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. The aim of this study was to compare these methods and correlate them with in vivo results. Six series of ODTs were prepared by direct compression. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. The highest correlation with oral disintegration time was found in the case of own-construction apparatus with additional weight and the employment of the method proposed by Narazaki et al. The correlation coefficients were 0.9994 (p < 0.001), and 0.9907 (p < 0.001) respectively. The pharmacopoeial method correlated with the in vivo data much worse (r = 0.8925, p < 0.05). These results have shown that development of novel biorelevant methods of ODT's disintegration time determination is eligible and scientifically justified.

Expedited Development of Diphenhydramine Orally Disintegrating Tablet through Integrated Crystal and Particle Engineering.

PubMed

Wang, Chenguang; Hu, Shenye; Sun, Changquan Calvin

2017-10-02

A palatable direct compression (DC) orally disintegrating tablet (ODT) product of a bitter drug, diphenhydramine (DPH), was developed using an integrated crystal and particle engineering approach. A DPH salt with a sweetener, acesulfame (Acs), DPH-Acs, was synthesized and its solid state properties were comprehensively characterized. Tablet formulation composition and compaction parameters were optimized by employing material sparing techniques. In vivo disintegration time, bitterness, and grittiness of the final ODT product, were evaluated by a taste panel. Physical stability of the ODT tablets was assessed to identify appropriate storage conditions. Phase-pure DPH-Acs exhibited significantly better tabletability and palatability than DPH-HCl. A DC formulation was designed and optimized to obtain a new ODT product with good manufacturability and excellent product characteristics, including fast in vivo disintegration, and acceptable bitterness and grittiness. A new ODT product of DPH with excellent pharmaceutical properties was successfully developed using 15 g of DPH and in two months. This example shows that integrated crystal and particle engineering is an effective approach for developing high quality ODT products using the DC process.

Correlation of Phosphorus Cross-Linking to Hydration Rates in Sodium Starch Glycolate Tablet Disintegrants Using MRI.

PubMed

Abraham, Anuji; Olusanmi, Dolapo; Ilott, Andrew J; Good, David; Murphy, Denette; Mcnamara, Daniel; Jerschow, Alexej; Mantri, Rao V

2016-06-01

Understanding the behavior of tablet disintegrants is valuable in the development of pharmaceutical solid dosage formulations. In this study, high-resolution magnetic resonance imaging has been used to understand the hydration behavior of a series of commercial sodium starch glycolate (SSG) samples, providing robust estimates of tablet disintegration rate that could be correlated with physicochemical properties of the SSGs, such as the extent of phosphorus (P) cross-linking as obtained from infra-red spectroscopy. Furthermore, elemental analysis together with powder X-ray diffraction has been used to quantify the presence of carboxymethyl groups and salt impurities, which also contribute to the disintegration behavior. The utility of Fast Low Angle SHot magnetic resonance imaging has been demonstrated as an approach to rapidly acquire approximations of the volume of a disintegrating tablet and, together with a robust voxel analysis routine, extract tablet disintegration rates. In this manner, a complete characterization of a series of SSG grades from different sources has been performed, showing the variability in their physicochemical properties and demonstrating a correlation between their disintegration rates and intrinsic characteristics. The insights obtained will be a valuable aid in the choice of disintegrant source as well as in managing SSG variability to ensure robustness of drug products containing SSG. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Kozeny-Carman permeability relationship with disintegration process predicted from early dissolution profiles of immediate release tablets.

PubMed

Kumari, Parveen; Rathi, Pooja; Kumar, Virender; Lal, Jatin; Kaur, Harmeet; Singh, Jasbir

2017-07-01

This study was oriented toward the disintegration profiling of the diclofenac sodium (DS) immediate-release (IR) tablets and development of its relationship with medium permeability k perm based on Kozeny-Carman equation. Batches (L1-L9) of DS IR tablets with different porosities and specific surface area were prepared at different compression forces and evaluated for porosity, in vitro dissolution and particle-size analysis of the disintegrated mass. The k perm was calculated from porosities and specific surface area, and disintegration profiles were predicted from the dissolution profiles of IR tablets by stripping/residual method. The disintegration profiles were subjected to exponential regression to find out the respective disintegration equations and rate constants k d . Batches L1 and L2 showed the fastest disintegration rates as evident from their bi-exponential equations while the rest of the batches L3-L9 exhibited the first order or mono-exponential disintegration kinetics. The 95% confidence interval (CI 95% ) revealed significant differences between k d values of different batches except L4 and L6. Similar results were also spotted for dissolution profiles of IR tablets by similarity (f 2 ) test. The final relationship between k d and k perm was found to be hyperbolic, signifying the initial effect of k perm on the disintegration rate. The results showed that disintegration profiling is possible because a relationship exists between k d and k perm . The later being relatable with porosity and specific surface area can be determined by nondestructive tests.

[Preparation and evaluation of taste masked orally disintegrating tablets with granules made by the wet granulation method].

PubMed

Kawano, Yayoi; Ito, Akihiko; Sasatsu, Masanaho; Machida, Yoshiharu; Onishi, Hiraku

2010-12-01

Using furosemide (FU) as a model drug, we examined the wet granulation method as a way to improve the taste masking and physical characteristics of orally disintegrating tablets (ODTs). In the wet granulation method, yogurt powder (YO) was used as a corrective and maltitol (MA) was used as a binding agent. The taste masked FU tablets were prepared using the direct compression method. Microcrystalline cellulose (Avicel® PH-302) and mannitol were added as excipients at a mixing ratio of 1/1 by weight. Based on the results of sensory test on taste, the prepared granules markedly improved the taste of FU, and a sufficient masking effect was obtained at the YO/FU ratio of 1 or more. Furthermore, it was found that the masking effect achieved by YO granules made with the wet granulation method was similar to or better than that produced by the granules made with dry granulation method. All types of tablets displayed sufficient hardness (over 3.5×10(-2) kN), and rapidly disintegrating tablets were obtained with YO granules produced at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s. Disintegration time lengthened as the mixing ratio of YO to FU increased. In the mixing ratio of FU/YO=1/1, the hardness of tablets with granules made by the wet granulation method exceeded that of tablets with granules made by the dry granulation method, with minimal differences in disintegration time. The hardness and disintegration time of the tablets with granules made by the wet granulation method could be controlled by varying the compression force. In conclusion, YO was found to be a useful additive for masking unpleasant tastes. FU ODTs with improved taste, rapid disintegration and greater hardness could be prepared with YO-containing granules made by the wet granulation method using MA as a binding agent.

A new apparatus for real-time assessment of the particle size distribution of disintegrating tablets.

PubMed

Quodbach, Julian; Kleinebudde, Peter

2014-11-01

The aim of this study is the introduction of a novel apparatus that is capable of continuously measuring the particle size reduction of disintegrating tablets and analysis of the obtained results. The apparatus is constructed such that no particles pass directly through the pumping system. Thereby, the overall energy input into the particle suspension is reduced, and continuous measurement is possible without rapid destruction of the generated particles. The detected particle sizes at the beginning and at the end of the measurement differ greatly, depending on the applied disintegrant. The median particle sizes at the end of the measurement vary between 621.5 and 178.0 μm for different disintegrants. It is demonstrated that the particle size reduction follows an exponential function and that the fit parameters can be used to describe the disintegration behavior. A strong correlation between the median particle size of crospovidone disintegrants and generated particle size of the tablets is observed. This could be due to a more homogeneous distribution of the disintegrant particles in the tablets. Similar trends are observed for sodium starch glycolate and croscarmellose sodium. The new apparatus provides an innovative method to describe disintegrant effectiveness and efficiency. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs)

PubMed Central

Brniak, Witold; Jachowicz, Renata; Pelka, Przemyslaw

2015-01-01

Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20 years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800–900 mL of distilled water. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. The aim of this study was to compare these methods and correlate them with in vivo results. Six series of ODTs were prepared by direct compression. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. The highest correlation with oral disintegration time was found in the case of own-construction apparatus with additional weight and the employment of the method proposed by Narazaki et al. The correlation coefficients were 0.9994 (p < 0.001), and 0.9907 (p < 0.001) respectively. The pharmacopoeial method correlated with the in vivo data much worse (r = 0.8925, p < 0.05). These results have shown that development of novel biorelevant methods of ODT’s disintegration time determination is eligible and scientifically justified. PMID:27134547

Effects of plantain and corn starches on the mechanical and disintegration properties of paracetamol tablets.

PubMed

Akin-Ajani, Olufunke D; Itiola, Oludele A; Odeku, Oluwatoyin A

2005-10-22

The effects of plantain starch obtained from the unripe fruit of the plant Musa paradisiaca L. (Musaceae) on the mechanical and disintegration properties of paracetamol tablets have been investigated in comparison with the effects of corn starch BP using a 2(3) factorial experimental design. The individual and combined effects of nature of starch binder (N), concentration of starch binder (C), and the relative density of tablet (RD) on the tensile strength (TS), brittle fracture index (BFI), and disintegration time (DT) of the tablets were investigated. The ranking of the individual effects on TS was RD > C > N, on BFI was C > RD > N and on DT was N > C > RD. The ranking for the interaction effects on TS and DT was N-C > N-RD > C-RD, while that on BFI was N-C > C-RD > N-RD. Changing nature of starch from a "low" (plantain starch) to a "high" (corn starch) level, increasing the concentration of starch binding agent from 2.5% to 10.0% wt/wt, and increasing relative density of the tablet from 0.80 to 0.90, led to increase in the values of TS and DT, but a decrease in BFI. Thus, tablets containing plantain starch had lower tensile strength and disintegration time values than those containing corn starch, but showed better ability to reduce the lamination and capping tendency in paracetamol tablet formulation. The interaction between N and C was significantly (P < .001) higher than those between N and RD and between C and RD. There is therefore the need to carefully choose the nature (N) and concentration (C) of starch used as binding agent in tablet formulations to obtain tablets of desired bond strength and disintegration properties. Furthermore, plantain starch could be useful as an alternative binding agent to cornstarch, especially where faster disintegration is required and the problems of lamination and capping are of particular concern.

Formulation and Evaluation of Mouth Disintegrating Tablets of Atenolol and Atorvastatin

PubMed Central

Sarfraz, R. M.; Khan, H. U.; Mahmood, A.; Ahmad, M.; Maheen, S.; Sher, M.

2015-01-01

In this study, mouth-disintegrating tablets of atenolol and atorvastatin combination were formulated using superdisintegrants to impart fast disintegration. Fifteen formulations were prepared based on different concentrations of two superdisintegrants, croscarmellose sodium and Kyron-T134. Three different techniques such as direct compression, effervescent and sublimation were used to study the effect of manufacturing processes, nature and concentration of superdisintegrants on various features of these tablets. Five formulations were made using each method. Precompression studies like bulk density, tapped density, angle of repose, Carr's compressibility index, Hausner's ratio and compatibility studies such as Fourier transform infrared spectroscopy and differential scanning calorimetry were performed. Various features such as hardness, thickness, diameter, weight variation, friability, disintegration time, dissolution studies, wetting time, wetting volume, water absorption ratio, modified disintegration, uniformity of contents and stability were evaluated. Finally results were statistically analyzed by the application of one way ANOVA test. Formulation F13 containing Kyron-T134 (6%) and croscarmellose sodium (2%) was found to be the best among all fifteen formulations prepared in all aspects evaluated. Sublimation method is found to be the best among three methods of preparation used. PMID:25767322

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets.

PubMed

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH's intrinsic characteristics.

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

PubMed Central

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets.

PubMed

Desai, Divyakant; Wong, Benjamin; Huang, Yande; Tang, Dan; Hemenway, Jeffrey; Paruchuri, Srinivasa; Guo, Hang; Hsieh, Daniel; Timmins, Peter

2015-01-01

To investigate the influence of the pH of the dissolution medium on immediate release 850 mg metformin hydrochloride tablets. A traditional wet granulation method was used to manufacture metformin hydrochloride tablets with or without a disintegrant. Tablet dissolution was conducted using the USP apparatus I at 100 rpm. In spite of its pH-independent high solubility, metformin hydrochloride tablets dissolved significantly slower in 0.1 N HCl (pH 1.2) and 50 mM pH 4.5 acetate buffer compared with 50 mM pH 6.8 phosphate buffer, the dissolution medium in the USP. Metformin hydrochloride API compressed into a round 1200 mg disk showed a similar trend. When basket rotation speed was increased from 100 to 250 rpm, the dissolution of metformin hydrochloride tablets was similar in all three media. Incorporation of 2% w/w crospovidone in the tablet formulation improved the dissolution although the pH-dependent trend was still evident, but incorporation of 2% w/w croscarmellose sodium resulted in rapid pH-independent tablet dissolution. In absence of a disintegrant in the tablet formulation, the dissolution was governed by the erosion-diffusion process. Even for a highly soluble drug, a super-disintegrant was needed in the formulation to overcome the diffusion layer limitation and change the dissolution mechanism from erosion-diffusion to disintegration.

Preparation of Orally Disintegrating Tablets Containing Powdered Tea Leaves with Enriched Levels of Bioactive Compounds by Means of Microwave Irradiation Technique.

PubMed

Tanaka, Hironori; Iwao, Yasunori; Izumikawa, Masahiro; Sano, Syusuke; Ishida, Hitoshi; Noguchi, Shuji; Itai, Shigeru

2016-01-01

In the present study, a microwave treatment process has been applied to prepare orally disintegrating tablets (ODTs) containing powdered tea leaves with enriched levels of the anti-inflammatory compounds such as chafuroside A (CFA) and chafuroside B (CFB). The use of distilled water as the adsorbed and granulation solvents in this preparation process afforded tablets with a long disintegration time (more than 120 s). The CFA and CFB contents of these tablets did not also change after 4 min of microwave irradiation due to the tablet temperature, which only increased to 100°C. In contrast, the tablet temperature increased up to 140°C after 3 min of microwave irradiation when a 1.68 M Na2HPO4 solution instead of distilled water. Notably, the disintegration time of these tablets was considerably improved (less than 20 s) compared with the microwave-untreated tablets, and there were 7- and 11-fold increases in their CFA and CFB contents. In addition, the operational conditions for the preparation of the tablets were optimized by face-centered composite design based on the following criteria: tablet hardness greater than 13 N, disintegration time less than 30 s and friability less than 0.5%. The requirements translated into X1 (the amount of granulation solvent), X2 (tableting pressure) and X3 (content of the powdered tea leaves) values of 45%, 0.43 kN and 32%, respectively, and the ODTs containing powdered tea leaves prepared under these optimized conditions were found to show excellent tablet properties and contain enriched levels of CFA and CFB.

Maltodextrin: a novel excipient used in sugar-based orally disintegrating tablets and phase transition process.

PubMed

Elnaggar, Yosra Shaaban R; El-Massik, Magda A; Abdallah, Ossama Y; Ebian, Abd Elazim R

2010-06-01

The recent challenge in orally disintegrating tablets (ODT) manufacturing encompasses the compromise between instantaneous disintegration, sufficient hardness, and standard processing equipment. The current investigation constitutes one attempt to fulfill this challenge. Maltodextrin, in the present work, was utilized as a novel excipient to prepare ODT of meclizine. Tablets were prepared by both direct compression and wet granulation techniques. The effect of maltodextrin concentrations on ODT characteristics--manifested as hardness and disintegration time--was studied. The effect of conditioning (40 degrees C and 75% relative humidity) as a post-compression treatment on ODT characteristics was also assessed. Furthermore, maltodextrin-pronounced hardening effect was investigated using differential scanning calorimetry (DSC) and X-ray analysis. Results revealed that in both techniques, rapid disintegration (30-40 s) would be achieved on the cost of tablet hardness (about 1 kg). Post-compression conditioning of tablets resulted in an increase in hardness (3 kg), while keeping rapid disintegration (30-40 s) according to guidance of the FDA for ODT. However, direct compression-conditioning technique exhibited drawbacks of long conditioning time and appearance of the so-called patch effect. These problems were, yet, absent in wet granulation-conditioning technique. DSC and X-ray analysis suggested involvement of glass-elastic deformation in maltodextrin hardening effect. High-performance liquid chromatography analysis of meclizine ODT suggested no degradation of the drug by the applied conditions of temperature and humidity. Overall results proposed that maltodextrin is a promising saccharide for production of ODT with accepted hardness-disintegration time compromise, utilizing standard processing equipment and phenomena of phase transition.

In situ, real time observation of the disintegration of paracetamol tablets in aqueous solution by magnetic resonance imaging.

PubMed

Tritt-Goc, Jadwiga; Kowalczuk, Joanna

2002-05-01

The disintegration behavior of paracetamol tablets was studied by magnetic resonance imaging (MRI) using the Snapshot FLASH method. The total time of the single experiment is 425 ms and allows the study of the disintegration process in real time. The study was carried out in vitro under acidic gastric pH conditions and may help to predict the behavior of paracetamol tablets in the stomach after oral administration. It was shown that in spite of identical conditions, the disintegration of the tablets under study was different. The distribution of protons of 4-(N-acetyl)aminophenol within the paracetamol tablet was shown to be homogeneous. The study was carried out in a non-destructive way by the SPI MRI method.

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

Evaluation of the ease of taking mini-tablets compared with other tablet formulations in healthy volunteers.

PubMed

Hayakawa, Yoshiyuki; Uchida, Shinya; Namiki, Noriyuki

2016-03-10

"Mini-tablets" (MTs) are tablets of diameter≤3mm and have been widely studied and developed. However, reports comparing MTs with other tablet formulations are few. We wished to evaluate the ease of taking a MT quantitatively in comparison with an orally disintegrating mini-tablet (ODMT), conventional tablet (CT) and conventional orally disintegrating tablet (ODT). Four types of tablets were prepared. We prepared tablets of two diameters (3mm for MTs and ODMTs vs. 8mm for CTs and ODTs) and two formulations (MTs and CTs vs. ODMTs and ODTs). Our randomized crossover trial in 18 healthy volunteers (8 men and 10 women; mean age, 22.5years) indicated that the visual analog scale (VAS) score for the ease and amount of water required for intake of MTs was significantly lower than those of CTs. An ODMT required the least amount of water and smallest VAS score for the ease of taking a tablet. Our results showed that the advantage of MTs with regard to the ease of taking and decreased amount of water required was exerted for a unit of dosing comprising <5 tablets. These data suggested the usefulness of MTs and the importance of the number of MTs for comfortable consumption by patients. Copyright © 2015. Published by Elsevier B.V.

Consumer vinegar test for determining calcium disintegration.

PubMed

Mason, N A; Patel, J D; Dressman, J B; Shimp, L A

1992-09-01

A consumer test and standardized methods were compared for measuring the disintegration of calcium tablets, and the disintegration results were compared with results of dissolution testing to determine the ability of the consumer test of disintegration to predict bioavailability of calcium. Disintegration of 17 calcium supplement products, in tablet form, was studied in Simulated Gastric Fluid Test Solution, USP, without pepsin (GF), in distilled water, and in white distilled vinegar. For disintegration testing with GF and with distilled water, six tablets of each product were placed in an apparatus and immersed in the solution at 37 degrees C for 60 minutes. Six tablets of each product were tested in 200 mL of vinegar at room temperature for 30 minutes. Disintegration was determined by visual observation. Seven products were tested for dissolution in GF or water. Three samples of each product were tested at intervals over 120 minutes for calcium content. Results of testing with an ion-selective electrode were converted to milligrams and compared with the calcium content of the tablets (as claimed on the package label). The mean disintegration times of various calcium products in vinegar ranged from 1.8 to greater than 30 minutes. The mean time in distilled water and GF ranged from 1.6 to greater than 60 minutes and from 1.0 to greater than 60 minutes, respectively. Results were in agreement in 87% to 93% of cases between the consumer vinegar test and the standardized disintegration test methods, a significant correlation. No correlation was found between disintegration time and the extent of dissolution. The disintegration and dissolution of commercially available calcium tablets was highly variable.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Formulation strategy towards minimizing viscosity mediated negative food effect on disintegration and dissolution of immediate release tablets.

PubMed

Zaheer, Kamran; Langguth, Peter

2018-03-01

Food induced viscosity can delay disintegration and subsequent release of API from solid dosage form which may lead to severe reduction in the bioavailability of BCS type III compounds. Formulations of such tablets need to be optimized in view of this postprandial viscosity factor. In this study, three super disintegrants, croscarmellose sodium (CCS), cross-linked polyvinylpolypyrrolidone (CPD), and sodium starch glycolate (SSG) were assessed for their efficiency under simulated fed state. Tablets containing these disintegrants were compressed at 10 and 30 KN, while taking lactose as a soluble filler. In addition to other compendial tests, disintegration force of these formulations was measured by texture analysis. Comparison of parameters derived from force - time curves revealed a direct relation of maximum disintegration force (F max ) and disintegration force development rate (DFDR) with compressional force in fasted state, whereas an inverse relationship of F max and DFDR with compressional force was observed in fed state. The gelling tendency of disintegrants influenced the rate of release of API in simulated fed and fasted states when compressional force was changed. These observations recommend the evaluation of formulations in simulated fed state, in the development stage, with an objective of minimizing the negative impact of food induced viscosity on disintegration. Use of disintegrants that act without gelling or can counteract the effect of gelling is recommended for tablet formulations with reduced disintegration time (DT) and mean dissolution time (MDT) in fed state, respectively.

Preparation of orally disintegrating tablets with taste-masking function: masking effect in granules prepared with correctives using the dry granulation method and evaluation of tablets prepared using the taste-masked granules.

PubMed

Kawano, Yayoi; Ito, Akihiko; Sasatsu, Masanaho; Machida, Yoshiharu

2010-01-01

We investigated several methods of taste masking in the preparation of orally disintegrating tablets (ODTs), using furosemide (FU) as a model drug. Four types of FU preparations were prepared: granules with maltitol (MA), granules with yogurt powder (YO), a physical mixture of FU and MA, and a physical mixture of FU and YO. All taste-masking granules were prepared using the dry granulation method. The taste of each type of preparation was evaluated. All four preparations markedly improved the taste of the FU tablets, but the mixing ratios of the correctives did not affect the masking effect. No difference in masking effect was found between MA and YO in the physical mixtures, but the masking effect in the granules with YO was superior to that of the granules with MA. Taste-masked FU tablets were prepared using the direct compression method; crystalline cellulose (Avicel PH-302) and mannitol were added as excipients at the mixing ratio of 1/1. All four types of tablets displayed sufficient hardness, but MA-containing tablets were harder than YO-containing tablets. The hardness of the tablets prepared from YO granules increased as the YO content increased. The most rapidly disintegrating tablets were those of YO granules prepared at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s, followed by the tablets of MA granules prepared at a mixing ratio of FU/MA=1/1. The disintegration times of the tablets made from physical mixtures, in contrast, were longer than 200 s. Disintegration time lengthened as the mixing ratio of YO or MA increased. The hardness and disintegration time of these tablets could be controlled by varying the compression pressure. We found that YO is more useful than MA in masking unpleasant tastes and confirmed that orally disintegrating tablets with taste-masking function can be prepared using granules of YO prepared using the dry granulation method as a new corrective.

Evaluation of the palatabilities in 10 different famotidine orally disintegrating tablets by combination of disintegration device and taste sensor.

PubMed

Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Uchida, Takahiro

2015-01-01

The purpose of this study was to evaluate the palatabilities of the original and nine generic versions of famotidine orally disintegrating tablets (FODTs) by means of disintegration times and bitterness intensities determined using in combination disintegration device and taste sensor comparison of human gustatory sensation tests. The disintegration times were determined using a new disintegration testing equipment for ODTs, the OD-mate and bitterness intensities were determined using the SA501C taste-sensing system. The disintegration time and bitterness of each FODT was evaluated in gustatory sensation tests. There was a good correlation between the disintegration times of 10 FODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of FODTs at 10, 20 and 30 s after starting the disintegration using the OD-mate and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. A combination of the OD-mate and the SA501C was capable of predicting the palatabilities, disintegration properties and bitterness intensity of FODTs.

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.

Latent structure analysis of the process variables and pharmaceutical responses of an orally disintegrating tablet.

PubMed

Hayashi, Yoshihiro; Oshima, Etsuko; Maeda, Jin; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2012-01-01

A multivariate statistical technique was applied to the design of an orally disintegrating tablet and to clarify the causal correlation among variables of the manufacturing process and pharmaceutical responses. Orally disintegrating tablets (ODTs) composed mainly of mannitol were prepared via the wet-granulation method using crystal transition from the δ to the β form of mannitol. Process parameters (water amounts (X(1)), kneading time (X(2)), compression force (X(3)), and amounts of magnesium stearate (X(4))) were optimized using a nonlinear response surface method (RSM) incorporating a thin plate spline interpolation (RSM-S). The results of a verification study revealed that the experimental responses, such as tensile strength and disintegration time, coincided well with the predictions. A latent structure analysis of the pharmaceutical formulations of the tablet performed using a Bayesian network led to the clear visualization of a causal connection among variables of the manufacturing process and tablet characteristics. The quantity of β-mannitol in the granules (Q(β)) was affected by X(2) and influenced all granule properties. The specific surface area of the granules was affected by X(1) and Q(β) and had an effect on all tablet characteristics. Moreover, the causal relationships among the variables were clarified by inferring conditional probability distributions. These techniques provide a better understanding of the complicated latent structure among variables of the manufacturing process and tablet characteristics.

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.

An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain.

PubMed

Nalamachu, Srinivas

2013-12-01

Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting <1 h. Thus, optimal relief from breakthrough pain is best attained by administering analgesics with dissolution times and bioavailabilities that closely match the onset and duration of breakthrough pain. The objective of this study was to assess complete disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. This was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral(®), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. Disintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.

A novel and discriminative method of in vitro disintegration time for preparation and optimization of taste-masked orally disintegrating tablets of carbinoxamine maleate.

PubMed

Liu, Yali; Li, Peng; Qian, Rong; Sun, Tianyu; Fang, Fangzhi; Wang, Zonghua; Ke, Xue; Xu, Bohui

2018-08-01

The primary objective of this study was to mask bitter taste and decrease the disintegration time of carbinoxamine maleate (CAM) orally disintegrating tablets (ODTs). In order to screen the prescription of ODTs, a novel modified in vitro disintegration method (MIVDM) was developed to measure the in vitro disintegration time. In this method, different concentrations of ethanol served as disintegration medium in order to delay the in vitro water absorption and disintegration process of tablets. The MIVDM demonstrated good in vitro and in vivo correlation and proved more precise and discriminative than other reported methods. In this research, ion exchange resins (IERs) were used to mask bitter taste for improving mouthfeel. The drug-resin ratio and reaction temperature were investigated to obtain the optimum carbinoxamine resin complexes (CRCs). The characterization of CRCs revealed an amorphous state. ODTs were prepared by direct compression. Superdisintegrants and diluents of ODTs were screened first. Further optimization was carried out by using Box-Behnken design. The effect of (X 1 ) mannitol/microcrystalline cellulose ratio, (X 2 ) the amount of low-substituted hydroxypropylcellulose and (X 3 ) the hardness was investigated for achieving the lowest (Y) in vitro disintegration time. Technological characterization, wetting time, water absorption ratio, and roughness degree were evaluated. The CRCs and ODTs proved successful taste-masking efficiency. The end product improved patients' compliance. The developed MIVDM was practical for commercial use.

Modulation of the wettability of excipients by surfactant and its impacts on the disintegration and release of tablets.

PubMed

Yang, Baixue; Xu, Lu; Wang, Qiuxiao; Li, Sanming

2016-12-01

To investigate the modulation of the wettability of excipients by different types of surfactants and its impacts on the disintegration of tablets and drug release. The critical micelle concentration (CMC) of surfactants, including sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), dodecyl trimethyl ammonium bromide (DTAB), cetyltrimethyl ammonium bromide (CTAB) and polysorbate (Tween-20 and Tween-80), was obtained using the platinum ring method. Contact angles of surfactant solutions on the excipient compacts and double-distilled water on the mixture of surfactant and the other excipient (magnesium stearate (MgSt) or sodium alginate (SA)) were measured by the sessile drop technique. Besides, surface free energy of excipients was calculated by the Owens method. Finally, the disintegration of tablets and in vitro dissolution testing were performed according to the method described in USP. The wettability of excipients could be enhanced to different extent with low concentration of surfactant solutions and maintained stable basically after CMC. For MgSt (hydrophobic excipient), the shorter the hydrophobic chain (C 12 , including SDS and DTAB), the better the wettability with the addition of surfactant in the formulation, leading to the shorter disintegration time of tablets and higher drug release rate. In contrast, the wettability of SA (hydrophilic excipient) was reduced by adding surfactant, resulting in the longer disintegration time of tablets and lower release rate. The modulation of the wetting of pharmaceutical excipients by surfactant had changed the disintegration time of tablets and drug release rate to a greater extent.

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.

Evaluation about wettability, water absorption or swelling of excipients through various methods and the correlation between these parameters and tablet disintegration.

PubMed

Yang, Baixue; Wei, Chen; Yang, Yang; Wang, Qifang; Li, Sanming

2018-04-06

To evaluate parameters about wettability, water absorption or swelling of excipients in forms of powders or dosage through various methods systematically and explore its correlation with tablet disintegration. The water penetration and swelling of powders with different proportions of excipients including microcrystalline cellulose (MCC), mannitol, low-substituted hydroxypropyl cellulose (L-HPC), crospolyvinylpyrrolidone (PVPP), carboxymethyl starch sodium (CMS-Na), croscarmellose sodium (CCMC-Na) and magnesium stearate (MgSt) were determined by Washburn capillary rise. Both contact angle of water on the excipient compacts and surface swelling volume were measured by sessile drop technique. Moreover, the test about water absorption and swelling of compacts was fulfilled by a modified method. Eventually, the disintegration of tablets with or without loratadine was performed according to the method described in USP. These parameters were successfully identified by the methods above, which proved that excipient wettability or swelling properties varied with the structure of excipients. For example, MgSt could improve the water uptake, while impeded tablet swelling. Furthermore, in the present study it is verified that tablet disintegration was closely related to these parameters, especially wetting rate and initial water absorption rate. The higher wetting rate of water on tablet or initial water absorption rate, the faster swelling it be, resulting in the shorter tablet disintegration time. The methods utilized in the present study were feasible and effective. The disintegration of tablets did relate to these parameters, especially wetting rate and initial water absorption rate.

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.

Evaluation of the in vivo disintegration of solid dosage forms of a bile acid sequestrant in dogs using gamma-scintigraphy and correlation to in vitro disintegration.

PubMed

Hussain, Munir A; Chang, Rong-Kun; Sandefer, Erik; Page, Richard C; Digenis, George A

2003-03-01

[corrected] To evaluate the in vivo disintegration behavior of tablets and capsules of a bile acid sequestrant, DMP 504, in beagle dogs and to assess the significance of the in vitro disintegration of the dosage forms on subsequent in vivo behavior in order to draw possible in vitro-in vivo correlations. Tablet and capsule formulations of a bile acid sequestrant, DMP 504, were formulated with samarium oxide and neutron activated to produce radioactive 53Sm to noninvasively evaluate their in vivo behavior in beagle dogs by gamma-scintigraphy. A four-way crossover design was completed (n = 4) in which (a) tablets from two different batches were administered under the fasted condition and manufactured using different lots of drug substance where one batch exhibited relatively faster in vitro disintegration time (30 min) than the other tablet batch, which resulted in slower disintegration (45 min), (b) a capsule formulation was administered to fasted beagles, and (c) the tablet having slower in vitro disintegration was also administered in the fed state, and its in vivo disintegration was compared to that observed in the fasted state. Tablets manufactured using a lot of DMP 504 having relatively fast in vitro disintegration (approximately 30 min) resulted in relatively rapid in vivo disintegration time (15 min) in the fasted condition. This in vivo disintegration time was comparable to the in vivo disintegration of the capsules (17 min) even though the in vitro capsule disintegration time was considerably faster (2 min). Tablets prepared using a drug substance that provided a longer in vitro disintegration time (approximately 45 min) resulted in a slower in vivo disintegration (63 min). There was no difference observed in the in vivo disintegration behavior in fasted and fed dogs for the tablets that provided slower in vitro disintegration. In vivo disintegration of tablets of the bile acid sequestrant DMP 504 correlated with in vitro disintegration times. Gamma

Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center, single-blind, six-period crossover study in healthy female subjects.

PubMed

Perkins, Alan C; Blackshaw, P Elaine; Hay, Peter D; Lawes, Simon C; Atherton, Clare T; Dansereau, Richard J; Wagner, Leigh K; Schnell, Dan J; Spiller, Robin C

2008-05-01

Delayed esophageal transit or disintegration of oral bisphosphonate tablets before they enter the stomach may be of concern with respect to iatrogenic complications among patients receiving longterm treatment. Different formulations of generic bisphosphonate tablets meeting regulatory requirements may have substantial differences in pharmaceutical attributes from the branded product that may result in different characteristics during esophageal transit. The primary objective of this study was to evaluate and compare esophageal transit times and in vivo disintegration of 3 bisphosphonate formulations, one branded and the others generic, that are commercially available in Canada and the United Kingdom. This was a single-center, randomized, singleblind, 6-period crossover study in healthy postmenopausal women aged >50 years. Each subject received a single oral dose of a branded risedronate sodium 35-mg tablet and 2 generic formulations of alendronic acid 70-mg tablets (Novopharm Limited, Toronto, Canada, and Teva UK Limited, Morley, United Kingdom) in both the erect and semisupine (45 degrees ) positions. Although the products are labeled to be taken in the erect position, the semisupine position was included to simulate dosing in bedridden patients. Subjects took tablets with 30 mL of water in the morning after an overnight fast. The tablets were radiolabeled with technetium-99m ion-exchange resins to enable visualization and measurement of esophageal transit time and disintegration using a gamma camera. Dynamic scintigraphic images were obtained for a total of 10 minutes: 2 images per second for the first 30 seconds and 1 image every 15 seconds for 9.5 minutes. This was a mechanistic study and tolerability was not assessed. The study was conducted in 20 healthy white female subjects with a mean age of 62 years (range, 51-77 years). The effect of body position was statistically significant (P = 0.043), with the estimated hazard ratio (HR) of 0.74 indicating longer

Assessment of disintegrant efficacy with fractal dimensions from real-time MRI.

PubMed

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

2014-11-20

An efficient disintegrant is capable of breaking up a tablet in the smallest possible particles in the shortest time. Until now, comparative data on the efficacy of different disintegrants is based on dissolution studies or the disintegration time. Extending these approaches, this study introduces a method, which defines the evolution of fractal dimensions of tablets as surrogate parameter for the available surface area. Fractal dimensions are a measure for the tortuosity of a line, in this case the upper surface of a disintegrating tablet. High-resolution real-time MRI was used to record videos of disintegrating tablets. The acquired video images were processed to depict the upper surface of the tablets and a box-counting algorithm was used to estimate the fractal dimensions. The influence of six different disintegrants, of different relative tablet density, and increasing disintegrant concentration was investigated to evaluate the performance of the novel method. Changing relative densities hardly affect the progression of fractal dimensions, whereas an increase in disintegrant concentration causes increasing fractal dimensions during disintegration, which are also reached quicker. Different disintegrants display only minor differences in the maximal fractal dimension, yet the kinetic in which the maximum is reached allows a differentiation and classification of disintegrants. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterization, optimisation and process robustness of a co-processed mannitol for the development of orally disintegrating tablets.

PubMed

Soh, Josephine Lay Peng; Grachet, Maud; Whitlock, Mark; Lukas, Timothy

2013-02-01

This is a study to fully assess a commercially available co-processed mannitol for its usefulness as an off-the-shelf excipient for developing orally disintegrating tablets (ODTs) by direct compression on a pilot scale (up to 4 kg). This work encompassed material characterization, formulation optimisation and process robustness. Overall, this co-processed mannitol possessed favourable physical attributes including low hygroscopicity and compactibility. Two design-of-experiments (DoEs) were used to screen and optimise the placebo formulation. Xylitol and crospovidone concentrations were found to have the most significant impact on disintegration time (p < 0.05). Higher xylitol concentrations retarded disintegration. Avicel PH102 promoted faster disintegration than PH101, at higher levels of xylitol. Without xylitol, higher crospovidone concentrations yielded faster disintegration and reduced tablet friability. Lubrication sensitivity studies were later conducted at two fill loads, three levels for lubricant concentration and number of blend rotations. Even at 75% fill load, the design space plot showed that 1.5% lubricant and 300 blend revolutions were sufficient to manufacture ODTs with ≤ 0.1% friability and disintegrated within 15 s. This study also describes results using a modified disintegration method based on the texture analyzer as an alternative to the USP method.

Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People.

PubMed

Hirata, Ayumu; Funato, Hiroki; Nakai, Megumi; Iizuka, Michiro; Abe, Noriaki; Yagi, Yusuke; Shiraishi, Hisashi; Jobu, Kohei; Yokota, Junko; Hirose, Kahori; Hyodo, Masamitsu; Miyamura, Mitsuhiko

2016-01-01

We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function.

Comparison of intramuscular olanzapine, orally disintegrating olanzapine tablets, oral risperidone solution, and intramuscular haloperidol in the management of acute agitation in an acute care psychiatric ward in Taiwan.

PubMed

Hsu, Wen-Yu; Huang, Si-Sheng; Lee, Bo-Shyan; Chiu, Nan-Ying

2010-06-01

The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward. Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours. There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection. These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

Chitin's Functionality as a Novel Disintegrant: Benchmarking Against Commonly Used Disintegrants in Different Physicochemical Environments.

PubMed

Chaheen, Mohammad; Soulairol, Ian; Bataille, Bernard; Yassine, Ahmad; Belamie, Emmanuel; Sharkawi, Tahmer

2017-07-01

Disintegrants are used as excipients to ensure rapid disintegration of pharmaceutical tablets and further ensure proper dissolution of the active pharmaceutical ingredient. This study investigates disintegration mechanisms of chitin and common disintegrants. Swelling assessment (swelling force and swelling ratio) in different media, and compaction behavior (pure or mixed with other excipients) tabletability, deformation (Heckel modeling), and compact disintegration times were investigated on the tested disintegrants (alginic acid calcium salt, crospovidone, sodium starch glycolate, croscarmellose sodium, and chitin). Results show that the physicochemical properties of the disintegration medium such as pH and ionic strength, as well as other formulation ingredients, affect the disintegrant functionalities. Heckel analysis using the mean yield pressure "Py" shows that alginic acid calcium salt is the most brittle among the studied disintegrants, while crospovidone has the most plastic deformation mechanism, followed by chitin. Chitin showed good tabletability and disintegration properties that were not influenced by the physicochemical formulation environment. Chitin is largely available and easily modifiable and thus a promising material that could be used as a multifunctional excipient in tablet formulation. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Evaluation of palatability of 10 commercial amlodipine orally disintegrating tablets by gustatory sensation testing, OD-mate as a new disintegration apparatus and the artificial taste sensor.

PubMed

Uchida, Takahiro; Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Furuno, Hiroyuki; Teraoka, Makoto; Ikezaki, Hidekazu

2013-09-01

The purpose of this study was to evaluate and compare the palatability of 10 formulations (the original manufacturer's formulation and nine generics) of amlodipine orally disintegrating tablets (ODTs) by means of human gustatory sensation testing, disintegration/dissolution testing and the evaluation of bitterness intensity using a taste sensor. Initially, the palatability, dissolution and bitterness intensity of the ODTs were evaluated in gustatory sensation tests. Second, the disintegration times of the ODTs were measured using the OD-mate, a newly developed apparatus for measuring the disintegration of ODTs, and lastly, the bitterness intensities were evaluated using an artificial taste sensor. Using factor analysis, the factors most affecting the palatability of amlodipine ODTs were found to be disintegration and taste. There was high correlation between the disintegration times of the 10 amlodipine ODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of amlodipine ODTs 10, 20 and 30 s after starting the conventional brief dissolution test and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. The OD-mate and the taste sensor may be useful for predicting the disintegration and bitterness intensity of amlodipine ODTs in the mouth. © 2013 Royal Pharmaceutical Society.

Stability of benzocaine formulated in commercial oral disintegrating tablet platforms.

PubMed

Köllmer, Melanie; Popescu, Carmen; Manda, Prashanth; Zhou, Leon; Gemeinhart, Richard A

2013-12-01

Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degradation. Benzocaine was selected as the model API due to known degradation through ester and primary amino groups. Benzocaine was either compressed at a constant pressure, 20 kN, or at pressure necessary to produce a set hardness, i.e., where a series of tablets were produced at different compression forces until an average hardness of approximately 100 N was achieved. Tablets were then stored for 6 months under International Conference on Harmonization recommended conditions, 25°C and 60% relative humidity (RH), or under accelerated conditions, 40°C and 75% RH. Benzocaine degradation was monitored by liquid chromatography-mass spectrometry. Regardless of the ODT platform, no degradation of benzocaine was observed in tablets that were kept for 6 months at 25°C and 60% RH. After storage for 30 days under accelerated conditions, benzocaine degradation was observed in a single platform. Qualitative differences in ODT platform behavior were observed in physical appearance of the tablets after storage under different temperature and humidity conditions.

A simple and inexpensive image analysis technique to study the effect of disintegrants concentration and diluents type on disintegration.

PubMed

Berardi, Alberto; Bisharat, Lorina; Blaibleh, Anaheed; Pavoni, Lucia; Cespi, Marco

2018-06-20

Tablets disintegration is often the result of a size expansion of the tablets. In this study, we quantified the extent and direction of size expansion of tablets during disintegration, using readily available techniques, i.e. a digital camera and a public domain image analysis software. After validating the method, the influence of disintegrants concentration and diluents type on kinetics and mechanisms of disintegration were studied. Tablets containing diluent, disintegrant (sodium starch glycolate-SSG, crospovidone-PVPP or croscarmellose sodium-CCS) and lubricant were prepared by direct compression. Projected area and aspect ratio of the tablets were monitored using image analysis techniques. The developed method could describe the kinetics and mechanisms of disintegration qualitatively and quantitatively. SSG and PVPP acted purely by swelling and shape recovery mechanisms. Instead, CCS worked by a combination of both mechanisms, the extent of which changed depending on its concentration and the diluent type. We anticipate that the method described here could provide a framework for the routine screening of tablets disintegration using readily available equipment. Copyright © 2018. Published by Elsevier Inc.

Comparative studies of binding potential of Prunus armeniaca and Prunus domestica gums in tablets formulations.

PubMed

Rahim, Haroon; Khan, Mir Azam; Sadiq, Abdul; Khan, Shahzeb; Chishti, Kamran Ahmad; Rahman, Inayat U

2015-05-01

The current study was undertaken to compare the binding potential of Prunus armeniaca L. and Prunus domestica L. gums in tablets' formulations. Tablet batches (F-1 to F-9) were prepared Diclofenac sodium as model drug using 5%, 7.5% and 10% of each Prunus armeniaca L., Prunus domestica L. gums as binder. PVP K30 was used as a standard binder. Magnesium stearate was used as lubricant. Flow properties of granules (like bulk density, tapped density, Carr's index, Hausner's ratio, angle of repose) as well as the physical parameters of compressed tablets including hardness, friability, thickness and disintegration time were determined. Flow parameters of granules of all the batches were found good. Physical parameters (drug content, weight variation, thickness, hardness, friability, disintegration time) of formulated tablets were found within limit when tested. The dissolution studies showed that tablets formulations containing each Prunus domestica showed better binding capacity compared to Prunus armeniaca gum. The binding potential increased as the concentration of gums increased. The FTIR spectroscopic investigation showed that the formulations containing plant gum are compatible with the drug and other excipients used.

[Pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in Beagle dogs determined with LC-MS/MS].

PubMed

Xia, Tian; Liu, De-Ding; Shi, Li-Fu; Hu, Jin-Hong

2011-08-01

The study aims to elucidate the characteristics of pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in healthy Beagle dogs. Chromatographic separation was performed on a C18 column (100 mm x 3.0 mm, 3.5 microm) with methanol - 2 mmol x L(-1) ammonium formate (25 : 75) as the mobile phase. A trip-quadrupole tandem mass spectrum with the electrospray ionization (ESI) source was applied and positive ion multiple reaction monitoring mode was operated. Six Beagle dogs were randomly devided into two groups. They received oral single dose of scopolamine hydrobromide oral disintegrative microencapsule tablets 0.6 mg (test tablet) or scopolamine hydrobromide normal tablets (reference tablet). Plasma samples were collected at designed time. Plasma concentration of scopolamine hydrobromide was determined by LC-MS/MS and pharmacokinetic parameters were calculated. The pharmacokinetic parameters of test tablet vs reference tablet were as follows: C(max): (8.16 +/- 0.67) ng x mL(-1) vs (3.54 +/- 0.64) ng x mL(-1); t1/2: (2.83 +/- 0.45) h vs (3.85 +/- 0.82) h; t(max): (1.25 +/- 0.27) h vs (0.42 +/- 0.09) h; AUC(0-12h): (25.06 +/- 3.75) h x ng x mL(-1) vs (9.59 +/- 1.02) h x ng x mL(-1); AUC(0-infinity): (26.30 +/- 3.92) h x ng x mL(-1) vs (10.80 +/- 1.45) h x ng x mL(-1); MRT(0-12h): (3.38 +/- 0.34) h vs (3.86 +/- 0.26) h; MRT(0-infinity): (3.98 +/- 0.63) h vs (5.37 +/- 1.00) h. The absorption rate and AUC of test tablet is different from that of reference tablet. The bioavailability of test tablet is better than those of reference tablet.

Evidence-Based Nanoscopic and Molecular Framework for Excipient Functionality in Compressed Orally Disintegrating Tablets

PubMed Central

Al-khattawi, Ali; Alyami, Hamad; Townsend, Bill; Ma, Xianghong; Mohammed, Afzal R.

2014-01-01

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2–10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. PMID:25025427

In vitro and in vivo correlation of disintegration and bitter taste masking using orally disintegrating tablet containing ion exchange resin-drug complex.

PubMed

Kim, Jong-Il; Cho, Sang-Min; Cui, Jing-Hao; Cao, Qing-Ri; Oh, Euichaul; Lee, Beom-Jin

2013-10-15

Although the taste-masking of bitter drug using ion exchange resin has been recognized, in vitro testing using an electronic tongue (e-Tongue) and in vivo bitterness test by human panel test was not fully understood. In case of orally disintegrating tablet (ODT) containing bitter medicine, in vitro and in vivo disintegration is also importance for dosage performance. Donepezil hydrochloride was chosen as a model drug due to its bitterness and requires rapid disintegration for the preparation of ODT. In this study, ion exchange resin drug complex (IRDC) at three different ratios (1:2, 1:1, 2:1) was prepared using a spray-drying method and then IRDC-loaded ODT containing superdisintegrants (crospovidone, croscarmellose sodium, and sodium starch glycolate) were prepared by the direct compression method. The physical properties and morphologies were then characterized by scanning electron microscopy (SEM), X-ray powder diffraction (PXRD) and electrophoretic laser scattering (ELS), respectively. The in vitro taste-masking efficiency was measured with an electronic tongue (e-Tongue). In vivo bitterness scale was also evaluated by human volunteers and then we defined new term, "bitterness index (BI)" to link in vitro e-Tongue. There was a good correlation of IRDC between in vitro e-Tongue values and in vivo BI. Furthermore, IRDC-loaded ODT showed good in vitro/in vivo correlation in the disintegration time. The optimal IRDC-loaded ODTs displayed similar drug release profiles to the reference tablet (Aricept(®) ODT) in release media of pH 1.2, pH 4.0, pH 6.8 and distilled water but had significantly better palatability in vivo taste-masking evaluation. The current IRDC-loaded ODT according to the in vitro and in vivo correlation of disintegration and bitter taste masking could provide platforms in ODT dosage formulations of donepezil hydrochloride for improved patient compliances. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of pigeon pea and plantain starches on the compressional, mechanical, and disintegration properties of paracetamol tablets.

PubMed

Dare, Kunle; Akin-Ajani, Dorothy O; Odeku, Oluwatoyin A; Itiola, Oludele A; Odusote, Omotunde M

2006-03-01

A study has been made of the effects of pigeon pea starch obtained from the plant Cajanus cajan (L) Millisp. (family Fabaceae) and plantain starch obtained from the unripe fruit of Musa paradisiaca L. (family Musaceae) on the compressional, mechanical, and disintegration properties of paracetamol tablets in comparison with official corn starch BP. Analysis of compressional properties was done by using density measurements, and the Heckel and Kawakita equations, whereas the mechanical properties of the tablets were evaluated by using tensile strength (T--a measure of bond strength) and brittle fracture index (BFI--a measure of lamination tendency). The ranking for the mean yield pressure, P(y), for the formulations containing the different starches was generally corn < pigeon pea < plantain starch while the ranking for P(k), an inverse measure of the amount of plasticity, was pigeon pea < plantain < corn starch, which indicated that formulations containing corn starch generally exhibited the fastest onset of plastic deformation, whereas those formulations containing pigeon pea starch exhibited the highest amount of plastic deformation during tableting. The tensile strength of the tablets increased with increase in concentration of the starches while the Brittle Fracture Index decreased. The ranking for T was pigeon pea > plantain > corn starch while the ranking for BFI was corn > plantain > pigeon pea starch. The bonding capacity of the formulations was in general agreement with the tensile strength results. The disintegration time (DT) of the formulation increased with concentration of plantain and corn starches but decreased with concentration of pigeon pea starch. The general ranking of DT values was plantain < pigeon pea < corn starch. Notably, formulations containing pigeon pea starch exhibited the highest bond strength and lowest brittleness, suggesting the usefulness of pigeon pea starch in producing strong tablets with minimal lamination tendency. Plantain

Formulation Development and Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate, Cetirizine Hydrochloride in Combined Pharmaceutical Dosage Form: A New Era in Novel Drug Delivery for Pediatrics and Geriatrics

PubMed Central

Sharma, Deepak; Singh, Gurmeet; Kumar, Dinesh; Singh, Mankaran

2015-01-01

The objective of the present study was to prepare the fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form for respiratory disorders such as bronchitis, asthma, and coughing for pediatrics and geriatrics. The tablets were prepared by direct compression technique. Superdisintegrant such as Sodium Starch Glycolate was optimized as 4% on the basis of least disintegration time. Different binders such as MCC and PVP K-30 were optimized along with optimized superdisintegrant concentration. 1% MCC was selected as optimum binder concentration on the basis of least disintegration time. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and drug content uniformity. Optimized formulation was further evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. Percent weight variation and content uniformity were within the acceptable limit. The friability was less than 1%. The wetting time and disintegration time were practically good for all formulations. FTIR studies and accelerated stability study showed that there was no interaction between the drug and excipients. It was concluded that, by employing commonly available pharmaceutical excipients such as superdisintegrants, hydrophilic and swellable excipients and proper filler, a fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form, were formulated successfully with desired characteristics. PMID:25810924

A Practical Framework Toward Prediction of Breaking Force and Disintegration of Tablet Formulations Using Machine Learning Tools.

PubMed

Akseli, Ilgaz; Xie, Jingjin; Schultz, Leon; Ladyzhynsky, Nadia; Bramante, Tommasina; He, Xiaorong; Deanne, Rich; Horspool, Keith R; Schwabe, Robert

2017-01-01

Enabling the paradigm of quality by design requires the ability to quantitatively correlate material properties and process variables to measureable product performance attributes. Conventional, quality-by-test methods for determining tablet breaking force and disintegration time usually involve destructive tests, which consume significant amount of time and labor and provide limited information. Recent advances in material characterization, statistical analysis, and machine learning have provided multiple tools that have the potential to develop nondestructive, fast, and accurate approaches in drug product development. In this work, a methodology to predict the breaking force and disintegration time of tablet formulations using nondestructive ultrasonics and machine learning tools was developed. The input variables to the model include intrinsic properties of formulation and extrinsic process variables influencing the tablet during manufacturing. The model has been applied to predict breaking force and disintegration time using small quantities of active pharmaceutical ingredient and prototype formulation designs. The novel approach presented is a step forward toward rational design of a robust drug product based on insight into the performance of common materials during formulation and process development. It may also help expedite drug product development timeline and reduce active pharmaceutical ingredient usage while improving efficiency of the overall process. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Current opinions and recommendations of paediatric healthcare professionals – The importance of tablets: Emerging orally disintegrating versus traditional tablets

PubMed Central

Alyami, Hamad; Koner, Jasdip; Terry, David; Mohammed, Afzal R.

2018-01-01

The appropriate prescribing of paediatric dosage forms is paramount in providing the desired therapeutic effect alongside successful medication adherence with the paediatric population. Often it is the opinion of the healthcare practitioner that dictates which type of dosage form would be most appropriate for the paediatric patient, with liquids being both the most commonly available and most commonly used. Orally disintegrating tablets (ODTs) are an emerging dosage form which provide many benefits over traditional dosage forms for paediatric patients, such as rapid disintegration within the oral cavity, and the reduction in the risk of choking. However the opinion and professional use of healthcare practitioners regarding ODT’s is not known. This study was designed to assess the opinions of several types of healthcare professionals (n = 41) regarding ODTs, using a survey across two hospital sites. Results reaffirmed the popularity of liquids for prescribing in paediatrics, with 58.0% of participants preferring this dosage form. ODTs emerged as the second most popular dosage form (30.0%), with healthcare practitioners indicating an increasing popularity amongst patients in the hospital setting, belief with 63.0% of practitioners agreeing that many liquid formulations could be substituted with a suitable ODT. The desired properties of an ideal ODT were also identified by healthcare practitioners preferring a small, fast disintegrating tablet (90.2% and 95.1% respectively), with the taste, disintegration time and flavour being the three most important attributes identified (29.5%, 28.7% and 21.7% respectively). This study provided a pragmatic approach in assessing healthcare professional’s opinions on ODTs, highlighting the ideas and thoughts of practitioners who are on the frontline of paediatric prescribing and treatment and gave an indication to their preference for ODT properties. PMID:29489871

Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States.

PubMed

Ascher-Svanum, Haya; Furiak, Nicolas M; Lawson, Anthony H; Klein, Timothy M; Smolen, Lee J; Conley, Robert R; Culler, Steven D

2012-01-01

Although the use of innovative drug delivery systems, like orally disintegrating antipsychotic tablets (ODT), may facilitate medication adherence and help reduce the risk of relapse and hospitalization, no information is available about the comparative cost-effectiveness of standard oral tablets (SOT) vs ODT formulations in the treatment of schizophrenia. This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of outpatients with schizophrenia from a US healthcare perspective. The study also compared olanzapine ODT with risperidone and aripiprazole, two other atypical antipsychotics available in both ODT and SOT formulations. Published medical literature and a clinical expert panel were used to populate a 1-year Monte Carlo Micro-simulation model. The model captures clinical and cost parameters including adherence levels, treatment discontinuation by reason, relapse with and without inpatient hospitalization, quality-adjusted life years (QALYs), treatment-emergent adverse events, healthcare resource utilization, and associated costs. Key outcomes were total annual direct cost per treatment, QALY, and incremental cost-effectiveness (ICER) per 1 QALY gained. Based on model projections, olanzapine ODT therapy was more costly ($9808 vs $9533), but more effective in terms of a lower hospitalization rate (15% vs 16%) and better QALYs (0.747 vs 0.733) than olanzapine SOT therapy. Olanzapine ODT was more cost-effective than olanzapine SOT (ICER: $19,643), more cost-effective than risperidone SOT therapy (ICER: $39,966), and dominant (meaning less costly and more effective) than risperidone ODT and aripiprazole in ODT or SOT formulations. Lack of head-to-head randomized studies comparing the three studied atypical antipsychotics required making input assumptions that need further study. This micro-simulation found that the utilization of olanzapine ODT for the treatment of schizophrenia is predicted to be more cost

Rapid disintegrating tablets of simvastatin dispersions in polyoxyethylene–polypropylene block copolymer for maximized disintegration and dissolution

PubMed Central

Balata, Gehan F; Zidan, Ahmad S; Abourehab, Mohamad AS; Essa, Ebtessam A

2016-01-01

The objective of this research was to improve the dissolution of simvastatin and to incorporate it in rapid disintegrating tablets (RDTs) with an optimized disintegration and dissolution characteristics. Polyoxyethylene–polypropylene block copolymer (poloxamer 188) was employed as a hydrophilic carrier to prepare simvastatin solid dispersions (SDs). Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffractometry were employed to understand the interaction between the drug and the carrier in the solid state. The results obtained from Fourier transform infrared spectroscopy showed absence of any chemical interaction between the drug and poloxamer. The results of differential scanning calorimetry and X-ray diffractometry confirmed the conversion of simvastatin to distorted crystalline state. The SD of 1:2 w/w drug to carrier ratio showed the highest dissolution; hence, it was incorporated in RDT formulations using a 32 full factorial design and response surface methodology. The initial assessments of RDTs demonstrated an acceptable flow, hardness, and friability to indicate good mechanical strength. The interaction and Pareto charts indicated that percentage of croscarmellose sodium incorporated was the most important factor affecting the disintegration time and dissolution parameter followed by the hardness value and their interaction effect. Compression force showed a superior influence to increase RDT’s porosity and to fasten disintegration rather than swelling action by croscarmellose sodium. On the other hand, croscarmellose sodium was most important for the initial simvastatin release. The results suggest the potential use of poloxamer 188-based SD in RDT for the oral delivery of poor water-soluble antihyperlipidemic drug, simvastatin. PMID:27757012

Formulation and evaluation of a montelukast sodium orally disintegrating tablet with a similar dissolution profile as the marketed product.

PubMed

Chen, Yong; Feng, Tingting; Li, Yong; Du, Bin; Weng, Weiyu

2017-03-01

A major challenge of orally disintegrating tablet (ODT) development is predicting its bioequivalence to its corresponding marketed product. Therefore, comparing ODT dissolution profiles to those of the corresponding marketed product is very important. The objective of this study was to develop a 5.2-mg montelukast sodium (MS) ODT with a similar dissolution profile to that of the marketed chewable tablet. Dissolution profiles were examined in different media to screen each formulation. We found that MS dissolution from ODTs in acidic medium heavily depended on manufacturing methods. All MS ODTs prepared using direct compression rapidly disintegrated in acidic medium. However, dispersed MS powders aggregated into sticky masses, resulting in slow dissolution. In contrast, MS ODTs prepared using wet granulation had much faster dissolution rates in acidic medium with no obvious aggregation. Additionally, the optimized formulation, prepared using wet granulation, displayed similar dissolution profiles to the marketed reference in all four types of media examined (f 2  >   50). The in vitro disintegration time of the optimized ODT was 9.5 ± 2.4 s, which meets FDA requirements. In conclusion, the wet granulation preparation method of MS ODTs resulted in a product with equivalent dissolution profiles as those of the marketed product.

[Comparative evaluation of the anionic superdisintegrant incorporation mode on the quality of ranitidine tablets].

PubMed

Postolache, Liliana; Gafiţanu, Eliza

2012-01-01

The present study was based on the impact of the superdisintegrants incorporation mechanism on the immediate realese of the tablets final performances. The aim was the selection of the working method to obtain Ranitidine 150 mg tablets with the desiderate quality and in reproducible conditions. The effect of the incorporation mode of sodium starch glycolate on the aspect, granules size distribution and flowing properties of the lubricated product, and also the weight uniformity, hardness, disintegration, friability, and dissolution of the Ranitidine 150 mg tablets prepared by dry granulation was studied. The addition mode of the disintegrant was realized in three ways: intragranular, extragranular, and distributed equally between the two phases. The distribution range for the tablets weight was established. Relative standard distribution was calculed for the weight and hardness of the uncoated tablets. The powder flow and, implicit, the weight uniformity of the uncoated tablets was positive influenced by the extragranular incorporation of the superdisintegrant. The disintegration time was identical for all the three disintegrant addition modes, and the hardness and the friability were not significantly influenced by working method, the obtained values were similar. For the developed formulations, the percent of the ranitidine dissolution was high, but higher in the extragranular incorporation. For the product quality the extragranular addition mode seemed the best method to incorporate the superdisintegrant.

Development and evaluation of orally disintegrating tablets comprising taste-masked mirtazapine granules.

PubMed

Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Vural, İmran; Ünlü, Nurşen

2018-06-01

Orally disintegrating tablets (ODTs) provide an important treatment option for pediatric, geriatric and psychiatric patients. In our previous study, we have performed the initial studies for the formulation development and characterization of new ODT formulations containing a bitter taste drug, mirtazapine, coated with 6% (w/w) Eudragit ® E-100 (first group of formulations, FGF) without taste evaluation. In present study, coating ratio of the drug was increased to 8% (w/w) (second group of formulations, SGF) to examine the effect of increased coating ratio of drug on in vitro characterization of the formulations including in vitro taste masking study. Coacervation technique using Eudragit ® E-100 was employed to obtain taste-masked mirtazapine granules. FGF and SGF were compared to original product (Remeron SolTab, an antidepressant drug which produced by pellet technology) in terms of in vitro permeability, in vitro taste masking efficiency which was performed by dissolution studies in salivary medium and dissolution stability. Also, the other tablet characteristics (such as diameter, thickness) of SGF were examined. The disintegration time of the SGF were found as A1 < A2 < A3 < A5 < A4 (8% Eudragit ® E-100), but all of the formulations dissolved under 30 seconds and friability values were less than 1%. In vitro taste masking efficiency studies demonstrated that C2 formulation (in FGF) had the most similar dissolution profile to Remeron SolTab. According to these findings, B2 or C2 (with citric acid or sodium bicarbonate, respectively, with 6% Eudragit ® E-100) formulations could be promising alternatives to Remeron SolTab.

The Disintegration Process in Microcrystalline Cellulose Based Tablets, Part 1: Influence of Temperature, Porosity and Superdisintegrants

PubMed Central

Yassin, Samy; Goodwin, Daniel J; Anderson, Andrew; Sibik, Juraj; Wilson, D Ian; Gladden, Lynn F; Zeitler, J Axel

2015-01-01

Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15 s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100 s, dominated by case II transport kinetics. The effect of adding superdisintegrant to the formulation and varying the temperature of the dissolution medium between 20°C and 37°C on the swelling and transport process was quantified. We have demonstrated that TPI can be used to non-invasively analyse the complex disintegration kinetics of formulations that take place on timescales of seconds and is a promising tool to better understand the effect of dosage form microstructure on its performance. By relating immediate-release formulations to mathematical models used to describe controlled release formulations, it becomes possible to use this data for formulation design. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3440–3450, 2015 PMID:26073446

Weight loss during therapy with olanzapine orally disintegrating tablets: two case reports.

PubMed

Kozumplik, Oliver; Uzun, Suzana; Jakovljević, Miro

2009-03-01

The aim of this article is to report weight loss in patients with schizophrenia after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT). In the first case report, the patient was switched to olanzapine ODT in daily dosage of 20 mg, while in the second case report, the patient was switched to olanzapine ODT in daily dosage of 15 mg, and weight loss was similar (14 kg vs. 15 kg). Switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained during 12 months in both case reports. Further controlled clinical investigations are necessary to evaluate change in weight during treatment with olanzapine ODT, and to improve our understanding of this change.

Gastrointestinal transit and disintegration of enteric coated magnetic tablets assessed by ac biosusceptometry.

PubMed

Corá, Luciana A; Romeiro, Fernando G; Américo, Madileine F; Oliveira, Ricardo Brandt; Baffa, Oswaldo; Stelzer, Murilo; Miranda, José Ricardo de Arruda

2006-01-01

The oral administration is a common route in the drug therapy and the solid pharmaceutical forms are widely used. Although much about the performance of these formulations can be learned from in vitro studies using conventional methods, evaluation in vivo is essential in product development. The knowledge of the gastrointestinal transit and how the physiological variables can interfere with the disintegration and drug absorption is a prerequisite for development of dosage forms. The aim of this work was to employing the ac biosusceptometry (ACB) to monitoring magnetic tablets in the human gastrointestinal tract and to obtain the magnetic images of the disintegration process in the colonic region. The ac biosusceptometry showed accuracy in the quantification of the gastric residence time, the intestinal transit time and the disintegration time (DT) of the magnetic formulations in the human gastrointestinal tract. Moreover, ac biosusceptometry is a non-invasive technique, radiation-free and harmless to the volunteers, as well as an important research tool in the pharmaceutical, pharmacological and physiological investigations.

In vitro disintegration studies of weekly generic and branded risedronate sodium formulations available in Canada.

PubMed

Walker, A D; Adachi, J D

2011-09-01

The aim of this study was to evaluate the in vitro disintegration of the five newly available Canadian generic risedronate 35 mg tablets compared to the innovator (branded) product, ACTONEL * *ACTONEL is a registered trade name of Warner Chilcott Company, LLC. (risedronate sodium) 35 mg. Tablets were inspected for colour and appearance. Disintegration times were determined using United States Pharmacopeia 33 (USP33-NF 28) methods. Disintegration onset time was also evaluated. The mean disintegration onset time values for the generic risedronate 35 mg tablets ranged from 2 to 29 seconds, and the mean disintegration completion times ranged from 81 to 260 seconds. The mean disintegration onset and completion time values for the ACTONEL 35 mg tablets were 23 and 43 seconds respectively. Four out of the five generic tablets tested had shorter disintegration onset times than the branded product; two of the generic tablet products had very fast disintegration onset times i.e. 2-3 seconds. Disintegration completion time for all five generic products tested was longer than that observed for the branded product; two generic products had disintegration completion time values five to six times longer than the branded product. Differences in the in vitro disintegration times were observed between the generic risedronate 35 mg tablets commercially available in Canada and the branded product, ACTONEL. The rapid disintegration onset times of two generic products may be important as this could increase the possibility of drug exposure in both the mouth and the esophagus during swallowing, resulting in unwanted localized irritation. However, it should be noted that an in vitro/in vivo correlation has not been established. Until such studies are completed it may be important to be aware of such in vitro disintegration differences when evaluating patients with newly presenting upper gastrointestinal complaints upon being switched from the branded product to generic formulations.

Application of water-insoluble polymers to orally disintegrating tablets treated by high-pressure carbon dioxide gas.

PubMed

Ito, Yoshitaka; Maeda, Atsushi; Kondo, Hiromu; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2016-09-10

The phase transition of pharmaceutical excipients that can be induced by humidifying or heating is well-known to increase the hardness of orally disintegrating tablets (ODTs). However, these conditions are not applicable to drug substances that are chemically unstable against such stressors. Here, we describe a system which enhances the hardness of tablets containing water-insoluble polymers by using high-pressure carbon dioxide (CO2). On screening of 26 polymeric excipients, aminoalkyl methacrylate copolymer E (AMCE) markedly increased tablet hardness (+155N) when maintained in a high-pressure CO2 environment. ODTs containing 10% AMCE were prepared and treatment with 4.0MPa CO2 gas at 25°C for 10min increased the hardness to +30N, whose level corresponded to heating at 70°C for 720min. In addition, we confirmed the effects of CO2 pressure, temperature, treatment time, and AMCE content on the physical properties of ODTs. Optimal pressure of CO2 gas was considered to be approximately 3.5MPa for an AMCE formula, as excessive pressure delayed the disintegration of ODTs. Combination of high-pressure CO2 gas and AMCE is a prospective approach for increasing the tablet hardness for ODTs, and can be conducted without additional heat or moisture stress using a simple apparatus. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of disintegrants functionality for orodispersible mini tablets.

PubMed

Soulairol, Ian; Chaheen, Mohammad; Tarlier, Nicolas; Aubert, Adrien; Bataille, Bernard; Sharkawi, Tahmer

2017-11-01

This work evaluates the functionalities of different superdisintegrants (SD) for manufacturing orodispersible mini tablets (ODMT) by direct compression. Twenty-three formulations varying in SD type, concentration, and lubricant were used to manufacture ODMT. The ODMT were then characterized for the following properties: friability, porosity, tensile strength, in vivo and in vitro disintegration time (DT). The results show that the presence, type, and concentration of SD did not influence friability, porosity, or tablet tensile strength. With regards to in vivo DT, only cross-linked poly (vinyl pyrrolidone) improved DT in all the tested formulations. Results also showed that when using microcrystalline cellulose (MCC) above 20% in the formulation, DT is longer. Cross-linked carboxymethyl cellulose accelerates DT when the MCC content is less than 20%. As for cross-linked carboxymethyl starch and calcium alginate showed no improvement on DT. Results for in vitro DT were all shorter than in vivo results and there was no correlation with the in vivo evaluation. This study shows that there is a need to develop better in vitro testing that precisely simulates in vivo conditions and that are adapted to ODMT. This standardization of the test methods for ODMTs must be accompanied by an improvement in the comprehension of SD mechanisms.

Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

PubMed Central

2012-01-01

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50 mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

An integrated, quality by design (QbD) approach for design, development and optimization of orally disintegrating tablet formulation of carbamazepine.

PubMed

Mishra, Saurabh M; Rohera, Bhagwan D

2017-11-01

The objective of the present study was to design and develop a formulation for orally disintegrating tablets (ODTs) of carbamazepine using quality by design principles. The target product profile (TPP) and quality target product profile (QTPP) of ODTs were identified. Risk assessment was carried out by leveraging prior knowledge and experience to define the criticality of factors based on their impact by Ishikawa fishbone diagram and preliminary hazard analysis tool. Box-Behnken response surface methodology was used to study the effect of critical factors on various attributes of ODTs. The independent factors selected were compression pressure (X 1 ), concentration of sublimating agent (volatile material) (X 2 ), disintegrant concentration (X 3 ) and the responses were tablet crushing strength, tablet porosity, disintegration time, water absorption time, tablet friability and drug dissolution. ANOVA and lack of fit test illustrated that selected independent variables had significant effect on the response variables, and excellent correlation was observed between actual and predicted values. Optimization by desirability function indicated that compression pressure, X 1 (1534 lbs), ammonium bicarbonate concentration, X 2 (7.68%) and Kollidon ® CL-SF concentration, X 3 (6%) were optimum to prepare ODT formulation of carbamazepine of desired attributes complying with QTPP. Thus, in the present study, a high level of assurance was established for ODT product quality and performance.

The Disintegration Process in Microcrystalline Cellulose Based Tablets, Part 1: Influence of Temperature, Porosity and Superdisintegrants.

PubMed

Yassin, Samy; Goodwin, Daniel J; Anderson, Andrew; Sibik, Juraj; Wilson, D Ian; Gladden, Lynn F; Zeitler, J Axel

2015-10-01

Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15 s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100 s, dominated by case II transport kinetics. The effect of adding superdisintegrant to the formulation and varying the temperature of the dissolution medium between 20°C and 37°C on the swelling and transport process was quantified. We have demonstrated that TPI can be used to non-invasively analyse the complex disintegration kinetics of formulations that take place on timescales of seconds and is a promising tool to better understand the effect of dosage form microstructure on its performance. By relating immediate-release formulations to mathematical models used to describe controlled release formulations, it becomes possible to use this data for formulation design. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3440-3450, 2015. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association.

Hot-stage microscopy for determination of API particles in a formulated tablet.

PubMed

Simek, Michal; Grünwaldová, Veronika; Kratochvíl, Bohumil

2014-01-01

Although methods exist to readily determine the particle size distribution (PSD) of an active pharmaceutical ingredient (API) before its formulation into a final product, the primary challenge is to develop a method to determine the PSD of APIs in a finished tablet. To address the limitations of existing PSD methods, we used hot-stage microscopy to observe tablet disintegration during temperature change and, thus, reveal the API particles in a tablet. Both mechanical and liquid disintegration were evaluated after we had identified optimum milling time for mechanical disintegration and optimum volume of water for liquid disintegration. In each case, hot-stage micrographs, taken before and after the API melting point, were compared with image analysis software to obtain the PSDs. Then, the PSDs of the APIs from the disintegrated tablets were compared with the PSDs of raw APIs. Good agreement was obtained, thereby confirming the robustness of our methodology. The availability of such a method equips pharmaceutical scientists with an in vitro assessment method that will more reliably determine the PSD of active substances in finished tablets.

[Method for the evaluation of the stability and usability after opening packages of orally disintegrating tablets: case of amlodipine besilate products].

PubMed

Hori, Katsuhito; Yoshida, Naoko; Okumura, Tomonori; Okamura, Yasufumi; Kawakami, Junichi

2010-08-01

Orally disintegrating (OD) tablets are widely used in clinical practice. However, drug information on the choice and dispensing based on their stability after opening packages and usability in patients and dispensaries is not sufficient. The aim of this study was to investigate possible evaluation methods of the stability and usability of amlodipine OD tablets. Additives of the brand were changed in April 2009, and therefore the previous and current forms and two generics, current and newly marketed (in November 2009) products of different firms, were used. OD tablets were stored at 25 degrees C and 75% relative humidity for 3 months after opening the packages, and their physicochemical properties were evaluated. Their weight, diameter, thickness, and color difference increased slightly from the initial state. The extent of the change in their hardness, disintegration time, and friability was different among products. These physicochemical changes were acceptable in dispensary practice. Storage after opening the packages did not affect their dissolution rate. The dissolution rate at the initial state of the current brand was slower than that of the previous one. All products used were able to be dispensed by an automatic tablet-packing machine and applied to the so-called simple suspension method for intubational administration. Sensory evaluation tests revealed no major difference in the oral disintegration time, taste, impression, and preference among products. In conclusion, the stability and usability of amlodipine OD tablets used in this study were examined using several methods, and they can be used equivalently from the stability and usability viewpoints.

Differences in In Vitro Disintegration Time among Canadian Brand and Generic Bisphosphonates

PubMed Central

Olszynski, Wojciech P.; Adachi, Jonathan D.; Davison, K. Shawn

2014-01-01

The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70 mg, alendronate 70 mg plus vitamin D 5600 IU, and risedronate 35 mg) and generic (Novo-alendronate 70 mg and Apo-alendronate 70 mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantly (P < 0.05) faster for Apo-alendronate (26 ± 5.6 seconds) and Novo-alendronate (13 ± 1.1 seconds) as compared to brand alendronate (147 ± 50.5 seconds), brand alendronate plus vitamin D (378 ± 60.5 seconds), or brand risedronate (101 ± 20.6 seconds). The significantly faster disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies. PMID:25349772

Differences in In Vitro Disintegration Time among Canadian Brand and Generic Bisphosphonates.

PubMed

Olszynski, Wojciech P; Adachi, Jonathan D; Davison, K Shawn

2014-01-01

The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70 mg, alendronate 70 mg plus vitamin D 5600 IU, and risedronate 35 mg) and generic (Novo-alendronate 70 mg and Apo-alendronate 70 mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantly (P < 0.05) faster for Apo-alendronate (26 ± 5.6 seconds) and Novo-alendronate (13 ± 1.1 seconds) as compared to brand alendronate (147 ± 50.5 seconds), brand alendronate plus vitamin D (378 ± 60.5 seconds), or brand risedronate (101 ± 20.6 seconds). The significantly faster disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies.

Controlled precipitation for enhanced dissolution rate of flurbiprofen: development of rapidly disintegrating tablets.

PubMed

Essa, Ebtessam A; Elmarakby, Amira O; Donia, Ahmed M A; El Maghraby, Gamal M

2017-09-01

The aim of this work was to investigate the potential of controlled precipitation of flurbiprofen on solid surface, in the presence or absence of hydrophilic polymers, as a tool for enhanced dissolution rate of the drug. The work was extended to develop rapidly disintegrated tablets. This strategy provides simple technique for dissolution enhancement of slowly dissolving drugs with high scaling up potential. Aerosil was dispersed in ethanolic solution of flurbiprofen in the presence and absence of hydrophilic polymers. Acidified water was added as antisolvent to produce controlled precipitation. The resultant particles were centrifuged and dried at ambient temperature before monitoring the dissolution pattern. The particles were also subjected to FTIR spectroscopic, X-ray diffraction and thermal analyses. The FTIR spectroscopy excluded any interaction between flurbiprofen and excipients. The thermal analysis reflected possible change in the crystalline structure and or crystal size of the drug after controlled precipitation in the presence of hydrophilic polymers. This was further confirmed by X-ray diffraction. The modulation in the crystalline structure and size was associated with a significant enhancement in the dissolution rate of flurbiprofen. Optimum formulations were successfully formulated as rapidly disintegrating tablet with subsequent fast dissolution. Precipitation on a large solid surface area is a promising strategy for enhanced dissolution rate with the presence of hydrophilic polymers during precipitation process improving the efficiency.

Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women.

PubMed

Lagenaur, Laurel A; Swedek, Iwona; Lee, Peter P; Parks, Thomas P

2015-01-01

MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody.

Robust Vaginal Colonization of Macaques with a Novel Vaginally Disintegrating Tablet Containing a Live Biotherapeutic Product to Prevent HIV Infection in Women

PubMed Central

Lagenaur, Laurel A.; Swedek, Iwona; Lee, Peter P.; Parks, Thomas P.

2015-01-01

MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody. PMID:25875100

Application of face centred central composite design to optimise compression force and tablet diameter for the formulation of mechanically strong and fast disintegrating orodispersible tablets.

PubMed

Pabari, Ritesh M; Ramtoola, Zebunnissa

2012-07-01

A two factor, three level (3(2)) face centred, central composite design (CCD) was applied to investigate the main and interaction effects of tablet diameter and compression force (CF) on hardness, disintegration time (DT) and porosity of mannitol based orodispersible tablets (ODTs). Tablet diameters of 10, 13 and 15 mm, and CF of 10, 15 and 20 kN were studied. Results of multiple linear regression analysis show that both the tablet diameter and CF influence tablet characteristics. A negative value of regression coefficient for tablet diameter showed an inverse relationship with hardness and DT. A positive value of regression coefficient for CF indicated an increase in hardness and DT with increasing CF as a result of the decrease in tablet porosity. Interestingly, at the larger tablet diameter of 15 mm, while hardness increased and porosity decreased with an increase in CF, the DT was resistant to change. The optimised combination was a tablet of 15 mm diameter compressed at 15 kN showing a rapid DT of 37.7s and high hardness of 71.4N. Using these parameters, ODTs containing ibuprofen showed no significant change in DT (ANOVA; p>0.05) irrespective of the hydrophobicity of the ibuprofen. Copyright © 2012 Elsevier B.V. All rights reserved.

Citric Acid Suppresses the Bitter Taste of Olopatadine Hydrochloride Orally Disintegrating Tablets.

PubMed

Sotoyama, Mai; Uchida, Shinya; Tanaka, Shimako; Hakamata, Akio; Odagiri, Keiichi; Inui, Naoki; Watanabe, Hiroshi; Namiki, Noriyuki

2017-01-01

Orally disintegrating tablets (ODTs) are formulated to disintegrate upon contact with saliva, allowing administration without water. Olopatadine hydrochloride, a second-generation antihistamine, is widely used for treating allergic rhinitis. However, it has a bitter taste; therefore, the development of taste-masked olopatadine ODTs is essential. Some studies have suggested that citric acid could suppress the bitterness of drugs. However, these experiments were performed using solutions, and the taste-masking effect of citric acid on ODTs has not been evaluated using human gustatory sensation tests. Thus, this study evaluated citric acid's taste-masking effect on olopatadine ODTs. Six types of olopatadine ODTs containing 0-10% citric acid were prepared and subjected to gustatory sensation tests that were scored using the visual analog scale. The bitterness and overall palatability of olopatadine ODTs during disintegration in the mouth and after spitting out were evaluated in 11 healthy volunteers (age: 22.8±2.2 years). The hardness of the ODTs was >50 N. Disintegration time and dissolution did not differ among the different ODTs. The results of the gustatory sensation tests suggest that citric acid could suppress the bitterness of olopatadine ODTs in a dose-dependent manner. Olopatadine ODTs with a high content of citric acid (5-10%) showed poorer overall palatability than that of those without citric acid despite the bitterness suppression. ODTs containing 2.5% citric acid, yogurt flavoring, and aspartame were the most suitable formulations since they showed low bitterness and good overall palatability. Thus, citric acid is an effective bitterness-masking option for ODTs.

Hydrophilic excipients modulate the time lag of time-controlled disintegrating press-coated tablets.

PubMed

Lin, Shan-Yang; Li, Mei-Jane; Lin, Kung-Hsu

2004-08-16

An oral press-coated tablet was developed by means of direct compression to achieve the time-controlled disintegrating or rupturing function with a distinct predetermined lag time. This press-coated tablet containing sodium diclofenac in the inner core was formulated with an outer shell by different weight ratios of hydrophobic polymer of micronized ethylcellulose (EC) powder and hydrophilic excipients such as spray-dried lactose (SDL) or hydroxypropyl methylcellulose (HPMC). The effect of the formulation of an outer shell comprising both hydrophobic polymer and hydrophilic excipients on the time lag of drug release was investigated. The release profile of the press-coated tablet exhibited a time period without drug release (time lag) followed by a rapid and complete release phase, in which the outer shell ruptured or broke into 2 halves. The lag phase was markedly dependent on the weight ratios of EC/SDL or EC/HPMC in the outer shell. Different time lags of the press-coated tablets from 1.0 to 16.3 hours could be modulated by changing the type and amount of the excipients. A semilogarithmic plot of the time lag of the tablet against the weight ratios of EC/SDL or EC/HPMC in the outer shell demonstrated a good linear relationship, with r = 0.976 and r = 0.982, respectively. The predetermined time lag prior to the drug release from a press-coated tablet prepared by using a micronized EC as a retarding coating shell can be adequately scheduled with the addition of hydrophilic excipients according to the time or site requirements.

Pharmaceutical and analytical evaluation of triphalaguggulkalpa tablets

PubMed Central

Savarikar, Shreeram S.; Barbhind, Maneesha M.; Halde, Umakant K.; Kulkarni, Alpana P.

2011-01-01

Aim of the Study: Development of standardized, synergistic, safe and effective traditional herbal formulations with robust scientific evidence can offer faster and more economical alternatives for the treatment of disease. The main objective was to develop a method of preparation of guggulkalpa tablets so that the tablets meet the criteria of efficacy, stability, and safety. Materials and Methods: Triphalaguggulkalpa tablet, described in sharangdharsanhita and containing guggul and triphala powder, was used as a model drug. Preliminary experiments on marketed triphalaguggulkalpa tablets exhibited delayed in vitro disintegration that indicated probable delayed in vivo disintegration. The study involved preparation of triphalaguggulkalpa tablets by Ayurvedic text methods and by wet granulation, dry granulation, and direct compression method. The tablets were evaluated for loss on drying, volatile oil content, % solubility, and steroidal content. The tablets were evaluated for performance tests like weight variation, disintegration, and hardness. Results: It was observed that triphalaguggulkalpa tablets, prepared by direct compression method, complied with the hardness and disintegration tests, whereas tablets prepared by Ayurvedic text methods failed. Conclusion: Direct compression is the best method of preparing triphalaguggulkalpa tablets. PMID:21731383

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.

IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS.

PubMed

Meka, Venkata Srikanth; Yee, Phung; Sheshala, Ravi

2016-01-01

In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose

Effect of repeated compaction of tablets on tablet properties and work of compaction using an instrumented laboratory tablet press.

PubMed

Gamlen, Michael John Desmond; Martini, Luigi G; Al Obaidy, Kais G

2015-01-01

The repeated compaction of Avicel PH101, dicalcium phosphate dihydrate (DCP) powder, 50:50 DCP/Avicel PH101 and Starch 1500 was studied using an instrumented laboratory tablet press which measures upper punch force, punch displacement and ejection force and operates using a V-shaped compression profile. The measurement of work compaction was demonstrated, and the test materials were ranked in order of compaction behaviour Avicel PH101 > DCP/Avicel PH101 > Starch > DCP. The behaviour of the DCP/Avicel PH101 mixture was distinctly non-linear compared with the pure components. Repeated compaction and precompression had no effect on the tensile fracture strength of Avicel PH101 tablets, although small effects on friability and disintegration time were seen. Repeated compaction and precompression reduced the tensile strength and the increased disintegration time of the DCP tablets, but improved the strength and friability of Starch 1500 tablets. Based on the data reported, routine laboratory measurement of tablet work of compaction may have potential as a critical quality attribute of a powder blend for compression. The instrumented press was suitable for student use with minimal supervisor input.

Neem gum as a binder in a formulated paracetamol tablet with reference to Acacia gum BP.

PubMed

Ogunjimi, Abayomi Tolulope; Alebiowu, Gbenga

2014-04-01

This study determined the physical, compressional, and binding properties of neem gum (NMG) obtained from the trunk of Azadirachta indica (A Juss) in a paracetamol tablet formulation in comparison with official Acacia gum BP (ACA). The physical and flow properties were evaluated using density parameters: porosity, Carr's index, Hausner's ratio, and flow rate. Compressional properties were analyzed using Heckel and Kawakita equations. The tensile strength, brittle fracture index, and crushing strength-friability/disintegration time ratio were used to evaluate the mechanical properties of paracetamol tablets while the drug release properties of the tablets were assessed using disintegration time and dissolution times. Tablet formulations containing NMG exhibited faster onset and higher amount of plastic deformation during compression than those containing ACA. Neem gum produced paracetamol tablets with lower mechanical strength; however, the tendency of the tablets to cap or laminate was lower when compared to those containing ACA. Inclusion of NMG improved the balance between binding and disintegration properties of paracetamol tablets produced than those containing ACA. Neem gum produced paracetamol tablets with lower disintegration and dissolution times than those containing ACA.

Disintegration/dissolution profiles of copies of Fosamax (alendronate).

PubMed

Epstein, S; Cryer, B; Ragi, S; Zanchetta, J R; Walliser, J; Chow, J; Johnson, M A; Leyes, A E

2003-01-01

Poor quality has been reported for some generics and other copies of original products. We performed a pilot study to compare the disintegration/dissolution profiles of FOSAMAX (alendronate) 70 mg tablets with those of copies of FOSAMAX that were manufactured outside the United States. We used the standard United States Pharmacopeia (USP) disintegration method to evaluate FOSAMAX 70 mg tablets and 13 copies. At least 12 (n = 12) dosage units were tested for each product (except Fosmin, n = 10). The dissolution profiles of FOSAMAX and one representative copy were also compared. Nine copies (Osteomax, Defixal, Fosmin, Endronax, Osteomix, Genalmen, Fixopan, Osteoplus, and Fosval) disintegrated two- to ten-fold faster than FOSAMAX. Three other copies (Neobon, Regenesis, and Ostenan) disintegrated at least five-fold slower than FOSAMAX. Neobon is a softgel capsule, so special consideration was given to this different dosage form. One copy (Arendal) did not fall into either category but exhibited potentially large inter- and intra-lot variability. Dissolution of alendronate from Regenesis lagged behind that from FOSAMAX. Slower disintegration may reduce efficacy because bisphosphonates must be taken in the fasting state and contact with food or even certain beverages severely reduces bioavailability. Faster disintegration (or the use of gel-caps or other alterations to the drug formulation) could increase the risk of esophagitis, an adverse event associated with prolonged contact of the esophagus with bisphosphonates. These disintegration and dissolution results suggest that important differences may exist between FOSAMAX and its copies with regard to bioavailability, pharmacokinetics, and clinical efficacy and safety profiles. Additional testing is warranted to evaluate the pharmacokinetics and clinical safety of these copies.

Comparative study on novel test systems to determine disintegration time of orodispersible films.

PubMed

Preis, Maren; Gronkowsky, Dorothee; Grytzan, Dominik; Breitkreutz, Jörg

2014-08-01

Orodispersible films (ODFs) are a promising innovative dosage form enabling drug administration without the need for water and minimizing danger of aspiration due to their fast disintegration in small amounts of liquid. This study focuses on the development of a disintegration test system for ODFs. Two systems were developed and investigated: one provides an electronic end-point, and the other shows a transferable setup of the existing disintegration tester for orodispersible tablets. Different ODF preparations were investigated to determine the suitability of the disintegration test systems. The use of different test media and the impact of different storage conditions of ODFs on their disintegration time were additionally investigated. The experiments showed acceptable reproducibility (low deviations within sample replicates due to a clear determination of the measurement end-point). High temperatures and high humidity affected some of the investigated ODFs, resulting in higher disintegration time or even no disintegration within the tested time period. The methods provided clear end-point detection and were applicable for different types of ODFs. By the modification of a conventional test system to enable application for films, a standard method could be presented to ensure uniformity in current quality control settings. © 2014 Royal Pharmaceutical Society.

A Novel Disintegration Tester for Solid Dosage Forms Enabling Adjustable Hydrodynamics.

PubMed

Kindgen, Sarah; Rach, Regine; Nawroth, Thomas; Abrahamsson, Bertil; Langguth, Peter

2016-08-01

A modified in vitro disintegration test device was designed that enables the investigation of the influence of hydrodynamic conditions on disintegration of solid oral dosage forms. The device represents an improved derivative of the compendial PhEur/USP disintegration test device. By the application of a computerized numerical control, a variety of physiologically relevant moving velocities and profiles can be applied. With the help of computational fluid dynamics, the hydrodynamic and mechanical forces present in the probe chamber were characterized for a variety of device moving speeds. Furthermore, a proof of concept study aimed at the investigation of the influence of hydrodynamic conditions on disintegration times of immediate release tablets. The experiments demonstrated the relevance of hydrodynamics for tablet disintegration, especially in media simulating the fasted state. Disintegration times increased with decreasing moving velocity. A correlation between experimentally determined disintegration times and computational fluid dynamics predicted shear stress on tablet surface was established. In conclusion, the modified disintegration test device is a valuable tool for biorelevant in vitro disintegration testing of solid oral dosage forms. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effect of sorbed water on disintegrant performance of four brands of Polacrilin Potassium NF.

PubMed

Bele, Mrudula H; Derle, Diliprao V

2012-03-01

Polacrilin Potassium NF is a commonly used weak cation exchange resin disintegrant in pharmaceutical tablets. The objective of this research was to evaluate the effects of sorbed moisture on physical characteristics and disintegrant performance of four brands of Polacrilin Potassium NF. The disintegrants were stored in five different relative humidity chambers and their dynamic vapor adsorption-desorption analysis, effect of moisture on their compressibility, compactability, particle size, morphology, water uptake rate, and disintegration ability were studied. Moisture seemed to plasticize the disintegrants, reducing their yield pressures. However, certain optimum amount of moisture was found to be useful in increasing the compactablity of the tablets containing disintegrants. The tablets, however, lost their tensile strengths beyond this optimum moisture content. Moisture caused two brands of the disintegrants to swell; however, two other brands aggregated upon exposure to moisture. Swelling without aggregation increased the water uptake, and in turn the disintegrant performance. However, aggregation probably reduced the porosities of the disintegrants, reducing their water uptake rate and disintegrant performance. Different brands of Polacrilin Potassium NF differed in the abilities to withstand the effects of moisture on their functionality. Effect of moisture on disintegrant performance of Polacrilin Potassium NF needs to be considered before its use in tablets made by wet granulation.

Rapidly-disintegrating sublingual tablets of epinephrine: role of non-medicinal ingredients in formulation development.

PubMed

Rachid, Ousama; Rawas-Qalaji, Mutasem; Simons, F Estelle R; Simons, Keith J

2012-11-01

Epinephrine is the drug of choice in the management of anaphylaxis. For first-aid treatment in the community, epinephrine autoinjectors (E-autos) are commonly prescribed, but are underutilized. In our laboratory, we developed a series of first-generation rapidly-disintegrating sublingual tablets (RDSTs) containing 40mg of epinephrine. One RDST had similar bioavailability to epinephrine 0.3mg from an auto-injector, as confirmed in a validated rabbit model, while other formulations containing different non-medicinal ingredients (NMIs) and with similar in vitro characteristics demonstrated much lower bioavailability. Subsequently, we evaluated the effect of changing the grade and proportion of NMIs, specifically mannitol and microcrystalline cellulose (MCC), on the in vitro characteristics of second- and third-generation RDSTs. Weight variation, content uniformity, breaking force, and friability were tested using official USP methods. Novel validated methods that simulate ambient conditions of the sublingual cavity were developed to test disintegration time, wetting time, and dissolution. Using these methods, it was possible to measure the effects of making small changes in NMIs on the in vitro characteristics of the formulations. The RDST formulation that resulted in the best in vitro characteristics contained the optimum proportion of mannitol and a specific ratio of coarse and fine particle grades of MCC. Appropriate comparative testing resulted in the selection of the RDST with the optimum in vitro characteristics. Copyright © 2012 Elsevier B.V. All rights reserved.

Taste-masked and affordable donepezil hydrochloride orally disintegrating tablet as promising solution for non-compliance in Alzheimer's disease patients.

PubMed

Liew, Kai Bin; Tan, Yvonne Tze Fung; Peh, Kok Khiang

2015-04-01

Manufacturing process and superdisintegrants used in orally disintegrating tablet (ODT) formulation are often time discussed. However, the effect of suitable filler for ODT formulation is not explored thoroughly. The aim of this study was to develop a novel taste masked and affordable donepezil hydrochloride ODT with fast disintegration time and stable to improve medication compliance of Alzheimer's disease patient. The ODT was manufactured using simple wet-granulation method. Crospovidone XL-10 was used as superdisintegrant and optimization was done by comparing the effect of three grades of lactose monohydrate compound as filler: Starlac®, Flowlac® and Tablettose®. Formulations containing higher amount of colloidal silicon dioxide showed increase in hardness, weight, disintegration time and wetting time after stability study. Formulation E which containing 50% of Starlac® was found with shortest in vitro disintegration time (21.7 ± 1.67 s), in vivo disintegration time (24.0 ± 1.05 s) and in vitro disintegration time in artificial salvia (22.5 ± 1.67 s). Physical stability studies at 40 °C/75% RH for 6 months, Fourier transform infrared spectroscopy analysis and X-ray diffraction results showed that the formulation was stable. The drug-released profile showed that 80% of donepezil hydrochloride was released within 1 min. A single-dose, fasting, four-period, seven-treatment, double-blinded study involving 16 healthy human volunteers was performed to evaluate the palatability of ODT. Formulation VII containing 10 mg of ammonium glycyrrhizinate was able to mask the bitter taste of the drug. The product has the potential to be commercialized and it might serve as solution for non-compliance among the Alzheimer's disease patients.

The Effects of Screw Configuration and Polymeric Carriers on Hot-Melt Extruded Taste-Masked Formulations Incorporated into Orally Disintegrating Tablets

PubMed Central

Morott, Joseph T.; Pimparade, Manjeet; Park, Jun-Bom; Worley, Chelsea P.; Majumdar, Soumyajit; Lian, Zhuoyang; Pinto, Elanor; Bi, Yunxia; Durig, Thomas; Repka, Michael A.

2015-01-01

The primary aim of this research was to produce successfully taste masked formulations of Sildenafil Citrate (SC) using hot-melt extrusion (HME) technology. Multiple screw configurations and polymeric carriers were evaluated for their effects on taste masking efficiency, which was assessed by both E-tongue analysis and in vitro dissolution in simulated salivary fluid (SSF, pH 6.8 artificial saliva). The screw configurations were further assessed for their effects on the morphology of the API using PXRD, FT-IR and mid-infrared chemical imaging. It was determined that the screw configuration had a profound effect on the taste masking efficiency of the formulations as a result of altering the physical state of the API. Selected extruded formulations using ethylcellulose (EC) with a pore former were further formulated into orally disintegrating tablets (ODTs), which were optimized by varying the grade and percentage of the superdisintegrant used. An optimized disintegration time of approximately 8 seconds was achieved. The final ODT formulation exhibited excellent taste masking properties with over 85% drug release in gastric media as well as physical tablet properties. Interestingly, friability, which tends to be a common concern when formulating ODTs, was well within the acceptable limits (<1%) for common tablets. PMID:25410968

Synthesis of a novel superdisintegrant by starch derivatization with polysuccinimide and its application for the development of Ondansetron fast dissolving tablet.

PubMed

Sadeghi, Mozhgan; Hemmati, Salar; Hamishehkar, Hamed

2016-01-01

Disintegrants are the key excipients administered in tablet formulations to boost the decomposition of the tablet into smaller pieces in the gastrointestinal environment, thereby increasing the available surface area and enhancing a more rapid release of the active ingredient. Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid, was reacted with starch and fully assessed by CHN, (1)H-NMR, and FTIR. PSI-grafted starch (PSI-St) was synthesized and applied as a disintegrant in the formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and vomiting medicine. The tablet formulated with the newly developed superdisintegrant was evaluated for hardness, friability, disintegration time, and dissolution rate, and the results were compared with tablets formulated with an identical composition of test formulation differing only in type of disintegrant. Tablets prepared with starch and tablets prepared with sodium starch glycolate (SSG) were used as negative and positive controls, respectively. Dissolution study results indicated that although the onset of disintegration action was faster for SSG than PSI-St, higher amounts of drug were released from tablets formulated from PSI-St than from those formulated from SSG during 10 min. It was concluded that the novel synthesized superdisintegrant has an appropriate potential for the application in the formulation of fast dissolving tablets.

Synthesis of a novel superdisintegrant by starch derivatization with polysuccinimide and its application for the development of Ondansetron fast dissolving tablet.

PubMed

Sadeghi, Mozhgan; Hemmati, Salar; Hamishehkar, Hamed

2016-05-01

Disintegrants are the key excipients administered in tablet formulations to boost the decomposition of the tablet into smaller pieces in the gastrointestinal environment, thereby increasing the available surface area and enhancing a more rapid release of the active ingredient. Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid, was reacted with starch and fully assessed by CHN, 1 H-NMR, and FTIR. PSI-grafted starch (PSI-St) was synthesized and applied as a disintegrant in the formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and vomiting medicine. The tablet formulated with the newly developed superdisintegrant was evaluated for hardness, friability, disintegration time, and dissolution rate, and the results were compared with tablets formulated with an identical composition of test formulation differing only in type of disintegrant. Tablets prepared with starch and tablets prepared with sodium starch glycolate (SSG) were used as negative and positive controls, respectively. Dissolution study results indicated that although the onset of disintegration action was faster for SSG than PSI-St, higher amounts of drug were released from tablets formulated from PSI-St than from those formulated from SSG during 10 min. It was concluded that the novel synthesized superdisintegrant has an appropriate potential for the application in the formulation of fast dissolving tablets.

How Deformation Behavior Controls Product Performance After Twin Screw Granulation With High Drug Loads and Crospovidone as Disintegrant.

PubMed

Meier, Robin; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

2017-01-01

This study addresses the quantitative influence of 12 different materials (active pharmaceutical ingredients and excipients as surrogate active pharmaceutical ingredients) on the critical quality attributes of twin screw granulated products and subsequently produced tablets. Prestudies demonstrated the significant influence of the chosen model materials (in combination with crospovidone) on the disintegration behavior of the resulting tablets, despite comparable tablet porosities. This study elucidates possible reasons for the varying disintegration behavior by investigating raw material, granule, and tablet properties. An answer could be found in the mechanical properties of the raw materials and the produced granules. Through compressibility studies, the materials could be classified into materials with high compressibility, which deform rather plastically under compression stress, and low compressibility, which display breakages under compression stress. In general, and apart from (pseudo)-polymorphic transformations, brittle materials featured excellent disintegration performance, even at low resulting tablet porosities <8%, whereas plastically deformable materials mostly did not reveal any disintegration. These findings must be considered in the development of simplified formulations with high drug loads, in which the active pharmaceutical ingredient predominantly defines the deformation behavior of the granule. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Formulation and evaluation of dried yeast tablets using different techniques.

PubMed

Al-Mohizea, Abdullah M; Ahmed, Mahrous O; Al-jenoobi, Fahad I; Mahrous, Gamal M; Abdel-Rahman, Aly A

2007-08-01

The aim of this study was to prepare and evaluate dried yeast tablets using both direct compression and dry granulation techniques in comparison with the conventional wet granulation as well as commercial product. Wet granulation technique is not favorable for producing the yeast tablets due to the problems of color darkening and the reduction of the fermentation power of the yeast as a result of the early start of the fermentation process due to the presence of moisture. Twenty six formulae of dried yeast tablets were prepared and evaluated. Certain directly compressible vehicles were employed for preparing these tablets. The quality control tests (weight uniformity, friability, disintegration time and hardness) of the prepared dried yeast tablets were performed according to B.P. 1998 limits. All batches of the prepared tablets complied with the B.P. limits of weight uniformity. Moreover, small values of friability % (1% or less) were obtained for all batches of dried yeast tablets with acceptable hardness values, indicating good mechanical properties which can withstand handling. On the other hand, not all batches complied with the limit of disintegration test which may be attributed to various formulation component variables. Therefore, four disintegrating agents were investigated for their disintegrating effect. It was found that the method of preparation, whether it is direct compression, dry granulation or wet granulation, has an effect on disintegration time of these dried yeast tablets and short disintegration times were obtained for some of the formulae. The shortest disintegration time was obtained with those tablets prepared by direct compression among the other techniques. Therefore, the direct compression is considered the best technique for preparation of dried yeast tablets and the best formula (which showed shorter disintegration time and better organoleptic properties than the available commercial yeast tablets) was chosen. Drug content for dried

A Review of Disintegration Mechanisms and Measurement Techniques.

PubMed

Markl, Daniel; Zeitler, J Axel

2017-05-01

Pharmaceutical solid dosage forms (tablets or capsules) are the predominant form to administer active pharmaceutical ingredients (APIs) to the patient. Tablets are typically powder compacts consisting of several different excipients in addition to the API. Excipients are added to a formulation in order to achieve the desired fill weight of a dosage form, to improve the processability or to affect the drug release behaviour in the body. These complex porous systems undergo different mechanisms when they come in contact with physiological fluids. The performance of a drug is primarily influenced by the disintegration and dissolution behaviour of the powder compact. The disintegration process is specifically critical for immediate-release dosage forms. Its mechanisms and the factors impacting disintegration are discussed and methods used to study the disintegration in-situ are presented. This review further summarises mathematical models used to simulate disintegration phenomena and to predict drug release kinetics.

Orally disintegrating films: A modern expansion in drug delivery system.

PubMed

Irfan, Muhammad; Rabel, Sumeira; Bukhtar, Quratulain; Qadir, Muhammad Imran; Jabeen, Farhat; Khan, Ahmed

2016-09-01

Over the past few decades, tendency toward innovative drug delivery systems has majorly increased attempts to ensure efficacy, safety and patient acceptability. As discovery and development of new chemical agents is a complex, expensive and time consuming process, so recent trends are shifting toward designing and developing innovative drug delivery systems for existing drugs. Out of those, drug delivery system being very eminent among pediatrics and geriatrics is orally disintegrating films (ODFs). These fast disintegrating films have superiority over fast disintegrating tablets as the latter are associated with the risks of choking and friability. This drug delivery system has numerous advantages over conventional fast disintegrating tablets as they can be used for dysphasic and schizophrenic patients and are taken without water due to their ability to disintegrate within a few seconds releasing medication in mouth. Various approaches are employed for formulating ODFs and among which solvent casting and spraying methods are frequently used. Generally, hydrophilic polymers along with other excipients are used for preparing ODFs which allow films to disintegrate quickly releasing incorporated active pharmaceutical ingredient (API) within seconds. Orally disintegrating films have potential for business and market exploitation because of their myriad of benefits over orally disintegrating tablets. This present review attempts to focus on benefits, composition, approaches for formulation and evaluation of ODFs. Additionally, the market prospect of this innovative dosage form is also targeted.

A pharmaceutical study on lornoxicam fast disintegrating tablets: formulation and in vitro and in vivo evaluation.

PubMed

Moutasim, Mohamed Yousif; ElMeshad, Aliaa Nabil; El-Nabarawi, Mohamed Ahmed

2017-06-01

Lornoxicam is an anti-inflammatory drug used to relieve rheumatoid arthritis pain, but the low water solubility and bitter taste of the drug present challenges for formulation as fast disintegrating tablets (FDTs). Complexation of the drug with β-cyclodextrin was initially carried out to increase the drug solubility and to mask its bitter taste. Tablets were prepared by direct compression of drug complex (DC), F-Melt, mannitol, crospovidone, and sodium starch glycolate (SSG). FDTs were characterized in terms of disintegration time (DT) and dissolution. A bioequivalence study was carried out using (Zeficam® tablets (Eva Pharma) as reference with the help of human volunteers (n = 4). The chosen formula (F2, DC 24 mg, F-Melt 88.4 mg, and crospovidone 5 mg) exhibited the shortest in vitro (18 s) and in vivo DT (13 s), and the percent drug released after Q6min was 95.90%. Following administration of F2 and Zeficam®, the respective maximum drug plasma concentrations (C max ) were 510 and 532.5 ng/mL, at times (T max ) of 1 and 2.5 h, of mean residence times (MRTs) of 12.25 and 11.35 h and of areas under the plasma curve [AUC(0-24)] of 5080.253 and 4815.775 ng/h/mL. There were significant differences in T max and MRT of both treatments (p < 0.05). Moreover, the volunteers found F2 to be palatable. FDTs could be considered as promising dosage forms for lornoxicam as they exhibited a short in vivo DT and an increased rate of drug release and attained a relative bioavailability of 105.49%. This could offer a fast relief of pain accompanying rheumatoid arthritis.

Evaluation of synthesized cross linked polyvinyl alcohol as potential disintegrant.

PubMed

Patel, Ashok R; Vavia, Pradeep R

2010-01-01

The present study deals with evaluation of crosslinked poly vinyl alcohol (PVA) as a potential disintegrant. Crosslinking of PVA was carried out using glutaraldehyde as a crosslinker, in presence of acidic conditions. The crosslinking reaction was optimized for a) polymer: crosslinker ratio; b) temperature requirement and c) reaction duration. Certain physical parameters of the disintegrant (including sedimentation volume, hydration capacity, specific surface area and bulk and tap density) were determined and compared to the known disintegrants. Characterization was carried out using FT-IR, DSC, XRD, SEM and Photo microscopy studies. The developed excipient was also studied for acute toxicity in rats and found to be safe for oral use. Disintegration property of formed product was compared to known disintegrant (Ac-Di-Sol) and it was found to give better results. The disintegration mechanism of developed disintegrant was postulated based on results obtained from various physical evaluations including: Study of effect of disintegrant concentration, fillers, and hardness, mode of incorporation and method of granulation on disintegration activity. By changing the condition parameters of well known crosslinking reaction of PVA, we obtained a crosslinked product which had excellent disintegration activity, good flow and optimal tableting properties.

Evaluation of disintegration testing of different fast dissolving tablets using the texture analyzer.

PubMed

el-Arini, Silvia Kocova; Clas, Sophie-Dorothée

2002-01-01

The in vitro disintegration behavior of fast dissolving systems manufactured by the main commercialized technologies was studied using the texture analyzer (TA) instrument. Quantitative parameters were employed to characterize the effect of the major test variables on the disintegration profiles. The average disintegration profiles of the products were compared using the test conditions that minimized these effects and at the same time mimicked the in vivo situation in the patient's mouth. The differences in the disintegration mechanisms of the fast dissolving systems were reflected in the shape of their disintegration profiles and in the parameters derived from the profiles. The differences were explained in relation to the technology and/or formulation characteristics involved in the manufacture of each product. The in vitro disintegration times obtained under the simulated in vivo conditions were correlated with the reported in vivo disintegration times.

An easy-to-use approach for determining the disintegration ability of disintegrants by analysis of available surface area.

PubMed

Iwao, Yasunori; Tanaka, Shoko; Uchimoto, Takeaki; Noguchi, Shuji; Itai, Shigeru

2013-05-01

With the aim of directly predicting the functionality and mechanism of disintegrants during the disintegration and dissolution of tablets, we investigated an analysis method based on available surface area, which is the surface area of a drug in a formulation in direct contact with the external solvent during dissolution. We evaluated the following disintegrants in this study: sodium starch glycolate (Glycolys), crospovidone (Kollidon CL), carboxymethylcellulose calcium (CMC-Ca), low-substituted hydroxypropylcellulose (L-HPC), and croscarmellose sodium (Ac-Di-Sol). When disintegrant was added to a 50% ethenzamide tablet formulation, an increase in the dissolution rate dependent on disintegrant concentration was observed, according to the type of disintegrant. In addition, the available surface area also differed between disintegrants. For Glycolys, CMC-Ca, and Ac-Di-Sol, a rapid increase in available surface area and a large increase in maximum available surface area (Smax) were observed due to high swellability and wicking, even when the disintegrant concentration was only 1.0%. In contrast, for Kollidon CL and LH-21, a gradual increase in available surface area was observed, depending on the disintegrant concentration. To evaluate the disintegrant ability, Δtmax and ΔSmax were calculated by subtracting peak time (tmax) at 5.0% from that at 1.0% and subtracting Smax at 1.0% from that at 5.0%, respectively, and it was found that the water absorption ratio had strong negative correlations with Δtmax and ΔSmax. Therefore, this study demonstrates that analysis of only available surface area and parameters thereby obtained can directly provide useful information, especially about the disintegration ability of disintegrants. Copyright © 2013 Elsevier B.V. All rights reserved.

Release kinetics of papaverine hydrochloride from tablets with different excipients.

PubMed

Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release.

Release Kinetics of Papaverine Hydrochloride from Tablets with Different Excipients

PubMed Central

Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

Abstract The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release. PMID:25853076

Influence of pH on in vitro disintegration of phosphate binders.

PubMed

Stamatakis, M K; Alderman, J M; Meyer-Stout, P J

1998-11-01

Hyperphosphatemia, a common complication in patients with end-stage renal disease, is treated with oral phosphate-binding medications that restrict phosphorus absorption from the gastrointestinal (GI) tract. Impaired product performance, such as failure to disintegrate and/or dissolve in the GI tract, could limit the efficacy of the phosphate binder. Disintegration may be as important as dissolution for predicting in vitro product performance for medications that act locally on the GI tract, such as phosphate binders. Furthermore, patients with end-stage renal disease have a wide range in GI pH, and pH can influence a product's performance. The purpose of this study was to determine the effect of pH on in vitro disintegration of phosphate binders. Fifteen different commercially available phosphate binders (seven calcium carbonate tablet formulations, two calcium acetate tablet formulations, three aluminum hydroxide capsule formulations, and three aluminum hydroxide tablet formulations) were studied using the United States Pharmacopeia (USP) standard disintegration apparatus. Phosphate binders were tested in simulated gastric fluid (pH 1.5), distilled water (pH 5.1), and simulated intestinal fluid (pH 7.5). Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within 30 minutes. Results indicate that 9 of the 15 phosphate binders tested showed statistically significant differences in disintegration time (DT) based on pH. The percentage of binders that passed the disintegration study test in distilled water, gastric fluid, and intestinal fluid were 80%, 80%, and 73%, respectively. The findings of this study show that the disintegration of commercially available phosphate binders is highly variable. The pH significantly affected in vitro disintegration in the majority of phosphate binders tested; how significantly this affects in vivo performance has yet to be studied.

[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.

Investigation of the performance of the disintegration test for dietary supplements.

PubMed

Almukainzi, May; Salehi, Mahnor; Araci Bou-Chacra, Nadia; Löbenberg, Raimar

2010-12-01

The aim of this study was to investigate how beaker size, basket assembly, use of disk, and immersion medium impact the disintegration time of dietary supplements. The disintegration times were determined for five tablet and two capsule products. A two-station disintegration tester was used with Apparatus A or Apparatus B as described in the United States Pharmacopeia (USP) chapters, <701> and <2040>. Two beakers complying with the harmonized specifications were used, one with a volume of 1,000 mL and one with a 1,500-mL volume. The disintegration data were analyzed using ANOVA for the following factors: beaker size, equipment (App A and B) and condition (with/without disk). Two tablet products were not sensitive to any changes in the test conditions or equipment configurations. One product was only partially sensitive to the test conditions. The other products showed impact on the disintegration time for all test conditions. The results revealed that these tablet products might pass or fail current USP disintegration requirements depending on the equipment configuration. Similar results were obtained for the two investigated capsule formulations. One product might fail current USP disintegration requirements if the large beaker was used, but might pass the disintegration requirements when the small beaker was used. Hydroxy propyl methyl cellulose capsules were mostly influenced if sodium instead of a potassium buffer was used as the immersion medium. The results demonstrate that the current harmonized ICH specifications for the disintegration test are insufficient to make the disintegration test into reliable test for dietary supplements.

Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique.

PubMed

Gohel, Mukesh; Patel, Madhabhai; Amin, Avani; Agrawal, Ruchi; Dave, Rikita; Bariya, Nehal

2004-04-26

The purpose of this research was to develop mouth dissolve tablets of nimesulide. Granules containing nimesulide, camphor, crospovidone, and lactose were prepared by wet granulation technique. Camphor was sublimed from the dried granules by exposure to vacuum. The porous granules were then compressed. Alternatively, tablets were first prepared and later exposed to vacuum. The tablets were evaluated for percentage friability, wetting time, and disintegration time. In the investigation, a 32 full factorial design was used to investigate the joint influence of 2 formulation variables: amount of camphor and crospovidone. The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of camphor and a higher percentage of crospovidone. A contour plot is also presented to graphically represent the effect of the independent variables on the disintegration time and percentage friability. A checkpoint batch was also prepared to prove the validity of the evolved mathematical model. Sublimation of camphor from tablets resulted in superior tablets as compared with the tablets prepared from granules that were exposed to vacuum. The systematic formulation approach helped in understanding the effect of formulation processing variables.

Stabilization Mechanism of Roxithromycin Tablets under Gastric pH Conditions.

PubMed

Inukai, Koki; Noguchi, Shuji; Kimura, Shin-Ichiro; Itai, Shigeru; Iwao, Yasunori

2018-05-31

Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of three widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A (EM), and azithromycin (AZM). The results indicated that not only CAM but also RXM gelated under acidic conditions. EM and AZM did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that two of the four macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides. Copyright © 2018. Published by Elsevier Inc.

Development and validation of NIR-chemometric methods for chemical and pharmaceutical characterization of meloxicam tablets.

PubMed

Tomuta, Ioan; Iovanov, Rares; Bodoki, Ede; Vonica, Loredana

2014-04-01

Near-Infrared (NIR) spectroscopy is an important component of a Process Analytical Technology (PAT) toolbox and is a key technology for enabling the rapid analysis of pharmaceutical tablets. The aim of this research work was to develop and validate NIR-chemometric methods not only for the determination of active pharmaceutical ingredients content but also pharmaceutical properties (crushing strength, disintegration time) of meloxicam tablets. The development of the method for active content assay was performed on samples corresponding to 80%, 90%, 100%, 110% and 120% of meloxicam content and the development of the methods for pharmaceutical characterization was performed on samples prepared at seven different compression forces (ranging from 7 to 45 kN) using NIR transmission spectra of intact tablets and PLS as a regression method. The results show that the developed methods have good trueness, precision and accuracy and are appropriate for direct active content assay in tablets (ranging from 12 to 18 mg/tablet) and also for predicting crushing strength and disintegration time of intact meloxicam tablets. The comparative data show that the proposed methods are in good agreement with the reference methods currently used for the characterization of meloxicam tablets (HPLC-UV methods for the assay and European Pharmacopeia methods for determining the crushing strength and disintegration time). The results show the possibility to predict both chemical properties (active content) and physical/pharmaceutical properties (crushing strength and disintegration time) directly, without any sample preparation, from the same NIR transmission spectrum of meloxicam tablets.

Evaluation of different fast melting disintegrants by means of a central composite design.

PubMed

Di Martino, Piera; Martelli, Sante; Wehrlé, Pascal

2005-01-01

Fast-disintegration technologies have encountered increased interest from industries in the past decades. In order to orientate the formulators to the choice of the best disintegrating agent, the most common disintegrants were selected and their ability to quickly disintegrate direct compressed tablets was evaluated. For this study, a central composite design was used. The main factors included were the concentration of disintegrant (X1) and the compression force (X2). These factors were studied for tablets containing either Zeparox or Pearlitol 200 as soluble diluents and six different disintegrants: L-HPC LH11 and LH31, Lycatab PGS, Vivasol, Kollidon CL, and Explotab. Their micromeritics properties were previously determined. The response variables were disintegration time (Y1), tensile strength (Y2), and porosity (Y3). Whatever the diluent, the longest disintegration time is obtained with Vivasol as the disintegrant, while Kollidon CL leads to the shortest disintegration times. Exception for Lycatab PGS and L-HPC LH11, formulations with Pearlitol 200 disintegrate faster. Almost the same results are obtained with porosity: no relevant effect of disintegrant concentration is observed, since porosity is mainly correlated to the compression force. In particular, highest values are obtained with Zeparox as the diluent when compared to Pearlitol 200 and, as the type of disintegrant is concerned, no difference is observed. Tensile strength models have been all statistically validated and are all highly dependent on the compression force. Lycatab PGS concentration does not affect disintegration time, mainly increased by the increase of compression pressure. When Pearlitol 200 is used with Vivasol, disintegration time is more influenced by the disintegrant concentration than by the compression pressure, an increase in concentration leading to a significant and relevant increase of the disintegration time. With Zeparox, the interaction between the two controlled variables

The Impact of Granule Density on Tabletting and Pharmaceutical Product Performance.

PubMed

van den Ban, Sander; Goodwin, Daniel J

2017-05-01

The impact of granule densification in high-shear wet granulation on tabletting and product performance was investigated, at pharmaceutical production scale. Product performance criteria need to be balanced with the need to deliver manufacturability criteria to assure robust industrial scale tablet manufacturing processes. A Quality by Design approach was used to determine in-process control specifications for tabletting, propose a design space for disintegration and dissolution, and to understand the permitted operating limits and required controls for an industrial tabletting process. Granules of varying density (filling density) were made by varying water amount added, spray rate, and wet massing time in a design of experiment (DoE) approach. Granules were compressed into tablets to a range of thicknesses to obtain tablets of varying breaking force. Disintegration and dissolution performance was evaluated for the tablets made. The impact of granule filling density on tabletting was rationalised with compressibility, tabletability and compactibility. Tabletting and product performance criteria provided competing requirements for porosity. An increase in granule filling density impacted tabletability and compactability and limited the ability to achieve tablets of adequate mechanical strength. An increase in tablet solid fraction (decreased porosity) impacted disintegration and dissolution. An attribute-based design space for disintegration and dissolution was specified to achieve both product performance and manufacturability. The method of granulation and resulting granule filling density is a key design consideration to achieve both product performance and manufacturability required for modern industrial scale pharmaceutical product manufacture and distribution.

Lallemantia reylenne seeds as superdisintegrant: Formulation and evaluation of nimesulide orodispersible tablets

PubMed Central

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

2011-01-01

Aim: Orodispersible tablets also known as fast dissolving tablets disintegrate instantaneously within the mouth and thus can be consumed without water. The present study was aimed to formulate orodispersible tablets of nimesulide by using Lallemantia reylenne seeds as natural superdisintegrant. Materials and Methods: Powdered lallemantia seeds were characterized for powder flow properties (bulk density, tapped density, carr's consolidation index, hausner ratio, angle of repose), swelling index, viscosity, pH, and loss on drying. The prepared tablets were evaluated for different tablet parametric tests, wetting time, water absorption ratio, effective pore radius, porosity, packing fraction, in vitro and in vivo disintegration time, in vitro dissolution and stability studies. Results and Discussion: Increase in Lallementia reylenne concentration had an appreciable effect on tablet hardness and friability which clearly indicated binding potential of the seeds. Water absorption ratio increased with increase in Lallemantia reylenne concentration from batch A1 to A4. Water uptake coupled natural polymer swelling could be the most probable mechanism for concentration dependent reduction in disintegration time by the Lallemantia reylenne seeds. Porosity of the formulated tablets was found to increase from batch A1-A4. The in vitro disintegration results were in line with in vivo disintegration results. Conclusion: It could be concluded that Lallemantia reylenne seeds could be used as natural superdisintegrant in the formulation of orodispersible tablets. PMID:23071942

Orodispersible tablets: A new trend in drug delivery

PubMed Central

Dey, Paramita; Maiti, Sabyasachi

2010-01-01

The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug-delivery system as they have improved patient compliance and have some additional advantages compared to other oral formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to super disintegrants in the formulation. Thus this type of drug delivery helps a proper peroral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method of preparation is the compression method. Other special methods are molding, melt granulation, phase-transition process, sublimation, freeze-drying, spray-drying, and effervescent method. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test, and dissolution test. PMID:22096326

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models.

PubMed

Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

2017-01-01

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer-Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

PubMed Central

Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

2017-01-01

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer–Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that

[Application of β-cyclodextrin in the formulation of ODT tablets containing ibuprofen].

PubMed

Zimmer, Łukasz; Kasperek, Regina; Poleszak, Ewa

2014-01-01

Oral disintegrating tablet (ODT) dissolves or disintegrates in saliva and then it is swallowed. Diluent in direct compression formulation has a dual role: it increases bulk of the dosage form and it promotes binding of the constituent particles of the formulation. Hence, selection of diluent is important in tablets produced by direct compression method. The aim of this work was to exame feasibility of preparing and optimizing oral disintegrating tablet formulation using β-cyclodextrin as a diluent. 400 mg round tablets were prepared by direct compression method on single punch tablet press using flat plain-face. 60% β-CD and MCC (microcrystalline cellulose - MCC-Vivapur 102) were used at different proportions for all the formulations. 5% of Kollidon CL was added as superdisintegrant. The eight formulations prepared were assessed for weight variation, thickness, disintegration time, hardness and dissolution rate according to FP IX. A dissolution test was performed at 37ºC using the paddle method at 50 rpm with 900 mL phosphate buffer (pH 6.8) as a dissolution medium. The content of ibuprofen sodium was found inside the ± 5% of the theoretical value. Hardness values of presented tablets were in the range 0.11-0.15 kG/mm2. Friability of the tablets lower than 1% indicates that the developed formulations can be processed and handled without excessive care. Disintegration time was in the range of 86 to 161 s. The results confirm the good mechanical properties of tablets containing β-CD. A composition with 20% β-CD and 40% MCC fulfilled a maximum requisite of an optimum formulation. These properties were similar to Ludiflash, the formulation used for comparison purposes. In the present study, higher concentration of β cyclodextrin was found to improve the hardness of tablets without increasing the disintegration time.

Compaction behaviour and mechanical strength of lactose-sodium starch glycolate and lactose-croscarmellose sodium binary tablets

NASA Astrophysics Data System (ADS)

Ashikin Yaakub, Nur; Shamsul Anuar, Mohd; Tahir, Suraya Mohd

2018-04-01

The focus of this study is to elucidate the effects of adding super disintegrants (SSG and Acdisol) to a filler (lactose) in terms of the compaction behaviour and mechanical strength of the formed binary tablets. The tablets were formed in a uniaxial die compaction process with compaction pressures ranging from 37.7MPa to 150.7 MPa. Consequently, the findings indicated that the increasing of the compaction pressure and the percentage mass composition of the super disintegrants would led to the increased in the strength of the tablets as well as their plastic energies, where this was more apparent for the case of the binary lactose/Acdisol tablets. In addition, as the compaction pressure increased, the maximum ejection pressure required to eject the tablet from the die cavity also increased. In contrast, a decreased in the maximum ejection pressure was observed as the composition of both super disintegrants increased in the lactose-super disintegrant binary tablets. In conclusion, the addition of super disintegrant; SSG with lactose and Acdisol with lactose; would enhanced the mechanical strength of lactose based tablets especially for the case of acdisol-lactose binary tablets in the experimental conditions adopted in this current work.

A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

PubMed

Low, Ariana; Kok, Si Ling; Khong, Yuet Mei; Chan, Sui Yung; Gokhale, Rajeev

2015-11-01

No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test. The DTU is an accessory to the USP disintegration apparatus. It holds the ODF in a horizontal position, allowing top-view of the ODF during testing. A Gauge R&R study was conducted to assign relative contributions of the total variability from the operator, sample or the experimental set-up. Precision was compared using commercial ODF products in different media. Agreement between the two measurement methods was analysed. The DTU showed improved repeatability and reproducibility compared to the USP disintegration system with tighter standard deviations regardless of operator or medium. There is good agreement between the two methods, with the USP disintegration test giving generally longer disintegration times possibly due to difficulty in end-point determination. The DTU provided clear end-point determination and is suitable for quality control of ODFs during product developmental stage or manufacturing. This may facilitate the development of a standardized methodology for disintegration time determination of ODFs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

The effect of superdisintegrants on the properties and dissolution profiles of liquisolid tablets containing rosuvastatin.

PubMed

Vraníková, Barbora; Gajdziok, Jan; Doležel, Petr

2017-03-01

The preparation of liquisolid systems (LSS) represents a promising method for enhancing a dissolution rate and bioavailability of poorly soluble drugs. The release of the drug from LSS tablets is affected by many factors, including the disintegration time. The evaluation of differences among LSS containing varying amounts and types of commercially used superdisintegrants (Kollidon® CL-F, Vivasol® and Explotab®). LSS were prepared by spraying rosuvastatin solution onto Neusilin® US2 and further processing into tablets. Varying amounts of superdisintegrants were used and the differences among LSS were evaluated. The multiple scatter plot method was used to visualize the relationships within the obtained data. All disintegrants do not showed negative effect on the flow properties of powder blends. The type and concentration of superdisintegrant had an impact on the disintegration time and dissolution profiles of tablets. Tablets with Explotab® showed the longest disintegration time and the smallest amount of released drug. Fastest disintegration and dissolution rate were observed in tablets containing Kollidon® CL-F (≥2.5% w/w). Also tablets with Vivasol® (2.5-4.0% w/w) showed fast disintegration and complete drug release. Kollidon® CL-F and Vivasol® in concentration ≥2.5% are suitable superdisintegrants for LSS with enhanced release of drug.

Quality-by-design approach for the development of telmisartan potassium tablets.

PubMed

Oh, Ga-Hui; Park, Jin-Hyun; Shin, Hye-Won; Kim, Joo-Eun; Park, Young-Joon

2018-05-01

A quality-by-design approach was adopted to develop telmisartan potassium (TP) tablets, which were bioequivalent with the commercially available Micardis ® (telmisartan free base) tablets. The dissolution pattern and impurity profile of TP tablets differed from those of Micardis ® tablets because telmisartan free base is poorly soluble in water. After identifying the quality target product profile and critical quality attributes (CQAs), drug dissolution, and impurities were predicted to be risky CQAs. To determine the exact range and cause of risks, we used the risk assessment (RA) tools, preliminary hazard analysis and failure mode and effect analysis to determine the parameters affecting drug dissolution, impurities, and formulation. The range of the design space was optimized using the face-centered central composite design among the design of experiment (DOE) methods. The binder, disintegrant, and kneading time in the wet granulation were identified as X values affecting Y values (disintegration, hardness, friability, dissolution, and impurities). After determining the design space with the desired Y values, the TP tablets were formulated and their dissolution pattern was compared with that of the reference tablet. The selected TP tablet formulated using design space showed a similar dissolution to that of Micardis ® tablets at pH 7.5. The QbD approach TP tablet was bioequivalent to Micardis ® tablets in beagle dogs.

[The Use of Synthetic Polymers (Superdisintegrants) in Technology Tablets Containing Ethanol Dry Extract from Asparagus officinalis].

PubMed

Linka, Wojciech Andrzej; Wojtaszek, Ilona; Zgoda, Marian Mikołaj; Kołodziejczyk, Michał Krzysztof

2015-01-01

Dry extracts are now frequently used in medicine as an alternative to synthetic drugs. In the case of tablet technology with dry plant extracts, the proper selection of disintegrants (superdisintegrants) is particularly important. Objectives. The aim of this study was to evaluate the usefulness of the polymers constituting superdisintegrants (Vivasol®, Vivastar®, Polyplasdone XL) in uncoated tablet formulation of alcoholic extracted from Asparagus officinalis. Dry the ethanol extract of Asparagus officinalis, Vivasol®, Vivastar®, Vivapur®, Kollidon VA64, Polyplasdone XL, magnesium stearate. Direct compression. Paddle method was carried out to study pharmacopoeial parameters and pharmaceutical availability. The calculation of equivalency factors: similarity [f2] and the difference [f1]. Approximation results. Tablets brownish-green, with a smooth and uniform surface, without stains, chipping and damage. The determined average weight of the tablets compiled with the standards. The test friability and crushing strength revealed that the most mechanically strong tablets contained Vivasol, Vivastar, Polyplasdone XL. These tablets also have a longer disintegration and dissolution time compared with tablets containing only Vivasol. These differences are also confirmed by the calculated f2 and f1. The addition of a mixture of Polyplasdone XL and Vivastar to Vivasol significantly increases the mechanical strength of the tablets (crushing strength, resistance to crushing). The addition of a mixture of Polyplasdone XL and Vivastar to Vivasol paradoxically increases the disintegration time of tablets (11.1 min). Single superdisintegrant breaks up the tablet more effectively than a mixture of superdisintegrants.

Formulation and Characterization of Oral Mucoadhesive Chlorhexidine Tablets Using Cordia myxa Mucilage.

PubMed

Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

2012-01-01

The dilution and rapid elimination of topically applied drugs due to the flushing action of saliva is a major difficulty in the effort to eradicate infections of oral cavity. Utilization a proper delivery system for incorporation of drugs has a major impact on drug delivery and such a system should be formulated for prolonged drug retention in oral cavity. The aim of the present study was the use of mucilage of Cordia myxa as a mucoadhesive material in production of chlorhexidine buccal tablets and its substitution for synthetic polymers such as HPMC. The influence of mucilage concentration on the physicochemical responses (hardness, friability, disintegration time, dissolution, swelling, and muco-adhesiveness strength) was studied and swelling of mucilage and HPMC were compared. The evaluated responses included pharmacopoeial characteristics of tablets, the force needed to separate tablets from mucosa, and the amount of water absorbed by tablets. In comparison to HPMC, the rise of mucilage concentration in the formulations increased disintegration time, drug dissolution rate, and reduced MDT. Also, compared to 30% HPMC, muco-adhesiveness strength of buccal tablets containing 20% mucilage was significantly higher. It can be concluded that the presence of Cordia myxa powdered mucilage may significantly affect the tablet characteristics, and increasing in muco-adhesiveness may be achieved by using 20% w/w mucilage.

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.

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.

Ocimum Sanctum seeds, a natural superdisintegrant: formulation and evaluation of fast melt tablets of nimesulide.

PubMed

Malik, Karan; Arora, Gurpreet; Singh, Inderbir

2012-01-01

Fast melt tablets, also known as fast dissolving tablets, disintegrate instantaneously within the mouth and thus can be consumed without water. The present study was aimed to formulate fast melt tablets of nimesulide by using Ocimum Sanctum seeds as a natural tablet superdisintegrant. Powdered Ocimum seeds were characterized for powder flow properties (bulk density, tapped density, Carr's consolidation index, Hausner ratio, angle of repose), swelling index, viscosity, pH, loss on drying and microbial load. The prepared tablets were evaluated for different tablet parametric tests, wetting time, water absorption ratio, effective pore radius, porosity, packing fraction, in vitro and in vivo disintegration time, in-vitro dissolution and stability studies. The swelling index was evaluated to be 1600. An appreciable effect of the natural material was seen on tablet hardness and friability. The water absorption ratio increased from 56.15 +/- 0.85 to 80.76 +/- 0.70 (A1-A4). Water uptake coupled natural polymer swelling could be the most probable mechanism for concentration dependent reduction in disintegration time by the Ocimum Sanctum seeds. Porosity of the formulated tablets was found to increase from batch A1-A4. The in vitro disintegration results were in line with in vivo disintegration results. The f2 values (in comparison with Nimulid MD) of 95.90 and 93.65 were obtained with A3 and A4 batches respectively. It could be concluded that Ocimum Sanctum seeds could be used as a natural superdisintegrant in the formulation of fast melt tablets.

Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers

PubMed Central

Yamagishi, Hatsushi; Koike, Tomoyuki; Ohara, Shuichi; Horii, Toru; Kikuchi, Ryousuke; Kobayashi, Shigeyuki; Abe, Yasuhiko; Iijima, Katsunori; Imatani, Akira; Suzuki, Kaori; Hishinuma, Takanori; Goto, Junichi; Shimosegawa, Tooru

2008-01-01

AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. METHODS: Eight H pylori-negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was performed on the day of treatment. Blood samples were also collected after the administration of each drug. RESULTS: LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study. CONCLUSION: In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg. PMID:18395905

Freeze drying of orally disintegrating tablets containing taste masked naproxen sodium granules in blisters.

PubMed

Stange, Ulrike; Führling, Christian; Gieseler, Henning

2014-09-15

Abstract Orally disintegrating tablets (ODTs) were freeze dried in blisters using the Lyostar® II SMART™ Freeze Dryer Technology. ODT formulations either without non-water soluble particles (placebo) or containing large fractions (717 mg) of taste-masked naproxen sodium (NaS) granules were freeze dried. The process data revealed differences between ODTs with and without embedded granules in the pressure rise curves as well as in the shelf (inlet) temperature adjustments during freeze-drying. Pressure rise curves of the placebo ODTs from eight hours process time showed no distinct temperature-dominated part, and the last optimization step of the shelf temperature to achieve -24.4 °C might be prone to errors. The final shelf temperature of ODTs containing granules was -23.3 °C. The detection of primary drying endpoints using SMART™ Technology or comparative pressure measurements was reliable for both ODT formulations, whereas the application of thermocouples resulted in premature endpoint indication. Product resistance of ODTs containing granules was generally elevated in comparison to ODTs without granules, but increased only slightly over the course of the drying process. In summary, the developed freeze-drying cycle was found applicable for production of elegant ODTs with incorporated taste masked NaS granules.

Orally Disintegrating Tablets Containing Melt Extruded Amorphous Solid Dispersion of Tacrolimus for Dissolution Enhancement.

PubMed

Ponnammal, Poovizhi; Kanaujia, Parijat; Yani, Yin; Ng, Wai Kiong; Tan, Reginald B H

2018-03-16

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus ® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w / w . Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form. Fourier transform Infrared (FTIR) spectroscopy results indicated formation of hydrogen bond between TAC and polymers leading to stabilization of TAC in amorphous form. The extrudates were found to be stable under accelerated storage conditions for 3 months with no re-crystallization, indicating that hot melt extrusion is suitable for producing stable amorphous solid dispersions of TAC in PVP VA64, Soluplus ® and HPC. Stable solid dispersions of amorphous TAC exhibited higher dissolution rate, with the solid dispersions releasing more than 80% drug in 15 min compared to the crystalline drug giving 5% drug release in two hours. These stable solid dispersions were incorporated into orally-disintegrating tablets in which the solid dispersion retained its solubility, dissolution and stability advantage.

Orally Disintegrating Tablets Containing Melt Extruded Amorphous Solid Dispersion of Tacrolimus for Dissolution Enhancement

PubMed Central

Ponnammal, Poovizhi; Kanaujia, Parijat; Ng, Wai Kiong; Tan, Reginald B. H.

2018-01-01

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w/w. Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form. Fourier transform Infrared (FTIR) spectroscopy results indicated formation of hydrogen bond between TAC and polymers leading to stabilization of TAC in amorphous form. The extrudates were found to be stable under accelerated storage conditions for 3 months with no re-crystallization, indicating that hot melt extrusion is suitable for producing stable amorphous solid dispersions of TAC in PVP VA64, Soluplus® and HPC. Stable solid dispersions of amorphous TAC exhibited higher dissolution rate, with the solid dispersions releasing more than 80% drug in 15 min compared to the crystalline drug giving 5% drug release in two hours. These stable solid dispersions were incorporated into orally-disintegrating tablets in which the solid dispersion retained its solubility, dissolution and stability advantage. PMID:29547585

Formulation and Characterization of Oral Mucoadhesive Chlorhexidine Tablets Using Cordia myxa Mucilage

PubMed Central

Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

2012-01-01

Background The dilution and rapid elimination of topically applied drugs due to the flushing action of saliva is a major difficulty in the effort to eradicate infections of oral cavity. Utilization a proper delivery system for incorporation of drugs has a major impact on drug delivery and such a system should be formulated for prolonged drug retention in oral cavity. Objectives The aim of the present study was the use of mucilage of Cordia myxa as a mucoadhesive material in production of chlorhexidine buccal tablets and its substitution for synthetic polymers such as HPMC. Materials and Methods The influence of mucilage concentration on the physicochemical responses (hardness, friability, disintegration time, dissolution, swelling, and muco-adhesiveness strength) was studied and swelling of mucilage and HPMC were compared. The evaluated responses included pharmacopoeial characteristics of tablets, the force needed to separate tablets from mucosa, and the amount of water absorbed by tablets. Results In comparison to HPMC, the rise of mucilage concentration in the formulations increased disintegration time, drug dissolution rate, and reduced MDT. Also, compared to 30% HPMC, muco-adhesiveness strength of buccal tablets containing 20% mucilage was significantly higher. Conclusions It can be concluded that the presence of Cordia myxa powdered mucilage may significantly affect the tablet characteristics, and increasing in muco-adhesiveness may be achieved by using 20% w/w mucilage. PMID:24624170

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach.

PubMed

Agrawal, Anjali; Dudhedia, Mayur; Deng, Weibin; Shepard, Kevin; Zhong, Li; Povilaitis, Edward; Zimny, Ewa

2016-02-01

The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10-15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.

Comparison of sublingual tablets with nitroglycerin complexed with beta-cyclodextrin or titrated with crosspovidone--technological approach.

PubMed

Centkowska, Katarzyna; Sznitowska, Małgorzata

2008-01-01

Fast disintegrating sublingual tablets containing nitroglycerin either complexed with beta-cyclodextrin (NTG-CD) or titrated with crosspovidone (NTG-CP) were prepared using Starch 1500 or StarLac as disintegrants. Regarding disintegration time and stability of the active substance Starch 1500 was more appropriate for NTG-CD while for NTG-CP StarLac was suitable. Stability of NTG was better in NTG-CD tablets than in NTG-CP tablets, however, within 12 months of storage at 25 degrees C the loss of NTG in all formulations was still greater than 10%.

Evaluation of polyvinyl alcohols as mucoadhesive polymers for mucoadhesive buccal tablets prepared by direct compression.

PubMed

Ikeuchi-Takahashi, Yuri; Ishihara, Chizuko; Onishi, Hiraku

2017-09-01

The purpose of the present work was to evaluate polyvinyl alcohols (PVAs) as a mucoadhesive polymer for mucoadhesive buccal tablets prepared by direct compression. Various polymerization degree and particle diameter PVAs were investigated for their usability. The tensile strength, in vitro adhesive force, and water absorption properties of the tablets were determined to compare the various PVAs. The highest values of the tensile strength and the in vitro adhesive force were observed for PVAs with a medium viscosity and small particle size. The optimal PVA was identified by a factorial design analysis. Mucoadhesive tablets containing the optimal PVA were compared with carboxyvinyl polymer and hydroxypropyl cellulose formulations. The optimal PVA gives a high adhesive force, has a low viscosity, and resulted in relatively rapid drug release. Formulations containing carboxyvinyl polymer had high tensile strengths but short disintegration times. Higher hydroxypropyl cellulose concentration formulations had good adhesion forces and very long disintegration times. We identified the optimal characteristics of PVA, and the usefulness of mucoadhesive buccal tablets containing this PVA was suggested from their formulation properties.

Formulation development and comparative in vitro study of metoprolol tartrate (IR) tablets.

PubMed

Husain, Tazeen; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Maboos, Madiha; Khan, Madeeha; Bashir, Lubna; Naz, Shazia

2016-05-01

The objective of the present work was to develop Immediate Release (IR) tablets of Metoprolol Tartrate (MT) and to compare trial formulations to a reference product. Six formulations (F1-F6) were designed using central composite method and compared to a reference brand (A). Two marketed products (brands B and C) were also evaluated. F1-F6 were prepared with Avicel PH101 (filler), Crospovidone (disintegrant) and Magnesium Stearate (lubricant) by direct compression. Pharmacopoeial and non-pharmacopoeial methods were used to assess their quality. Furthermore, drug profiles were characterized using model dependent and independent (f(2)) approaches. Brands B and C and F5 and F6 did not qualify the tests for content uniformity. Moreover, brand B did not meet weight variation criteria and brand C did not satisfy requirements for single point dissolution test. Of the trial formulations, F2 failed the test for uniformity in thickness while F4 did not disintegrate within time limit. Only F1 and F3 met all quality parameters and were subjected to accelerated stability testing without significant alterations in their physicochemical characteristics. Based on AIC and r(2)(adjusted) values obtained by applying various kinetic models, drug release was determined to most closely follow Hixson-Crowell cube root law. F1 was determined to be the optimized formulation.

Orodispersible tablets containing taste-masked solid lipid pellets with metformin hydrochloride: Influence of process parameters on tablet properties.

PubMed

Petrovick, Gustavo Freire; Kleinebudde, Peter; Breitkreutz, Jörg

2018-01-01

Compaction of multiparticulates into tablets, particularly into orodispersible tablets (ODTs), is challenging. The compression of pellets, made by solid lipid extrusion/spheronization processes, presents peculiar difficulties since solid lipids usually soften or melt at relatively low temperature ranges and due to applied mechanical forces. Until now, there are no reports in literature about the development of ODTs based on solid lipid pellets. To investigate the feasibility of producing such tablets, a design of experiment (DoE) approach was performed to elucidate the influence of compression force and amount of two co-processed excipients (Ludiflash ® and Parteck ® ODT) on properties of the tablets (friability, tensile strength, and disintegration time). ODTs (15 mm, flat-faced) with solid lipid pellets (250-1000 µm in diameter) containing 500 mg of metformin HCl, presenting immediate drug release profile and taste-masked properties, were targeted. During compression, a strong lamination of the tablets containing Parteck ® ODT was observed. This phenomenon was prominently observed when high compression forces (≥5 kN) and high excipient amounts (≥40%; w/w) were used. On the other hand, the DoE focused on tablets with Ludiflash ® showed better results regarding the production of ODTs. A positive influence of the compression force on the tensile strength and disintegration time of the tablets, regarding specifications of the Ph. Eur., was observed. The increase in the amount of this excipient resulted in fast disintegrating tablets, however, a negative influence on the tensile strength was noticed. After optimization of the parameters and formulation, based on the DoE results and considering the Ph. Eur. specifications for tablets, ODTs based on lipid pellets containing metformin HCl presenting immediate release profile (85% drug release in less than 30 min) and taste-masked properties (determined by an electronic tongue) were successfully

Pharmacokinetics of a New Orally Disintegrating Tablet Formulation of Aripiprazole 15 mg Administered Without Water in Healthy Middle-aged Korean Subjects.

PubMed

Kim, Yunjeong; Jeon, Ji-Young; Chung, Young-Chul; Kim, Min-Gul

2015-12-01

The main objective of this study was to compare the pharmacokinetic properties and relative bioavailability of two 15-mg aripiprazole formulations (an orally disintegrating tablet [ODT] as the test drug and a conventional tablet as the reference drug) in healthy middle-aged Korean subjects. This study was conducted in a population of healthy middle-aged Korean subjects as a randomized, open-label, single-dose, 2-sequence, 2-period crossover trial. After administration of a single dose of a 15-mg aripiprazole standard tablet with 240 mL water or an aripiprazole 15-mg ODT without water, blood samples were collected at specific time intervals from 0 to 240 hours. Concentrations of aripiprazole in plasma were analyzed by using a LC-MS/MS method of detection. Data on the pharmacokinetic parameters were recorded, and the 90% CIs of the ratios of the geometric means of the parameters were determined from the logarithmically transformed data by using an ANOVA model. Thirty-nine healthy middle-aged Korean subjects were enrolled (mean age, 52.7 years; mean height, 167 cm; mean weight, 67.6 kg); 33 participants completed the study (29 male subjects and 4 female subjects). The 90% CIs of the geometric means ratio (test drug/reference drug) of Cmax, AUC0-last, and AUC0-∞ values were 0.95 to 1.14, 0.98 to 1.09, and 0.97 to 1.08, respectively. All of the subjects who experienced adverse events recovered without sequelae, and no serious adverse events were observed. The aripiprazole pharmacokinetics was similar for the ODT and standard tablet of 15-mg aripiprazole in these healthy middle-aged Korean subjects. The aripiprazole ODT formulation is therefore expected to offer a convenient alternative for patients who have difficulty swallowing tablets without water. The study was registered at http://cris.nih.go.kr (registration number: KCT0001677). Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Disintegration performance of renal multivitamin supplements.

PubMed

Stamatakis, M K; Meyer-Stout, P J

1999-04-01

Vitamins have traditionally been regulated as dietary supplements and have not been required to meet the same rigorous product quality performance standards as drug products. Impaired product performance, such as failure to disintegrate and/or dissolve in the gastrointestinal tract, could limit the absorption of vitamins. Furthermore, patients with renal disease have been reported to experience a wide range in gastrointestinal pH, which could influence a product's performance. The purpose of this study was to determine the effect of pH on the in vitro disintegration of renal multivitamin supplements. Products were studied using the United States Pharmacopeial Convention standard disintegration apparatus. Products were tested in simulated gastric fluid, neutral fluid, and intestinal fluid. Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within compendial limits. Of 11 products tested, 4 products failed the disintegration study test in all pH conditions. Sixty-four percent of the products showed statistically significant differences in disintegration time (DT) based on pH. As pH increased, time to disintegration increased. The DT of commercially available renal multivitamin supplements was highly variable. Poorest product performance was shown in simulated intestinal fluid. The pH significantly affected in vitro disintegration in greater than half the products tested. How this affects dissolution and in vivo performance has yet to be studied.

Effect of crospovidone and hydroxypropyl cellulose on carbamazepine in high-dose tablet formulation.

PubMed

Flicker, Felicia; Betz, Gabriele

2012-06-01

The aim of this study was to develop a high-dose tablet formulation of the poorly soluble carbamazepine (CBZ) with sufficient tablet hardness and immediate drug release. A further aim was to investigate the influence of various commercial CBZ raw materials on the optimized tablet formulation. Hydroxypropyl cellulose (HPC-SL) was selected as a dry binder and crospovidone (CrosPVP) as a superdisintegrant. A direct compacted tablet formulation of 70% CBZ was optimized by a 3² full factorial design with two input variables, HPC (0--10%) and CrosPVP (0--5%). Response variables included disintegration time, amount of drug released at 15 and 60 min, and tablet hardness, all analyzed according to USP 31. Increasing HPC-SL together with CrosPVP not only increased tablet hardness but also reduced disintegration time. Optimal condition was achieved in the range of 5--9% HPC and 3--5% CrosPVP, where tablet properties were at least 70 N tablet hardness, less than 1 min disintegration, and within the USP requirements for drug release. Testing the optimized formulation with four different commercial CBZ samples, their variability was still observed. Nonetheless, all formulations conformed to the USP specifications. With the excipients CrosPVP and HPC-SL an immediate release tablet formulation was successfully formulated for high-dose CBZ of various commercial sources.

FDA-Approved Natural Polymers for Fast Dissolving Tablets

PubMed Central

Alam, Md Tausif; Parvez, Nayyar; Sharma, Pramod Kumar

2014-01-01

Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing), in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets. PMID:26556207

Self-organizing map analysis using multivariate data from theophylline tablets predicted by a thin-plate spline interpolation.

PubMed

Yasuda, Akihito; Onuki, Yoshinori; Obata, Yasuko; Yamamoto, Rie; Takayama, Kozo

2013-01-01

The "quality by design" concept in pharmaceutical formulation development requires the establishment of a science-based rationale and a design space. We integrated thin-plate spline (TPS) interpolation and Kohonen's self-organizing map (SOM) to visualize the latent structure underlying causal factors and pharmaceutical responses. As a model pharmaceutical product, theophylline tablets were prepared based on a standard formulation. The tensile strength, disintegration time, and stability of these variables were measured as response variables. These responses were predicted quantitatively based on nonlinear TPS. A large amount of data on these tablets was generated and classified into several clusters using an SOM. The experimental values of the responses were predicted with high accuracy, and the data generated for the tablets were classified into several distinct clusters. The SOM feature map allowed us to analyze the global and local correlations between causal factors and tablet characteristics. The results of this study suggest that increasing the proportion of microcrystalline cellulose (MCC) improved the tensile strength and the stability of tensile strength of these theophylline tablets. In addition, the proportion of MCC has an optimum value for disintegration time and stability of disintegration. Increasing the proportion of magnesium stearate extended disintegration time. Increasing the compression force improved tensile strength, but degraded the stability of disintegration. This technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline tablet formulations.

A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets.

PubMed

ElShaer, Amr; Kaialy, Waseem; Akhtar, Noreen; Iyire, Affiong; Hussain, Tariq; Alany, Raid; Mohammed, Afzal R

2015-10-01

The acceleration of solid dosage form product development can be facilitated by the inclusion of excipients that exhibit poly-/multi-functionality with reduction of the time invested in multiple excipient optimisations. Because active pharmaceutical ingredients (APIs) and tablet excipients present diverse densification behaviours upon compaction, the involvement of these different powders during compaction makes the compaction process very complicated. The aim of this study was to assess the macrometric characteristics and distribution of surface charges of two powders: indomethacin (IND) and arginine (ARG); and evaluate their impact on the densification properties of the two powders. Response surface modelling (RSM) was employed to predict the effect of two independent variables; Compression pressure (F) and ARG percentage (R) in binary mixtures on the properties of resultant tablets. The study looked at three responses namely; porosity (P), tensile strength (S) and disintegration time (T). Micrometric studies showed that IND had a higher charge density (net charge to mass ratio) when compared to ARG; nonetheless, ARG demonstrated good compaction properties with high plasticity (Y=28.01MPa). Therefore, ARG as filler to IND tablets was associated with better mechanical properties of the tablets (tablet tensile strength (σ) increased from 0.2±0.05N/mm(2) to 2.85±0.36N/mm(2) upon adding ARG at molar ratio of 8:1 to IND). Moreover, tablets' disintegration time was shortened to reach few seconds in some of the formulations. RSM revealed tablet porosity to be affected by both compression pressure and ARG ratio for IND/ARG physical mixtures (PMs). Conversely, the tensile strength (σ) and disintegration time (T) for the PMs were influenced by the compression pressure, ARG ratio and their interactive term (FR); and a strong correlation was observed between the experimental results and the predicted data for tablet porosity. This work provides clear evidence of the

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.

Effect of gel formation on the dissolution behavior of clarithromycin tablets.

PubMed

Inukai, Koki; Takiyama, Kei; Noguchi, Shuji; Iwao, Yasunori; Itai, Shigeru

2017-04-15

Clarithromycin (CAM) is a macrolide antibiotic that is widely used at clinical sites. We found that release of CAM is suppressed when tablets of CAM were exposed to an external solvent containing carboxylate buffers such as citrate. The suppressed release of CAM can be attributed to the formation of gels on the tablet surfaces, which inhibits penetration of the solvent into the tablet and thus disintegration of the tablets. Delayed disintegration of the tablets was also observed for commercial tablets. This suggests that taking CAM and carboxylates at the same time might be avoided. The crystal structure of CAM citrate reveals that molecular chains of CAM are cross-linked by hydrogen bond between citrate groups in the crystal. The crystal structure indicates that cross-linked CAM chains of the three-dimensional mesh structure might also be formed in high concentration CAM solutions in the presence of carboxylates, resulting in gel formation. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations.

PubMed

Ono, Asami; Sugano, Kiyohiko

2014-11-20

The aim of this study was to compare the dissolution profiles of oral disintegrating tablets (ODTs) and immediate release (IR) formulations in order to experimentally validate the regulatory biowaiver scheme (BWS) for biopharmaceutical classification system (BCS) class III drugs. We examined six drugs that show clinical bioequivalence between the ODTs and IR formulations: taltirelin, olopatadine, droxidopa, famotidine, fexofenadine, and hydrochlorothiazide. The dissolution profiles of these drugs were evaluated using the compendium paddle apparatus at pH 1.2 and 6.8. Taltirelin and olopatadine showed very rapid dissolution and met the dissolution criteria in the BWS, whereas droxidopa, famotidine, fexofenadine, and hydrochlorothiazide did not. Furthermore, in the case of famotidine, fexofenadine, and hydrochlorothiazide, the ODTs and IR formulations showed dissimilar dissolution profiles. The dose-to-solubility ratio (D:S) of these drugs was larger than that of the other drugs. The results of this study suggest that extension of the BCS-BWS to ODTs and IR formulations of BCS class III drugs is appropriate. Furthermore, for BCS class III drugs with relatively high D:S, clinical bioequivalence would be achievable even when two formulations showed different dissolution profiles in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

[Preparation and evaluation of press-coated aminophylline tablet using crystalline cellulose and polyethylene glycol in the outer shell for timed-release dosage forms].

PubMed

Watanabe, Yoshiteru; Mukai, Baku; Kawamura, Ken-ichi; Ishikawa, Tatsuya; Namiki, Michihiro; Utoguchi, Naoki; Fujii, Makiko

2002-02-01

In an attempt to achieve chronopharmacotherapy for asthma, press-coated tablets (250 mg), which contained aminophylline in the core tablet in the form of low-substituted hydroxypropylcellulose (L-HPC) and coated with crystalline cellulose (PH-102) and polyethylene glycol (PEG) at various molecular weights and mixing ratios in the amounts of PH-102 and PEG as the outer shell (press-coating material), were prepared (chronopharmaceutics). Their applicability as timed-release (delayed-release) tablets with a lag time of disintegration and a subsequent rapid drug release phase was investigated. Various types of press-coated tablets were prepared using a tableting machine, and their aminophylline dissolution profiles were evaluated by the JP paddle method. Tablets with the timed-release characteristics could be prepared, and the lag time of disintegration was prolonged as the molecular weight and the amount of PEG, for example PEG 500,000, in the outer shell were increased. The lag time of disintegration could be controlled by the above-mentioned method, however, the pH of the medium had no effect on disintegration of the tablet and dissolution behavior of theophylline. The press-coated tablet (core tablet:aminophylline 50 mg, L-HPC and PEG 6000; outer shell:PH-102:PEG = 8:2 200 mg) with the timed-release characteristics was administered orally to rabbits for an in vivo test. Theophylline was first detected in plasma more than 2 h after administration; thus, this tablet showed a timed-release characteristics in the gastrointestinal tract. The time (tmax) required to reach the maximum plasma theophylline concentration (Cmax) observed after administration of the press-coated tablet was significantly (p < 0.05) delayed compared with that observed after administration of aminophylline solution in the control experiment. However, there was no difference in Cmax and area under the plasma theophylline concentration-time curve (AUC0-->24) between the press-coated tablet and

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

PubMed Central

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-01-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant. PMID:28368030

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation.

PubMed

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-03

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

NASA Astrophysics Data System (ADS)

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

Relationships between response surfaces for tablet characteristics of placebo and API-containing tablets manufactured by direct compression method.

PubMed

Hayashi, Yoshihiro; Tsuji, Takahiro; Shirotori, Kaede; Oishi, Takuya; Kosugi, Atsushi; Kumada, Shungo; Hirai, Daijiro; Takayama, Kozo; Onuki, Yoshinori

2017-10-30

In this study, we evaluated the correlation between the response surfaces for the tablet characteristics of placebo and active pharmaceutical ingredient (API)-containing tablets. The quantities of lactose, cornstarch, and microcrystalline cellulose were chosen as the formulation factors. Ten tablet formulations were prepared. The tensile strength (TS) and disintegration time (DT) of tablets were measured as tablet characteristics. The response surfaces for TS and DT were estimated using a nonlinear response surface method incorporating multivariate spline interpolation, and were then compared with those of placebo tablets. A correlation was clearly observed for TS and DT of all APIs, although the value of the response surfaces for TS and DT was highly dependent on the type of API used. Based on this knowledge, the response surfaces for TS and DT of API-containing tablets were predicted from only two and four formulations using regression expression and placebo tablet data, respectively. The results from the evaluation of prediction accuracy showed that this method accurately predicted TS and DT, suggesting that it could construct a reliable response surface for TS and DT with a small number of samples. This technique assists in the effective estimation of the relationships between design variables and pharmaceutical responses during pharmaceutical development. Copyright © 2017 Elsevier B.V. All rights reserved.

Orodispersible films and tablets with prednisolone microparticles.

PubMed

Brniak, Witold; Maślak, Ewelina; Jachowicz, Renata

2015-07-30

Orodispersible tablets (ODTs) and orodispersible films (ODFs) are solid oral dosage forms disintegrating or dissolving rapidly when placed in the mouth. One of the main issues related to their preparation is an efficient taste masking of a bitter drug substance. Therefore, the aim of this study was to prepare and evaluate the microparticles intended to mask a bitter taste of the prednisolone and use them in further preparation of two orodispersible dosage forms. Microparticles based on the Eudragit E PO or E 100 as a taste-masking agent were prepared with spray-drying technique. Tablets containing microparticles, co-processed ODT excipient Pharmaburst, and lubricant were directly compressed with single-punch tablet press. Orodispersible films were prepared by casting polymeric solutions of hydroxypropyl methylcellulose containing uniformly dispersed microparticles. Physicochemical properties of microparticles were evaluated, as well as mechanical properties analysis, disintegration time measurements and dissolution tests were performed for prepared dosage forms. Both formulations showed good mechanical resistance while maintaining excellent disintegration properties. The dissolution studies showed good masking properties of microparticles with Eudragit E 100. The amount of prednisolone released during the first minute in phosphate buffer 6.8 was around 0.1%. After incorporation into the orodispersible forms, the amount of released prednisolone increased significantly. It was probably the effect of faster microparticles wetting in orodispersible forms and their partial destruction by compression force during tableting process. Copyright © 2015 Elsevier B.V. All rights reserved.

A study of the properties of tablets from coprocessed dry binders composed of alpha-lactose monohydrate and different types of cellulose.

PubMed

Muzíková, J; Zvolánková, J

2007-12-01

The paper evaluates the differences between the properties of tablets from two coprocessed dry binders based on alpha-lactose monohydrate and cellulose, MicroceLac 100 and Cellactose 80. The substances differ in the type of contained cellulose; MicroceLac 100 contains 25% of microcrystalline cellulose, Cellactose 80, 25% of powdered cellulose. The properties under study included the tensile strength and disintegration time in dependence on compression force, addition of two concentrations of the lubricant sodium stearylfumarate (Pruv) and a 50% addition of the active ingredients ascorbic acid and acetylsalicylic acid. Using one of the compression forces, the effect of Pruv and magnesium stearate on the above-mentioned properties were compared. In the compression forces of 6 and 8 kN the strength of the compacts from pure Cellactose 80 was lower than that of those from MicroceLac 100 both without and with the lubricant. The lubricant sensitivity of dry binders depended on compression force. Pruv decreased the strength of compacts less than magnesium stearate. The tablets from Cellactose 80 possessed a longer disintegration time than those from MicroceLac 100, excepting the tableting materials containing 0.4 Pruv with a compression force of 6 kN. Disintegration time was prolonged with the use of sodium stearylfumarate and it was increased with compression force much more markedly in the case of Cellactose 80. In the presence of ascorbic acid, the strength of tablets was decreased in the case of both dry binders, but it was higher with MicroceLac100, disintegration time was very short and independent of the type of the dry binder. In the case of acetylsalicylic acid, the strength of tablets was higher with a lesser influence of the type of the dry binder, and disintegration time was longer and especially in the case of Cellactose 80 increased with increasing concentration of Pruv.

Effect of polacrilin potassium as disintegrant on bioavailability of diclofenac potassium in tablets : a technical note.

PubMed

Bele, Mrudula H; Derle, Diliprao V

2012-09-01

Polacrilin potassium is an ion exchange resin used in oral pharmaceutical formulations as a tablet disintegrant. It is a weakly acidic cation exchange resin. Chemically, it is a partial potassium salt of a copolymer of methacrylic acid with divinyl benzene. It ionizes to an anionic polymer chain and potassium cations. It was hypothesized that polacrilin potassium may be able to improve the permeability of anionic drugs according to the Donnan membrane phenomenon. The effect of polacrilin potassium on the permeability of diclofenac potassium, used as a model anionic drug, was tested in vitro using diffusion cells and in vivo by monitoring serum levels in rats. The amount of drug permeated across a dialysis membrane in vitro was significantly more in the presence of polacrilin potassium. Significant improvement was found in the extent of drug absorption in vivo. It could be concluded that polacrilin potassium may be used as a high-functionality excipient for improving the bioavailability of anionic drugs having poor gastrointestinal permeability.

NEW METHODOLOGY FOR DEVELOPMENT OF ORODISPERSIBLE TABLETS USING HIGH-SHEAR GRANULATION PROCESS.

PubMed

Ali, Bahaa E; Al-Shedfat, Ramadan I; Fayed, Mohamed H; Alanazi, Fars K

2017-05-01

Development of orodispersible delivery system of high mechanical properties and low disintegration time is a big challenge. The aim of the current work was to assess and optimize the high shear granulation process as a new methodology for development of orodispersible tablets of high quality attributes using design of experiment approach. A two factor, three levels (32), full factorial design was carried out to investigate the main and interaction effects of independent variables, water amount (XI) and granulation time (X2) on the characteristics of granules and final product, tablet. The produced granules were analyzed for their granule size, density and flowability. Furthermore, the produced tablets were tested for: weight variation, breaking force/ crushing strength, friability, disintegration time and drug dissolution. Regression analysis results of multiple linear models showed a high correlation between the adjusted R-squared and predicted R-squared for all granules and tablets characteristics, the difference is less than 0.2. All dependent responses of granules and tablets were found to be impacted significantly (p < 0.05) by the two independent variables. However, water amount demonstrated the most dominant effect for all granules and tablet characteristics as shown by higher its coefficient estimate for all selected responses. Numerical optimization using desirability function was performed to optimize the variables under study to provide orodispersible system within the USP limit with respect of mechanical properties and disintegration time. It was found that the higher desirability (0.915) could be attained at the low level pf water (180 g) and short granulation time (1.65 min). Eventually, this study provides the formulator with helpful information in selecting the proper level of water and granulation time to provide an orodispersible system of high crushing strength and very low disintegration time, when high shear granulation methodology was used as

Pharmaceutics, Drug Delivery and Pharmaceutical Technology: A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

PubMed

Low, Ariana; Kok, Si Ling; Khong, Yuetmei; Chan, Sui Yung; Gokhale, Rajeev

2015-11-01

No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test. The DTU is an accessory to the USP disintegration apparatus. It holds the ODF in a horizontal position, allowing top-view of the ODF during testing. A Gauge R&R study was conducted to assign relative contributions of the total variability from the operator, sample or the experimental set-up. Precision was compared using commercial ODF products in different media. Agreement between the two measurement methods was analysed. The DTU showed improved repeatability and reproducibility compared to the USP disintegration system with tighter standard deviations regardless of operator or medium. There is good agreement between the two methods, with the USP disintegration test giving generally longer disintegration times possibly due to difficulty in end-point determination. The DTU provided clear end-point determination and is suitable for quality control of ODFs during product developmental stage or manufacturing. This may facilitate the development of a standardized methodology for disintegration time determination of ODFs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3893-3903, 2015. Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

External scintigraphy in monitoring the behavior of pharmaceutical formulations in vivo I: technique for acquiring high-resolution images of tablets

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

Theodorakis, M.C.; Simpson, D.R.; Leung, D.M.

1983-02-01

A new method for monitoring tablet disintegration in vivo was developed. In this method, the tablets were labeled with a short-lived radionuclide, technetium 99m, and monitored by a gamma camera. Several innovations were introduced with this method. First, computer reconstruction algorithms were used to enhance the scintigraphic images of the disintegrating tablet in vivo. Second, the use of a four-pinhole collimator to acquire multiple views of the tablet resulted in high count rates and reduced acquisition times of the scintigraphic images. Third, the magnification of the scintigraphic images achieved by pinhole collimation led to significant improvement in resolution. Fourth, themore » radioinuclide was incorporated into the granulation so that the whole mass of the tablet was uniformly labeled with high levels of activity. This technique allowed the continuous monitoring of the disintegration process of tablets in vivo in experimental animals. Multiple pinhole collimation and the labeling process permitted the acquisition of quality scintigraphic images of the labeled tablet every 30 sec. The resolution of the method was tested in vitro and in vivo.« less

Absence of food effect on the extent of alprazolam absorption from an orally disintegrating tablet.

PubMed

Erdman, Keith; Stypinski, Daria; Combs, Michelle; Witt, Patricia; Stiles, Mark; Pollock, Steve

2007-08-01

To evaluate the effect of a standardized meal on the bioavailability of alprazolam formulated as an immediate-release orally disintegrating tablet (ODT) in healthy volunteers. Single-dose, randomized, open-label, two-period crossover study. Contract research organization clinic. Sixteen healthy volunteers (seven men, nine women), aged 20-50 years. Intervention. Subjects were administered a single dose of alprazolam ODT 1.0 mg during two treatment periods-under fasting conditions and after a standard high-fat breakfast-separated by a 7-day washout period, Blood samples for determination of alprazolam pharmacokinetics were collected by venipuncture up to 72 hours after dosing. A validated liquid chromatography with tandem mass spectrometry detection method was used to quantify the alprazolam plasma concentration. The overall extent of alprazolam absorption from the ODT formulation, as measured by area under the concentration-time curve, was unaffected during fed conditions. However, the rate of alprazolam absorption was slower after administration during fed relative to fasted conditions. The mean maximum observed plasma concentration (Cmax) decreased approximately 25%, and time to Cmax (Tmax) was delayed approximately 1.5 hours when food was administered before dosing. Coadministration of food was shown to have no effect on extent of absorption of immediate-release alprazolam ODT 1.0 mg when compared with drug administration in the fasted condition; however, the rate of drug absorption was decreased. The clinical significance of the difference in rate of alprazolam absorption is unknown but thought to be minimal.

Suppressed Release of Clarithromycin from Tablets by Crystalline Phase Transition of Metastable Polymorph Form I.

PubMed

Fujiki, Sadahiro; Watanabe, Narumi; Iwao, Yasunori; Noguchi, Shuji; Mizoguchi, Midori; Iwamura, Takeru; Itai, Shigeru

2015-08-01

The pharmaceutical properties of clarithromycin (CAM) tablets containing the metastable form I of crystalline CAM were investigated. Although the dissolution rate of form I was higher than that of stable form II, the release of CAM from form I tablet was delayed. Disintegration test and liquid penetration test showed that the disintegration of the tablet delayed because of the slow penetration of an external solution into form I tablet. Investigation by scanning electron microscopy revealed that the surface of form I tablet was covered with fine needle-shaped crystals following an exposure to the external solution. These crystals were identified as form IV crystals by powder X-ray diffraction. The phenomenon that CAM releases from tablet was inhibited by fine crystals spontaneously formed on the tablet surface could be applied to the design of sustained-release formulation systems with high CAM contents by minimizing the amount of functional excipients. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Long-term weight loss observed with olanzapine orally disintegrating tablets in overweight patients with chronic schizophrenia. A 1 year open-label, prospective trial.

PubMed

Chawla, Bharat; Luxton-Andrew, Heather

2008-04-01

To investigate the long-term weight loss outcomes during usual clinical practice after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT). In this open-label prospective study, 26 patients with schizophrenia who were clinically stable on olanzapine SOT treatment were switched to olanzapine ODT. All other aspects of treatment remained constant. Weight was recorded at 3, 6, and 12 months. Patients incurred an average weight loss of 2.7 +/- 0.7 kg (p = 0.001) after switching patients from olanzapine SOT to olanzapine ODT at 12 months. Peak weight loss was observed at 6 months; however, significant weight loss was achieved as early as 3 months. The majority (81.9%) of patients lost weight, while 18.1% had no weight change or weight gain. Body mass index (BMI) significantly decreased by 1.0 +/- 0.3 kg/m(2) (p = 0.001). Interestingly, patients treated with higher doses of olanzapine (> or = 20 mg) incurred a greater weight loss of their body weight (5.6%), compared to those treated with lower doses (< 20 mg), who lost 1.9% of their body weight (p = 0.04). This study demonstrated that, in usual clinical practice, switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained over 12 months. 2008 John Wiley & Sons, Ltd.

Development and evaluation of novel antihypertensive orodispersible tablets.

PubMed

Khan, Hafeez Ullah; Hanif, Muhammad; Sarfraz, Rai M; Maheen, Safirah; Afzal, Samina; Sher, Muhammad; Afzal, Khurram; Mahmood, Asif; Shamim, Ayesha

2017-09-01

Objective of present study was to enhance patient compliance in pediatrics and geriatrics patients of Hypertension. To achieve this target, innovative orodispersible tablets of atenolol and atorvastatin was developed to produce instant action by rapidly disintegrating into oral cavity. Three different techniques like direct compression, effervescent and sublimation methods were used to prepare these tablets (Five batches of tablets by each method) by using two superdisintegrants like Sodium starch glycolate and pregelatinized starch alone and in combination. Pre-formulation studies including rheological analysis (Bulk density, tapped density, Angle of repose, Carr's compressibility index, Hausner's ratio), compatibility studies such as Fourier transform infrared spectrophotometry (FTIR) and Differential scanning colorimetry (DSC), Post-compression and stability studies were also performed. Finally, results were statistically evaluated by the applying one way ANOVA test and mean. It was concluded that the formulation F8 containing Sodium starch glycolate 2% and pregelatinized starch 6% found best regarding disintegration time, wetting volume, wetting time, release studies etc. The order in which drug release was quicker is Pregelatinized starch plus Sodium starch glycolate > Pregelatinized starch > Sodium starch glycolate (primojel). It was concluded that sublimation method was the best among three methods used for orodispersible tablets formulations.

An attempt to calculate in silico disintegration time of tablets containing mefenamic acid, a low water-soluble drug.

PubMed

Kimura, Go; Puchkov, Maxim; Leuenberger, Hans

2013-07-01

Based on a Quality by Design (QbD) approach, it is important to follow International Conference on Harmonization (ICH) guidance Q8 (R2) recommendations to explore the design space. The application of an experimental design is, however, not sufficient because of the fact that it is necessary to take into account the effects of percolation theory. For this purpose, an adequate software needs to be applied, capable of detecting percolation thresholds as a function of the distribution of the functional powder particles. Formulation-computer aided design (F-CAD), originally designed to calculate in silico the drug dissolution profiles of a tablet formulation is, for example, a suitable software for this purpose. The study shows that F-CAD can calculate a good estimate of the disintegration time of a tablet formulation consisting of mefenamic acid. More important, F-CAD is capable of replacing expensive laboratory work by performing in silico experiments for the exploration of the formulation design space according to ICH guidance Q8 (R2). As a consequence, a similar workflow existing as best practice in the automotive and aircraft industry can be adopted by the pharmaceutical industry: The drug delivery vehicle can be first fully designed and tested in silico, which will improve the quality of the marketed formulation and save time and money. Copyright © 2013 Wiley Periodicals, Inc.

Implementation of quality by design approach in manufacturing process optimization of dry granulated, immediate release, coated tablets - a case study.

PubMed

Teżyk, Michał; Jakubowska, Emilia; Milanowski, Bartłomiej; Lulek, Janina

2017-10-01

The aim of this study was to optimize the process of tablets compression and identification of film-coating critical process parameters (CPPs) affecting critical quality attributes (CQAs) using quality by design (QbD) approach. Design of experiment (DOE) and regression methods were employed to investigate hardness, disintegration time, and thickness of uncoated tablets depending on slugging and tableting compression force (CPPs). Plackett-Burman experimental design was applied to identify critical coating process parameters among selected ones that is: drying and preheating time, atomization air pressure, spray rate, air volume, inlet air temperature, and drum pressure that may influence the hardness and disintegration time of coated tablets. As a result of the research, design space was established to facilitate an in-depth understanding of existing relationship between CPPs and CQAs of intermediate product (uncoated tablets). Screening revealed that spray rate and inlet air temperature are two most important factors that affect the hardness of coated tablets. Simultaneously, none of the tested coating factors have influence on disintegration time. The observation was confirmed by conducting film coating of pilot size batches.

Channelled tablets: An innovative approach to accelerating drug release from 3D printed tablets.

PubMed

Sadia, Muzna; Arafat, Basel; Ahmed, Waqar; Forbes, Robert T; Alhnan, Mohamed A

2018-01-10

Conventional immediate release dosage forms involve compressing the powder with a disintegrating agent that enables rapid disintegration and dissolution upon oral ingestion. Among 3D printing technologies, the fused deposition modelling (FDM) 3D printing technique has a considerable potential for patient-specific dosage forms. However, the use of FDM 3D printing in tablet manufacturing requires a large portion of polymer, which slows down drug release through erosion and diffusion mechanisms. In this study, we demonstrate for the first time the use of a novel design approach of caplets with perforated channels to accelerate drug release from 3D printed tablets. This strategy has been implemented using a caplet design with perforating channels of increasing width (0.2, 0.4, 0.6, 0.8 or 1.0mm) and variable length, and alignment (parallel or at right angle to tablet long axis). Hydrochlorothiazide (BCS class IV drug) was chosen as the model drug as enhanced dissolution rate is vital to guarantee oral bioavailability. The inclusion of channels exhibited an increase in the surface area/volume ratio, however, the release pattern was also influenced by the width and the length of the channel. A channel width was ≥0.6mm deemed critical to meet the USP criteria of immediate release products. Shorter multiple channels (8.6mm) were more efficient at accelerating drug release than longer channels (18.2mm) despite having comparable surface area/mass ratio. This behaviour may be linked to the reduced flow resistance within the channels and the faster fragmentation during dissolution of these tablets. In conclusion, the width and length of the channel should be carefully considered in addition to surface area/mass when optimizing drug release from 3D printed designs. The incorporation of short channels can be adopted in the designs of dosage forms, implants or stents to enhance the release rate of eluting drug from polymer-rich structures. Copyright © 2017 Elsevier B.V. All

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.

Evaluation of hot-melt extrusion and injection molding for continuous manufacturing of immediate-release tablets.

PubMed

Melocchi, Alice; Loreti, Giulia; Del Curto, Maria Dorly; Maroni, Alessandra; Gazzaniga, Andrea; Zema, Lucia

2015-06-01

The exploitation of hot-melt extrusion and injection molding for the manufacturing of immediate-release (IR) tablets was preliminarily investigated in view of their special suitability for continuous manufacturing, which represents a current goal of pharmaceutical production because of its possible advantages in terms of improved sustainability. Tablet-forming agents were initially screened based on processability by single-screw extruder and micromolding machine as well as disintegration/dissolution behavior of extruded/molded prototypes. Various polymers, such as low-viscosity hydroxypropylcellulose, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymer, various sodium starch glycolate grades (e.g., Explotab(®) CLV) that could be processed with no need for technological aids, except for a plasticizer, were identified. Furthermore, the feasibility of both extruded and molded IR tablets from low-viscosity hydroxypropylcellulose or Explotab(®) CLV was assessed. Explotab(®) CLV, in particular, showed thermoplastic properties and a very good aptitude as a tablet-forming agent, starting from which disintegrating tablets were successfully obtained by either techniques. Prototypes containing a poorly soluble model drug (furosemide), based on both a simple formulation (Explotab(®) CLV and water/glycerol as plasticizers) and formulations including dissolution/disintegration adjuvants (soluble and effervescent excipients) were shown to fulfill the USP 37 dissolution requirements for furosemide tablets. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Comparison of properties of tablets and energy profile of compaction of two spray-dried lactoses.

PubMed

Muzíková, Jitka; Sináglová, Pavla

2013-01-01

The paper compared two spray-dried lactoses Flowlac 100 and SuperTab 14SD from the standpoint of tensile strength and disintegration time of tablets, the effect of an addition of the lubricant magnesium stearate and silicified microcrystalline cellulose on these properties, and also from the standpoint of the energy profile of compression. The comparison of the values was performed at the compression force of 15 kN. The strength of tablets was higher in the case of SuperTab 14SD, an increase in the concentration of magnesium stearate did not decrease tablet strength. Prosolv SMCC 90 increased the strength of tablets and made it equal for both lactoses, but it also increased the sensitivity to the added lubricant. The disintegration time of tablets was shorter in the case of SuperTab 14SD, an increased concentration of magnesium stearate prolonged it, and an addition of Prosolv SMCC 90 shortened it and made it equal for both lactoses. From the energy standpoint, the maximal energy was higher in the case of SuperTab 14SD, an addition of Prosolv SMCC 90 increased it and again made it equal for both lactoses. The differences in the values of the maximal energy were primarily due to the values of the energy for friction and the energy accumulated by the tablet after compression, and there was no marked difference in the values of the energy of decompression. SuperTab 14SD showed a higher plasticity than Flowlac 100.

[The use of natural and synthetic hydrophilic polymers in the formulation of metformin hydrochloride tablets with different profile release].

PubMed

Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2012-01-01

-dissolving of a tablet, is conducive to the reduction of gastrointestinal side effects and better tolerance of the therapeutic product by a patient. The study on pharmaceutical availability indicated relevant kinetic differences between tested therapeutic products. They are particularly visible between standard formulations and the one with prolonged release (Glucophage XR500). Its release profile bears features of kinetics similar to zero-order reactions. Tested therapeutic products contain a large amount of the biologically active substance in relation to the content of excipients. A higher content of excipients in a single tablet mass distinguishes Siofor in comparison with Glucophage i Metformax. The excipients used in the formulations of tested preparations are comparable. A higher percentage of binding agents (HPMC, PVP) is observed, but there is a lack of typical disintegrants which results in a longer disintegration time up to 15 minutes. Siofor disintegrates at the same time as Formetic, but longer than Glucophage i Metformax. Considering the large content of the active substance and pharmacological properties of metformin hydrochloride, such a disintegration might have beneficial consequences, because the amount of the free active substance in the gastrointestinal tract will increase over the longer time period what will reduce the level of gastrointestinal side effects. The release profiles of metformin hydrochloride from tested therapeutic products are comparable. The Glucophage XR 500 formulation with the release kinetics of metformin hydrochloride similar to the zero-order kinetics is completely different from the others. The above is confirmed by the mathematical analysis of release profiles of metformin hydrochloride from tested preparations where equations of lines describing the release profile are characterized by similar values of correlation coefficients.

Phase transformation in thiamine hydrochloride tablets: Influence on tablet microstructure, physical properties, and performance.

PubMed

Chakravarty, Paroma; Suryanarayanan, Raj; Govindarajan, Ramprakash

2012-04-01

The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH → HH transformation in tablets, within 30 h of storage at 40°C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH-MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual but less dramatic changes in properties. The phase transformation and the complex interparticulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior. Copyright © 2011 Wiley Periodicals, Inc.

A Pilot Stability Study of Dehydroepiandrosterone Rapid-dissolving Tablets Prepared by Extemporaneous Compounding.

PubMed

Rush, Steven D; Vernak, Charlene; Zhao, Fang

2017-01-01

Dehydroepiandrosterone supplementation is used to treat a variety of conditions. Rapid-dissolving tablets are a relatively novel choice for compounded dehydroepiandrosterone dosage forms. While rapid-dissolving tablets offer ease of administration, there are uncertainties about the physical and chemical stability of the drug and dosage form during preparation and over long-term storage. This study was designed to evaluate the stability of dehydroepiandrosterone rapid-dissolving tablets just after preparation and over six months of storage. The Professional Compounding Centers of America rapid-dissolving tablet mold and base formula were used to prepare 10-mg strength dehydroepiandrosterone rapid-dissolving tablets. The formulation was heated at 100°C to 110°C for 30 minutes, released from the mold, and cooled at room temperature for 30 minutes. The resulting rapid-dissolving tablets were individually packaged in amber blister packs and stored in a stability chamber maintained at 25°C and 60% relative humidity. The stability samples were pulled at pre-determined time points for evaluation, which included visual inspection, tablet weight check, United States Pharmacopeia disintegration test, and stability-indicating high-performance liquid chromatography. The freshly prepared dehydroepiandrosterone rapiddissolving tablets exhibited satisfactory chemical and physical stability. Time 0 samples disintegrated within 40 seconds in water kept at 37°C. The high-performance liquid chromatographic results confirmed that the initial potency was 101.9% of label claim and that there was no chemical degradation from the heating procedure. Over six months of storage, there were no significant changes in visual appearance, physical integrity, or disintegration time for any of the stability samples. The high-performance liquid chromatographic results also indicated that dehydroepiandrosterone rapid-dissolving tablets retained >95% label claim with no detectable degradation

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.

Cyclodextrins as excipients in tablet formulations.

PubMed

Conceição, Jaime; Adeoye, Oluwatomide; Cabral-Marques, Helena Maria; Lobo, José Manuel Sousa

2018-04-22

This paper aims to provide a critical review of cyclodextrins as excipients in tablet formulations, highlighting: (i) the principal pharmaceutical applications of cyclodextrins; (ii) the most relevant technological aspects in pharmaceutical formulation development; and (iii) the actual regulatory status of cyclodextrins. Moreover, several illustrative examples are presented. Cyclodextrins can be used as complexing excipients in tablet formulations for low-dose drugs. By contrast, for medium-dose drugs and/or when the complexation efficiency is low, the methods to enhance the complexation efficiency play a key part in reducing the cyclodextrin quantity. In addition, these compounds are used as fillers, disintegrants, binders and multifunctional direct compression excipients of the tablets. Copyright © 2018 Elsevier Ltd. All rights reserved.

A STUDY OF COMPRESSION PROCESS AND PROPERTIES OF TABLETS WITH MICROCRYSTALLINE CELLULOSE AND COLLOIDAL SILICON DIOXIDE.

PubMed

Muzikova, Jitka; Louzenska, Marketa; Pekarek, Tomas

2016-09-01

This paper compares the compressibility and properties of tablets from Prosolv SMCC 90 and a mixture of Avicel PH-102 and colloidal silicon dioxide with a different specific surface. The effect of an addition of the lubricant magnesium stearate on these parameters under varying conditions of mixing and the homogeneity of the lubricant in the mixtures are also examined. Compressibility is evaluated by means of the energy balance of the compression process; the examined properties of tablets are tensile strength and disintegration time. The total energy of compression was increased with compression force, the highest being in Prosolv SMCC 90. Its values did not differ for differing conditions of mixing with the lubricant. Plasticity was slightly decreased with compression force and in the mixture with magnesium stearate it was not influenced by the conditions of mixing. Tablets made from Prosolv SMCC 90 and Avicel PH-102 were stronger than those from the mixtures from Avicel PH-102 and both types of Aerosil. The addition of magnesium stearate markedly decreased the strength of tablets from Avicel PH-102. An increase in the period and frequency of mixing with the lubricant resulted in a further decrease in strength. Disintegration time was longer in tablets from Avicel PH-102 and Prosolv SMCC 90, and it was further prolonged by an addition of magnesium stearate.

Influence of Prosolv and Prosolv:Mannitol 200 direct compression fillers on the physicomechanical properties of atorvastatin oral dispersible tablets.

PubMed

Gowda, Veeran; Pabari, Ritesh M; Kelly, John G; Ramtoola, Zebunnissa

2015-06-01

The objective of the present study was to evaluate the influence of Prosolv® and Prosolv®: Mannitol 200 direct compression (DC) fillers on the physicomechanical characteristics of oral dispersible tablets (ODTs) of crystalline atorvastatin calcium. ODTs were formulated by DC and were analyzed for weight uniformity, hardness, friability, drug content, disintegration and dissolution. Three disintegration time (DT) test methods; European Pharmacopoeia (EP) method for conventional tablets (Method 1), a modification of this method (Method 2) and the EP method for oral lyophilisates (Method 3) were compared as part of this study. All ODTs showed low weight variation of <2.5%. Prosolv® only ODTs showed the highest tablet hardness of ∼ 73 N, hardness decreased with increasing mannitol content. Friability of all formulations was <1% although friability of Prosolv®:Mannitol ODTs was higher than for pure Prosolv®. DT of all ODTs was <30 s. Method 2 showed the fastest DT. Method 3 was non-discriminatory giving a DT of 13-15 s for all formulations. Atorvastatin dissolution from all ODTs was >60% within 5 min despite the drug being crystalline. Prosolv® and Prosolv®:Mannitol-based ODTs are suitable for ODT formulations by DC to give ODTs with high mechanical strength, rapid disintegration and dissolution.

INFLUENCE OF TYPE AND NEUTRALISATION CAPACITY OF ANTACIDS ON DISSOLUTION RATE OF CIPROFLOXACIN AND MOXIFLOXACIN FROM TABLETS

PubMed Central

Uzunović, Alija; Vranić, Edina

2009-01-01

Dissolution rate of two fluoroquinolone antibiotics (ciprofloxacin and moxifloxacin) was analysed in presence/absence of three antacid formulations. Disintegration time and neutralisation capacity of antacid tablets were also checked. Variation in disintegration time indicated the importance of this parameter, and allowed evaluation of the influence of postponed antacid-fluoroquinolone contact. The results obtained in this study showed decreased dissolution rate of fluoroquinolone antibiotics from tablets in simultaneous presence of antacids, regardless of their type and neutralisation capacity. PMID:19284403

Setting Ideal Lubricant Mixing Time for Manufacturing Tablets by Evaluating Powder Flowability.

PubMed

Nakamura, Shohei; Yamaguchi, Saori; Hiraide, Rikiha; Iga, Kumi; Sakamoto, Takatoshi; Yuasa, Hiroshi

2017-10-01

We investigated the effectiveness of using Carr's flowability index (FI) and practical angle of internal friction (Φ) as indexes for setting the target Mg-St mixing time needed for preparing tablets with the target physical properties. We used FI as a measure of flowability under non-loaded conditions, and Φ as a measure of flowability under loaded conditions for pharmaceutical powders undergoing direct compression with varying concentrations of Mg-St and mixing times. We evaluated the relationship between Mg-St mixing conditions and pharmaceutical powder flowability, analyzed the correlation between the physical properties of the tablets (i.e., tablet weight variation, drug content uniformity, hardness, friability, and disintegration time of tablets prepared using the pharmaceutical powder), and studied the effect of Mg-St mixing conditions and pharmaceutical powder flowability on tablet properties. Mg-St mixing time highly correlated with pharmaceutical powder FI (R 2  = 0.883) while Mg-St concentration has low correlation with FI, and FI highly correlated with the physical properties of the tablet (R 2 values: weight variation 0.509, drug content variation 0.314, hardness 0.525, friability 0.477, and disintegration time 0.346). Therefore, using pharmaceutical powder FI as an index could enable prediction of the physical properties of a tablet without the need for tableting, and setting the Mg-St mixing time by using pharmaceutical powder FI could enable preparation of tablets with the target physical properties. Thus, the FI of the intermediate product (i.e., pharmaceutical powder) is an effective index for controlling the physical properties of the finished tablet.

An Evaluation of the Binding Strength of Okra Gum and the Drug Release Characteristics of Tablets Prepared from It.

PubMed

Hussain, Amjad; Qureshi, Farah; Abbas, Nasir; Arshad, Muhammad Sohail; Ali, Ejaz

2017-06-02

The aim of this study is to evaluate the adhesion ability of okra gum, which is gaining popularity as a tablet binder. For this purpose, gum was extracted from okra pods, and the binding strength of different concentrations (1%, 3%, and 5%) was determined quantitatively. Additionally, naproxen sodium tablets were prepared by using okra gum as a binder and were evaluated for their properties including hardness, friability, disintegration time, and dissolution rate. The binding strength values were compared with that of pre-gelatinized starch, a commonly used tablet binder. The results from universal testing machine indicate that the binding strengths of all dispersions of okra increase as the concentration increases from 1% to 5% and ranges from 2.5 to 4.5 N, which are almost twice a high as those of pre-gelatinized starch. The tablets prepared with okra gum have shown good mechanical strength with hardness values of 7-8.5 kg/cm² and a friability <1%, comparable to tablets prepared with starch. The disintegration time was longer (7.50 min with okra gum and 5.05 min with starch paste), and the drug release from these tablets was slower than the formulations with starch. The higher binding ability of okra gum probably linked with its chemical composition as it mainly contains galactose, rhamnose, and galacturonic acid. This study concludes that okra gum is a better binder than pre-gelatinized starch, it might be explored in future for introduction as a cost-effective binder in the pharmaceutical industry.

Voltammetric Studies of Zomepirac Sodium and Its Determination in Tablets by Differential-Pulse Polarography.

DTIC Science & Technology

1984-01-06

min in order to promote disintegration of the tablets . The remaining larger lumps of tablet mass were crushed with a glass rod and the mixture stirred...D-A136 982 VOLTAMMETRIC STUDIES OF ZOMEPIRAC SODIUM AND ITS i/i DETERMINATION IN TABLETS .. U) UTAH UNIV SALT LAKE CITY DEPT OF CHEMISTRY L G CHATTEN...TYPE OF REPORT &PEMOCVE Voltaninetric Studies of Zomepirac Sodium and its Dete~rmrination in Tablets by Differential-Pulse ,Technical Reportf 24 Pol

Development of Coprocessed Chitin-Calcium Carbonate as Multifunctional Tablet Excipient for Direct Compression.

PubMed

Chaheen, Mohammad; Sanchez-Ballester, Noelia M; Bataille, Bernard; Yassine, Ahmad; Belamie, Emmanuel; Sharkawi, Tahmer

2018-04-24

Owing to the increasing interest in multifunctional excipients for tableting, coprocessing of individual excipients is regularly used to produce excipients of improved multifunctionality superior to individual excipients or their physical mix. The use of chitin as an excipient in tablet formulation is limited because of certain drawbacks such as poor flowability and low true density. The objective of this work is to improve these properties through coprocessing of chitin with calcium carbonate (CaCO 3 ) by precipitating CaCO 3 on chitin particles using different methods. In addition, optimization of the coprocessed chitin was carried out to improve the excipient's properties. Physicochemical (CaCO 3 content, true density, X-ray diffraction, infrared spectroscopy, and scanning electron microscopy) and functional testing (swelling force, flowability, tensile strength, deformation mechanism, and disintegration time) were used to characterize the coprocessed product. Results showed that the calcite CaCO 3 polymorph is precipitated on the chitin surface and that it interacts with chitin at carbonyl- and amide-group level. In addition, the coprocessed excipient has an improved true density and powder flowability, with CaCO 3 forming single layer on the chitin particles surface. Tableting studies showed that the coprocessed powder exhibited an intermediate deformation behavior between CaCO 3 (most brittle) and chitin (most plastic). Tablets showed acceptable tensile strength and rapid disintegration (2-4 s). These results show the potential use of coprocessed chitin-CaCO 3 as a multifunctional excipient for fast disintegration of tablets produced by direct compression. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Differing disintegration and dissolution rates, pharmacokinetic profiles and gastrointestinal tolerability of over the counter ibuprofen formulations.

PubMed

Bjarnason, Ingvar; Sancak, Ozgur; Crossley, Anne; Penrose, Andrew; Lanas, Angel

2018-02-01

Formulations of over the counter (OTC) NSAIDs differ substantially, but information is lacking on whether this alters their gastrointestinal profiles. To assess disintegration and dissolution rates and pharmacokinetics of four preparations of OTC ibuprofen and relate these with spontaneously reported gastrointestinal adverse events. Disintegration and dissolution rates of ibuprofen tablets as (a) acid, (b) sodium salt, (c) lysine salt, and (d) as a liquid gelatine capsule were assessed. Pharmacokinetic data gastrointestinal and spontaneously reported adverse events arising from global sales were obtained from files from Reckitt Benckiser. Disintegration at low pH was progressively shorter for the preparations from a-to-d with formation of correspondingly smaller ibuprofen crystals, while dissolution was consistently poor. Dissolution at a neutral pH was least rapid for the liquid gelatine capsule. Pharmacokinetic data showed a shorter t max and a higher C max for preparations b-d as compared with ibuprofen acid. Spontaneously reported abdominal symptoms were rare with the liquid gelatine preparation. The formulations of OTC ibuprofen differ in their disintegration and dissolution properties, pharmacokinetic profiles and apparent gastrointestinal tolerability. Spontaneously reported abdominal symptoms were five times lower with the liquid gelatine capsule as compared with ibuprofen acid despite a 30% increase in C max . © 2017 Royal Pharmaceutical Society.

Formulation and Evaluation of Mouth Dissolving Tablets of Cinnarizine

PubMed Central

Patel, B. P.; Patel, J. K.; Rajput, G. C.; Thakor, R. S.

2010-01-01

The purpose of this research was to develop mouth dissolve tablets of cinnarizine by effervescent, superdisintegrant addition and sublimation methods. All the three formulations were evaluated for disintegration time, hardness and friability, among these superdisintegrant addition method showed lowest disintegration time; hence it was selected for further studies. Further nine batches (B1-B9) were prepared by using crospovidone, croscarmellose sodium and L-HPC in different concentrations such as 5, 7.5 and 10%. All the formulations were evaluated for weight variation, hardness, friability, drug content, in vitro disintegration time, wetting time, in vitro dissolution. Formulation with 10% L-HPC showed the less disintegration time (25.3 s) and less wetting time (29.1 s). In vitro dissolution studies showed total drug release at the end of 6 min. PMID:21218071

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

3D extrusion printing of high drug loading immediate release paracetamol tablets.

PubMed

Khaled, Shaban A; Alexander, Morgan R; Wildman, Ricky D; Wallace, Martin J; Sharpe, Sonja; Yoo, Jae; Roberts, Clive J

2018-03-01

The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 s and release of most of the drug within 5 min. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of the material and tablet formation properties of modified forms of Dioscorea starches.

PubMed

Odeku, Oluwatoyin A; Picker-Freyer, Katharina M

2009-11-01

Starches obtained from four different Dioscorea species-namely, White yam (Dioscorea rotundata), Bitter yam (Dioscorea dumetorum), Chinese yam (Dioscorea oppositifolia), and Water yam (Dioscorea alata)-were modified by cross-linking, hydroxypropylation, and dual modification-cross-linking followed by hydroxypropylation. The physicochemical, material, and tablet properties of the modified starches were investigated with the aim of understanding their properties to determine their potential use for different applications. The tablet formation properties were assessed using 3D modeling, the Heckel equation, and force-displacement profiles. The analyzed tablet properties were elastic recovery, compactibility, and disintegration. The result indicates that the modifications generally increased the swelling power for all the starches in the rank order hydroxypropyl > hydroxypropylated cross-linked > cross-linked (CL) while the solubility did not show a clear-cut pattern. This indicates that hydroxypropylation generally showed the strongest effects on swelling. Furthermore, hydroxypropylation improved the hot water swelling of the CL starches. The modifications did not cause any detectable morphological change in the starch granules shape or size although slight rupture was observed in some granules. CL starch had the lowest water sorption capacity and hydroxypropylation increased the sorption capacity of the CL starches. The material property results indicate that hydroxypropylation and cross-linking did not significantly improve the flowability and compressibility but improved bonding, which resulted in an increased compaction and higher tablet crushing force even though they all disintegrated rapidly. Thus, the modified Dioscorea starches showed potentials for development as new excipients in solid dosage form design, and they could be useful as disintegrants or for Soft tableting.

Dissolution Studies of Papaverine Hydrochloride from Tablets in Three Pharmacopoeia Apparatuses.

PubMed

Polski, Andrzej; Kasperek, Regina; Rogowska, Magdalena; Iwaniak, Karol; Sobòtka-Polska, Karolina; Poleszak, Ewa

2015-01-01

In tablet production, the most important aspects are the physical properties of the tablets and their dissolution studies, which can be performed in four pharmacopoeial apparatuses. There are differences between them in construction and action, so differences in the results obtained are possible. The aim of the study was to compare the release of a model drug substance (papaverine hydrochloride) from tablets in three pharmacopoeial dissolution apparatus: a basket, a paddle (closed system) and flow-through cell (open system). The one series of tablets were produced by direct compression in a tablet press. The physical properties of the tablets (weight and size uniformity test, friability and hardness tests, disintegration time test), drug content and the release study of papaverine hydrochloride from tablets were studied in three dissolution apparatuses. The content of the active substance was studied spectrophotometrically. All tablets met the pharmacopoeic requirements. Over 80% of the model substance released from the tablets after 14 min in flow through the cell apparatus, while in the basket and paddle apparatuses after about 7 min 30 sec. After 20 min, the amount of the substance released in all apparatuses was over 90%. The release profiles of the drug substance in paddle and basket apparatuses were similar, while in the flow-through cell apparatus it was slightly slower. When the study conditions and composition of the tablets are the same, the release profile of the drug can be affected by the type of dissolution apparatus.

Bioenhanced sublingual tablet of drug with limited permeability using novel surfactant binder and microencapsulated polysorbate: In vitro/in vivo evaluation.

PubMed

El-Setouhy, Doaa Ahmed; Basalious, Emad B; Abdelmalak, Nevine Shawky

2015-08-01

Formulation of sublingual tablets of drugs with limited permeability poses a great challenge due to their poor absorption. In this study, bioenhanced sublingual tablets (BESTs) of zolmitriptan were prepared using novel surfactant binder (Pluronic® p123/Syloid® mixture) to enhance tablet disintegration and dissolution. Microencapsulated polysorbate 80 (Sepitrap™ 80) were included in the composition of BESTs to enhance the drug transport through the sublingual mucosa. Tablets were evaluated for in vitro/in vivo disintegration, in vitro dissolution and ex vivo permeation. Solubility studies confirmed that phosphate buffer; pH 6.8 could be used as dissolution medium for sublingual tablets of zolmitriptan. BEST-5 containing Pluronic® p123/Syloid® mixture and Sepitrap™ 80 exhibited the shortest in vitro/in vivo disintegration times (<30s), the highest dissolution at early time dissolution points and the highest enhancement of drug transport through mucosal membrane. The in vivo pharmacokinetic study using human volunteers showed a significant increase in the rate and extent of sublingual absorption with less variations of Tmax after sublingual administration of both BEST-5 and Zomig-ZMT ODT. Our results proposed that Pluronic® p123/Syloid® mixture and Sepitrap™ 80 could be promising for the development of sublingual tablets for rapid onset of action of drugs with limited permeability. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation and evaluation of sublingual tablets containing Sumatriptan succinate

PubMed Central

Prajapati, Shailesh T; Patel, Parth B; Patel, Chhagan N

2012-01-01

Objective: Sumatriptan succinate is a selective 5-hydroxytryptamine-1 receptor agonist effective in the acute treatment of migraine headaches, having low bioavailability of about 15% orally due to first-pass metabolism. The purpose of this research was to mask the intensely bitter taste of Sumatriptan succinate and to formulate fast-acting, taste-masked sublingual tablet formulation. Materials and Methods: Taste masking was performed by solid dispersion method with mannitol and ion exchange with Kyron T 114 because it releases the drug in salivary pH. The resultant batches were evaluated for in-vivo taste masking as well compatability study (Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC)). For a better feel in the mouth, menthol and sweetener Na saccharine were added to the tablet formulation. The tablets were prepared by direct compression and evaluated for weight variation, thickness, friability, drug content, hardness, disintegration time, wetting time, in vitro drug release, and in vitro permeation study. Results and Discussion: Optimized batches disintegrated in vitro within 28-34 s. Maximum drug release could be achieved with in 10 min for the solid dispersion batches and 14-15 min for the ion-exchange batches with Kyron T 114. The optimized tablet formulation showed better taste and the formulated sublingual tablets may act as a potential alternate for the Sumatriptan succinate oral tablet. Conclusion: Sumatriptan succinate can be successfully taste-masked by both the solid dispersion method using mannitol by the melting method and Ion exchange resin with Kyron T114. It was also concluded that prepared formulation improve bioavailability by prevention of first pass metabolism. PMID:23373008

Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin.

PubMed

Chua, Hui Ming; Hauet Richer, Nathalie; Swedrowska, Magda; Ingham, Stephen; Tomlin, Stephen; Forbes, Ben

2016-01-07

Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used "off-label" to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58), whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

Novel levocetirizine HCl tablets with enhanced palatability: synergistic effect of combining taste modifiers and effervescence technique

PubMed Central

Labib, Gihan S

2015-01-01

Objectives Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-β-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients’ will. Materials and methods Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability. Results All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets. Conclusion Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. PMID:26379426

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.

Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

PubMed

Al-Gousous, Jozef; Langguth, Peter

2016-02-01

To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Enabling the Tablet Product Development of 5-Fluorocytosine by Conjugate Acid Base Cocrystals.

PubMed

Perumalla, Sathyanarayana R; Paul, Shubhajit; Sun, Changquan C

2016-06-01

5-Fluorocytosine (FC) is a high-dose antifungal drug that challenges the development of a tablet product due to poor solid-state stability and tabletability. Using 2 pharmaceutically acceptable conjugate acid base (CAB) cocrystals of FC with HCl and acesulfame, we have developed commercially viable high loading FC tablets. The tablets were prepared by direct compression using nano-coated microcrystalline cellulose Avicel PH105 as a tablet binder, which provided both excellent tabletability and good flowability. Commercial manufacturability of formulations based on both CAB cocrystals was verified on a compaction simulator. The results from an expedited friability study were used to set the compaction force, which yielded tablets with sufficient mechanical strength and rapid tablet disintegration. This work demonstrates the potential value of CAB cocrystals in drug product development. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

A newly developed lubricant, chitosan laurate, in the manufacture of acetaminophen tablets.

PubMed

Bani-Jaber, Ahmad; Kobayashi, Asuka; Yamada, Kyohei; Haj-Ali, Dana; Uchimoto, Takeaki; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2015-04-10

To study the usefulness of chitosan laurate (CS-LA), a newly developed chitosan salt, as a lubricant, lubrication properties such as the pressure transmission ratio and ejection force were determined at different concentrations of CS-LA in tableting. In addition, tablet properties such as the tensile strength, disintegration time, and dissolution behavior, were also determined. When CS-LA was mixed at concentrations of 0.1%-3.0%, the pressure transmission ratio was increased in a concentration-dependent manner, and the value at a CS-LA concentration of 3% was equal to that of magnesium stearate (Mg-St), a widely used lubricant. Additionally, a reduction in the ejection force was observed at a concentration from 1%, proving that CS-LA has good lubrication performance. A prolonged disintegration time and decreased tensile strength, which are known disadvantages of Mg-St, were not observed with CS-LA. Furthermore, with CS-LA, retardation of dissolution of the drug from the tablets was not observed. Conjugation of CS with LA was found to be quite important for both lubricant and tablet properties. In conclusion, CS-LA should be useful as an alternative lubricant to Mg-St. Copyright © 2015 Elsevier B.V. All rights reserved.

Challenges in detecting magnesium stearate distribution in tablets.

PubMed

Lakio, Satu; Vajna, Balázs; Farkas, István; Salokangas, Henri; Marosi, György; Yliruusi, Jouko

2013-03-01

Magnesium stearate (MS) is the most commonly used lubricant in pharmaceutical industry. During blending, MS particles form a thin layer on the surfaces of the excipient and drug particles prohibiting the bonding from forming between the particles. This hydrophobic layer decreases the tensile strength of tablets and prevents water from penetrating into the tablet restraining the disintegration and dissolution of the tablets. Although overlubrication of the powder mass during MS blending is a well-known problem, the lubricant distribution in tablets has traditionally been challenging to measure. There is currently no adequate analytical method to investigate this phenomenon. In this study, the distribution of MS in microcrystalline cellulose (MCC) tablets was investigated using three different blending scales. The crushing strength of the tablets was used as a secondary response, as its decrease is known to result from the overlubrication. In addition, coating of the MCC particles by MS in intact tablets was detected using Raman microscopic mapping. MS blending was more efficient in larger scales. Raman imaging was successfully applied to characterize MS distribution in MCC tablets despite low concentration of MS. The Raman method can provide highly valuable visual information about the proceeding of the MS blending process. However, the measuring set-up has to be carefully planned to establish reliable and reproducible results.

Hexagonal boron nitride as a tablet lubricant and a comparison with conventional lubricants.

PubMed

Uğurlu, Timuçin; Turkoğlu, Murat

2008-04-02

The objective of this study was to investigate the lubrication properties of hexagonal boron nitride (HBN) as a new tablet lubricant and compare it with conventional lubricants such as magnesium stearate (MGST), stearic acid (STAC), and glyceryl behenate (COMP). Tablets were manufactured on an instrumented single-station tablet press to monitor lower punch ejection force (LPEF) containing varied lubricants in different ratio (0.5, 1, 2%). Tablet crushing strength, disintegration time and thickness were measured. Tensile strength of compacted tablets were measured by applying a diametrical load across the edge of tablets to determine mechanical strength. The deformation mechanism of tablets was studied during compression from the Heckel plots with or without lubricants. MGST was found to be the most effective lubricant based on LPEF-lubrication concentration profile and LPEF of HBN was found very close to that of MGST. HBN was better than both STAC and COMP. A good lubrication was obtained at 0.5% for MGST and HBN (189 and 195N, respectively). Where COMP and STAC showed 20 and 35% more LPEF compare to that of MGST (239 and 288N, respectively). Even at the concentration of 2% COMP and STAC did not decrease LPEF as much as 0.5% of MGST and HBN. Like all conventional lubricants the higher the concentration of HBN the lower the mechanical properties of tablets because of its hydrophobic character. However, this deterioration was not as pronounced as MGST. HBN had no significant effect on tablet properties. Based on the Heckel plots, it was observed that after the addition of 1% lubricant granules showed less plastic deformation.

Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion.

PubMed

Sammour, Omaima A; Hammad, Mohammed A; Megrab, Nagia A; Zidan, Ahmed S

2006-06-16

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1:9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 3(2) randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug.

Design and Optimization of Domperidone Fast Dissolving Tablet Using Central Composite Design.

PubMed

Shailendra, Bhatt; Shailendra, Mandge; Manish, Jaimini; Singh, Tanwar Yuveraj; Priti, Trivedi

2015-01-01

The main aim present work was to optimize fast dissolving tablet (FDT) formulation using response surface approach. The variables studied were sodium bicarbonate (X1), citric acid (X2), and superdisintegrant, Ac-Di-Sol (X3). The main aspect of present work was to develop FDT of Domperidone which possesses fast disintegration and high mechanical strength. It was found that the response was affected by all the three factors studied. The statistical models were successfully used to prepare FDT of Domperidone with fast disintegration (31.08 seconds) and adequate hardness (4.1 kg/cm(2)). Pharmacokinetic studies in rats showed statistically insignificant difference (p>0.05) between Domperidone fast dissolving tablet (DFDT) and market product. This concluded that optimized FDT is bioequivalent with the marketed formulation. The values of Tmax were found to be 0.5 h and 0.75 h for DFDT and reference product, respectively. Conditioned place aversion study was performed on Swiss Albino mice and the study showed the better anti emetic potency of optimized FDT in nauseated condition over market product (p<0.05). Thus, the present investigation conclusively demonstrates the potential role in terms of rapid disintegration and high mechanical strength.

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability.

PubMed

Dennison, Thomas J; Smith, Julian C; Badhan, Raj K; Mohammed, Afzal R

2017-01-01

Cardiovascular disease (CVD) is the leading cause of death among men and women worldwide. In CVD, hypertension and dyslipidemia commonly coexist and are managed through coadministration of amlodipine and atorvastatin, respectively. The case for fixed-dose combination (FDC) oral dosage forms and orally disintegrating tablet (ODT) technology to enhance outcomes and compliance is strong. This work follows the development and characterization of single and FDC ODTs containing amlodipine and atorvastatin, followed by bioequivalence comparison between these single and FDC formulations, using in vitro dissolution and Caco-2 apparent permeability (P app ) and in silico physiologically based pharmacokinetic modeling approaches. ODTs containing amlodipine (5 mg) and atorvastatin (10 mg) either alone or in combination rapidly disintegrated (<30 s) while displaying a radial crushing strength in excess of 100 N and friability ≤1%. In vitro dissolution test was performed in fasted and fed-state simulated intestinal fluid (FeSSIF) and analyzed using high-performance liquid chromatography. Dissolution profiles for single and FDC ODTs were compared using US FDA recommended difference (f 1 ) and similarity (f 2 ) factor testing for bioequivalence. In all cases, there was no difference in active pharmaceutical ingredient dissolution between single or FDC ODTs, with the exception of amlodipine in FeSSIF. Pharmacokinetic clinical trial simulations were conducted using Simcyp (Version 14), incorporating P app and dissolution data. Simulated clinical trials in healthy volunteers showed no difference in bioavailability based on pharmacokinetic parameters between single and combination doses with either active pharmaceutical ingredient. An increase in C max and AUC for atorvastatin in fed subjects was attributed to extended transit along the gut lumen and reduced atorvastatin metabolism due to lower CYP3A4 expression at more distal small intestine absorption sites. The results

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability

PubMed Central

Dennison, Thomas J; Smith, Julian C; Badhan, Raj K; Mohammed, Afzal R

2017-01-01

Cardiovascular disease (CVD) is the leading cause of death among men and women worldwide. In CVD, hypertension and dyslipidemia commonly coexist and are managed through coadministration of amlodipine and atorvastatin, respectively. The case for fixed-dose combination (FDC) oral dosage forms and orally disintegrating tablet (ODT) technology to enhance outcomes and compliance is strong. This work follows the development and characterization of single and FDC ODTs containing amlodipine and atorvastatin, followed by bioequivalence comparison between these single and FDC formulations, using in vitro dissolution and Caco-2 apparent permeability (Papp) and in silico physiologically based pharmacokinetic modeling approaches. ODTs containing amlodipine (5 mg) and atorvastatin (10 mg) either alone or in combination rapidly disintegrated (<30 s) while displaying a radial crushing strength in excess of 100 N and friability ≤1%. In vitro dissolution test was performed in fasted and fed-state simulated intestinal fluid (FeSSIF) and analyzed using high-performance liquid chromatography. Dissolution profiles for single and FDC ODTs were compared using US FDA recommended difference (f1) and similarity (f2) factor testing for bioequivalence. In all cases, there was no difference in active pharmaceutical ingredient dissolution between single or FDC ODTs, with the exception of amlodipine in FeSSIF. Pharmacokinetic clinical trial simulations were conducted using Simcyp (Version 14), incorporating Papp and dissolution data. Simulated clinical trials in healthy volunteers showed no difference in bioavailability based on pharmacokinetic parameters between single and combination doses with either active pharmaceutical ingredient. An increase in Cmax and AUC for atorvastatin in fed subjects was attributed to extended transit along the gut lumen and reduced atorvastatin metabolism due to lower CYP3A4 expression at more distal small intestine absorption sites. The results demonstrated

Pure drug nanoparticles in tablets: what are the dissolution limitations?

NASA Astrophysics Data System (ADS)

Heng, Desmond; Ogawa, Keiko; Cutler, David J.; Chan, Hak-Kim; Raper, Judy A.; Ye, Lin; Yun, Jimmy

2010-06-01

There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 ± 2.7% to 72.3 ± 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.

Tablet splitting of a narrow therapeutic index drug: a case with levothyroxine sodium.

PubMed

Shah, Rakhi B; Collier, Jarrod S; Sayeed, Vilayat A; Bryant, Arthur; Habib, Muhammad J; Khan, Mansoor A

2010-09-01

Levothyroxine is a narrow therapeutic index, and to avoid adverse effect associated with under or excessive dosage, the dose response is carefully titrated. The tablets are marketed with a score providing an option to split. However, there are no systematic studies evaluating the effect of splitting on dose accuracy, and current study was undertaken to evaluate effects of splitting and potential causes for uniformity failures by measuring assay and content uniformity in whole and split tablets. Stability was evaluated by assaying drug for a period of 8 weeks. Effect of formulation factors on splittability was evaluated by a systematic investigation of formulation factors by preparing levothyroxine tablets in house by varying the type of excipients (binder, diluent, disintegrant, glidant) or by varying the processing factors (granulating liquid, mixing type, compression pressure). The tablets were analyzed using novel analytical tool such as near infrared chemical imaging to visualize the distribution of levothyroxine. Assay was not significantly different for whole versus split tablets irrespective of method of splitting (hand or splitter), and splitting also had no measurable impact on the stability. Split tablets either by hand or splitter showed higher rate of content uniformity failures as compared to whole tablets. Tablet splitter produced more fragmentation and, hence, more content uniformity and friability failures. Chemical imaging data revealed that the distribution of levothyroxine was heterogeneous and was dependent on type of binder and the process used in the manufacture of tablets. Splitting such tablets could prove detrimental if sub- or super-potency becomes an issue.

New multifunctional pharmaceutical excipient in tablet formulation based on citric acid-cyclodextrin polymer.

PubMed

Garcia-Fernandez, Maria José; Tabary, Nicolas; Chai, Feng; Cazaux, Frédéric; Blanchemain, Nicolas; Flament, Marie-Pierre; Martel, Bernard

2016-09-25

A β-cyclodextrin (β-CD) polymer obtained by crosslinking β-CD with citric acid in its water-insoluble (PCD-I) and soluble (PCD-S) forms was used as a multifunctional direct compression excipient for tablet designing. PCD-I powder was obtained after grinding the solid fraction through a 200μm grid. PCD-S powder was recovered after lyophilization or spray drying of the PCD-S aqueous solutions, eventually followed by a wet granulation step. Both PCD-I and PCD-S powders were characterized, separately and mixed in variable ratios, based on dynamic water vapor sorption, SEM, particle size distribution, tapped density, compressibility, and flowability. PCD-I and spray dried and lyophilized/wet granulated PCD-S, as well as the mixture PCD-I/PCD-S=90/10, presented optimal free flowing characteristics. Then, PCD-I or PCD-S powders - separately or mixed in variable ratios - were used for tablets preparation by direct compression without adding any other excipient (e.g. binder, lubricant, disintegrant etc). As PCD-I decreased, tablets resistance to crushing and disintegration time increased from 15s to 15min (against 30min for β-CD), showing the improved disintegrant functionality of PCD-I, that rapidly swelled once in contact with water. Finally, PCD was force-fed to Sprague-Dawley rats (2g/kg) which were then observed during 14days for any clinical signs of toxicity. Copyright © 2016. Published by Elsevier B.V.

[A study of the properties of tablets from mixtures of two size degrees of alpha-lactose monohydrate and microcrystalline cellulose].

PubMed

Muzíková, J

2006-03-01

The paper examines the strength and disintegration time of compacts from the mixtures of two types of Tablettosas. Tablettosa 70 and Tablettosa 100 with microcrystalline cellulose represented by Vivapur 102. The mixtures of dry binders were prepared in the ratios of 3:1, 1:1, and 1:3. The effect of two concentrations of the lubricant magnesium stearate on the strength and disintegration time of compacts was also examined. Tablet strength increased with higher representation of microcrystalline cellulose in the mixture, and decreased with higher stearate concentration. The compacts from the mixtures with Tablettosa 100 showed higher strength. Disintegration time was highest in the compacts with the largest perccintage of microcrystalline cellulose, and longer in the case of the mixtures with Tablettosa 100. Stearate did not exert a negative effect on disintegration time. In the mixtures of Tablettosas with Vivapur 102 in a ratio of 1:1, the effect of the model active ingredient acetylsalicylic acid on the above-mentioned properties of tablets was tested. acetylsalicylic acid produced a further decrease in the strength of compacts and shortened the disintegration time in more instances in the cased of the mixtures with Tahlettosa 100.

Quality-by-design case study: investigation of the role of poloxamer in immediate-release tablets by experimental design and multivariate data analysis.

PubMed

Kaul, Goldi; Huang, Jun; Chatlapalli, Ramarao; Ghosh, Krishnendu; Nagi, Arwinder

2011-12-01

The role of poloxamer 188, water and binder addition rate, on retarding dissolution in immediate-release tablets of a model drug from BCS class II was investigated by means of multivariate data analysis (MVDA) combined with design of experiments (DOE). While the DOE analysis yielded important clues into the cause-and-effect relationship between the responses and design factors, multivariate data analysis of the 40+ variables provided additional information on slowdown in tablet dissolution. A steep dependence of both tablet dissolution and disintegration on the poloxamer and less so on other design variables was observed. Poloxamer was found to increase dissolution rates in granules as expected of surfactants in general but retard dissolution in tablets. The unexpected effect of poloxamer in tablets was accompanied by an increase in tablet-disintegration-time-mediated slowdown of tablet dissolution and by a surrogate binding effect of poloxamer at higher concentrations. It was additionally realized through MVDA that poloxamer in tablets either acts as a binder by itself or promotes binder action of the binder povidone resulting in increased intragranular cohesion. Additionally, poloxamer was found to mediate tablet dissolution on stability as well. In contrast to tablet dissolution at release (time zero), poloxamer appeared to increase tablet dissolution in a concentration-dependent manner on accelerated open-dish stability. Substituting polysorbate 80 as an alternate surfactant in place of poloxamer in the formulation was found to stabilize tablet dissolution.

Colonic delivery of indometacin loaded PGA-co-PDL microparticles coated with Eudragit L100-55 from fast disintegrating tablets.

PubMed

Tawfeek, Hesham M; Abdellatif, Ahmed A H; Dennison, Thomas J; Mohammed, Afzal R; Sadiq, Younis; Saleem, Imran Y

2017-10-05

The aim of this work was to investigate the efficient targeting and delivery of indometacin (IND), as a model anti-inflammatory drug to the colon for treatment of inflammatory bowel disease. We prepared fast disintegrating tablets (FDT) containing IND encapsulated within poly(glycerol-adipate-co-ɷ-pentadecalactone), PGA-co-PDL, microparticles and coated with Eudragit L100-55 at different ratios (1:1.5, 1:1, 1:0.5). Microparticles encapsulated with IND were prepared using an o/w single emulsion solvent evaporation technique and coated with Eudragit L-100-55 via spray drying. The produced coated microparticles (PGA-co-PDL-IND/Eudragit) were formulated into optimised FTD using a single station press. The loading, in vitro release, permeability and transport of IND from PGA-co-PDL-IND/Eudragit microparticles was studied in Caco-2 cell lines. IND was efficiently encapsulated (570.15±4.2μg/mg) within the PGA-co-PDL microparticles. In vitro release of PGA-co-PDL-IND/Eudragit microparticles (1:1.5) showed significantly (p<0.05, ANOVA/Tukey) lower release of IND 13.70±1.6 and 56.46±3.8% compared with 1:1 (89.61±2.5, 80.13±2.6%) and 1:0.5 (39.46±0.9 & 43.38±3.12) after 3 and 43h at pH 5.5 and 6.8, respectively. The permeability and transport studies indicated IND released from PGA-co-PDL-IND/Eudragit microparticles had a lower permeability coefficient of 13.95±0.68×10 -6 cm/s compared to free IND 23.06±3.56×10 -6 cm/s. These results indicate the possibility of targeting anti-inflammatory drugs to the colon using FDTs containing microparticles coated with Eudragit. Copyright © 2017 Elsevier B.V. All rights reserved.

Roller compaction of different pseudopolymorphic forms of theophylline: Effect on compressibility and tablet properties.

PubMed

Hadzović, Ervina; Betz, Gabriele; Hadzidedić, Seherzada; El-Arini, Silvia Kocova; Leuenberger, Hans

2010-08-30

The effect of roller compaction on disintegration time, dissolution rate and compressibility of tablets prepared from theophylline anhydrate powder, theophylline anhydrate fine powder and theophylline monohydrate was studied. In addition, the influence of adding microcrystalline cellulose, a commonly used excipient, in mixtures with these materials was investigated. Theophylline anhydrate powder was used as a model drug to investigate the influence of different compaction pressures on the tablet properties. Tablets with same porosity were prepared by direct compaction and by roller compaction/re-compaction. Compressibility was characterized by Heckel and modified Heckel equations. Due to the property of polymorphic materials to change their form during milling and compression, X-ray diffraction analysis of theophylline anhydrate powder, theophylline anhydrate fine powder and theophylline monohydrate powders and granules was carried out. After roller compaction the disintegration time and the dissolution rate of the tablets were significantly improved. Compressibility of theophylline anhydrate powder and theophylline anhydrate fine powder was decreased, while theophylline monohydrate showed higher compressibility after roller compaction. Microcrystalline cellulose affected compressibility of theophylline anhydrate powder, theophylline anhydrate fine powder and theophylline monohydrate whereby the binary mixtures showed higher compressibility than the individual materials. X-ray diffraction analyses confirmed that there were no polymorphic/pseudopolymorphic changes after roller compaction. Copyright 2010 Elsevier B.V. All rights reserved.

Effects of ultrasonic disintegration of excess sludge obtained in disintegrators of different constructions.

PubMed

Zielewicz, Ewa; Tytła, Malwina

2015-01-01

The ultrasonic disintegration of excess sludge is placed after the mechanical thickening but before the digestion tanks in order to intensify the process of sludge stabilization. The effects obtained directly after ultrasonic disintegration depend on many factors and can be grouped in two main categories: factors affecting the quality of sludge and those associated with the construction of disintegrators and its parameters. The ultrasonic disintegration research was carried out using three types of structural solutions of disintegrators. Two of them, that is, WK-2000 ultrasonic generator (P = 400 W) working with a thin sonotrode and WK-2010 ultrasonic generator (P = 100-1000 W) working with a new type construction emitter lens sonotrode, were compared with the influence of a washer with a flat emitter. The investigations have shown that in the same sludge, using the same value of volumetric energy, the resulting effect depends on the construction of the ultrasonic disintegrator, that is, design of the head and the ratio between the field of the emitter and the field of the chamber in sonicated medium.

Comparing Paper and Tablet Modes of Retrospective Activity Space Data Collection.

PubMed

Yabiku, Scott T; Glick, Jennifer E; Wentz, Elizabeth A; Ghimire, Dirgha; Zhao, Qunshan

2017-01-01

Individual actions are both constrained and facilitated by the social context in which individuals are embedded. But research to test specific hypotheses about the role of space on human behaviors and well-being is limited by the difficulty of collecting accurate and personally relevant social context data. We report on a project in Chitwan, Nepal, that directly addresses challenges to collect accurate activity space data. We test if a computer assisted interviewing (CAI) tablet-based approach to collecting activity space data was more accurate than a paper map-based approach; we also examine which subgroups of respondents provided more accurate data with the tablet mode compared to paper. Results show that the tablet approach yielded more accurate data when comparing respondent-indicated locations to the known locations as verified by on-the-ground staff. In addition, the accuracy of the data provided by older and less healthy respondents benefited more from the tablet mode.

Comparing Paper and Tablet Modes of Retrospective Activity Space Data Collection*

PubMed Central

Yabiku, Scott T.; Glick, Jennifer E.; Wentz, Elizabeth A.; Ghimire, Dirgha; Zhao, Qunshan

2018-01-01

Individual actions are both constrained and facilitated by the social context in which individuals are embedded. But research to test specific hypotheses about the role of space on human behaviors and well-being is limited by the difficulty of collecting accurate and personally relevant social context data. We report on a project in Chitwan, Nepal, that directly addresses challenges to collect accurate activity space data. We test if a computer assisted interviewing (CAI) tablet-based approach to collecting activity space data was more accurate than a paper map-based approach; we also examine which subgroups of respondents provided more accurate data with the tablet mode compared to paper. Results show that the tablet approach yielded more accurate data when comparing respondent-indicated locations to the known locations as verified by on-the-ground staff. In addition, the accuracy of the data provided by older and less healthy respondents benefited more from the tablet mode. PMID:29623133

A systematic and mechanistic evaluation of aspartic acid as filler for directly compressed tablets containing trimethoprim and trimethoprim aspartate.

PubMed

ElShaer, Amr; Hanson, Peter; Mohammed, Afzal R

2013-04-01

The generally accepted paradigm of 'inert' and 'mono functional' excipient in dosage form has been recently challenged with the development of individual excipients capable of exhibiting multiple functions (e.g. binder-disintegrants, surfactant which affect P-gp function). The proposed study has been designed within the realm of multifunctionality and is the first and novel investigation towards evaluation of aspartic acid as a filler and disintegration enhancing agent for the delivery of biopharmaceutical class IV model drug trimethoprim. The study investigated powder characteristics using angle of repose, laser diffractometry and scanning electron microscopy (SEM). The prepared tablets were characterised using Heckel analysis, disintegration time and tensile strength measurements. Although Heckel analysis revealed that both TMP and TMP aspartate salt have high elasticity, the salt form produced a stronger compact which was attributed to the formation of agglomerates. Aspartic acid was found to have high plasticity, but its incorporation into the formulations was found to have a negative impact on the compaction properties of TMP and its salt. Surface morphology investigations showed that mechanical interlocking plays a vital role in binding TMP crystals together during compaction, while the small particle size of TMP aspartate agglomerates was found to have significant impact on the tensile strength of the tablets. The study concluded that aspartic acid can be employed as filler and disintegrant and that compactability within tablets was independent of the surface charge of the excipients. Copyright © 2012 Elsevier B.V. All rights reserved.

Methylphenidate disintegration from oral formulations for intravenous use by experienced substance users.

PubMed

Bjarnadottir, G D; Johannsson, M; Magnusson, A; Rafnar, B O; Sigurdsson, E; Steingrimsson, S; Asgrimsson, V; Snorradottir, I; Bragadottir, H; Haraldsson, H M

2017-09-01

Methylphenidate (MPH) is a prescription stimulant used to treat attention-deficit hyperactivity disorder. MPH is currently the preferred substance among most intravenous (i.v.) substance users in Iceland. Four types of MPH preparations were available in Iceland at the time of study: Immediate-release (IR), sustained-release (SR), osmotic controlled-release oral delivery (OROS) tablet and osmotic-controlled release (OCR). MPH OROS has previously been rated the least desirable by i.v. users and we hypothesized that this was associated with difficulty of disintegrating MPH from OROS formulation. The aim of the study was to measure the amount of MPH and the viscosity of the disintegrated solutions that were made from the four MPH formulations by four i.v.-users and non-users. A convenience sample of four i.v. substance users and 12 non-users. Non-users imitated the methods applied by experienced i.v. substance users for disintegrated MPH formulations. Both groups managed to disintegrate over 50% of MPH from IR and SR formulations but only 20% from OROS (p<0.0001). The viscosity of the disintegrated MPH was significantly higher for MPH OROS and MPH OCR and the preparation was significantly more time-consuming than for the other MPH samples. No differences were observed between users and non-users. To our knowledge, this is the first investigation of viscosity and the amount of disintegrated MPH from prescription drugs for i.v. use. The results indicate that the ease of disintegration, amount of MPH and viscosity may explain the difference in popularity for i.v. use between different MPH formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

PubMed

Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

2015-01-01

In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin

Ondansetron, orally disintegrating tablets versus intravenous injection for prevention of intrathecal morphine-induced nausea, vomiting, and pruritus in young males.

PubMed

Pirat, Arash; Tuncay, Senay F; Torgay, Adnan; Candan, Selim; Arslan, Gulnaz

2005-11-01

In this study we compared the efficacy of orally disintegrating tablets (ODT) and IV ondansetron for preventing spinal morphine-induced pruritus and postoperative nausea and vomiting (PONV) in healthy young male patients. Patients who received bupivacaine with 0.20 mg morphine for spinal anesthesia were randomly assigned to the ODT group (ODT ondansetron 8 mg, n = 50), the IV group (4 mg ondansetron IV, n = 50), or the placebo group (n = 50). Each individual was assessed for pruritus, postoperative nausea and vomiting, and pain at 0, 2, 6, 12, 18, and 24 h after surgery using three distinct visual analog scales. The frequencies of postoperative nausea and vomiting and frequencies of requirement for rescue antiemetic and antipruritic were recorded. There were no significant differences among the three groups with respect to incidence or severity of PONV or postoperative pain visual analog scale scores. The incidences of pruritus in the ODT (56%) and IV (66%) groups were significantly different from that in the placebo group (86%) (P < 0.02 for both). Only the ODT group had significantly lower mean pruritus visual analog scale scores at 0, 2, 6, and 12 h postsurgery than the placebo group (P < 0.023 for all). The frequency of requirement for rescue antipruritic was significantly less in the ODT group than the placebo group (P = 0.013). Both ODT ondansetron 8 mg and IV ondansetron 4 mg are more effective than placebo for preventing spinal morphine-induced pruritus, but neither form of this agent reduces spinal morphine-induced postoperative nausea and vomiting in this patient group.

HIGH SHEAR GRANULATION PROCESS: ASSESSING IMPACT OF FORMULATION VARIABLES ON GRANULES AND TABLETS CHARACTERISTICS OF HIGH DRUG LOADING FORMULATION USING DESIGN OF EXPERIMENT METHODOLOGY.

PubMed

Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Ali, Bahaa E

2017-03-01

High shear wet granulation is a significant component procedure in the pharmaceutical industry. The objective of the study was to investigate the influence of two independent formulation variables; polyvinypyrrolidone (PVP) as a binder (X,) and croscarmellose sodium (CCS) as a disintegrant (X2) on the crit- ical quality attributes of acetaminophen granules and their corresponding tablets using design of experiment (DoE) approach. A two factor, three level (32) full factorial design has been applied; each variable was investi- gated at three levels to characterize their strength and interaction. The dried granules have been analyzed for their density, granule size and flowability. Additionally, the produced tablets have been investigated for: break- ing force, friability, disintegration time and t. of drug dissolution. The analysis of variance (ANOVA) showed that the two variables had a significant impact (p < 0.05) on granules and tablets characteristics, while only the binder concentration influenced the tablets friability. Furthermore, significant interactions (p < 0.05) between the two variables, for granules and tablets attributes, were also found. However, variables interaction showed minimal effect for granules flowability as well as tablets friability. Desirability function was carried out to opti- mize the variables under study to obtain product within the USP limit. It was found that the higher desirability (0.985) could be obtained at the medium level of PVP and low level of CCS. Ultimately, this study supplies the formulator with beneficial tools in selecting the proper level of binder and disintegrant to attain product with desired characteristics.

Pharmacokinetics of ketorolac tromethamine compression-coated tablets for colon delivery.

PubMed

Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

2014-08-01

Present research efforts are focused in developing compression-coated ketorolac tromethamine tablets to improve the drug levels in colon by retarding the drug release in the stomach and small intestine. To achieve this objective, core tablets containing ketorolac tromethamine were prepared by direct compression and compression coated with sodium alginate. The developed tablets were evaluated for physical properties, in vitro drug release, X-ray imaging, and pharmacokinetic studies in human volunteers. Based on the in vitro drug release study, the optimized formulation showed very little drug release (6.75 ± 0.49 %) in the initial lag period of 5 h, followed by progressive release up to 97.47 ± 0.93 % within 24 h. The X-ray imaging of tablets in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. From the pharmacokinetic study, the C max of colon-targeted tablets was 3,486.70 ng/ml at T max 10 h, whereas in the case of immediate-release tablets, the C max of 4,506.31 ng/ml at T max 2 h signifies the ability of compression-coated tablets to target the colon. In conclusion, compression-coated tablets are suitable to deliver ketorolac tromethamine to the colon.

A randomized crossover study to assess the pharmacokinetics of a novel amphetamine extended-release orally disintegrating tablet in healthy adults.

PubMed

Stark, Jeffrey G; Engelking, Dorothy; McMahen, Russ; Sikes, Carolyn

2016-09-01

In this pharmacokinetic (PK) study in healthy adults, we sought to: (1) compare the PK properties of a novel amphetamine extended-release orally disintegrating tablet formulation (Adzenys XR-ODT™ [AMP XR-ODT]) to a reference extended-release mixed amphetamine salts (MAS ER) formulation and (2) assess the effect of food on AMP XR-ODT. Forty-two adults were enrolled in a single-dose, open-label, 3-period, 3-treatment, randomized crossover study and received an 18.8-mg dose of AMP XR-ODT (fasted or fed) or equivalent dose (30 mg) of MAS ER (fasted). Plasma samples were analyzed for d-and l-amphetamine. Maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), elimination half-life (T1/2), area under the concentration-time curve from time zero to last quantifiable concentration (AUClast), from time zero to infinity (AUCinf), relevant partial AUCs, and weight-normalized clearance (CL/F/kg) were assessed. The PK parameters were compared across treatments using an ANOVA. Safety was also assessed. A total of 39 adults completed this study. The geometric mean ratios (90% confidence interval [CI]) for AMP XR-ODT/MAS ER Cmax, AUC5-last, AUClast, and AUCinf were within 80%-125% for both d-and l-amphetamine. The 90% CIs for AUC0-5 were slightly below the 80%-125% range. When AMP XR-ODT was administered with food, there was a slight decrease in the d-and l-amphetamine Cmax and approximately a 2-hour delay in Tmax. The most common adverse events reported (>5% of participants) were dry mouth, palpitations, nausea, dizziness, headache, anxiety, and nasal congestion. AMP XR-ODT displayed a PK profile similar to MAS ER, and no clinically relevant food effect was observed.

Dextrose monohydrate as a non-animal sourced alternative diluent in high shear wet granulation tablet formulations.

PubMed

Mitra, Biplob; Wolfe, Chad; Wu, Sy-Juen

2018-05-01

The feasibility of dextrose monohydrate as a non-animal sourced diluent in high shear wet granulation (HSWG) tablet formulations was determined. Impacts of granulation solution amount and addition time, wet massing time, impeller speed, powder and solution binder, and dry milling speed and screen opening size on granule size, friability and density, and tablet solid fraction (SF) and tensile strength (TS) were evaluated. The stability of theophylline tablets TS, disintegration time (DT) and in vitro dissolution were also studied. Following post-granulation drying at 60 °C, dextrose monohydrate lost 9% water and converted into the anhydrate form. Higher granulation solution amounts and faster addition, faster impeller speeds, and solution binder produced larger, denser and stronger (less friable) granules. All granules were compressed into tablets with acceptable TS. Contrary to what is normally observed, denser and larger granules (at ≥21% water level) produced tablets with a higher TS. The TS of the weakest tablets increased the most after storage at both 25 °C/60% RH and 40 °C/75% RH. Tablet DT was higher for stronger granules and after storage. Tablet dissolution profiles for 21% or less water were comparable and did not change on stability. However, the dissolution profile for tablets prepared with 24% water was slower initially and continued to decrease on stability. The results indicate a granulation water amount of not more than 21% is required to achieve acceptable tablet properties. This study clearly demonstrated the utility of dextrose monohydrate as a non-animal sourced diluent in a HSWG tablet formulation.

Preparation and in vitro/in vivo characterization of porous sublingual tablets containing ternary kneaded solid system of vinpocetine with î-cyclodextrin and hydroxy Acid.

PubMed

Aburahma, Mona H; El-Laithy, Hanan M; Hamza, Yassin El-Said

2010-01-01

The demand for sublingual tablets has been growing during the previous decades especially for drugs with extensive hepatic first-pass metabolism. Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor aqueous solubility and marked first-pass metabolism. Accordingly, the aim of this work was to develop tablets for the sublingual delivery of vinpocetine. Initially, the feasibility of improving vinpocetineâs poor aqueous solubility by preparing kneaded solid systems of the drug with Î-Cyclodextrin and hydroxy acids (citric acid and tartaric acid) was assessed. The solid system with improved solubility and dissolution properties was incorporated into porous tablets that rapidly disintegrate permitting fast release of vinpocetine into the sublingual cavity. The pores were induced into these tablets by directly compressing the tabletsâ excipients with a sublimable material, either camphor or menthol, which was eventually sublimated leaving pores. The obtained results demonstrated that the tablets prepared using camphor attained sufficient mechanical strength for practical use together with rapid disintegration and dissolution. In vivo absorption study performed in rabbits indicated that the sublingual administration of the proposed porous tablets containing vinpocetine solid system with Î-Cyclodextrin and tartaric acid could be useful for therapeutic application.

Mathematical modelling of liquid transport in swelling pharmaceutical immediate release tablets.

PubMed

Markl, Daniel; Yassin, Samy; Wilson, D Ian; Goodwin, Daniel J; Anderson, Andrew; Zeitler, J Axel

2017-06-30

Oral dosage forms are an integral part of modern health care and account for the majority of drug delivery systems. Traditionally the analysis of the dissolution behaviour of a dosage form is used as the key parameter to assess the performance of a drug product. However, understanding the mechanisms of disintegration is of critical importance to improve the quality of drug delivery systems. The disintegration performance is primarily impacted by the hydration and subsequent swelling of the powder compact. Here we compare liquid ingress and swelling data obtained using terahertz pulsed imaging (TPI) to a set of mathematical models. The interlink between hydration kinetics and swelling is described by a model based on Darcy's law and a modified swelling model based on that of Schott. Our new model includes the evolution of porosity, pore size and permeability as a function of hydration time. Results obtained from two sets of samples prepared from pure micro-crystalline cellulose (MCC) indicate a clear difference in hydration and swelling for samples of different porosities and particle sizes, which are captured by the model. Coupling a novel imaging technique, such as TPI, and mathematical models allows better understanding of hydration and swelling and eventually tablet disintegration. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

In vitro and in vivo investigation of taste-masking effectiveness of Eudragit E PO as drug particle coating agent in orally disintegrating tablets.

PubMed

Drašković, Milica; Medarević, Djordje; Aleksić, Ivana; Parojčić, Jelena

2017-05-01

Considering that bitter taste of drugs incorporated in orally disintegrating tablets (ODTs) can be the main reason for avoiding drug therapy, it is of the utmost importance to achieve successful taste-masking. The evaluation of taste-masking effectiveness is still a major challenge. The objective of this study was to mask bitter taste of the selected model drugs by drug particle coating with Eudragit ® E PO, as well as to evaluate taste-masking effectiveness of prepared ODTs using compendial dissolution testing, dissolution in the small-volume shake-flask assembly and trained human taste panel. Model drugs were coated in fluidized bed. Disintequik™ ODT was used as a novel co-processed excipient for ODT preparation. Selected formulations were investigated in vitro and in vivo using techniques for taste-masking assessment. Significantly slower drug dissolution was observed from tablets with coated drug particles during the first 3 min of investigation. Results of in vivo taste-masking assessment demonstrated significant improvement in drug bitterness suppression in formulations with coated drug. Strong correlation between the results of drug dissolution in the small-volume shake-flask assembly and in vivo evaluation data was established (R ≥ 0.970). Drug particle coating with Eudragit ® E PO can be a suitable approach for bitter taste-masking. Strong correlation between in vivo and in vitro results implicate that small-volume dissolution method may be used as surrogate for human panel taste-masking assessment, in the case of physical taste-masking approach application.

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.

Investigation of an artificial intelligence technology--Model trees. Novel applications for an immediate release tablet formulation database.

PubMed

Shao, Q; Rowe, R C; York, P

2007-06-01

This study has investigated an artificial intelligence technology - model trees - as a modelling tool applied to an immediate release tablet formulation database. The modelling performance was compared with artificial neural networks that have been well established and widely applied in the pharmaceutical product formulation fields. The predictability of generated models was validated on unseen data and judged by correlation coefficient R(2). Output from the model tree analyses produced multivariate linear equations which predicted tablet tensile strength, disintegration time, and drug dissolution profiles of similar quality to neural network models. However, additional and valuable knowledge hidden in the formulation database was extracted from these equations. It is concluded that, as a transparent technology, model trees are useful tools to formulators.

The Impact of Disintegrant Type, Surfactant, and API Properties on the Processability and Performance of Roller Compacted Formulations of Acetaminophen and Aspirin.

PubMed

Zhao, Junshu; Koo, Otilia; Pan, Duohai; Wu, Yongmei; Morkhade, Dinesh; Rana, Sandeep; Saha, Partha; Marin, Arturo

2017-09-01

In formulation development, certain excipients, even though used in small quantities, can have a significant impact on the processability and performance of the dosage form. In this study, three common disintegrants, croscarmellose sodium (CCS), crospovidone (xPVP), and sodium starch glycolate (SSG) as well as the surfactant sodium lauryl sulfate (SLS) were evaluated for their impact on the processability and performance of a typical dry granulation formulation. Two model compounds, the mechanically brittle and chemically inert acetaminophen and the mechanically ductile carboxylic acid aspirin, were used for the evaluation. It was found that the disintegrants were generally identical in their impact on the processability and little difference was observed in the granulation and compression processes. The exception is that when xPVP was used in the formulation of the brittle acetaminophen, lower compression forces were needed to reach the same tablet hardness, suggesting a binding effect of xPVP for such systems. In general, CCS and xPVP tend to provide slightly better disintegration than SSG. However, in the case of aspirin, a strong hydrogen bonding interaction between the carboxylic acid group of aspirin and the carbonyl group of xPVP was observed, resulting in slower release of the drug after fast disintegration. SLS was found to have a significant impact on the processability due to its lubricating effect, resulting in higher compression forces needed to achieve the target tablet hardness. Due to the higher degree of compression, the disintegration and dissolution of both drugs became slower despite the wetting effect of SLS.

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.

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.

Comparing alkaline and thermal disintegration characteristics for mechanically dewatered sludge.

PubMed

Tunçal, Tolga

2011-10-01

Thermal drying is one of the advanced technologies ultimately providing an alternative method of sludge disposal. In this study, the drying kinetics of mechanically dewatered sludge (MDS) after alkaline and thermal disintegration have been studied. In addition, the effect of total organic carbon (TOC) on specific resistance to filtration and sludge bound water content were also investigated on freshly collected sludge samples. The combined effect of pH and TOC on the thermal sludge drying rate for MDS was modelled using the two-factorial experimental design method. Statistical assessment of the obtained results proposed that sludge drying potential has increased exponentially for both increasing temperature and lime dosage. Execution of curve fitting algorithms also implied that drying profiles for raw and alkaline-disintegrated sludge were well fitted to the Henderson and Pabis model. The activation energy of MDS decreased from 28.716 to 11.390 kJ mol(-1) after disintegration. Consequently, the unit power requirement for thermal drying decreased remarkably from 706 to 281 W g(-1) H2O.

In vivo determination of the time and location of mucoadhesive drug delivery systems disintegration in the gastrointestinal tract.

PubMed

Kremser, Christian; Albrecht, Karin; Greindl, Melanie; Wolf, Christian; Debbage, Paul; Bernkop-Schnürch, Andreas

2008-06-01

The objective of this study was to use magnetic resonance imaging (MRI) to detect the time when and the location at which orally delivered mucoadhesive drugs are released. Drug delivery systems comprising tablets or capsules containing a mucoadhesive polymer were designed to deliver the polymer to the intestine in dry powder form. Dry Gd-DTPA [diethylenetriaminepentaacetic acid gadolinium(III) dihydrogen salt hydrate] powder was added to the mucoadhesive polymer, resulting in a susceptibility artifact that allows tracking of the application forms before their disintegration and that gives a strong positive signal on disintegration. Experiments were performed with rats using T(1)-weighted spin-echo imaging on a standard 1.5-T MRI system. The susceptibility artifact produced by the dry Gd-DTPA powder in tablets or capsules was clearly visible within the stomach of the rats and could be followed during movement towards the intestine. Upon disintegration, a strong positive signal was unambiguously observed. The time between ingestion and observation of a positive signal was significantly different for different application forms. Quantification of the remaining mucoadhesive polymer in the intestine 3 h after observed release showed significant differences in mucoadhesive effectiveness. MRI allows detection of the exact time of release of the mucoadhesive polymer in vivo, which is a prerequisite for a reliable quantitative comparison between different application forms.

Novel mesalamine-loaded beads in tablets for delayed release of drug to the colon.

PubMed

Nguyen, Chien; Christensen, J Mark; Ayres, James W

2012-01-01

Novel 'beads-in-a-tablet' formulations (total weight ∼740-780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit(®) S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry(®)) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab(®)) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease(®) (ethylcellulose):Opadry(®) = 1:0.5 ranging from 1.5-2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.

Leaching of indium from obsolete liquid crystal displays: Comparing grinding with electrical disintegration in context of LCA

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

Dodbiba, Gjergj, E-mail: dodbiba@sys.t.u-tokyo.ac.jp; Nagai, Hiroki; Wang Lipang

2012-10-15

Highlights: Black-Right-Pointing-Pointer Two pre-treatment methods, prior to leaching of indium from obsolete LCD modules, were described. Black-Right-Pointing-Pointer Conventional grinding and electrical disintegration have been evaluated and compared in the context of LCA. Black-Right-Pointing-Pointer Experimental data on the leaching capacity for indium and the electricity consumption of equipment were inputted into the LCA model in order to compare the environmental performance of each method. Black-Right-Pointing-Pointer An estimate for the environmental performance was calculated as the sum of six impact categories. Black-Right-Pointing-Pointer Electrical disintegration method outperforms conventional grinding in all impact categories. - Abstract: In order to develop an effective recycling systemmore » for obsolete Liquid Crystal Displays (LCDs), which would enable both the leaching of indium (In) and the recovery of a pure glass fraction for recycling, an effective liberation or size-reduction method would be an important pre-treatment step. Therefore, in this study, two different types of liberation methods: (1) conventional grinding, and (2) electrical disintegration have been tested and evaluated in the context of Life Cycle Assessment (LCA). In other words, the above-mentioned methods were compared in order to find out the one that ensures the highest leaching capacity for indium, as well as the lowest environmental burden. One of the main findings of this study was that the electrical disintegration was the most effective liberation method, since it fully liberated the indium containing-layer, ensuring a leaching capacity of 968.5 mg-In/kg-LCD. In turn, the estimate for the environmental burden was approximately five times smaller when compared with the conventional grinding.« less

Preparation and In Vitro/In Vivo Characterization of Porous Sublingual Tablets Containing Ternary Kneaded Solid System of Vinpocetine with β-Cyclodextrin and Hydroxy Acid

PubMed Central

Aburahma, Mona H.; El-Laithy, Hanan M.; Hamza, Yassin El-Said

2010-01-01

The demand for sublingual tablets has been growing during the previous decades especially for drugs with extensive hepatic first-pass metabolism. Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor aqueous solubility and marked first-pass metabolism. Accordingly, the aim of this work was to develop tablets for the sublingual delivery of vinpocetine. Initially, the feasibility of improving vinpocetine’s poor aqueous solubility by preparing kneaded solid systems of the drug with β-Cyclodextrin and hydroxy acids (citric acid and tartaric acid) was assessed. The solid system with improved solubility and dissolution properties was incorporated into porous tablets that rapidly disintegrate permitting fast release of vinpocetine into the sublingual cavity. The pores were induced into these tablets by directly compressing the tablets’ excipients with a sublimable material, either camphor or menthol, which was eventually sublimated leaving pores. The obtained results demonstrated that the tablets prepared using camphor attained sufficient mechanical strength for practical use together with rapid disintegration and dissolution. In vivo absorption study performed in rabbits indicated that the sublingual administration of the proposed porous tablets containing vinpocetine solid system with β-Cyclodextrin and tartaric acid could be useful for therapeutic application. PMID:21179352

Comparative stability of repackaged metoprolol tartrate tablets.

PubMed

Yang, Yongsheng; Gupta, Abhay; Carlin, Alan S; Faustino, Patrick J; Lyon, Robbe C; Ellison, Christopher D; Rothman, Barry; Khan, Mansoor A

2010-01-29

The stability of metoprolol tartrate tablets packaged in original high density polyethylene containers and repackaged in USP Class A unit-dose blister packs was investigated. Studies were conducted at 25 degrees C/60% relative humidity (RH) for 52 weeks and at 40 degrees C/75% RH for 13 weeks. The potency, dissolution, water content, loss on drying and hardness of the drug products were analyzed. Results indicated no differences in the stability between the tablets in both packages stored under 25 degrees C/60% RH. No difference in potency was found in both packages under either condition. However, a significant weight increase due to moisture uptake was observed for the repackaged tablets stored under 40 degrees C/75% RH. The weight increase was accompanied by a decrease in tablet hardness (6.5-0 kp) and a increase in dissolution rate (51-92%) in 5 min. Near-infrared (NIR) chemical imaging also monitored moisture uptake of the tablet non-invasively through the package. The observed changes in product stability may adversely affect the products bioavailability profile, even though the potency of the active drug remained within USP specification range of 90-110%. Study results suggest product quality can be negatively impacted even when using USP Class A repackaging materials. Published by Elsevier B.V.

Preparation and biological efficacy of haddock bone calcium tablets

NASA Astrophysics Data System (ADS)

Huo, Jiancong; Deng, Shanggui; Xie, Chao; Tong, Guozhong

2010-03-01

To investigate the possible use of waste products obtained after processing haddock, the present study prepared haddock bone calcium powder by NaOH and ethanol soaking (alkalinealcohol method) and prepared haddock bone calcium tablets using the powder in combination with appropriate excipients. The biological efficacy of the haddock bone calcium tablets was investigated using Wistar rats as an experiment model. Results show that the optimal parameters for the alkalinealcohol method are: NaOH concentration 1 mol/L, immersion time 30 h; ethanol concentration 60%, immersion time 15 h. A mixture of 2% polyvinylpyrrolidone in ethanol was used as an excipient at a ratio of 1:2 to full-cream milk powder, without the use of a disintegrating agent. This process provided satisfactory tablets in terms of rigidity and taste. Animal studies showed that the haddock bone calcium tablets at a dose of 2 g·kg-1·d-1 or 5g·kg-1·d-1 significantly increased blood calcium and phosphorus levels and bone calcium content in rats. Therefore, these tablets could be used for calcium supplementation and prevent osteoporosis. Although the reasons of high absorption in the rats fed with haddock bone calcium tablets are unclear, it is suggested that there are some factors, such as treatment with method of alkaline-alcohol or the added milk, may play positive roles in increasing absorption ratio.

Bioequivalence study of levothyroxine tablets compared to reference tablets and an oral solution.

PubMed

Koytchev, Rossen; Lauschner, Reinhard

2004-01-01

The study was designed to evaluate the bioequivalence of three levothyroxine sodium (CAS 51-48-9) formulations, i.e. a test and a reference tablet and an oral solution. A bioequivalence study was carried out in 25 healthy volunteers, who were administered a single dose of 600 microg levothyroxine in the form of the test formulation (levothyroxine sodium tablets 200 microg; Eferox), the originator product, and an oral solution. The trial was performed in one study center according to an open, randomized, three-way cross-over design with wash-out periods of 35 days between administration. Blood samples were taken up to 48 h post dose, the plasma was separated and the concentrations of levothyroxine and triiodothyronine were determined by radioimmunoassay with I125 labeling method. The levothyroxine mean Cmax were 112.0+/-17.3 ng/ml, 113.4+/-18.5 ng/ ml and 111.3+/-15.1 ng/ml, while the mean AUC0-24 were 2263.7+/-332.8 ng x h/ ml, 2307.3+/-351.3 ng x h/ml and 2286.1+/-331.0 ng x h/ml for the test and reference tablets as well as for the oral solution, respectively. No significant differences were found of principal pharmacokinetic parameters between the studied formulations. The 90%-confidence interval for the primary target parameters, intra-individual ratios of AUC0-24 and Cmax of levothyroxine were within the acceptance ranges for bioequivalence trials, i.e. AUC0-24 0.954-1.016 and 0.966-1.011 as well as Cmax 0.948-1.027 and 0.968-1.032 for test tablets versus reference tablets and the oral solution, respectively. Similar results were observed for triiodothyronine. In the light of the present study it can be concluded that the levothyroxine test tablet is bioequivalent to the reference formulation in respect of extent and rate of absorption. The results of the present trial confirm the findings of a previous study, performed under steady-state conditions with Eferox tablets 100 microg in patients without thyroid function.

Effect of moisture content, temperature and exposure time on the physical stability of chitosan powder and tablets.

PubMed

Viljoen, Joe M; Steenekamp, Jan H; Marais, Andries F; Kotzé, Awie F

2014-06-01

Chitosan does not rank highly regarding its employment as tablet filler due to certain limitations. Undesirable properties that limit its utilization as excipient in solid dosage forms include its hydration propensity that negatively affects tablet stability, strength and disintegration. The objective of this study was to investigate the physical stability of chitosan powder, mixtures, granules and tablets under accelerated conditions such as elevated temperatures and humidity over different periods of time. Selected physico-chemical properties of pure chitosan powder, physical mixtures of chitosan with Kollidon® VA64 (BASF, Ludwigshafen, Germany), chitosan granules, as well as tablets were evaluated under conditions of elevated humidity and temperature. The physical stability of chitosan tablets exhibited sensitivity towards varying exposure conditions. It was furthermore evident that the presence of moisture (sorbed water) had a marked influence on the physical stability of chitosan powder and tablets. It was evident that the presence of Kollidon® VA64 as well as the method of inclusion of this binder influenced the properties of chitosan tablets. The physical stability of chitosan powder deteriorated to a greater extent compared to that of the chitosan tablets, which were subjected to the same conditions. It is recommended that tablets containing chitosan should be stored at a temperature not exceeding 25 °C as well as at a relatively low humidity (<60%) to prevent deterioration of physical properties. Direct compression of chitosan granules which contained 5%w/w Kollidon® VA64 produced the best formulation in terms of physical stability at the different conditions.

Effect of different excipients on the physical characteristics of granules and tablets with carbamazepine prepared with polyethylene glycol 6000 by fluidized hot-melt granulation (FHMG).

PubMed

Kraciuk, Radosław; Sznitowska, Malgorzata

2011-12-01

The objective of this study was to investigate the properties of granules and tablets with carbamazepine which were prepared employing a fluidized hot-melt granulation (FHMG) technique. The FHMG process was carried out at 65°C. Macrogol 6000 (PEG 6000) was used as a binder at the content 10% (w/w) of the granulated mass. Granules containing up to 70% (w/w) of the drug and 20-90% (w/w) of a filler (lactose, mannitol, calcium hydrogen phosphate (Di-Cafos), pregelatinized starch, and microcrystalline cellulose (MCC)) were produced. When the drug content was 30% (w/w), the yield of the process was satisfying (>95%) and flowability of the granules was better than placebo granules or drug-loaded granules prepared by wet granulation. Type of a filler had strong impact on physical properties of granules, and size distribution of the particles was the most homogenous when lactose or Di-Cafos were used. The FHMG technique enabled preparation of granules with better compressability compared with the wet-granulated product or with non-granulated powders. Tablets with shorter disintegration time than 10 min were obtained with 2.0% crospovidone added as a disintegrant. In comparison to tablets prepared from the wet-granulated mass, employment of the FHMG method resulted in tablets with faster dissolution of carbamazepine (more than 80% of the drug released within 15 min). This was achieved with mannitol or lactose/MCC, as fillers.

Bioequivalence of saxagliptin/dapagliflozin fixed-dose combination tablets compared with coadministration of the individual tablets to healthy subjects.

PubMed

Vakkalagadda, Blisse; Vetter, Marion L; Rana, Jignasa; Smith, Charles H; Huang, Jian; Karkas, Jennifer; Boulton, David W; LaCreta, Frank

2015-12-01

Saxagliptin and dapagliflozin are individually indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The bioequivalence of saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg fixed-dose combination (FDC) tablets compared with coadministration of the individual tablets and the food effect on both strengths of saxagliptin/dapagliflozin FDCs were evaluated in this open-label, randomized, single-dose crossover study. Healthy subjects were randomized to saxagliptin 2.5 mg + dapagliflozin 5 mg fasted, 2.5/5 mg FDC fasted, 2.5/5 mg FDC fed (Cohort 1) or saxagliptin 5 mg + dapagliflozin 10 mg fasted, 5/10 mg FDC fasted, 5/10 mg FDC fed (Cohort 2). Serial blood samples for pharmacokinetics of saxagliptin and dapagliflozin were obtained predose and up to 60 h postdose. Bioequivalence of FDC tablets versus individual components was concluded if the 90% CIs for FDC to individual component geometric mean ratios of C max, AUC 0-T, and AUC inf of both analytes were between 0.80 and 1.25. Seventy-two subjects were randomized; 71 (98.6%) completed the study. Saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg FDC tablets were bioequivalent to the individual tablets administered concomitantly. Food had no clinically meaningful effect on saxagliptin or dapagliflozin overall systemic exposure. Saxagliptin/dapagliflozin FDC tablets were bioequivalent to coadministration of the individual components in healthy subjects under fasted conditions and food had no clinically meaningful effect on bioavailability.

Optimization of formulation and processing of Moringa oleifera and spirulina complex tablets.

PubMed

Zheng, Yi; Zhu, Fan; Lin, Dan; Wu, Jun; Zhou, Yichao; Mark, Bohn

2017-01-01

Objective: To prepare a more comprehensive nutrition, more balanced proportion of natural nutritional supplement tablets with Moringa oleifera leaves and spirulina the two nutrients which have complementary natural food ingredients. Method: On the basis of research M. oleifera leaves with spirulina nutrient composition was determined on M. oleifera leaves and spirulina ratio of raw materials, and the choice of microcrystalline cellulose, sodium salt of caboxy methyl cellulose(CMC),magnesium stearate excipient, through single factor and orthogonal experiment, selecting the best formula tablets prepared by powder direct compression technology, for preparation of M. oleifera and spirulina complex tablets. Results: The best ratio of raw material for the M. oleifera leaves powder: spirulina powder was 7:3, the best raw materials for the tablet formulation was 88.5%, 8.0% microcrystalline cellulose, CMC 2.0%, stearin magnesium 1.5%, the optimum parameters for the raw material crushing 200-300 mesh particle size, moisture content of 7%, tableting pressure 40 kN. Conclusion: Through formulation and process optimization, we can prepare more comprehensive and balanced nutrition M. oleifera and spirulina complex tablets, its sheet-shaped appearance, piece weight variation, hardness, friability, disintegration and other indicators have reached the appropriate quality requirements.

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.

Food effect: The combined effect of media pH and viscosity on the gastrointestinal absorption of ciprofloxacin tablet.

PubMed

Radwan, Asma; Zaid, Abdel Naser; Jaradat, Nidal; Odeh, Yousef

2017-04-01

The clinical implications of food-drug interactions may have to be taken seriously into account with oral drugs administration in order to minimize variations in drug bioavailability. Food intake may alter physiological changes in the pH and viscosity of the gastrointestinal lumen, which could affect the oral absorption of drugs. The aim of the present study was to have an insight on the effect of media parameters: viscosity and pHon the oral absorption of ciprofloxacin HCl from solid formulations using a model food: Corchorus olitorius (Jute) Soup. In vitro disintegration and dissolution rates of ciprofloxacin tablet were evaluated using compendia buffer media in the presence/absence of C. olitorius leaves. These in vitro data were then input to GastroPlus™ to predict ciprofloxacin absorption profiles under fasted and fed states. The present study demonstrated the significance of luminal pH and viscosity on the dissolution and disintegration of solid formulations following postprandial ingestion of the viscous soup. The tablets showed prolonged disintegration times and reduced dissolution rates in this soup, which could be attributed to the postprandial elevation in media viscosity and reduced solubility at elevated gastricpH. The predicted model under fed state showed no impact on AUC but prolonged T max and a decrease in C max . Concomitant intake of C. olitorius soup with ciprofloxacin might have negative effect on the rate of drug release from conventional immediate release tablets. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and evaluation of an economic taste-masked dispersible tablet of pyridostigmine bromide, a highly soluble drug with an extremely bitter taste.

PubMed

Tan, Qunyou; Zhang, Li; Zhang, Liangke; Teng, Yongzhen; Zhang, Jingqing

2012-01-01

Pyridostigmine bromide (PTB) is a highly soluble and extremely bitter drug. Here, an economic complexation technology combined with direct tablet compression method has been developed to meet the requirements of a patient friendly dosage known as taste-masked dispersible tablets loaded PTB (TPDPTs): (1) TPDPTs should have optimal disintegration and good physical resistance (hardness); (2) a low-cost, simple but practical preparation method suitable for industrial production is preferred from a cost perspective. Physicochemical properties of the inclusion complex of PTB with beta-cyclodextrin were investigated by Fourier transformed infrared spectroscopy, differential scanning calorimetry and UV spectroscopy. An orthogonal design was chosen to properly formulate TPDPTs. All volunteers regarded acceptable bitterness of TPDPTs. The properties including disintegration time, weight variation, friability, hardness, dispersible uniformity and drug content of TPDPTs were evaluated. The dissolution profile of TPDPTs in distilled water exhibited a fast rate. Pharmacokinetic results demonstrated that TPDPTs and the commercial tablets were bioequivalent.

A study of the properties of tablets made of directly compressible maltose.

PubMed

Muzíková, J; Balhárková, J

2008-01-01

The paper deals with the study of the strength and disintegration time of tablets made of directly compressible maltose Advantose 100. It studies the differences of the effects of two types of lubricants, magnesium stearate and sodium stearylfumarate, on the above-mentioned properties, and it also tests the mixtures of the substance with microcrystalline cellulose Vivapur 102 in a ratio of 1:1 and with ascorbic and acetylsalicylic acids. The compacts are obtained by using three compression forces, excepting mixtures with active ingredients, where one compression force is used. In the compression forces of 6 and 8 kN, no statistically significant difference was found in the intervention of the lubricants into the strength of the compacts made of Advantose 100, only in the compression force of 10 kN Pruv decreased the strength more than stearate. The mixture of Advantose 100 and Vivapur 102 yielded the strongest tablets, an addition of Pruv to it decreased the strength of compacts more than stearate. The periods of disintegration time of Advantose compacts as well as those of the mixture of dry binders were longer with an addition of Pruv. The compacts with acetylsalicylic acid possessed higher strength and a longer period of disintegration than those with ascorbic acid. There was no statistically significant difference within the type of the lubricant employed, both in the case of Advantose 100 and its mixture with Vivapur 102, between the values of strength of the compacts with acetylsalicylic acid.

Optimization of orodispersible and conventional tablets using simplex lattice design: Relationship among excipients and banana extract.

PubMed

Duangjit, Sureewan; Kraisit, Pakorn

2018-08-01

The objective of this study was focused on the optimization of the pharmaceutical excipients and banana extract in the preparation of orally disintegrating banana extract tablets (OD-BET) and conventional banana extract tablets (CO-BET) using a simplex lattice design. Various ratios of banana extract (BE), dibasic calcium phosphate (DCP) and microcrystalline cellulose (MCC) were used to prepare banana extract tablets (BET). The results indicated that the optimal OD-BET and CO-BET consisted of BE: DCP: MCC at 10.0, 88.8, 1.2, 10.0, 83.8: and 6.2, respectively. AFM demonstrated that the surface of BET with BE + MCC was smooth and compacted when compared to BET with BE + DCP + MCC and BE + DCP. FTIR and XRD showed a correlation in the results and indicated that no interaction of each ingredient occurred in the process of BET formulation. Therefore, the experimental design is potentially useful in formulated OD-BET and CO-BET by using only one design simultaneously. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pharmacokinetics of colon-specific pH and time-dependent flurbiprofen tablets.

PubMed

Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

2015-09-01

Present research deals with the development of compression-coated flurbiprofen colon-targeted tablets to retard the drug release in the upper gastro intestinal system, but progressively release the drug in the colon. Flurbiprofen core tablets were prepared by direct compression method and were compression coated using sodium alginate and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery. The optimized formulation showed negligible drug release (4.33 ± 0.06 %) in the initial lag period followed by progressive release (100.78 ± 0.64 %) for 24 h. The X-ray imaging in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C max of colon-targeted tablets was 12,374.67 ng/ml at T max 10 h, where as in case of immediate release tablets the C max was 15,677.52 ng/ml at T max 3 h, that signifies the ability of compression-coated tablets to target the colon. Development of compression-coated tablets using combination of time-dependent and pH-sensitive approaches was suitable to target the flurbiprofen to colon.

Fabricating 3D printed orally disintegrating printlets using selective laser sintering.

PubMed

Fina, Fabrizio; Madla, Christine M; Goyanes, Alvaro; Zhang, Jiaxin; Gaisford, Simon; Basit, Abdul W

2018-04-25

Selective laser sintering (SLS) is a three-dimensional printing (3DP) technology employed to manufacture plastic, metallic or ceramic objects. The aim of this study was to demonstrate the feasibility of using SLS to fabricate novel solid dosage forms with accelerated drug release properties, and with a view to create orally disintegrating formulations. Two polymers (hydroxypropyl methylcellulose (HPMC E5) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon ® VA 64)) were separately mixed with 5% paracetamol (used as a model drug) and 3% Candurin ® Gold Sheen colorant; the powder mixes were subjected to SLS printing, resulting in the manufacture of printlets (3DP tablets). Modulating the SLS printing parameters altered the release characteristics of the printlets, with faster laser scanning speeds accelerating drug release from the HPMC formulations. The same trend was observed for the Kollidon ® based printlets. At a laser scanning speed of 300 mm/s, the Kollidon ® printlets exhibited orally disintegrating characteristics by completely dispersing in <4 s in a small volume of water. X-ray micro-CT analysis of these printlets indicated a reduction in their density and an increase in open porosity, therefore, confirming the unique disintegration behaviour of these formulations. The work reported here is the first to demonstrate the feasibility of SLS 3DP to fabricate printlets with accelerated drug release and orally disintegrating properties. This investigation has confirmed that SLS is amenable to the pharmaceutical research of modern medicine manufacture. Copyright © 2018 Elsevier B.V. All rights reserved.

Simplified formulations with high drug loads for continuous twin-screw granulation.

PubMed

Meier, R; Thommes, M; Rasenack, N; Krumme, M; Moll, K-P; Kleinebudde, P

2015-12-30

As different batches of the same excipients will be intermixed during continuous processes, the traceability of batches is complicated. Simplified formulations may help to reduce problems related to batch intermixing and traceability. Twin-screw granulation with subsequent tableting was used to produce granules and tablets, containing drug, disintegrant and binder (binary and ternary mixtures), only. Drug loads up to 90% were achieved and five different disintegrants were screened for keeping their disintegration suitability after wetting. Granule size distributions were consistently mono-modal and narrow. Granule strength reached higher values, using ternary mixtures. Tablets containing croscarmellose-Na as disintegrant displayed tensile strengths up to 3.1MPa and disintegration times from 400 to 466s, resulting in the most robust disintegrant. Dissolution was overall complete and above 96% within 30 min. Na-starch glycolate offers tensile strengths up to 2.8MPa at disintegration times from 25s to 1031s, providing the broadest application window, as it corresponds in some parts to different definitions of orodispersible tablets. Tablets containing micronized crospovidone are not suitable for immediate release, but showed possibilities to produce highly drug loaded, prolonged release tablets. Tablets and granules from simplified formulations offer great opportunities to improve continuous processes, present performances comparable to more complicated formulations and are able to correspond to requirements of the authorities. Copyright © 2015 Elsevier B.V. All rights reserved.

Development and analytical characterization of a new antiparasitic fenbendazole compound tablet and pharmacokinetic investigations after its oral administration to dogs.

PubMed

Dai, Cunchun; Qu, Shaoqi; Zhang, Ruili; Zhao, Li; Li, Yuwen; Zhu, Jiajia; Wang, Chunmei; Guo, Hui; Hao, Zhihui

2018-02-01

The objective of this study was to prepare a new compound fenbendazole tablet containing 29.7 % fenbendazole, 1.50 % praziquantel and 0.059 % ivermectin for oral administration. The tablets were successfully prepared using mannitol as filler agent, polyvinyl polypyrrolidone as disintegrant, 5 % povidone (PVAK30) as a binder agent and magnesium stearate as lubricant. The appearance, hardness, fragility, time limit of disintegration and fenbendazole dissolution at 45 min all met the technical standards of the Ministry of Agriculture for the People's Republic of China. We used high performance liquid chromatography and electrospray-mass spectrometry for drug detection. Oral administration of 100 mg/kg fenbendazole, 5 mg/kg praziquantel and 0.2 mg/kg ivermectin using a non-compartmental model defined peak plasma concentrations (Cmax) of 495, 826, 73 ng/mL, and 218 ng/mL for the metabolite oxfendazole, respectively. The area under the curve (AUClast) values for these drugs were 4653, 1045, 1971 and 5525 h×ng/mL, respectively. This study enriches the pharmacokinetic data of compound fenbendazole tablets using dogs as a model system. The new tablet formulation was assimilated quickly and systemically and this study will be beneficial for the clinical application of parasite treatments in dogs.

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

Preparation and optimization of tablets containing a self-nano-emulsifying drug delivery system loaded with rosuvastatin.

PubMed

Salem, Heba F; Kharshoum, Rasha M; Halawa, Abdel Khalek A; Naguib, Demiana M

2018-06-01

Rosuvastatin (ROS) calcium is the latest synthetic drug in the statin group that has an anti-hyperlipidemic activity. It is available as tablets, and its poor aqueous solubility, slow dissolution rate and low-absorption extent result in less than 20% bioavailability and about 80% being excreted unchanged in the feces without absorption. To utilize nanotechnology to reformulate ROS as a self-nano-emulsifying drug delivery system (SNEDDS), and utilizing design optimization to fabricate the SNEDDS as a tablet. The solubility of ROS in different oils, surfactants and co-surfactants was tested. Pseudo-ternary phase diagrams were developed and various SNEDDS formulations were prepared and evaluated regarding globule size, self-emulsification, viscosity and transmittance. The optimized system was examined using transmission electron microscopy. The self-nano-emulsifying tablets were prepared using two types of nano-silica and different percentages of Avicel as a binder and Ac-Di-Sol as a disintegrant. The prepared tablets were evaluated for their physicochemical properties. Bioavailability in human volunteers was assessed. A SNEDDS system was successfully developed with a droplet size range of 15 nm and a composition of 10% Labrafac, 80% Cremophore RH40 and 10% Propylene glycol. The optimized tablet formula contained: hydrophilic nano-silica, 3% Ac-Di-Sol and 30% Avicel. The pharmacokinetic study revealed that the bioavailability was enhanced by more than 2.4-fold compared with the commercially available tablet. Tablets containing SNEDDS loaded with ROS represent a promising novel formula that has higher gastrointestinal absorption and enhanced systemic bioavailability.

Mechanical property characterization of bilayered tablets using nondestructive air-coupled acoustics.

PubMed

Akseli, Ilgaz; Dey, Dipankar; Cetinkaya, Cetin

2010-03-01

A noncontact/nondestructive air-coupled acoustic technique to be potentially used in mechanical property determination of bilayer tablets is presented. In the reported experiments, a bilayer tablet is vibrated via an acoustic field of an air-coupled transducer in a frequency range sufficiently high to excite several vibrational modes (harmonics) of the tablet. The tablet vibrational transient responses at a number of measurement points on the tablet are acquired by a laser vibrometer in a noncontact manner. An iterative computational procedure based on the finite element method is utilized to extract the Young's modulus, the Poisson's ratio, and the mass density values of each layer material of a bilayer tablet from a subset of the measured resonance frequencies. For verification purposes, a contact ultrasonic technique based on the time-of-flight data of the longitudinal (pressure) and transverse (shear) acoustic waves in each layer of a bilayer tablet is also utilized. The extracted mechanical properties from the air-coupled acoustic data agree well with those determined from the contact ultrasonic measurements. The mechanical properties of solid oral dosage forms have been shown to impact its mechanical integrity, disintegration profile and the release rate of the drug in the digestive tract, thus potentially affecting its therapeutic response. The presented nondestructive technique provides greater insight into the mechanical properties of the bilayer tablets and has the potential to identify quality and performance problems related to the mechanical properties of the bilayer tablets early on the production process and, consequently, reduce associated cost and material waste.

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

Enhanced dissolution of sildenafil citrate as dry foam tablets.

PubMed

Sawatdee, Somchai; Atipairin, Apichart; Sae Yoon, Attawadee; Srichana, Teerapol; Changsan, Narumon

2017-01-30

Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5 kg, friability test <1% with a disintegration time <5 min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.

Orally disintegrating dosage forms and taste-masking technologies; 2010.

PubMed

Douroumis, Dennis

2011-05-01

In the last decade the development of orally disintegrating tablets (ODTs) and thin-film platforms has grown enormously in the field of pharmaceutical industry. A wide variety of new masking technologies combined with the aforementioned platforms have been developed in order to mask the taste of bitter active substances and achieve patient compliance. The commercial success and viability of such products requires the development of robust formulations with excellent palatability, disintegration times, physicochemical stability and pharmacokinetic profiles. In this review, emerging taste-masking technologies applied to solid dosage form manufacturing are summarized. The unique features and principles of taste-masking approaches used with ODT platforms are discussed, including the advantages and limitations of each technology. A brief discussion is also included on the taste masking of thin-film technologies, owing to their similar applications and requirements. This review elucidates the unique features of current commercially available or highly promising ODT and thin-film technologies, along with taste-masking approaches used in the manufacturing of oral solid dosage forms. A better understanding of these drug delivery approaches will help researchers to select the appropriate platform, or to develop innovative products with improved safety, compliance and clinical value.

Orally disintegrating and oral standard olanzapine tablets similarly elevate the homeostasis model assessment of insulin resistance index and plasma triglyceride levels in 12 healthy men: a randomized crossover study.

PubMed

Vidarsdottir, Solrun; Vlug, Pauline; Roelfsema, Ferdinand; Frölich, Marijke; Pijl, Hanno

2010-09-01

Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than oral standard tablets (OST). The aim of this study was to compare the effect of short-term treatment with these 2 distinct olanzapine formulations on glucose and lipid metabolism in healthy men. Twelve healthy men (mean ± SEM age: 25.1 ± 5.5 years) received olanzapine ODT (10 mg od, 8 days), olanzapine OST (10 mg od, 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, glucose, insulin, free fatty acids (FFA), and triglyceride concentrations were measured at 10-minute intervals from 30 minutes prior to 2 hours after ingestion of standard meals. Leptin and adiponectin concentrations were measured at 20- and 30-minute intervals, respectively, between 0000h-1200h. Physical activity was assessed with an accelerometer. Fuel oxidation was measured in fasting condition by indirect calorimetry. The study was conducted from April 2006 through September 2006. Treatment with olanzapine ODT and OST equally elevated the homeostasis model assessment of insulin resistance (HOMA-IR) (P = .005). At breakfast, both formulations equally increased fasting and postprandial triglyceride concentrations (P = .013 and P = .005, respectively) while decreasing fasting and postprandial FFA concentrations (P = .004 and P = .009, respectively). Body weight, body composition, physical activity, or fuel oxidation did not differ between treatment modalities. Eight days of treatment with both olanzapine formulations similarly increased HOMA-IR and triglyceride concentrations and decreased FFA concentrations in response to standard meals without affecting anthropometrics or physical activity. These data suggest that olanzapine hampers insulin action via mechanistic routes other than body adiposity or physical inactivity. controlled-trials.com. Identifier: ISRCTN17632637. © Copyright

Development and evaluation of fixed dose bi therapy sublingual tablets for treatment stress hypertension and anxiety

PubMed Central

El-Nabarawi, Mohamed A.; Tayel, Saadia A.; Soliman, Nadia A.; Abo Enin, Hadel A.

2013-01-01

Objective: A stress induced rise in the blood pressure. Some believe that patients with hypertension are characterized by a generalized state of increased anxiety. Aim: The purpose of this study is to prepare a fixed dose bi therapy using bisoprolol hemifumarate (BH) as antihypertensive drug and buspirone hydrochloride (BuHCl) as anxiolytic drug, which can be used to treat both diseases concomitantly. Using sublingual tablets is hopeful to improve the BuHCl poor oral bioavailability and to facilitate administration to patients experiencing problems with swallowing. Materials and Methods: A total of 5mg BH and 10mg BuHCl were selected based on compatibility study. A 3×22 full factorial design was adopted for the optimization of the tablets prepared by direct compression method. The effects of the filler type, the binder molecular weight, and the binder type were studied. The prepared formulae were evaluated according to their physical characters as hardness, friability, disintegration time (new modified method and in vivo disintegration time) and wetting properties. In vitro drugs dissolute, permeation through the buccal mucosa and the effect of storage were analyzed by a new valid high pressure liquid chromatography (HPLC) method. Bioavailability study of the selected formula study was carried out and followed by the clinical. Results: The optimized tablet formulation showed accepted average weight, hardness, wetting time, friability, content uniformity, disintegration time (less than 3 min). Maximum drug release could be achieved with in 10 min. In addition enhancing drug permeation through the buccal mucosa and, the maximum concentration of the drug that reached the blood was in the first 10 min which means a rapid onset of action and improved the extent of both drug's absorption. Conclusion: The results revealed that sublingual (F6) tablets containing both drugs would maintain rapid onset of action, and increase bioavailability. BuHCl with BH can be attributed

Comparative Bioavailability of Sulindac in Capsule and Tablet Formulations

PubMed Central

Reid, Joel M.; Mandrekar, Sumithra J.; Carlson, Elsa C.; Harmsen, W. Scott; Green, Erin M.; McGovern, Renee M.; Szabo, Eva; Ames, Matthew M.; Boring, Daniel; Limburg, Paul J.

2008-01-01

The cyclooxygenase-2 (COX-2) enzyme appears to be an important target for cancer chemoprevention. Given the recent emergence of potentially serious cardiovascular toxicity associated with selective COX-2 inhibitors, nonsteroidal antiinflammatory drugs (NSAIDs), which inhibit both COX-1 and COX-2, have received renewed attention as candidate chemoprevention agents. Sulindac has demonstrated consistent chemopreventive potential in preclinical studies, as well as in a limited number of clinical trials reported to date. For the current pharmacokinetic study, sulindac capsules were prepared to facilitate ample agent supplies for future intervention studies. Encapsulation of the parent compound (sulindac sulfoxide) can be readily accomplished, but the effects of alternate formulations on bioavailability have not been rigorously examined. In the present single-dose, two-period crossover trial, we conducted pharmacokinetic analyses of sulindac in capsule (test) versus tablet (reference) formulations. Overall, bioavailability appeared to be higher for the capsule compared to the tablet formulation, based on test-to-reference pharmacokinetic parameter ratios for the parent compound. However, additional analyses based on the sulfide and sulfone metabolites of sulindac with the same pharmacokinetic parameters indicated similar chemopreventive exposures between the capsule and tablet formulations. These data support the use of sulindac capsules, which can be readily prepared with matching placebos, in future blinded chemoprevention trials. PMID:18349286

Bioavailability, safety, and pharmacodynamics of delayed-release dexlansoprazole administered as two 30 mg orally disintegrating tablets or one 60 mg capsule.

PubMed

Kukulka, Michael; Nudurupati, Sai; Perez, Maria Claudia

2016-11-01

Dual delayed-release dexlansoprazole is approved for use in adults as a 30 mg orally disintegrating tablet (ODT) or as 30 mg and 60 mg capsules. The pharmacokinetics, pharmacodynamics, and safety profile of two dexlansoprazole 30 mg ODTs were compared with one dexlansoprazole 60 mg capsule in this randomized, phase I, open-label, single-center, multiple-dose, two-period crossover study. Participants were randomized in one of two treatment sequences, each comprised two 5-day treatment periods during which two dexlansoprazole 30 mg ODTs or one 60 mg capsule was administered once daily. Pharmacokinetic parameters and the mean intragastric pH profile for the 24-hour period after dosing on days 1 and 5 were described. Adverse events were monitored during study duration and followed up with a phone call 5-10 days after the last dose of study drug. On day 1, peak observed plasma concentration ( C max ) values were similar between two 30 mg ODTs (1047 ng/ml) and one 60 mg capsule (1164 ng/ml). Systemic exposure, measured by the area under the plasma concentration-time curve (AUC), was approximately 25% lower after ODT administration. On day 5, mean pH after daily doses of two 30 mg ODT or one 60 mg capsule was 4.33 and 4.36, respectively; both regimens maintained intragastric pH above 4.0 for 60% of the 24-hour period. Headache was the most commonly reported adverse event (observed in 19.2% of participants); no adverse events leading to study withdrawal occurred. While systemic exposure (AUC) was 25% lower with ODT, peak concentrations ( C max ) after administration of two dexlansoprazole 30 mg ODTs and one 60 mg capsule were similar. The 24-hour intragastric pH control after administration of two dexlansoprazole 30 mg ODTs was equivalent to one dexlansoprazole 60 mg capsule. Both ODT and capsule were well tolerated.

[The use of semi-synthetic polymers in the formulation of sucking and chewable tablets containing sage extract and zinc gluconate].

PubMed

Linka, Wojciech Andrzej; Golenia, Ewa; Zgoda, Marian Mikołaj; Kołodziejczyk, Michał Krzysztof

2014-01-01

Halitosis and gingivitis are most common pathologies (15-60% of population) which, if left untreated, lead to periodontal diseases and tooth loss. The aim of this study was to develop, based on polymers of dry sage extract and zinc gluconate, tablets intended for sucking and chewing that can be applied in the treatment of halitosis and gingivitis. Dried aqueous sage extract, zinc gluconate, Pharmagum M, Prosolv SMCC90 and SMCCHD90, Vivapur 102, sorbitol, mannitol, ludipress. Direct tableting. Testing pharmacopeial parameters and pharmaceutical availability (using basket and rotating disk methods) of tablets intended for sucking and chewing. Approximation of the obtained results. Grey and green color tablets were obtained with smooth and uniform surface, without stains, spalls or mechanical damage. The determined average mass (weight) of a tablet complied with the standard. The friability and crushing strength test revealed that tablets containing Prosolv SMCCHD90, Vivapur 102 and mannitol demonstrated the highest mechanical strength. Tablets containing these substances and intended for sucking had prolonged disintegration and release time. Tablets intended for chewing had a hardness at the level of 124 N.They demonstrated compressibility, low friability and prolonged release. The release profiles of tablets intended for sucking (v2) and those for chewing, obtained by basket and rotating disk methods, were similar. The addition of Prosolv SMCCHD90, Vivapur 102 and mannitol increased significantly the mechanical strength (higher hardness, lower friability), prolonged the disintegration time and slowed the release from the obtained tablets intended for sucking and chewing. The application of Prosolv SMCCHD90 in the formulation of tablets for chewing carries the risk for sorption of active components to the polymer structure. This process takes place in the early stage of the release. Rotating disk method used in pharmaceutical availability testing gives better results

Enhancement of the Oral Bioavailability of Fexofenadine Hydrochloride via Cremophor® El-Based Liquisolid Tablets

PubMed Central

Yehia, Soad Ali; El-Ridi, Mohamed Shafik; Tadros, Mina Ibrahim; El-Sherif, Nolwa Gamal

2015-01-01

Purpose: The current work aimed to develop promising Fexofenadine hydrochloride (FXD) liquisolid tablets able to increase its oral bioavailability and shorten time to reach maximum plasma concentrations (Tmax). Methods: Eighteen liquisolid powders were developed based on 3 variables; (i) vehicle type [Propylene glycol (PG) or Cremophor® EL (CR)], (ii) carrier [Avicel® PH102] to coat [Aerosil® 200] ratio (15, 20, 25) and (iii) FXD concentration in vehicle (30, 35, 40 %, w/w). Pre-compression studies involved identification of physicochemical interactions and FXD crystallinity (FT-IR, DSC, XRD), topographic visualization (SEM) and estimation of flow properties (angle of repose, Carr’s index, Hausner’s ratio). CR-based liquisolid powders were compressed as liquisolid tablets (LST 9 – 18) and evaluated for weight-variation, drug-content, friability-percentage, disintegration-time and drug-release. The pharmacokinetics of LST-18 was evaluated in healthy volunteers relative to Allegra® tablets. Results: Pre-compression studies confirmed FXD dispersion in vehicles, conversion to amorphous form and formation of liquisolid powders. CR-based liquisolid powders showed acceptable-to-good flow properties suitable for compaction. CR-based LSTs had appropriate physicochemical properties and short disintegration times. Release profile of LST-18 showed a complete drug release within 5 min. Conclusion: LST-18 succeeded in increasing oral FXD bioavailability by 62% and reducing Tmax to 2.16 h. PMID:26819931

Feasibility testing of smart tablet questionnaires compared to paper questionnaires in an amputee rehabilitation clinic.

PubMed

Payne, Michael; Janzen, Shannon; Earl, Eric; Deathe, Barry; Viana, Ricardo

2017-08-01

Capturing the variability that exists among patients attending an amputee clinic using standardized paper-based questionnaires is time-consuming and may not be practical for routine clinical use. Electronic questionnaires are a potential solution; however, the benefits are dependent on the feasibility and acceptance of this mode of data collection among patients. To determine the feasibility and patient preference/comfort in using a tablet-based questionnaire for data collection in an outpatient amputee rehabilitation clinic compared to a traditional paper-based questionnaire. Observational study. In all, 48 patients with major extremity amputations completed both tablet and paper questionnaires related to their amputation and prosthetic use. Both trials were timed; patients then completed a semi-structured questionnaire about their experience. In all, 20.5% of patients needed hands-on assistance completing the paper questionnaire compared to 20.8% for the tablet. The majority of participants (52.1%) indicated a preference for the tablet questionnaire; 64.6% of patients felt the tablet collected a more complete and accurate representation of their status and needs. In all, 70.8% of participants described themselves as comfortable using the tablet. Despite comorbidities, patients with amputations demonstrated excellent acceptance of the electronic tablet-based questionnaire. Tablet questionnaires have significant potential advantages over paper questionnaires and should be further explored. Clinical relevance A custom electronic questionnaire was found to be beneficial for routine clinic use and was well received by patients in an amputee rehabilitation clinic. Development of such questionnaires can provide an efficient mechanism to collect meaningful data that can be used for individual patient care and program quality improvement initiatives.

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

Pharmacokinetics of fixed-dose combinations of empagliflozin/metformin compared with individual tablets in healthy subjects.

PubMed

Rojas, Christina; Link, Jasmin; Meinicke, Thomas; Macha, Sreeraj

2016-04-01

To compare the pharmacokinetics of fixed-dose combination (FDC) tablets of empagliflozin/metformin with individual tablets taken together. In 3 randomized, open-label studies, healthy subjects received a single FDC tablet of empagliflozin/metformin in 1 of 6 dose combinations (empagliflozin 12.5 mg or 5 mg; metformin 500 mg, 850 mg, or 1,000 mg) in 1 period and the individual tablets taken together under fed conditions in another period. Empagliflozin 12.5 mg/metformin 1,000 mg FDC and individual tablets were also given under fasted conditions. Adjusted geometric mean ratios (GMRs) of empagliflozin area under the plasma concentration-time curve (AUC(0-∞)) for the FDCs vs. individual tablets ranged from 97.92 to 106.00%, and 90% CIs ranged from 93.53 to 109.39%. Adjusted GMRs of empagliflozin maximum plasma concentrations (C(max)) for the FDCs vs. individual tablets ranged from 100.97 to 106.52%, and 90% CIs ranged from 95.86 to 118.35%. Adjusted GMRs of metformin AUC(0-∞) for the FDCs vs. individual tablets ranged from 96.25 to 101.61%, and 90% CIs ranged from 88.54 to 106.62%. Adjusted GMRs of metformin C(max) for the FDCs vs. individual tablets ranged from 93.83 to 102.95%, and 90% CIs ranged from 88.01 to 109.08%. Bioequivalence was also established under fasted conditions for empagliflozin 12.5 mg/metformin 1,000 mg FDC vs. individual tablets taken together. All treatments were well tolerated. Empagliflozin/metformin FDC tablets were found to be bioequivalent to individual tablets taken together at all tested dose strengths.

HIGH-SHEAR GRANULATION PROCESS: INFLUENCE OF PROCESSING PARAMETERS ON CRITICAL QUALITY ATTRIBUTES OF ACETAMINOPHEN GRANULES AND TABLETS USING DESIGN OF EXPERIMENT APPROACH.

PubMed

Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Al-Shedfat, Ramadan I

2017-01-01

Application of quality by design (QbD) in high shear granulation process is critical and need to recognize the correlation between the granulation process parameters and the properties of intermediate (granules) and corresponding final product (tablets). The present work examined the influence of water amount (X,) and wet massing time (X2) as independent process variables on the critical quality attributes of granules and corresponding tablets using design of experiment (DoE) technique. A two factor, three level (32) full factorial design was performed; each of these variables was investigated at three levels to characterize their strength and interaction. The dried granules have been analyzed for their size distribution, density and flow pattern. Additionally, the produced tablets have been investigated for weight uniformity, crushing strength, friability and percent capping, disintegration time and drug dissolution. Statistically significant impact (p < 0.05) of water amount was identified for granule growth, percent fines and distribution width and flow behavior. Granule density and compressibility were found to be significantly influenced (p < 0.05) by the two operating conditions. Also, water amount has significant effect (p < 0.05) on tablet weight unifornity, friability and percent capping. Moreover, tablet disintegration time and drug dissolution appears to be significantly influenced (p < 0.05) by the two process variables. On the other hand, the relationship of process parameters with critical quality attributes of granule and final product tablet was identified and correlated. Ultimately, a judicious selection of process parameters in high shear granulation process will allow providing product of desirable quality.

Formulation development and in vitro evaluation of solidified self-microemulsion in the form of tablet containing atorvastatin calcium.

PubMed

Ali, Kazi Asraf; Mukherjee, Biswajit; Bandyopadhyay, Amal Kumar

2013-11-01

The objective of our present study was to prepare solid self-microemulsion in the form of tablet of a poorly water soluble drug, Atorvastatin calcium (ATNC) to increase the solubility, dissolution rate, and minimize the hazards experienced from liquid emulsions. Self-microemulsifying ATNC tablet was formulated mainly by using self-emulsifying base, solidifying agent silicon dioxide and sodium starch glycolate as tablet disintegrant. Self-emulsifying base containing Transcutol P, Gelucire 44/14, and Lutrol F68 with their ratios in the formulation, were best selected by solubility study and ternary phase diagram in different vehicles. Particle size of microemulsion from tablet, physical parameters of the tablet and drug content has been checked. In vitro drug release rate has been carried out in phosphate buffer medium (pH 6.8). Physicochemical characterization of the drug in the optimized formulation has been performed to check drug-excipient incompatibility, if any. Average particle diameter of the emulsions formed from the tablet was found to be below 100 nm in case of formulation F4 and F5, which indicated microemulsions has been formed. In vitro drug release from the formulations F3, F4, and F5 was found to be >90%, indicated the enhancement of solubility of ATNC compared to parent drug. Differential thermal analysis (DTA), Powder X-ray Diffraction (X-RD) and Fourier transform infra red (FTIR) study proved the identity of the drug in the optimized formulation. The tablet form of self-microemulsifying (SME) drug delivery is good for solubility enhancement.

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.

Development, evaluation and pharmacokinetics of time-dependent ketorolac tromethamine tablets.

PubMed

Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy

2013-01-01

The present study was intended to develop a time-dependent colon-targeted compression-coated tablets of ketorolac tromethamine (KTM) using hydroxypropyl methylcellulose (HPMC) that release the drug slowly but completely in the colonic region by retarding the drug releases in stomach and small intestine. KTM core tablets were prepared by direct compression method and were compression coated with HPMC. The formulation is optimized based on the in vitro drug release studies and further evaluated by X-ray imaging technique in healthy humans to ensure the colonic delivery. To prove these results, in vivo pharmacokinetic studies in human volunteers were designed to study the in vitro-in vivo correlation. From the in vitro dissolution study, optimized formulation F3 showed negligible drug release (6.75 ± 0.49%) in the initial lag period followed by slow release (97.47 ± 0.93%) for 24 h which clearly indicates that the drug is delivered to the colon. The X-ray imaging studies showed that the tablets reached the colon without disintegrating in upper gastrointestinal system. From the pharmacokinetic evaluation, the immediate-release tablets producing peak plasma concentration (C(max)) was 4482.74 ng/ml at 2 h T(max) and colon-targeted tablets showed C(max) = 3562.67 ng/ml at 10 h T(max). The area under the curve for the immediate-release and compression-coated tablets was 10595.14 and 18796.70 ng h/ml and the mean resident time was 3.82 and 10.75 h, respectively. Thus, the compression-coated tablets based on time-dependent approach were preferred for colon-targeted delivery of ketorolac.

The combined effect of wet granulation process parameters and dried granule moisture content on tablet quality attributes.

PubMed

Gabbott, Ian P; Al Husban, Farhan; Reynolds, Gavin K

2016-09-01

A pharmaceutical compound was used to study the effect of batch wet granulation process parameters in combination with the residual moisture content remaining after drying on granule and tablet quality attributes. The effect of three batch wet granulation process parameters was evaluated using a multivariate experimental design, with a novel constrained design space. Batches were characterised for moisture content, granule density, crushing strength, porosity, disintegration time and dissolution. Mechanisms of the effect of the process parameters on the granule and tablet quality attributes are proposed. Water quantity added during granulation showed a significant effect on granule density and tablet dissolution rate. Mixing time showed a significant effect on tablet crushing strength, and mixing speed showed a significant effect on the distribution of tablet crushing strengths obtained. The residual moisture content remaining after granule drying showed a significant effect on tablet crushing strength. The effect of moisture on tablet tensile strength has been reported before, but not in combination with granulation parameters and granule properties, and the impact on tablet dissolution was not assessed. Correlations between the energy input during granulation, the density of granules produced, and the quality attributes of the final tablets were also identified. Understanding the impact of the granulation and drying process parameters on granule and tablet properties provides a basis for process optimisation and scaling. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

PubMed

Ghimire, Manish; McInnes, Fiona J; Watson, David G; Mullen, Alexander B; Stevens, Howard N E

2007-09-01

The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.

Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

PubMed

Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

2015-01-01

A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included

Development and optimization of carvedilol orodispersible tablets: enhancement of pharmacokinetic parameters in rabbits

PubMed Central

Aljimaee, Yazeed HM; El-Helw, Abdel-Rahim M; Ahmed, Osama AA; El-Say, Khalid M

2015-01-01

Background Carvedilol (CVD) is used for the treatment of essential hypertension, heart failure, and systolic dysfunction after myocardial infarction. Due to its lower aqueous solubility and extensive first-pass metabolism, the absolute bioavailability of CVD does not exceed 30%. To overcome these drawbacks, the objective of this work was to improve the solubility and onset of action of CVD through complexation with hydroxypropyl-β-cyclodextrin and formulation of the prepared complex as orodispersible tablets (ODTs). Methods Compatibility among CVD and all tablet excipients using differential scanning calorimetry and Fourier transform infrared spectroscopy, complexation of CVD with different polymers, and determination of the solubility of CVD in the prepared complexes were first determined. A Box-Behnken design (BBD) was used to study the effect of tablet formulation variables on the characteristics of the prepared tablets and to optimize preparation conditions. According to BBD design, 15 formulations of CVD-ODTs were prepared by direct compression and then evaluated for their quality attributes. The relative pharmacokinetic parameters of the optimized CVD-ODTs were compared with those of the marketed CVD tablet. A single dose, equivalent to 2.5 mg/kg CVD, was administered orally to New Zealand white rabbits using a double-blind, randomized, crossover design. Results The solubility of CVD was improved from 7.32 to 22.92 mg/mL after complexation with hydroxypropyl-β-cyclodextrin at a molar ratio of 1:2 (CVD to cyclodextrin). The formulated CVD-ODTs showed satisfactory results concerning tablet hardness (5.35 kg/cm2), disintegration time (18 seconds), and maximum amount of CVD released (99.72%). The pharmacokinetic data for the optimized CVD-ODT showed a significant (P<0.05) increase in maximum plasma concentration from 363.667 to 496.4 ng/mL, and a shortening of the time taken to reach maximum plasma concentration to 2 hours in comparison with the marketed tablet

Influence of drug load on dissolution behavior of tablets containing a poorly water-soluble drug: estimation of the percolation threshold.

PubMed

Wenzel, Tim; Stillhart, Cordula; Kleinebudde, Peter; Szepes, Anikó

2017-08-01

Drug load plays an important role in the development of solid dosage forms, since it can significantly influence both processability and final product properties. The percolation threshold of the active pharmaceutical ingredient (API) corresponds to a critical concentration, above which an abrupt change in drug product characteristics can occur. The objective of this study was to identify the percolation threshold of a poorly water-soluble drug with regard to the dissolution behavior from immediate release tablets. The influence of the API particle size on the percolation threshold was also studied. Formulations with increasing drug loads were manufactured via roll compaction using constant process parameters and subsequent tableting. Drug dissolution was investigated in biorelevant medium. The percolation threshold was estimated via a model dependent and a model independent method based on the dissolution data. The intragranular concentration of mefenamic acid had a significant effect on granules and tablet characteristics, such as particle size distribution, compactibility and tablet disintegration. Increasing the intragranular drug concentration of the tablets resulted in lower dissolution rates. A percolation threshold of approximately 20% v/v could be determined for both particle sizes of the API above which an abrupt decrease of the dissolution rate occurred. However, the increasing drug load had a more pronounced effect on dissolution rate of tablets containing the micronized API, which can be attributed to the high agglomeration tendency of micronized substances during manufacturing steps, such as roll compaction and tableting. Both methods that were applied for the estimation of percolation threshold provided comparable values.

A Pharmacokinetic Bioequivalence Study Comparing Pirfenidone Tablet and Capsule Dosage Forms in Healthy Adult Volunteers.

PubMed

Pan, Lin; Belloni, Paula; Ding, Han Ting; Wang, Jianshuang; Rubino, Christopher M; Putnam, Wendy S

2017-09-01

Pirfenidone film-coated tablets were developed to offer an alternative to the marketed capsule formulation. This study assessed the bioequivalence of the tablet and capsule formulations under fed and fasted states. A Phase I, open-label, randomized, four-treatment-period, four-sequence, crossover pharmacokinetics study (NCT02525484) was conducted. Each subject received an 801-mg single dose of pirfenidone as three 267-mg capsules or one 801-mg tablet under fasted and fed conditions. Pirfenidone plasma C max , AUC 0-t and AUC 0-∞ were used to assess bioequivalence. Forty-four subjects were randomized to treatment. The 801-mg tablet in the fasted state met bioequivalence criteria [90% confidence intervals (CI) 80.00-125.00%] for the GLSM ratios of natural log-transformed C max , AUC 0-t and AUC 0-∞ . Under fed conditions, the 801-mg tablet met the bioequivalence criteria for AUC 0-t and AUC 0-∞ , but slightly exceeded the bioequivalence criteria for the C max (90% CI of 108.26-125.60%). The tablet C max was approximately 17% higher than that of the capsules. In the fed state, the tablet C max , and both AUC 0-t and AUC 0-∞ were reduced by 39% and 17%, respectively, relative to the fasted state. The tablet and capsules had acceptable tolerability profiles. The pirfenidone 801-mg tablet met bioequivalence criteria when compared with three 267-mg capsules in the fasted state. The tablet C max was slightly higher relative to capsules in the fed state, but this is not expected to have a clinically meaningful impact on the benefit-risk profile of pirfenidone. This work was supported by F. Hoffmann-La Roche Ltd.

Comparison of neurofuzzy logic and decision trees in discovering knowledge from experimental data of an immediate release tablet formulation.

PubMed

Shao, Q; Rowe, R C; York, P

2007-06-01

Understanding of the cause-effect relationships between formulation ingredients, process conditions and product properties is essential for developing a quality product. However, the formulation knowledge is often hidden in experimental data and not easily interpretable. This study compares neurofuzzy logic and decision tree approaches in discovering hidden knowledge from an immediate release tablet formulation database relating formulation ingredients (silica aerogel, magnesium stearate, microcrystalline cellulose and sodium carboxymethylcellulose) and process variables (dwell time and compression force) to tablet properties (tensile strength, disintegration time, friability, capping and drug dissolution at various time intervals). Both approaches successfully generated useful knowledge in the form of either "if then" rules or decision trees. Although different strategies are employed by the two approaches in generating rules/trees, similar knowledge was discovered in most cases. However, as decision trees are not able to deal with continuous dependent variables, data discretisation procedures are generally required.

Latent structure analysis in the pharmaceutical process of tablets prepared by wet granulation.

PubMed

Uehara, Naoto; Hayashi, Yoshihiro; Mochida, Hiroshi; Otoguro, Saori; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2016-01-01

Granule characteristics are some of the important intermediate qualities that determine tablet properties. However, the relationships between granule and tablet characteristics are poorly understood. The aim of this study was to elucidate relationships among formulation factors, granule characteristics, and tablet properties using a non-linear response surface method (RSM) incorporating a thin-plate spline interpolation (RSM-S) and a Bayesian network (BN). Tablets containing lactose (Lac), cornstarch (CS), and microcrystalline cellulose (MCC) were prepared by wet granulation. Ten formulations were prepared by an extreme vertices design. The angle of repose (Y 1 ), compressibility (Y 2 ), cohesion force (Y 3 ), internal friction angle (Y 4 ), and mean particle size (Y 5 ) were measured as granule characteristics. Tensile strength (TS) and disintegration time (DT) were measured as tablet properties. RSM-S results showed that TS increased with increasing amounts of MCC and Lac. DT decreased with increasing amounts of MCC and CS. The optimal BN models were predicted using four evaluation indices -Y 3 was shown to be the most important factor for TS, whereas Y 2 , Y 3 , and Y 4 were relatively important for predicting DT. Moreover, tablets with excellent tablet properties (i.e. high TS and low DT) were produced by relatively high Y 1 , low Y 2 , high Y 3 , high Y 4 , and middle Y 5 values, and resulted from the middle of MCC, middle-to-low CS, low Lac, and middle-to-low magnesium stearate (Mg-St) amounts. The RSM-S and BN techniques are useful for revealing complex relationships among formulation factors, granule characteristics, and tablet properties.

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.

Structural changes of polymer-coated microgranules and excipients on tableting investigated by microtomography using synchrotron X-ray radiation.

PubMed

Kajihara, Ryusuke; Noguchi, Shuji; Iwao, Yasunori; Suzuki, Yoshio; Terada, Yasuko; Uesugi, Kentaro; Itai, Shigeru

2015-03-15

Multiple-unit tablets consisting of polymer-coated microgranules and excipients have a number of advantageous pharmaceutical properties. Polymer-coated microgranules are known to often lose their functionality because of damage to the polymer coating caused by tableting, and the mechanism of polymer coating damage as well as the structural changes of excipients upon tableting had been investigated but without in-situ visualization and quantitative analysis. To elucidate the mechanism of coating damage, the internal structures of multiple-unit tablets were investigated by X-ray computed microtomography using synchrotron X-rays. Cross sectional images of the tablets with sub-micron spatial resolution clearly revealed that void spaces remained around the compressed excipient particles in the tablets containing an excipient composed of cellulose and lactose (Cellactose(®) 80), whereas much smaller void spaces remained in the tablets containing an excipient made of sorbitol (Parteck(®) SI 150). The relationships between the void spaces and the physical properties of the tablets such as hardness and disintegration were investigated. Damage to the polymer coating in tablets was found mainly where polymer-coated microgranules were in direct contact with each other in both types of tablets, which could be attributed to the difference in hardness of excipient particles and the core of the polymer-coated microgranules. Copyright © 2015 Elsevier B.V. All rights reserved.

[Stability of disintegration in health food].

PubMed

Ma, Lan; Zhao, Xin; Zhou, Shuang; Yang, Dajin

2012-11-01

To study the change of disintegration of different formulation samples which stored in the artificial climate box or room temperature and provide the technical support for health food monitoring. According to the method of Chinese Pharmacopoeia and British Pharmacopoeia. Appendix XII A. Disintegration 2010. Disintegration of the non-accelerate, accelerated after 1, 2 and 3 months samples were determined by the disintegrator, respectively. Sample properties, the ingredients of the samples, the proportions of the capsule and treatment methods have some effect on the stability of the disintegration. The disintegration time of health food will be changed particularly after they were accelerated under the condition of (38 +/- 1) degrees C/75% RH. Especially the disintegration time of soft capsules were significantly prolonged. The composition and properties of samples were the main factors that affected the disintegration.

Sewage sludge disintegration by high-pressure homogenization: a sludge disintegration model.

PubMed

Zhang, Yuxuan; Zhang, Panyue; Ma, Boqiang; Wu, Hao; Zhang, Sheng; Xu, Xin

2012-01-01

High-pressure homogenization (HPH) technology was applied as a pretreatment to disintegrate sewage sludge. The effects of homogenization pressure, homogenization cycle number, and total solid content on sludge disintegration were investigated. The sludge disintegration degree (DD(COD)), protein concentration, and polysaccharide concentration increased with the increase of homogenization pressure and homogenization cycle number, and decreased with the increase of sludge total solid (TS) content. The maximum DD(COD) of 43.94% was achieved at 80 MPa with four homogenization cycles for a 9.58 g/L TS sludge sample. A HPH sludge disintegration model of DD(COD) = kNaPb was established by multivariable linear regression to quantify the effects of homogenization parameters. The homogenization cycle exponent a and homogenization pressure exponent b were 0.4763 and 0.7324 respectively, showing that the effect of homogenization pressure (P) was more significant than that of homogenization cycle number (N). The value of the rate constant k decreased with the increase of sludge total solid content. The specific energy consumption increased with the increment of sludge disintegration efficiency. Lower specific energy consumption was required for higher total solid content sludge.

Disintegration impact on sludge digestion process.

PubMed

Dauknys, Regimantas; Rimeika, Mindaugas; Jankeliūnaitė, Eglė; Mažeikienė, Aušra

2016-11-01

The anaerobic sludge digestion is a widely used method for sludge stabilization in wastewater treatment plant. This process can be improved by applying the sludge disintegration methods. As the sludge disintegration is not investigated enough, an analysis of how the application of thermal hydrolysis affects the sludge digestion process based on full-scale data was conducted. The results showed that the maximum volatile suspended solids (VSS) destruction reached the value of 65% independently on the application of thermal hydrolysis. The average VSS destruction increased by 14% when thermal hydrolysis was applied. In order to have the maximum VSS reduction and biogas production, it is recommended to keep the maximum defined VSS loading of 5.7 kg VSS/m(3)/d when the thermal hydrolysis is applied and to keep the VSS loading between 2.1-2.4 kg VSS/m(3)/d when the disintegration of sludge is not applied. The application of thermal hydrolysis leads to an approximately 2.5 times higher VSS loading maintenance comparing VSS loading without the disintegration; therefore, digesters with 1.8 times smaller volume is required.

Experimental study of tensile strength of pharmaceutical tablets: effect of the diluent nature and compression pressure

NASA Astrophysics Data System (ADS)

Juban, Audrey; Briançon, Stéphanie; Puel, François; Hoc, Thierry; Nouguier-Lehon, Cécile

2017-06-01

In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API) which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA) or plastic (MCC), had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.

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

Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

PubMed Central

Radicioni, Milko; Castiglioni, Chiara; Giori, Andrea; Cupone, Irma; Frangione, Valeria; Rovati, Stefano

2017-01-01

A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra®) after single-dose administration to 53 healthy male volunteers (aged 18–51 years) in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax) and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t) of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg orodispersible film and film-coated tablet were nearly superimposable. The bioequivalence test was fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and extent of bioavailability. Adverse events occurred at similar rates for the two formulations and were of mild-to-moderate severity. The results suggest that the new orodispersible film

Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers.

PubMed

Radicioni, Milko; Castiglioni, Chiara; Giori, Andrea; Cupone, Irma; Frangione, Valeria; Rovati, Stefano

2017-01-01

A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra ® ) after single-dose administration to 53 healthy male volunteers (aged 18-51 years) in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; C max ) and extent (area under the curve [AUC] from administration to last observed concentration time; AUC 0-t ) of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration-time profiles up to 24 h after single-dose administration of sildenafil 100 mg orodispersible film and film-coated tablet were nearly superimposable. The bioequivalence test was fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and extent of bioavailability. Adverse events occurred at similar rates for the two formulations and were of mild-to-moderate severity. The results suggest that the new orodispersible film

Entirely S-protected chitosan: A promising mucoadhesive excipient for metronidazole vaginal tablets.

PubMed

Lupo, Noemi; Fodor, Benjamin; Muhammad, Ijaz; Yaqoob, Muhammad; Matuszczak, Barbara; Bernkop-Schnürch, Andreas

2017-12-01

Synthesis and evaluation of an entirely S-protected chitosan as mucoadhesive excipient for vaginal drug delivery. N-acetyl-cysteine was linked to 6-mercaptonicotinamide via disulphide exchange reaction. The obtained ligand, NAC-6-MNA, was subsequently attached to chitosan by carbodiimide mediated amide bond formation in two concentrations. The synthesized S-protected chitosan was chemically characterized and mucoadhesive properties and stability against oxidation were investigated. Moreover, metronidazole tablets comprising the S-protected chitosan were evaluated regarding water uptake capacity, disintegration behaviour, residence time on vaginal mucosa, release of the encapsulated drug and antimicrobial activity. S-protected chitosan displayed 160±19 (CS-MNA-160) and 320±38 (CS-MNA-320)µmol of ligand per gram of polymer. At pH 4.2, CS-MNA-160 and CS-MNA-320 showed 5.2-fold and 6.2-fold increase in mucus viscosity in comparison to unmodified chitosan (One-way ANOVA, p<.001), whereas, 9.9-fold (CS-MNA-160) and 15.6-fold (CS-MNA-320) (One-way ANOVA, p<.001) increase in viscosity was measured at pH 6. The S-protected chitosan remained stable against oxidation in presence of 0.5%v/v hydrogen peroxide. Metronidazole tablets consisting in S-protected chitosan showed prolonged residence time on vaginal mucosa and improved water uptake capacity and disintegration time in comparison to tablets consisting of unmodified chitosan. Moreover, CS-MNA-320 metronidazole tablets displayed prolonged drug release and antimicrobial activity. On the basis of the achieved results, entirely S-protected chitosan represents a promising excipient for the development of metronidazole vaginal tablets. S-protected thiomers are polymers modified with thiol groups protected by aromatic ligands and characterized by strong mucoadhesive properties and high stability against oxidation. Up to date, the entirely S-protection of thiol groups was achieved via the synthesis of the ligand 2-((2-amino-2

Comparing Book- and Tablet-Based Picture Activity Schedules: Acquisition and Preference.

PubMed

Giles, Aimee; Markham, Victoria

2017-09-01

Picture activity schedules consist of a sequence of images representing the order of tasks for a person to complete. Although, picture activity schedules have traditionally been presented in a book format, recently picture activity schedules have been evaluated on technological devices such as an iPod™ touch. The present study compared the efficiency of picture activity schedule acquisition on book- and tablet-based modalities. In addition, participant preference for each modality was assessed. Three boys aged below 5 years with a diagnosis of autism participated. Participants were taught to follow the schedules using both modalities. Following mastery of each modality of picture activity schedule, a concurrent-chains preference assessment was conducted to evaluate participant preference for each modality. Differences in acquisition rates across the two modalities were marginal. Preference for book- or tablet-based schedules was idiosyncratic across participants.

In vitro and in vivo evaluation of medicinal carbon granules and tablet on the adsorption of acetaminophen.

PubMed

Yamamoto, Kenta; Onishi, Hiraku; Ito, Akihiko; Machida, Yoshiharu

2007-01-10

Medicinal carbon (MC) granules were prepared by wet granulation using maltitol (MT), and the MC tablet was produced by compression of the granules. The physical properties and the in vitro adsorption capacity for AA of the formulations were examined. Further, the effects of MC alone and the granules on gastrointestinal absorption of AA were examined in rats when they were administered intragastrically at 15 or 45 min after the intragastrical administration of AA. AA was rapidly adsorbed by MC, and the maximum adsorption capacity of MC was 0.329g AA per gram MC. The granules and tablet exhibited adequate strength, and the tablet disintegrated rapidly. The granules and tablet showed similar adsorption profiles, but somewhat lower adsorption capacity than MC alone. MC alone and granules administered at 15 min reduced the AUC(0-infinity) significantly against the control (no treatment); however, the suppression effect on the plasma concentration was lower with the granules than with MC alone. Thus, granules and tablet are useful as a compact dosage form of MC; though the reduced adsorption capacity must be taken into account in order to expect efficacy equivalent to that of MC alone.

Twice-daily dosing of a repaglinide/metformin fixed-dose combination tablet provides glycaemic control comparable to rosiglitazone/metformin tablet.

PubMed

Raskin, P; Lewin, A; Reinhardt, R; Lyness, W

2009-09-01

To assess the use of a new repaglinide/metformin fixed-dose combination (FDC) tablet for the treatment of type 2 diabetes. In this 26-week, multicentre, open-label, parallel-group trial, subjects poorly controlled with mono- or dual-oral antidiabetic therapy were randomized 1 : 1 : 1 to receive a repaglinide/metformin FDC tablet either two times daily (BID) or three times daily (TID) or a rosiglitazone/metformin FDC tablet BID. The primary objective comprised two hypotheses tested in a hierarchical order: (i) that treatment with the repaglinide/metformin FDC BID is non-inferior to that of a rosiglitazone/metformin FDC tablet BID as measured by changes in haemoglobin A1c (HbA1c) (results presented here) and (ii) if true, that treatment with the repaglinide/metformin FDC BID was non-inferior to that of the repaglinide/metformin FDC TID as measured by changes in HbA1c (results presented in a companion paper). Additional efficacy and safety end-points were also assessed. Of the 561 subjects randomized, 383 completed the study. Reductions in HbA1c values became apparent at earlier times for repaglinide/metformin FDC BID treatment than rosiglitazone/metformin FDC BID, and final changes in HbA1c were not significantly different between treatment arms (p = 0.8186); thus, the predefined statistical criterion for non-inferiority was met. Overall adverse event profiles were comparable between treatment groups, and no major hypoglycaemic episodes were reported during the study. The repaglinide/metformin FDC BID regimen showed efficacy that was non-inferior to that of the rosiglitazone/metformin FDC BID regimen currently in clinical use and a more rapid reduction of HbA1c values. Thus, repaglinide/metformin FDC BID is a clinically feasible alternative to rosiglitazone/metformin FDC BID.

Application of guar gum biopolymer in the prescription of tablets with sodium ibuprofen--quality tests and pharmaceutical availability in vitro.

PubMed

Berner-Strzelczyk, Aneta; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2006-01-01

The increasing interest of the technology of drug form in natural biopolymers has become the reason for undertaking investigations on the possibility of guar gum application in the prescription of oral solid form of a drug. Alternative compositions and technology of the production of tablets of regulated in time sodium ibuprofen release were worked out for children. Two series of tablets were prepared with guar gum (5 and 10% content) and a series without the biopolymer. The tablet mass in each case contained keryostatic sorbitol and bioadhesive polyvinylpyrrolidone. All tablets were tested as regards the quality of production, compliance with the requirements of Polish Pharmacopoeia VI and potential therapeutic usefulness, manifestation of which is pharmaceutical availability of the therapeutic agent (sodium ibuprofen). The tests demonstrated that the produced tablets with sodium ibuprofen have proper physicochemical properties, in compliance with Polish Pharmacopoeia VI requirements. Application of biopolymer of guar gum type as adjuvant substance contributes to the improvement of the tablet hardness parameters and prevents technological problems (lining mixture of powders to tableting machine punch). The designed tablets demonstrate proper pharmaceutical availability of over 80%. Introduction of guar gum into their prescription prolonged their disintegration time and the rate of sodium ibuprofen release, which predisposes the produced form of a drug to have the function of a tablet with slowed-down release.

Comparative bioavailability study of cefuroxime axetil (equivalent to 500 mg cefuroxime/tablet) tablets (Zednad® versus Zinnat®) in healthy male volunteers.

PubMed

Asiri, Y A; Al-Hadiya, B M; Kadi, A A; Al-Khamis, K I; Mowafy, H A; El-Sayed, Y M

2011-09-01

This study was performed to investigate the bioequivalence of cefuroxime axetil tablets between a generic test product (A) Zednad® Tablet (500 mg cefuroxime/ tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat® Tablet (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability study was carried out for 24 healthy male volunteers. The subjects received 1 Zednad® Tablet (500 mg/ tablet) and 1 Zinnat® Tablet (500 mg/tablet) in a randomized, two-way crossover design fashion on 2 treatment days, after an overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma samples was accomplished by HPLC method, which was developed and validated in accordance with international guidelines. Pharmacokinetic parameters, determined by standard non-compartmental methods, and ANOVA statistics were calculated using SAS Statistical Software. The significance of a sequence effect was tested using the subjects nested in sequence as the error term. The 90% confidence intervals for the ratio between the test and reference product pharmacokinetic parameters of AUC0→t, AUC0→∞, and Cmax were calculated and found to be within the confidence limits of 80.00 - 125.00% for AUC0→t, AUC0→∞ and Cmax. The study demonstrated that the test product (A) was found bioequivalent to the reference product (B) following an oral dose of 500 mg tablet. Therefore, the two formulations were considered to be bioequivalent.

Development of Orodispersible Tablets of Candesartan Cilexetil-β-cyclodextrin Complex

PubMed Central

Sravya, Maddukuri; Deveswaran, Rajamanickam; Bharath, Srinivasan; Basavaraj, Basappa Veerbadraiah; Madhavan, Varadharajan

2013-01-01

The aim of this study was to investigate the use of inclusion complexation technique employing β-cyclodextrin in improving the dissolution profile of candesartan cilexetil, a BCS class-II drug, and to formulate the inclusion complex into orodispersible tablets. The inclusion complexes were formed by physical mixing, kneading, coevaporation, and lyophilisation methods. Inclusion complexes were characterized by FTIR, DSC, XRD, NMR, and mass spectral studies. Inclusion complexes prepared using kneading, and lyophilisation techniques in the molar ratio 1 : 5 with β-cyclodextrin were used for formulating orodispersible tablets by direct compression with different superdisintegrants like croscarmellose sodium, crospovidone, sodium starch glycolate, and low substituted hydroxypropyl cellulose in varying concentrations. The directly compressible powder was evaluated for precompression parameters, and the prepared orodispersible tablets were evaluated for postcompression parameters. Drug-excipient compatibility studies showed no interaction, and characterization proved the formation of inclusion complex. In vitro disintegration time was found to be within 3 minutes, and all the formulations showed complete drug release of 100% within 20 minutes. The optimized formulation was found to be stable after 6 months and showed no significant change in drug content. This work proved β-cyclodextrins to be effective solubilizing agent in improving the solubility of poorly water soluble drugs. PMID:26555987

Physicochemical and tablet properties of Cyperus alulatus rhizomes starch granules.

PubMed

Paramakrishnan, N; Jha, S; Kumar, K Jayaram

2015-05-01

The starch extracted from rhizomes of Cyperus alulatus (CA) was characterized for its physicochemical, morphological and tableting properties. Rhizomes of CA yield a significant quantity of starch granules (CASG) i.e., 11.93%. CASG was characterized in terms of moisture, ash and amylose contents, solubility and swelling power, paste clarity and water retention capacity. The swelling power was found to be significantly improved with the increase in temperature. Scanning electron micrographs revealed that the granule's surface was smooth, the granules were spherical, mostly round, disc like, and the size range was 6.65-12.13 μm. Finger print region in FTIR spectra confirmed its carbohydrate nature. The evaluated micromeritic properties of extracted granule's bulk density, tapped density, Carr's index, Hausner ratio, true density and porosity render unique practicability of CASG being used as an adjuvant in pharmaceutical solid dosage forms. Tablets prepared by using CASG showed higher mechanical strength and more disintegration time, which depicted the characteristic binding nature of the starch granules. As CASG is imparting better binding properties in less concentration and also it can be used in combination with the established starches to get the synergistic effect; this starch can be used commercially in the tablet preparation. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimization of thermo-alkaline disintegration of sewage sludge for enhanced biogas yield.

PubMed

Shehu, Muhammad Sani; Abdul Manan, Zainuddin; Alwi, Sharifah Rafidah Wan

2012-06-01

Optimization of thermo-alkaline disintegration of sewage sludge for enhanced biogas yield was carried out using response surface methodology (RSM) and Box-Behnken design of experiment. The individual linear and quadratic effects as well as the interactive effects of temperature, NaOH concentration and time on the degree of disintegration were investigated. The optimum degree of disintegration achieved was 61.45% at 88.50 °C, 2.29 M NaOH (24.23%w/w total solids) and 21 min retention time. Linear and quadratic effects of temperature are most significant in affecting the degree of disintegration. The coefficient of determination (R(2)) of 99.5% confirms that the model used in predicting the degree of disintegration process has a very good fitness with the experimental variables. The disintegrated sludge increased the biogas yield by 36%v/v compared to non-disintegrated sludge. The RSM with Box-Behnken design is an effective tool in predicting the optimum degree of disintegration of sewage sludge for increased biogas yield. Copyright © 2012 Elsevier Ltd. All rights reserved.

Formulation design of taste-masked particles, including famotidine, for an oral fast-disintegrating dosage form.

PubMed

Mizumoto, Takao; Tamura, Tetsuya; Kawai, Hitoshi; Kajiyama, Atsushi; Itai, Shigeru

2008-04-01

In this study, the taste-masking of famotidine, which could apply to any fast-disintegrating tablet, was investigated using the spray-dry method. The target characteristics of taste-masked particles were set as follows: the dissolution rate is not to be more than 30% at 1 min and not less than 85% at 15 min, and the particle size is not to be more than 150 microm in diameter to avoid a gritty feeling in the mouth. The target dissolution profiles of spray-dried particles consisting of Aquacoat ECD30 and Eudragit NE30D or triacetin was accomplished by the screening of formulas and the appropriate lab-scale manufacturing conditions. Lab-scale testing produced taste-masked particles that met the formulation targets. On the pilot scale, spray-dried particles with attributes, such as dissolution rate and particle size, of the same quality were produced, and reproducibility was also confirmed. This confirmed that the spray-dry method produced the most appropriate taste-masked particles for fast-disintegrating dosage forms.

Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.

PubMed

Vaithianathan, Soundarya; Raman, Siddarth; Jiang, Wenlei; Ting, Tricia Y; Kane, Maureen A; Polli, James E

2015-07-06

The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classified as a BCS class IIb drug, exhibiting pH-dependent aqueous solubility and dissolution. At pH 1.2 and 4.5, lamotrigine exhibited high solubility, whereas lamotrigine exhibited low solubility at pH 6.8, including non-sink dissolution. Lamotrigine showed high Caco-2 permeability. The apparent permeability (Papp) of lamotrigine was (73.7 ± 8.7) × 10(-6) cm/s in the apical-to-basolateral (AP-BL) direction and (41.4 ± 1.6) × 10(-6) cm/s in the BL-AP direction, which were higher than metoprolol's AP-BL Papp of (21.2 ± 0.9) × 10(-6) cm/s and BL-AP Papp of (34.6 ± 4.6) × 10(-6) cm/s. Overall, lamotrigine's favorable biopharmaceutics from a drug substance perspective and favorable quality characteristics from a tablet formulation perspective suggest that multisource lamotrigine tablets exhibit a low biopharmaceutic risk.

Comparative evaluation of in vitro efficacy of colesevelam hydrochloride tablets.

PubMed

Krishnaiah, Yellela S R; Yang, Yongsheng; Bykadi, Srikant; Sayeed, Vilayat A; Khan, Mansoor A

2014-09-01

Colesevelam hydrochloride is used as an adjunct to diet and exercise to reduce elevated low-density lipoprotein (LDL) cholesterol in patients with primary hyperlipidemia as well as to improve glycemic control in patients with type 2 diabetes. This is likely to result in submission of abbreviated new drug applications (ANDA). This study was conducted to compare the efficacy of two tablet products of colesevelam hydrochloride based on the in vitro binding of bile acid sodium salts of glycocholic acid (GC), glycochenodeoxycholic acid (GCDA) and taurodeoxycholic acid (TDCA). Kinetic binding study was carried out with constant initial bile salt concentrations as a function of time. Equilibrium binding studies were conducted under conditions of constant incubation time and varying initial concentrations of bile acid sodium salts. The unbound concentration of bile salts was determined in the samples of these studies. Langmuir equation was utilized to calculate the binding constants k1 and k2. The amount of the three bile salts bound to both the products reached equilibrium at 3 h. The similarity factor (f2) was 99.5 based on the binding profile of total bile salts to the test and reference colesevelam tablets as a function of time. The 90% confidence interval for the test to reference ratio of k2 values were 96.06-112.07 which is within the acceptance criteria of 80-120%. It is concluded from the results that the test and reference tablets of colesevelam hydrochloride showed a similar in vitro binding profile and capacity to bile salts.

Application of freeze-drying technology in manufacturing orally disintegrating films.

PubMed

Liew, Kai Bin; Odeniyi, Michael Ayodele; Peh, Kok-Khiang

2016-01-01

Freeze drying technology has not been maximized and reported in manufacturing orally disintegrating films. The aim of this study was to explore the freeze drying technology in the formulation of sildenafil orally disintegrating films and compare the physical properties with heat-dried orally disintegrating film. Central composite design was used to investigate the effects of three factors, namely concentration of carbopol, wheat starch and polyethylene glycol 400 on the tensile strength and disintegration time of the film. Heat-dried films had higher tensile strength than films prepared using freeze-dried method. For folding endurance, freeze-dried films showed improved endurance than heat-dried films. Moreover, films prepared using freeze-dried methods were thicker and had faster disintegration time. Formulations with higher amount of carbopol and starch showed higher tensile strength and thickness whereas formulations with higher PEG 400 content showed better flexibility. Scanning electron microscopy showed that the freeze-dried films had more porous structure compared to the heat-dried film as a result of the release of water molecule from the frozen structure when it was subjected to freeze drying process. The sildenafil film was palatable. The dissolution profiles of freeze-dried and heat-dried films were similar to Viagra® with f2 of 51.04 and 65.98, respectively.

Ondansetron

MedlinePlus

... by your doctor.If you are taking the rapidly disintegrating tablet, remove the tablet from the package just before ... of reach of children. Store the tablets and rapidly disintegrating tablets away from light, at room temperature or in ...

Preparation and Evaluation of Solid Dispersion Tablets by a Simple and Manufacturable Wet Granulation Method Using Porous Calcium Silicate.

PubMed

Fujimoto, Yumi; Hirai, Nobuaki; Takatani-Nakase, Tomoka; Takahashi, Koichi

2016-01-01

The aim of this study was to prepare and evaluate solid dispersion tablets containing a poorly water-soluble drug using porous calcium silicate (PCS) by a wet granulation method. Nifedipine (NIF) was used as the model poorly water-soluble drug. Solid dispersion tablets were prepared with the wet granulation method using ethanol and water by a high-speed mixer granulator. The binder and disintegrant were selected from 7 and 4 candidates, respectively. The dissolution test was conducted using the JP 16 paddle method. The oral absorption of NIF was studied in fasted rats. Xylitol and crospovidone were selected as the binder and disintegrant, respectively. The dissolution rates of NIF from solid dispersion formulations were markedly enhanced compared with NIF powder and physical mixtures. Powder X-ray diffraction (PXRD) confirmed the reduced crystallinity of NIF in the solid dispersion formulations. Fourier transform infrared (FT-IR) showed the physical interaction between NIF and PCS in the solid dispersion formulations. NIF is present in an amorphous state in granules prepared by the wet granulation method using water. The area under the plasma concentration-time curve (AUC) and peak concentration (C(max)) values of NIF after dosing rats with the solid dispersion granules were significantly greater than those after dosing with NIF powder. The solid dispersion formulations of NIF prepared with PCS using the wet granulation method exhibited accelerated dissolution rates and superior oral bioavailability. This method is very simple, and may be applicable to the development of other poorly water-soluble drugs.

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.

Disintegrating Comet 73P

NASA Astrophysics Data System (ADS)

Jewitt, David

2017-08-01

Disintegration may be the leading cause of the demise of cometary nuclei yet is rarely observed and not well understood. We propose to use an amazing but largely unpublished archival dataset on comet 73P/Schwassmann-Wachmann 3 from HST in order to characterize the breakup of this body, focussing on components 73-B, 73-C and 73-G from GO 8699, 10625 and 10992. We will measure the number, sizes, velocities and (short-term) photometric variability of the fragments in 73-B and 73-G and derive the ejection speeds and times. A nucleus/coma convolution model will be used to extract the best estimates of fragment and nucleus size. The size distributions and integral masses will be compared to the parent body masses to estimate lifetimes. Lightcurves will be determined to the test the possibility that disintegration is due to rotational instability.

Using the Slug Mucosal Irritation Assay to Investigate the Tolerability of Tablet Excipients on Human Skin in the Context of the Use of a Nipple Shield Delivery System.

PubMed

Kendall, Richard; Lenoir, Joke; Gerrard, Stephen; Scheuerle, Rebekah L; Slater, Nigel K H; Tuleu, Catherine

2017-04-01

Neonates are particularly challenging to treat. A novel patented drug delivery device containing a rapidly disintegrating tablet held within a modified nipple shield (NSDS) was designed to deliver medication to infants during breastfeeding. However concerns exist around dermatological nipple tolerability with no pharmaceutical safety assessment guidance to study local tissue tolerance of the nipple and the areola. This is the first Slug Mucosal Irritation (SMI) study to evaluate irritancy potential of GRAS excipients commonly used to manufacture rapidly disintegrating immediate release solid oral dosage form METHODS: Zinc sulphate selected as the antidiarrheal model drug that reduces infant mortality, was blended with functional excipients at traditional levels [microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium, magnesium stearate]. Slugs were exposed to blends slurried in human breast milk to assess their stinging, itching or burning potential, using objective values such as mucus production to categorize irritation potency RESULTS: Presently an in vivo assay, previously validated for prediction of ocular and nasal irritation, was used as an alternative to vertebrate models to anticipate the potential maternal dermatological tolerability issues to NSDS tablet components. The excipients did not elicit irritancy. However, mild irritancy was observed when zinc sulphate was present in blends. These promising good tolerability results support the continued investigation of these excipients within NSDS rapidly disintegrating tablet formulations. Topical local tolerance effects being almost entirely limited to irritation, the slug assay potentially adds to the existing preformulation toolbox, and may sit in between the in vitro and existing in vivo assays.

Effect of X-ray exposure on the pharmaceutical quality of drug tablets using X-ray inspection equipment.

PubMed

Uehara, Kazuaki; Tagami, Tatsuaki; Miyazaki, Itaru; Murata, Norikazu; Takahashi, Yoshifumi; Ohkubo, Hiroshi; Ozeki, Tetsuya

2015-06-01

X-ray inspection equipment is widely used to detect missing materials and defective goods in opaque containers. Its application has been expanded to the pharmaceutical industry to detect the presence of drug tablets in aluminum foil press-through packaging. However, the effect of X-rays on the pharmaceutical quality of drug tablets is not well known. In this study, the effect of X-rays on the pharmaceutical quality of drug tablets was investigated. Exposure of acetaminophen, loxoprofen and mefenamic acid tablets to X-ray doses of 0.34 mGy (thrice the dose by X-ray scanning) to 300 Gy (maximum dose from our X-ray equipment) was demonstrated, and the samples were evaluated by formulation tests. Exposure to X-rays did not affect the pharmaceutical quality of the drug content. The samples exposed to X-rays exhibited almost the same profile in formulation tests (dissolution test, disintegrating test and hardness test) as control samples (0 Gy). The combination of X-ray exposure with accelerated temperature and humidity tests (six months) also did not affect the pharmaceutical quality. The color change of light-sensitive drugs (nifedipine and furosemide tablets) after X-ray exposure was negligible (< 1.0). In contrast, tablet color was remarkably changed by light from a D65 lamp. The X-ray scanning and X-ray exposure under our experimental conditions did not affect the pharmaceutical quality of drug tablets.

A quality-by-design study for an immediate-release tablet platform: examining the relative impact of active pharmaceutical ingredient properties, processing methods, and excipient variability on drug product quality attributes.

PubMed

Kushner, Joseph; Langdon, Beth A; Hicks, Ian; Song, Daniel; Li, Fasheng; Kathiria, Lalji; Kane, Anil; Ranade, Gautam; Agarwal, Kam

2014-02-01

The impact of filler-lubricant particle size ratio variation (3.4-41.6) on the attributes of an immediate-release tablet was compared with the impacts of the manufacturing method used (direct compression or dry granulation) and drug loading (1%, 5%, and 25%), particle size (D[4,3]: 8-114 μm), and drug type (theophylline or ibuprofen). All batches were successfully manufactured, except for direct compression of 25% drug loading of 8 μm (D[4,3]) drug, which exhibited very poor flow properties. All manufactured tablets possessed adequate quality attributes: tablet weight uniformity <4% RSD, tablet potency: 94%-105%, content uniformity <6% RSD, acceptance value ≤ 15, solid fraction: 0.82-0.86, tensile strength >1 MPa, friability ≤ 0.2% weight loss, and disintegration time < 4 min. The filler-lubricant particle size ratio exhibited the greatest impact on blend and granulation particle size and granulation flow, whereas drug property variation dominated blend flow, ribbon solid fraction, and tablet quality attributes. Although statistically significant effects were observed, the results of this study suggest that the manufacturability and performance of this immediate-release tablet formulation is robust to a broad range of variation in drug properties, both within-grade and extra-grade excipient particle size variations, and the choice of manufacturing method. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

PubMed

Ohashi-Doi, Katsuyo; Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Ipsen, Henrik; Gudmann, Pernille; Lund, Kaare

2017-01-01

In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time. © 2017 S. Karger AG, Basel.

COMPARISON OF HYDROCORTISONE 10 MG TABLETS: TABLET HARDNESS OPTIMISED FOR ADULT USE HAS NEGATIVE CONSEQUENCES FOR PAEDIATRIC USE.

PubMed

Saimbi, Sarina; Madden, Valerie; Stirling, Heather; Yahyouche, Asma; Batchelor, Hannah

2016-09-01

Children's medicines are not always readily available as an age appropriate product and manipulation of adult products is often required. Recently the commercial manufacturing process for 10 mg hydrocortisone tablets has changed and the compression force increased due to tablets fracturing on removal from the blister pack. However, this change led to parents of children requiring hydrocortisone reporting that the tablets were more difficult to manipulate.This study evaluated 10 mg hydrocortisone tablets for their suitability for manipulation in order to deliver an appropriate dose to children (2 mg dose). The physical properties of tablets with the old and new compression force were compared as well as the accuracy of obtaining the paediatric dose. The tablets compared were hydrocortisone Auden 10 mg tablets (Brand A, PL16876/002)-these are the newer, harder tablets- and hydrocortisone 10 mg tablets (Brand B, PL17507/0097). Tablet physical properties including friability (Copley FRV200) and tablet hardness (Copley TBF1000) were compared. The accuracy of split doses (halve and quarter tablets) were recorded on a Sartorius analytical balance. The accuracy of the 2 mg paediatric dosing was assessed by crushing the tablet, adding 10 mL of water and extracting 2 mL. The concentration was measured using UV analysis (Jenway Genova Plus) according to a calibration curve (wavelength=246 nm). Two devices were used to crush the tablets: a spoon onto a plate and a commercially available crushing device (Apothecary Ezy Crush Pill Crusher With Ergo Grip). As anticipated Brand A tablets were harder (51.85 ±5.1 N) compared to Brand B (30.99±4.1 N). Brand A tablets passed the friability testing with <1% weight loss whereas Brand B failed as 5 tablets broke during testing.The accuracy of split doses using the score lines to halve and quarter the tablets showed that Brand A were generally better with smaller ranges for both halves (Range for A=41-55%; B=29

A comparative study of the influence of alpha-lactose monohydrate particle morphology on granule and tablet properties after roll compaction/dry granulation.

PubMed

Grote, Simon; Kleinebudde, Peter

2018-05-29

The influence of particle morphology and size of alpha-lactose monohydrate on dry granules and tablets was studied. Four different morphologies were investigated: Two grades of primary crystals, which differed in their particle size and structure (compact crystals vs. agglomerates). The materials were roll compacted at different specific compaction forces and changes in the particle size distribution and the specific surface area were measured. Afterwards, two fractions of granules were pressed to tablets and the tensile strength was compared to that from tablets compressed from the raw materials. The specific surface area was increased induced by roll compaction/dry granulation for all materials. At increased specific compaction forces, the materials showed sufficient size enlargement. The morphology of lactose determined the strength of direct compressed tablets. In contrast, the strength of granule tablets was leveled by the previous compression step during roll compaction/dry granulation. Thus, the tensile strength of tablets compressed directly from the powder mixtures determined whether materials exhibited a loss in tabletability after roll compaction/dry granulation or not. The granule size had only a slight influence on the strength of produced tablets. In some cases, the fraction of smaller granules showed a higher tensile strength compared to the larger fraction.