Sample records for tablet dosage forms

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

    PubMed

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

    2010-01-04

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

  2. A survey of caregivers of Nigerian children less than 6 years of age to determine the experience and perception of acceptability of oral solid dosage forms.

    PubMed

    Orubu, Samuel; Okwelogu, Chinyere; Opanuga, Olabisi; Tuleu, Catherine

    2018-02-05

    The World Health Organization (WHO) recommends flexible solid oral dosage forms such as dispersible tablet as the preferred formulation for (young) children, especially in developing/low- and middle-income countries, LMIC. The aim of this study was to assess experience, perceptions of acceptability, and formulation preferences, among 10 oral dosage forms for young children in a sample of end-users in Nigeria as an exemplar LMIC. Using a semi-structured and validated questionnaire, 148 caregivers were surveyed. Acceptability was assessed by level of liking using a 3-point Likert scale and ease of administration. Preference was assessed from participants' dosage form of choice. Oral dosage forms assessed were those mentioned in the British National Formulary for children, 2013. The formulation perceived as the most acceptable was the chewable/suckable tablet. However, preference was for liquids. Specifically with the dispersible tablet, whilst 89% (n=111) of caregivers of young children found it easy-to-administer, only 50% of children liked it. There is a gap between the proposal of dispersible tablet as the preferred dosage form for young children and caregivers' perceptions of acceptability and preference. Educational strategies to increase acceptability of dispersible tablets as the preferred formulation for young children would be required. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Correlation of ibuprofen bioavailability with gastrointestinal transit by scintigraphic monitoring of /sup 171/Er-labeled sustained-release tablets

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

    Parr, A.F.; Beihn, R.M.; Franz, R.M.

    1987-12-01

    External gamma scintigraphy was used to monitor the gastrointestinal (GI) transit of radiolabeled sustained-release tablets containing 800 mg ibuprofen in eight fasted healthy volunteers. Ibuprofen serum concentrations were determined from blood samples drawn sequentially over a 24-hr period. Serum concentrations and related parameters were correlated to the position of the dosage form in the GI tract from the scintiphotos. The sustained-release tablets were radiolabeled intact utilizing a neutron activation procedure, by incorporating 0.18% of /sup 170/Er2O3 (enriched to greater than 96% /sup 170/Er) into the bulk formulation. After manufacture of the final dosage forms, the tablets were irradiated in amore » neutron flux (4.4 x 10(13) n/cm2.sec) for 2 min, converting the stable /sup 170/Er to radioactive /sup 171/Er (t1/2 = 7.5 hr). Each tablet contained 50 microCi of /sup 171/Er at the time of administration. The scintigraphy studies suggested that the greatest proportion of ibuprofen was absorbed from this dosage form while the tablet was in the large bowel. The dosage forms eroded slowly in the small bowel and appeared to lose their integrity in the large bowel. In vitro studies showed only minimal effects of the neutron irradiation procedure on the dosage form performance.« less

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

    PubMed

    Gröning, R; Cloer, C; Müller, R S

    2006-07-01

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

  5. [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.

  6. Controlled-release tablet formulation of isoniazid.

    PubMed

    Jain, N K; Kulkarni, K; Talwar, N

    1992-04-01

    Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

  7. Microbicide dosage forms.

    PubMed

    Rohan, L C; Devlin, B; Yang, H

    2014-01-01

    Microbicides are topically applied, user controlled dosage forms that are being developed to prevent the transmission of HIV during coitus. Early candidates focused on coitally dependent dosage forms such as gels and creams. More recent development has focused on broadening the coitally dependent options through the introduction of films and fast dissolving tablets. Additionally, it has become important to have longer acting products to minimize the burden of user compliance and thus vaginal rings have been developed providing sustained delivery of antiretroviral drugs. This chapter discusses the history of microbicides along with a detailed description of coitally dependent products, gels, films, tablets diaphragms, as well as coitally independent dosage forms such as vaginal rings and the introduction of a new technology, electrospun fibers.

  8. Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children's Acceptability of Oral Formulations (CALF) Study.

    PubMed

    Ranmal, Sejal R; Cram, Anne; Tuleu, Catherine

    2016-11-30

    A lack of evidence to guide the design of age-appropriate and acceptable dosage forms has been a longstanding knowledge gap in paediatric formulation development. The Children's Acceptability of Oral Formulations (CALF) study captured end-user perceptions and practices with a focus on solid oral dosage forms, namely tablets, capsules, chewables, orodispersibles, multiparticulates (administered with food) and mini-tablets (administered directly into the mouth). A rigorous development and testing phase produced age-adapted questionnaires as measurement tools with strong evidence of validity and reliability. Overall, 590 school children and adolescents, and 428 adult caregivers were surveyed across hospitals and various community settings. Attitudes towards dosage forms primarily differed based on age and prior use. Positive attitudes to tablets and capsules increased with age until around 14 years. Preference was seen for chewable and orodispersible preparations across ages, while multiparticulates were seemingly less favourable. Overall, 59.6% of school children reported willingness to take 10mm diameter tablets, although only 32.1% of caregivers perceived this size to be suitable. While not to be taken as prescriptive guidance, the results of this study provide some evidence towards rational dosage form design, as well as methodological approaches to help design tools for further evaluation of acceptability within paediatric studies. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2013-02-01

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

  10. Comparative drug release measurements in limited amounts of liquid: a suppository formulation study.

    PubMed

    Welch, Ken; Ek, Ragnar; Strømme, Maria

    2006-07-01

    A novel method for the investigation of drug formulations in limited liquid volumes is presented. The experimental setup consists of a measurement cell containing an absorbent sponge cloth placed between two parallel electrodes. Conductivity measurements are used to monitor the drug release from the dosage form. By varying the amount of water contained in the absorbent cloth surrounding the dosage form, it is possible to measure the drug release performance of the dosage form in very limited amounts of water. The method was employed to test four different tablet formulations consisting of the model drug NaCl incorporated in excipient matrices of hard fat, polyethylene glycol, microcrystalline cellulose and a mixture of microcrystalline cellulose and croscarmellose sodium (Ac-Di-Sol). The drug release rates of the different formulations in limited water volumes differed markedly from the release rates in an excess of water. Whereas the release rates from all tablet types in an excess of water showed only minor differences among the tablet types, the release rates from the tablets formulated with disintegrating excipients were clearly superior in limited water volumes. The developed method for drug release in limited volumes of liquid should be suitable for evaluation of rectal dosage forms.

  11. Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging.

    PubMed

    Zeitler, J Axel; Shen, Yaochun; Baker, Colin; Taday, Philip F; Pepper, Michael; Rades, Thomas

    2007-02-01

    Three dimensional terahertz pulsed imaging (TPI) was evaluated as a novel tool for the nondestructive characterization of different solid oral dosage forms. The time-domain reflection signal of coherent pulsed light in the far infrared was used to investigate film-coated tablets, sugar-coated tablets, multilayered controlled release tablets, and soft gelatin capsules. It is possible to determine the spatial and statistical distribution of coating thickness in single and multiple coated products using 3D TPI. The measurements are nondestructive even for layers buried underneath other coating structures. The internal structure of coating materials can be analyzed. As the terahertz signal penetrates up to 3 mm into the dosage form interfaces between layers in multilayered tablets can be investigated. In soft gelatin capsules it is possible to measure the thickness of the gelatin layer and to characterize the seal between the gelatin layers for quality control. TPI is a unique approach for the nondestructive characterization and quality control of solid dosage forms. The measurements are fast and fully automated with the potential for much wider application of the technique in the process analytical technology scheme. Copyright (c) 2006 Wiley-Liss, Inc.

  12. 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.

  13. 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

  14. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium liothyronine tablets. 520.1284 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

  15. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium liothyronine tablets. 520.1284 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

  16. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium liothyronine tablets. 520.1284 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

  17. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium liothyronine tablets. 520.1284 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

  18. Spectrophotometric estimation of ambroxol and cetirizine hydrochloride from tablet dosage form.

    PubMed

    Gowekar, N M; Pande, V V; Kasture, A V; Tekade, A R; Chandorkar, J G

    2007-07-01

    Fixed dose combination tablets containing ambroxol HCl and cetirizine HCl are clinically used as mucolytic and antiallergic. Several spectrophotometric and HPLC methods have been reported for simultaneous estimation of these drugs with other drugs. The drugs individually and in mixture obeys Beer's law over conc. range 1.2-4.4 microg/mL for cetirizine HCL and for ambroxol HCL 15-52 microg/mL at all five sampling wavelengths (correlation coeff. well above 0.995). The mean recoveries from tablet by standard addition method were 100.18% (+/-2.4) and 100.66 % (+/-2.31). The present work reports simple, accurate and precise spectrophotometric methods for their simultaneous estimation from tablet dosage form.

  19. A mechanistic model for the prediction of in-use moisture uptake by packaged dosage forms.

    PubMed

    Remmelgas, Johan; Simonutti, Anne-Laure; Ronkvist, Asa; Gradinarsky, Lubomir; Löfgren, Anders

    2013-01-30

    A mechanistic model for the prediction of in-use moisture uptake of solid dosage forms in bottles is developed. The model considers moisture transport into the bottle and moisture uptake by the dosage form both when the bottle is closed and when it is open. Experiments are carried out by placing tablets and desiccant canisters in bottles and monitoring their moisture content. Each bottle is opened once a day to remove one tablet or desiccant canister. Opening the bottle to remove a tablet or canister also causes some exchange of air between the bottle headspace and the environment. In order to ascertain how this air exchange might depend on the customer, tablets and desiccant canisters are removed from the bottles by either carefully removing only one or by pouring all of the tablets or desiccant canisters out of the bottle, removing one, and pouring the remaining ones back into the bottle. The predictions of the model are found to be in good agreement with experimental data for moisture sorption by desiccant canisters. Moreover, it is found experimentally that the manner in which the tablets or desiccant canisters were removed does not appreciably affect their moisture content. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 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

  1. 21 CFR 520.82b - Aminopropazine fumarate, neomycin sulfate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aminopropazine fumarate, neomycin sulfate tablets... Aminopropazine fumarate, neomycin sulfate tablets. (a) Specifications. The drug is in tablet form. Each tablet... administered at a dosage level of one to two tablets per 10 pounds of body weight twice daily for 3 days.1 (3...

  2. 21 CFR 520.1310 - Marbofloxacin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Marbofloxacin tablets. 520.1310 Section 520.1310... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1310 Marbofloxacin tablets. (a) Specifications. Each tablet contains 25, 50, 100, or 200 milligrams (mg) marbofloxacin. (b...

  3. 21 CFR 520.2330 - Sulfisoxazole tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfisoxazole tablets. 520.2330 Section 520.2330... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2330 Sulfisoxazole tablets. (a) Specifications. Each tablet contains 260 milligrams (4 grains) of sulfisoxazole. (b) Sponsor. See...

  4. 21 CFR 520.1872 - Praziquantel, pyrantel pamoate, and febantel tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS... food as follows: Weight of animal Kilograms Pounds Number of tablets per dose Tablet no. 1 Tablet no. 2... tapeworms (Dipylidium caninum, Taenia pisiformis, Echinococcus granulosus); hookworms (Ancylostoma caninum...

  5. 21 CFR 520.1872 - Praziquantel, pyrantel pamoate, and febantel tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS... food as follows: Weight of animal Kilograms Pounds Number of tablets per dose Tablet no. 1 Tablet no. 2... tapeworms (Dipylidium caninum, Taenia pisiformis, Echinococcus granulosus); hookworms (Ancylostoma caninum...

  6. 21 CFR 520.1872 - Praziquantel, pyrantel pamoate, and febantel tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS... food as follows: Weight of animal Kilograms Pounds Number of tablets per dose Tablet no. 1 Tablet no. 2... tapeworms (Dipylidium caninum, Taenia pisiformis, Echinococcus granulosus); hookworms (Ancylostoma caninum...

  7. 21 CFR 520.1872 - Praziquantel, pyrantel pamoate, and febantel tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS... food as follows: Weight of animal Kilograms Pounds Number of tablets per dose Tablet no. 1 Tablet no. 2... tapeworms (Dipylidium caninum, Taenia pisiformis, Echinococcus granulosus); hookworms (Ancylostoma caninum...

  8. 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.

  9. Evaluation of the viability of Lactobacillus spp. after the production of different solid dosage forms.

    PubMed

    Brachkova, Mariya I; Duarte, Aida; Pinto, João F

    2009-09-01

    The work aims to provide evidence on the viability of Lactobacillus spp. and a spore form of Bacillus subtilis from nonprocessed bacteria to coated dosage forms (i.e., mini-tablets, pellets, and their coated forms). Lactobacillus spp. were cultivated overnight in MRS broth (10(9) cfu/mL) and B. subtilis spores were produced on plate count agar (10(7) cfu/mL) for 2 weeks. Bacteria and spores were freeze-dried in skim milk enriched with glycerol. The cakes were further processed into tablets (2.5 mm diameter) by direct compression with or without microcrystalline cellulose and inulin. Pellets (1-1.4 mm diameter) were produced by extrusion-spheronization of bacterial and spore suspensions with microcrystalline cellulose, lactose, inulin, and skim milk. Both tablets and pellets were film coated. The properties of the dosage forms, particularly the bacterial viability, were evaluated immediately after production and throughout storage for 6 months at 4 degrees C. The study has shown that for an adequate stabilization of the bacteria a protective matrix (e.g., skim milk) and cryoprotectors (e.g., glycerol) must be present at early stages of bacterial de-hydration. Tabletting had a less deleterious effect (<2 log units) on bacteria when compared to pelletization (in some cases 3 log units). Enteric coating (15%, w/w) of either tablets or pellets did not affect the viability of the bacteria.

  10. Characterisation of pore structures of pharmaceutical tablets: A review.

    PubMed

    Markl, Daniel; Strobel, Alexa; Schlossnikl, Rüdiger; Bøtker, Johan; Bawuah, Prince; Ridgway, Cathy; Rantanen, Jukka; Rades, Thomas; Gane, Patrick; Peiponen, Kai-Erik; Zeitler, J Axel

    2018-03-01

    Traditionally, the development of a new solid dosage form is formulation-driven and less focus is put on the design of a specific microstructure for the drug delivery system. However, the compaction process particularly impacts the microstructure, or more precisely, the pore architecture in a pharmaceutical tablet. Besides the formulation, the pore structure is a major contributor to the overall performance of oral solid dosage forms as it directly affects the liquid uptake rate, which is the very first step of the dissolution process. In future, additive manufacturing is a potential game changer to design the inner structures and realise a tailor-made pore structure. In pharmaceutical development the pore structure is most commonly only described by the total porosity of the tablet matrix. Yet it is of great importance to consider other parameters to fully resolve the interplay between microstructure and dosage form performance. Specifically, tortuosity, connectivity, as well as pore shape, size and orientation all impact the flow paths and play an important role in describing the fluid flow in a pharmaceutical tablet. This review presents the key properties of the pore structures in solid dosage forms and it discusses how to measure these properties. In particular, the principles, advantages and limitations of helium pycnometry, mercury porosimetry, terahertz time-domain spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Studies of phase transitions in the aripiprazole solid dosage form.

    PubMed

    Łaszcz, Marta; Witkowska, Anna

    2016-01-05

    Studies of the phase transitions in an active substance contained in a solid dosage form are very complicated but essential, especially if an active substance is classified as a BCS Class IV drug. The purpose of this work was the development of sensitive methods for the detection of the phase transitions in the aripiprazole tablets containing initially its form III. Aripiprazole exhibits polymorphism and pseudopolymorphism. Powder diffraction, Raman spectroscopy and differential scanning calorimetry methods were developed for the detection of the polymorphic transition between forms III and I as well as the phase transition of form III into aripiprazole monohydrate in tablets. The study involved the initial 10 mg and 30 mg tablets, as well as those stored in Al/Al blisters, a triplex blister pack and HDPE bottles (with and without desiccant) under accelerated and long term conditions. The polymorphic transition was not observed in the initial and stored tablets but it was visible on the DSC curve of the Abilify(®) 10 mg reference tablets. The formation of the monohydrate was observed in the diffractograms and Raman spectra in the tablets stored under accelerated conditions. The monohydrate phase was not detected in the tablets stored in the Al/Al blisters under long term conditions. The results showed that the Al/Al blisters can be recommended as the packaging of the aripiprazole tablets containing form III. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. 21 CFR 520.1157 - Iodinated casein tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Iodinated casein tablets. 520.1157 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1157 Iodinated casein tablets. (a) Specifications. Each 1-gram tablet contains 25 milligrams of iodinated casein. (b) Sponsor...

  13. 21 CFR 520.1157 - Iodinated casein tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Iodinated casein tablets. 520.1157 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1157 Iodinated casein tablets. (a) Specifications. Each 1-gram tablet contains 25 milligrams of iodinated casein. (b) Sponsor...

  14. 21 CFR 520.455 - Clomipramine tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a) Specifications. Each tablet contains 5, 20, 40, or 80 milligrams (mg) clomipramine hydrochloride. (b) Sponsor...

  15. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cefpodoxime tablets. 520.370 Section 520.370 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets. (a) Specifications. Each tablet contains cefpodoxime proxetil equivalent to 100 or 200 milligrams (mg) cefpodoxime...

  16. 21 CFR 520.2088 - Roxarsone tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Roxarsone tablets. 520.2088 Section 520.2088 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2088 Roxarsone tablets. (a)(1) Specifications. Each tablet contains 36 milligrams of roxarsone (3-nitro-4-hydroxyphenylarsonic acid). (2...

  17. 21 CFR 520.1380 - Methocarbamol tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methocarbamol tablets. 520.1380 Section 520.1380... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet...

  18. 21 CFR 520.1870 - Praziquantel tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Praziquantel tablets. 520.1870 Section 520.1870... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1870 Praziquantel tablets. (a) Specifications. Each tablet contains: (1) 34 milligrams (mg) praziquantel. (2) 11.5 or 23 mg praziquantel. (b...

  19. 21 CFR 520.1331 - Meclofenamic acid tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Meclofenamic acid tablets. 520.1331 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1331 Meclofenamic acid tablets. (a) Specifications. Each tablet contains either 10 or 20 milligrams of meclofenamic acid. (b...

  20. Development and validation of multivariate calibration methods for simultaneous estimation of Paracetamol, Enalapril maleate and hydrochlorothiazide in pharmaceutical dosage form

    NASA Astrophysics Data System (ADS)

    Singh, Veena D.; Daharwal, Sanjay J.

    2017-01-01

    Three multivariate calibration spectrophotometric methods were developed for simultaneous estimation of Paracetamol (PARA), Enalapril maleate (ENM) and Hydrochlorothiazide (HCTZ) in tablet dosage form; namely multi-linear regression calibration (MLRC), trilinear regression calibration method (TLRC) and classical least square (CLS) method. The selectivity of the proposed methods were studied by analyzing the laboratory prepared ternary mixture and successfully applied in their combined dosage form. The proposed methods were validated as per ICH guidelines and good accuracy; precision and specificity were confirmed within the concentration range of 5-35 μg mL- 1, 5-40 μg mL- 1 and 5-40 μg mL- 1of PARA, HCTZ and ENM, respectively. The results were statistically compared with reported HPLC method. Thus, the proposed methods can be effectively useful for the routine quality control analysis of these drugs in commercial tablet dosage form.

  1. Over-the-counter pharmaceuticals: exploratory research of consumer preference toward solid oral dosage forms.

    PubMed

    Reisenwitz, T H; Wimbish, G J

    1996-01-01

    The capsule dosage form in nonprescription pharmaceuticals persists as being one of the most vulnerable to product tampering. This study examines consumer preference toward three solid oral dosage forms (capsules, caplets, and tablets) in nonprescription products. Thirteen independent variables representing dosage form attributes are measured on semantic differential scales. The data are analyzed using analysis of variance (ANOVA) and factor analysis. Implications for the pharmaceutical marketer are noted. Future directions for research are also outlined.

  2. 21 CFR 520.816 - Epsiprantel tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Epsiprantel tablets. 520.816 Section 520.816 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.816 Epsiprantel tablets. (a) Specifications. Each tablet contains either 12.5, 25, 50, or 100 milligrams of epsiprantel. (b) Sponsor. See No...

  3. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a) Specifications. Each tablet contains 10 milligrams of carnidazole. (b) Sponsor. See 053923 in § 510.600(c) of...

  4. 21 CFR 520.1288 - Lufenuron tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Lufenuron tablets. 520.1288 Section 520.1288 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1288 Lufenuron tablets. (a) Specifications—(1) Tablets containing 45, 90, 204.9, or 409.8 milligrams (mg) lufenuron for use as in paragraphs...

  5. 21 CFR 520.1900 - Primidone tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Primidone tablets. 520.1900 Section 520.1900 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1900 Primidone tablets. (a) Specifications. Each tablet contains 50 or 250 milligrams of primidone. (b) Sponsor. See No. 000010 in § 510.600...

  6. 21 CFR 520.1451 - Moxidectin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Moxidectin tablets. 520.1451 Section 520.1451 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1451 Moxidectin tablets. (a) Specifications. Each tablet contains 30, 68, or 136 micrograms of moxidectin. (b) Sponsor. See No. 000856 in...

  7. 21 CFR 520.1510 - Nitenpyram tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Nitenpyram tablets. 520.1510 Section 520.1510 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1510 Nitenpyram tablets. (a) Specifications. Each tablet contains 11.4 or 57 milligrams (mg) nitenpyram. (b) Sponsor. See No. 058198 in § 510...

  8. 21 CFR 520.1696d - Penicillin V tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin V tablets. 520.1696d Section 520.1696d... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000...

  9. 21 CFR 520.1696d - Penicillin V tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin V tablets. 520.1696d Section 520.1696d... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000...

  10. 21 CFR 520.812 - Enrofloxacin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications. Each tablet contains either 22.7, 68.0, or 136.0 milligrams of enrofloxacin. (b) Sponsor. See No...

  11. Pasteurization as a tool to control the bio-burden in solid herbal dosage forms: A pilot study of formulating Ashoka tablets with an industrial perspective.

    PubMed

    Pushpalatha, Hulikal Basavarajaiah; Pramod, Kumar; Sundaram, Ramachandran; Shyam, Ramakrishnan

    2014-10-01

    Irradiation and use of preservatives are routine procedures to control bio-burden in solid herbal dosage forms. Use of steam or pasteurization is even though reported in the literature, not many studies are available with respect to its application in reducing the bio-burden in herbal drug formulations. Hence, we undertook a series of studies to explore the suitability of pasteurization as a method to reduce bio-burden during formulation and development of herbal dosage forms, which will pave the way for preparing preservative-free formulations. Optimized Ashoka (Saraca indica) tablets were formulated and developed. The optimized formula was then subjected to pasteurization during formulation, with an aim to keep the microbial count well within the limits of pharmacopoeial standards. Then, three variants of the optimized Ashoka formulation - with preservative, without preservative and formulation without preservative and subjected to pasteurization, were compared by routine in-process parameters and stability studies. The results obtained indicate that Ashoka tablets manufactured by inclusion of the pasteurization technique not only showed the bio-burden to be within the limits of pharmacopoeial standards, but also exhibited the compliance with other parameters, such as stability and quality. The outcome of this pilot study shows that pasteurization can be employed as a distinctive method for reducing bio-burden during the formulation and development of herbal dosage forms, such as tablets.

  12. Non-Conventional Applications of Computerized Tomography: Analysis of Solid Dosage Forms Produced by Pharmaceutical Industry

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

    Martins de Oliveira, Jose Jr.; Germano Martins, Antonio Cesar

    X-ray computed tomography (CT) refers to the cross-sectional imaging of an object measuring the transmitted radiation at different directions. In this work, we describe a non-conventional application of computerized tomography: visualization and improvements in the understanding of some internal structural features of solid dosage forms. A micro-CT X-ray scanner, with a minimum resolution of 30 mum was used to characterize some pharmaceutical tablets, granules, controlled-release osmotic tablet and liquid-filled soft-gelatin capsules. The analysis presented in this work are essentially qualitative, but quantitative parameters, such as porosity, density distribution, tablets dimensions, etc. could also be obtained using the related CT techniques.

  13. 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-Scintigraphy continues to be a good tool to use during early stages of product development to investigate in vivo performance of dosage forms. The results of this study provided evidence that the physical chemical specifications of the drug substance may not always be indicative of in vitro or in vivo performance of tablet dosage form, even when formulation and process are not changed.

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

    PubMed

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

    2014-12-30

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

  15. 21 CFR 520.903e - Febantel tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Febantel tablets. 520.903e Section 520.903e Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.903e Febantel tablets. (a) Specifications. Each scored tablet contains 27.2 milligrams of febantel for use in dogs, puppies, cats, and...

  16. 21 CFR 520.804 - Enalapril tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enalapril tablets. 520.804 Section 520.804 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets. (a) Specifications. Each tablet contains either 1.0, 2.5, 5.0, 10.0, or 20.0 milligrams of enalapril maleate. (b...

  17. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Stanozolol tablets. 520.2150a Section 520.2150a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2150a Stanozolol tablets. (a) Specifications. Each tablet contains 2 milligrams of stanozolol. (b) Sponsor. No. 000009 in § 510.600(c) of this...

  18. 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.

  19. 21 CFR 206.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.3 Definitions. The following... 600.3(t) of this chapter. Solid oral dosage form means capsules, tablets, or similar drug products...

  20. 21 CFR 206.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.3 Definitions. The following... 600.3(t) of this chapter. Solid oral dosage form means capsules, tablets, or similar drug products...

  1. 21 CFR 206.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.3 Definitions. The following... 600.3(t) of this chapter. Solid oral dosage form means capsules, tablets, or similar drug products...

  2. A report from the pediatric formulations task force: perspectives on the state of child-friendly oral dosage forms.

    PubMed

    Zajicek, Anne; Fossler, Michael J; Barrett, Jeffrey S; Worthington, Jeffrey H; Ternik, Robert; Charkoftaki, Georgia; Lum, Susan; Breitkreutz, Jörg; Baltezor, Mike; Macheras, Panos; Khan, Mansoor; Agharkar, Shreeram; MacLaren, David Douglas

    2013-10-01

    Despite the fact that a significant percentage of the population is unable to swallow tablets and capsules, these dosage forms continue to be the default standard. These oral formulations fail many patients, especially children, because of large tablet or capsule size, poor palatability, and lack of correct dosage strength. The clinical result is often lack of adherence and therapeutic failure. The American Association of Pharmaceutical Scientists formed a Pediatric Formulations Task Force, consisting of members with various areas of expertise including pediatrics, formulation development, clinical pharmacology, and regulatory science, in order to identify pediatric, manufacturing, and regulatory issues and areas of needed research and regulatory guidance. Dosage form and palatability standards for all pediatric ages, relative bioavailability requirements, and small batch manufacturing capabilities and creation of a viable economic model were identified as particular needs. This assessment is considered an important first step for a task force seeking creative approaches to providing more appropriate oral formulations for children.

  3. Bioavailability of AREDS1 micronutrients from softgel capsules and tablets: a pilot study

    PubMed Central

    Johnson, Elizabeth J.; Vishwanathan, Rohini; Rasmussen, Helen M.

    2014-01-01

    Purpose The benefits of antioxidant micronutrients in slowing progression to advanced stages of age-related macular degeneration (AMD) was supported by the 4/day tablet form investigated in the Age-related Eye Disease Study 1 (AREDS1) and the 2/day softgel form in the Age-related Eye Disease Study 2 (AREDS2). However, the choices of excipient, dosage form, and ingredient chemistry as well as the patient physiologies and pathologies can influence bioavailability and efficacy. The objective of the study was to explore the influence of dosage form on the bioavailability of the five primary AREDS1 and Tier-2 AREDS2 micronutrients: the metals zinc and copper, β-carotene, and vitamins E and C. The intent was to establish by chemical analysis the relative bioavailabilities of these five micronutrients in plasma, or serum for the metals, as well as to identify any opportunities for improvements. Methods A total of 15 healthy men (5) and women (10) were recruited for a controlled, randomized, three-arm, crossover trial of the AREDS1 micronutrients. The study investigated responses in bioabsorption to a single dose of either four tablets or two softgels at the full dose level, or one softgel at the half-dose level. The bioavailability of each micronutrient was based on the pharmacokinetic profiles established through 15 samplings for each ingredient/dosage form in plasma/serum over the course of one week. Results Bioavailability was estimated using model-independent and model-dependent procedures. A statistical advantage of the dosage form was observed in only two cases from the exaggerated effects using the half-dose softgel and for the tablet dosage form for β-carotene and vitamin E. An unanticipated complexity was suggested by the bimodal absorption of zinc. For these micronutrients, no disadvantage (though potential advantage) was inferred for the water-soluble components presented in a softgel formulation. Increased fractional absorption was observed for the smaller dose (one capsule versus two), but it was not sufficient to reach the level achieved by the full dose of either four tablets or two softgels. A model-dependent analysis permitted an estimation of the percentage of micronutrients absorbed, with zinc, the single most important ingredient, absorbed at about a 10% level. Conclusions The results suggest modestly contradictory requirements in the dosage form for water-soluble and lipid-soluble ingredients, as based on a goal of improved bioavailability. Comparative consistency in bioavailability was observed across dosage forms, and most nutrients between AREDS1 and AREDS2 (full dose) formulations relative to the significant variations observed within this controlled population. The results emphasize the importance of defining the requisite bioavailability of each micronutrient and the influence of the dosage form that provides it. With the recognition of global and population-specific micronutrient deficiencies, notably in the elderly populations afflicted with AMD and their significant metabolic and health consequences, establishing efficient means of supplementation are of continuing epidemiologic interest. PMID:25352732

  4. Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs

    PubMed Central

    Sun, Jin; Shi, Jie-Ming; Zhang, Tian-Hong; Gao, Kun; Mao, Jing-Jing; Li, Bing; Sun, Ying-Hua; He, Zhong-Gui

    2005-01-01

    AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride (SM•HCl) on its pharmacokinetics in beagle dogs. METHODS: The in vitro release behavior of two SM•HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM•HCl pharmacokinetics was investigated and compared. RESULTS: The optimal SM•HCl sustained-release formulation was achieved by mixing slow- and rapid-release pellets (9:1, w/w). The SM•HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs 68.7%. From a pharmacokinetic standpoint, the 24-h SM•HCl sustained-release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67×0.52 h vs 9.83×0.98 h and the Cmax being 1 334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM•HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM•HCl percentage absorption in vivo and the cumulative percentage release in vitro. CONCLUSION: The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves. PMID:16052686

  5. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Cefpodoxime tablets. 520.370 Section 520.370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets. (a...

  6. 21 CFR 520.455 - Clomipramine tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a...

  7. 21 CFR 520.804 - Enalapril tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Enalapril tablets. 520.804 Section 520.804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets. (a...

  8. 21 CFR 520.455 - Clomipramine tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a...

  9. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Cefpodoxime tablets. 520.370 Section 520.370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets. (a...

  10. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a...

  11. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Cefpodoxime tablets. 520.370 Section 520.370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets. (a...

  12. 21 CFR 520.812 - Enrofloxacin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a...

  13. 21 CFR 520.455 - Clomipramine tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a...

  14. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a...

  15. 21 CFR 520.581 - Dichlorophene tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dichlorophene tablets. 520.581 Section 520.581 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a...

  16. 21 CFR 520.455 - Clomipramine tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a...

  17. 21 CFR 520.804 - Enalapril tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Enalapril tablets. 520.804 Section 520.804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets. (a...

  18. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a...

  19. Application of a radiotelemetric system to evaluate the performance of enteric coated and plain aspirin tablets.

    PubMed

    Lui, C Y; Oberle, R; Fleisher, D; Amidon, G L

    1986-05-01

    The bioavailability of enteric coated and plain aspirin tablets was studied in four beagle dogs. Blood sampling for enteric coated tablets was planned with the aid of a radiotelemetric system. The release of aspirin from its dosage form was detected by monitoring the change in intestinal pH. Aspirin and salicylic acid levels in plasma obtained from the enteric coated dosage form exhibited familiar concentration versus time absorption profiles. Variation in the plasma concentrations of these two compounds within each dog studied (four runs each) was relatively small when time zero was adjusted to the commencement of tablet dissolution. The plasma levels obtained from plain aspirin (three runs each), however, show atypical absorption. The estimated absolute bioavailability was 0.432 +/- 0.0213 and 0.527 +/- 0.0260 for enteric coated and plain aspirin, respectively. Other pharmacokinetic parameters for these two dosage forms such as the highest observed plasma concentration (Cmax) (10.9 +/- 0.535 microgram/mL versus 13.6 +/- 1.88 micrograms/mL) and the time to reach Cmax (tmax) (26.6 +/- 1.94 min versus 31.0 +/- 7.04 min) agree well. The mean values for gastric emptying time, in vivo coating dissolution time, and in vivo disintegration/dissolution time of the tablet core for enteric coated aspirin are 48.7 +/- 7.23 min, 44.3 +/- 3.80 min, and 34.7 +/- 2.04 min, respectively.

  20. An introduction to fast dissolving oral thin film drug delivery systems: a review.

    PubMed

    Kathpalia, Harsha; Gupte, Aasavari

    2013-12-01

    Many pharmaceutical companies are switching their products from tablets to fast dissolving oral thin films (OTFs). Films have all the advantages of tablets (precise dosage, easy administration) and those of liquid dosage forms (easy swallowing, rapid bioavailability). Statistics have shown that four out of five patients prefer orally disintegrating dosage forms over conventional solid oral dosages forms. Pediatric, geriatric, bedridden, emetic patients and those with Central Nervous System disorders, have difficulty in swallowing or chewing solid dosage forms. Many of these patients are non-compliant in administering solid dosage forms due to fear of choking. OTFs when placed on the tip or the floor of the tongue are instantly wet by saliva. As a result, OTFs rapidly hydrate and then disintegrate and/or dissolve to release the medication for local and/or systemic absorption. This technology provides a good platform for patent non- infringing product development and for increasing the patent life-cycle of the existing products. The application of fast dissolving oral thin films is not only limited to buccal fast dissolving system, but also expands to other applications like gastroretentive, sublingual delivery systems. This review highlights the composition including the details of various types of polymers both natural and synthetic, the different types of manufacturing techniques, packaging materials and evaluation tests for the OTFs.

  1. 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.

  2. 21 CFR 520.903e - Febantel tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Febantel tablets. 520.903e Section 520.903e Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.903e Febantel tablets. (a...

  3. Development of a multi-layered vaginal tablet containing dapivirine, levonorgestrel and acyclovir for use as a multipurpose prevention technology.

    PubMed

    McConville, Christopher; Major, Ian; Devlin, Brid; Brimer, Andrew

    2016-07-01

    Multipurpose prevention technologies (MPTs) are preferably single dosage forms designed to simultaneously address multiple sexual and reproductive health needs, such as unintended pregnancy, HIV infection and other sexually transmitted infections (STIs). This manuscript describes the development of a range of multi-layered vaginal tablets, with both immediate and sustained release layers capable of delivering the antiretroviral drug dapivirine, the contraceptive hormone levonorgestrel, and the anti-herpes simplex virus drug acyclovir at independent release rates from a single dosage form. Depending on the design of the tablet in relation to the type (immediate or sustained release) or number of layers, the dose of each drug could be individually controlled. For example one tablet design was able to provide immediate release of all three drugs, while another tablet design was able to provide immediate release of both acyclovir and levonorgestrel, while providing sustained release of Dapivirine for up to 8h. A third tablet design was able to provide immediate release of both acyclovir and levonorgestrel, a large initial burst of Dapivirine, followed by sustained release of Dapivirine for up to 8h. All of the tablets passed the test for friability with a percent friability of less than 1%. The hardness of all tablet designs was between 115 and 153N, while their drug content met the European Pharmacopeia 2.9.40 Uniformity of Dosage units acceptance value at levels 1 and 2. Finally, the accelerated stability of all three actives was significantly enhanced in comparison with a mixed drug control. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Comparison of directly compressed vitamin B12 tablets prepared from micronized rotary-spun microfibers and cast films.

    PubMed

    Sebe, István; Bodai, Zsolt; Eke, Zsuzsanna; Kállai-Szabó, Barnabás; Szabó, Péter; Zelkó, Romána

    2015-01-01

    Fiber-based dosage forms are potential alternatives of conventional dosage forms from the point of the improved extent and rate of drug dissolution. Rotary-spun polymer fibers and cast films were prepared and micronized in order to direct compress after homogenization with tabletting excipients. Particle size distribution of powder mixtures of micronized fibers and films homogenized with tabletting excipients were determined by laser scattering particle size distribution analyzer. Powder rheological behavior of the mixtures containing micronized fibers and cast films was also compared. Positron annihilation lifetime spectroscopy was applied for the microstructural characterization of micronized fibers and films. The water-soluble vitamin B12 release from the compressed tablets was determined. It was confirmed that the rotary spinning method resulted in homogeneous supramolecularly ordered powder mixture, which was successfully compressed after homogenization with conventional tabletting excipients. The obtained directly compressed tablets showed uniform drug release of low variations. The results highlight the novel application of micronized rotary-spun fibers as intermediate for further processing reserving the original favorable powder characteristics of fibrous systems.

  5. A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice.

    PubMed

    Richey, Roberta H; Hughes, Clare; Craig, Jean V; Shah, Utpal U; Ford, James L; Barker, Catrin E; Peak, Matthew; Nunn, Anthony J; Turner, Mark A

    2017-02-25

    This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Alternative antiretroviral therapy formulations for patients unable to swallow solid oral dosage forms.

    PubMed

    Duggan, Joan M; Akpanudo, Barbara; Shukla, Vipul; Gutterson, Glen; Eitniear, Lindsey; Sahloff, Eric G

    2015-09-15

    Evidence-based guidance is presented to assist clinicians in selecting alternative formulations of antiretroviral (ARV) agents for patients with human immunodeficiency virus (HIV) infection who are unable to swallow tablets or capsules. The inability to take medications in standard oral dosage forms can be associated with nonadherence or the use of alternative administration strategies such as capsule or tablet breaking, crushing, or chewing. Patients with HIV infection require long-term ARV therapy to maintain viral suppression; ARV agents are predominately available as tablets and capsules that may pose swallowing difficulties for some patients. Using a variety of sources (the primary literature, pharmaceutical package inserts, and requests for unpublished data from drug manufacturers), available evidence on the bioavailability of ARV medications after disruption of the capsule or tablet matrix was reviewed; information on alternative formulations of ARV agents was also assessed. With several ARV agents, disruption of the solid oral dosage form by crushing, chewing, or breaking tablets or opening capsules prior to ingestion has been shown to result in altered bioavailability or pharmacokinetics and thus the potential for incomplete virological suppression, increased adverse effects, and suboptimal health outcomes. Of the 33 single-agent ARV medications and combination ARV products in five classes available at the time of review, approximately half exist as powders, liquids, injectables, or chewable or dissolvable tablets. If alternative ARV formulations or administration methods are used, close monitoring for achievement of virological and immunologic success and potential toxicities is recommended. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  7. Evaluation of various processes for simultaneous complexation and granulation to incorporate drug-cyclodextrin complexes into solid dosage forms.

    PubMed

    Gyanani, Vijay; Siddalingappa, Basavaraj; Betageri, Guru V

    2015-01-01

    Insoluble drugs often formulated with various excipients to enhance the dissolution. Cyclodextrins (CDs) are widely used excipients to improve dissolution profile of poorly soluble drugs. Drug-CD complexation process is complex and often requires multiple processes to produce solid dosage form. Hence, this study explored commonly used granulation processes for simultaneous complexation and granulation. Poorly soluble drugs ibuprofen and glyburide were selected as experimental drugs. Co-evaporation of drug:CD mixture from a solvent followed by wet granulation with water was considered as standard process for comparison. Spray granulation and fluid bed processing (FBP) using drug:CD solution in ethanol were evaluated as an alternative processes. The dissolution data of glyburide tablets indicated that tablets produced by spray granulation, FBP and co-evaporation-granulation have almost identical dissolution profile in water and 0.1% SLS (>70% in water and >60% in SLS versus 30 and 34%, respectively for plain tablet, in 120 min). Similarly, ibuprofen:CD tablets produced by co-evaporation-granulation and FBP displayed similar dissolution profile in 0.01 M HCl (pH 2.0) and buffer pH 5.5 (>90 and 100% versus 44 and 80% respectively for plain tablets, 120 min). Results of this study demonstrated that spray granulation is simple and cost effective process for low dose poorly soluble drugs to incorporate drug:CD complex into solid dosage form, whereas FBP is suitable for poorly soluble drugs with moderate dose.

  8. Solid oral forms availability in children: a cost saving investigation

    PubMed Central

    Lajoinie, Audrey; Henin, Emilie; Kassai, Behrouz; Terry, David

    2014-01-01

    Aim To assess the suitability and potential cost savings, from both the hospital and community perspective, of prescribed oral liquid medicine substitution with acceptable solid forms for children over 2 years. Method Oral liquid medicines dispensed from a paediatric hospital (UK) in 1 week were assessed by screening for existence of the solid form alternative and evaluating the acceptability of the available solid form, firstly related to the prescribed dose and secondly to acceptable size depending on the child's age. Costs were calculated based on providing treatment for 28 days or prescribed duration for short term treatments. Results Over 90% (440/476) of liquid formulations were available as a marketed solid form. Considering dosage acceptability (maximum of 10% deviation from prescribed dosage or 0% for narrow therapeutic range drugs, maximum tablet divisions into quarters) 80% of liquids could be substituted with a solid form. The main limitation for liquid substitution would be solid form size. However, two-thirds of prescribed liquids could have been substituted with a suitable solid form for dosage and size, with estimated savings being of £5K and £8K in 1 week, respectively based on hospital and community costs, corresponding to a projected annual saving of £238K and £410K (single institution). Conclusion Whilst not all children over 2 years will be able to swallow tablets, drug cost savings if oral liquid formulations were substituted with suitable solid dosage forms would be considerable. Given the numerous advantages of solid forms compared with liquids, this study may provide a theoretical basis for investing in supporting children to swallow tablets/capsules. PMID:24965935

  9. 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.

    PubMed

    Verstraete, G; Samaro, A; Grymonpré, W; Vanhoorne, V; Van Snick, B; Boone, M N; Hellemans, T; Van Hoorebeke, L; Remon, J P; Vervaet, C

    2018-01-30

    It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies.

    PubMed

    Missaghi, Shahrzad; Young, Cara; Fegely, Kurt; Rajabi-Siahboomi, Ali R

    2010-02-01

    Formulation of proton pump inhibitors (PPIs) into oral solid dosage forms is challenging because the drug molecules are acid-labile. The aim of this study is to evaluate different formulation strategies (monolithic and multiparticulates) for three PPI drugs, that is, rabeprazole sodium, lansoprazole, and esomeprazole magnesium, using delayed release film coating applications. The core tablets of rabeprazole sodium were prepared using organic wet granulation method. Multiparticulates of lansoprazole and esomeprazole magnesium were prepared through drug layering of sugar spheres, using powder layering and suspension layering methods, respectively. Tablets and drug-layered multiparticulates were seal-coated, followed by delayed release film coating application, using Acryl-EZE(R), aqueous acrylic enteric system. Multiparticulates were then filled into capsules. The final dosage forms were evaluated for physical properties, as well as in vitro dissolution testing in both compendial acid phase, 0.1N HCl (pH 1.2), and intermediate pH, acetate buffer (pH 4.5), followed by phosphate buffer, pH 6.8. The stability of the delayed release dosage forms was evaluated upon storage in accelerated conditions [40 degrees C/75% relative humidity] for 3 months. All dosage forms demonstrated excellent enteric protection in the acid phase, followed by rapid release in their respective buffer media. Moreover, the delayed release dosage forms remained stable under accelerated stability conditions for 3 months. Results showed that Acryl-EZE enteric coating systems provide excellent performance in both media (0.1N HCl and acetate buffer pH 4.5) for monolithic and multiparticulate dosage forms.

  11. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets. (a.... For the treatment of skin infections (wounds and abscesses) caused by susceptible strains of...

  12. Oral Medicines for Children in the European Paediatric Investigation Plans

    PubMed Central

    van Riet – Nales, Diana A.; Römkens, Erwin G. A. W.; Saint-Raymond, Agnes; Kozarewicz, Piotr; Schobben, Alfred F. A. M.; Egberts, Toine C. G.; Rademaker, Carin M. A.

    2014-01-01

    Introduction Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. Methods All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports. Results A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. Conclusion The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound. PMID:24897509

  13. Oral medicines for children in the European paediatric investigation plans.

    PubMed

    van Riet-Nales, Diana A; Römkens, Erwin G A W; Saint-Raymond, Agnes; Kozarewicz, Piotr; Schobben, Alfred F A M; Egberts, Toine C G; Rademaker, Carin M A

    2014-01-01

    Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports. A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound.

  14. 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.

  15. Physicochemical characterization and mechanisms of release of theophylline from melt-extruded dosage forms based on a methacrylic acid copolymer.

    PubMed

    Young, Christopher R; Dietzsch, Caroline; Cerea, Matteo; Farrell, Thomas; Fegely, Kurt A; Rajabi-Siahboomi, Ali; McGinity, James W

    2005-09-14

    The purpose of the current study was to investigate the physicochemical properties of melt-extruded dosage forms based on Acryl-EZE and to determine the influence of gelling agents on the mechanisms and kinetics of drug release from thermally processed matrices. Acryl-EZE is a pre-mixed excipient blend based on a methacrylic acid copolymer that is optimized for film-coating applications. Powder blends containing theophylline, Acryl-EZE, triethyl citrate and an optional gelling agent, Methocel K4M Premium (hydroxypropyl methylcellulose, HPMC, hypromellose 2208) or Carbopol 974P (carbomer), were thermally processed using a Randcastle single-screw extruder. The physical and chemical stability of materials during processing was determined using thermal gravimetric analysis and HPLC. The mechanism of drug release was determined using the Korsmeyer-Peppas model and the hydration and erosion of tablets during the dissolution studies were investigated. The excipient blends were physically and chemically stable during processing, and the resulting dosage forms exhibited pH-dependent dissolution properties. Extrusion of blends containing HPMC or carbomer changed the mechanism and kinetics of drug release from the thermally processed dosage forms. At concentrations of 5% or below, carbomer was more effective than HPMC at extending the duration of theophylline release from matrix tablets. Furthermore, carbomer containing tablets were stable upon storage for 3 months at 40 degrees C/75% RH. Thus, hot-melt extrusion was an effective process for the preparation of controlled release matrix systems based on Acryl-EZE.

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

    PubMed Central

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

    2014-01-01

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

  17. Determination of dasatinib in the tablet dosage form by ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis.

    PubMed

    Gonzalez, Aroa Garcia; Taraba, Lukáš; Hraníček, Jakub; Kozlík, Petr; Coufal, Pavel

    2017-01-01

    Dasatinib is a novel oral prescription drug proposed for treating adult patients with chronic myeloid leukemia. Three analytical methods, namely ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis, were developed, validated, and compared for determination of the drug in the tablet dosage form. The total analysis time of optimized ultra high performance liquid chromatography and capillary zone electrophoresis methods was 2.0 and 2.2 min, respectively. Direct ultraviolet detection with detection wavelength of 322 nm was employed in both cases. The optimized sequential injection analysis method was based on spectrophotometric detection of dasatinib after a simple colorimetric reaction with folin ciocalteau reagent forming a blue-colored complex with an absorbance maximum at 745 nm. The total analysis time was 2.5 min. The ultra high performance liquid chromatography method provided the lowest detection and quantitation limits and the most precise and accurate results. All three newly developed methods were demonstrated to be specific, linear, sensitive, precise, and accurate, providing results satisfactorily meeting the requirements of the pharmaceutical industry, and can be employed for the routine determination of the active pharmaceutical ingredient in the tablet dosage form. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. A Simple RP-HPLC Method for Quantitation of Itopride HCl in Tablet Dosage Form.

    PubMed

    Thiruvengada, Rajan Vs; Mohamed, Saleem Ts; Ramkanth, S; Alagusundaram, M; Ganaprakash, K; Madhusudhana, Chetty C

    2010-10-01

    An isocratic reversed phase high-performance liquid chromatographic method with ultraviolet detection at 220 nm has been developed for the quantification of itopride hydrochloride in tablet dosage form. The quantification was carried out using C(8) column (250 mm × 4.6 mm), 5-μm particle size SS column. The mobile phase comprised of two solvents (Solvent A: buffer 1.4 mL ortho-phosphoric acid adjusted to pH 3.0 with triethyl amine and Solvent B: acetonitrile). The ratio of Solvent A: Solvent B was 75:25 v/v. The flow rate was 1.0 mL (-1)with UV detection at 220 nm. The method has been validated and proved to be robust. The calibration curve was linear in the concentration range of 80-120% with coefficient of correlation 0.9995. The percentage recovery for itopride HCl was 100.01%. The proposed method was validated for its selectivity, linearity, accuracy, and precision. The method was found to be suitable for the quality control of itopride HCl in tablet dosage formulation.

  19. A Simple RP-HPLC Method for Quantitation of Itopride HCl in Tablet Dosage Form

    PubMed Central

    Thiruvengada, Rajan VS; Mohamed, Saleem TS; Ramkanth, S; Alagusundaram, M; Ganaprakash, K; Madhusudhana, Chetty C

    2010-01-01

    An isocratic reversed phase high-performance liquid chromatographic method with ultraviolet detection at 220 nm has been developed for the quantification of itopride hydrochloride in tablet dosage form. The quantification was carried out using C8 column (250 mm × 4.6 mm), 5-μm particle size SS column. The mobile phase comprised of two solvents (Solvent A: buffer 1.4 mL ortho-phosphoric acid adjusted to pH 3.0 with triethyl amine and Solvent B: acetonitrile). The ratio of Solvent A: Solvent B was 75:25 v/v. The flow rate was 1.0 mL -1with UV detection at 220 nm. The method has been validated and proved to be robust. The calibration curve was linear in the concentration range of 80-120% with coefficient of correlation 0.9995. The percentage recovery for itopride HCl was 100.01%. The proposed method was validated for its selectivity, linearity, accuracy, and precision. The method was found to be suitable for the quality control of itopride HCl in tablet dosage formulation. PMID:21264104

  20. 21 CFR 520.816 - Epsiprantel tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.816 Epsiprantel tablets. (a... of feline cestodes D. caninum and T. taeniaeformis. (3) Limitations. For oral use only as a single...

  1. 21 CFR 520.816 - Epsiprantel tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.816 Epsiprantel tablets. (a... of feline cestodes D. caninum and T. taeniaeformis. (3) Limitations. For oral use only as a single...

  2. 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

  3. A novel electrostatic dry powder coating process for pharmaceutical dosage forms: immediate release coatings for tablets.

    PubMed

    Qiao, Mingxi; Zhang, Liqiang; Ma, Yingliang; Zhu, Jesse; Chow, Kwok

    2010-10-01

    An electrostatic dry powder coating process for pharmaceutical solid dosage forms was developed for the first time by electrostatic dry powder coating in a pan coater system. Two immediate release coating compositions with Opadry® AMB and Eudragit® EPO were successfully applied using this process. A liquid plasticizer was sprayed onto the surface of the tablet cores to increase the conductivity of tablet cores to enhance particle deposition, electrical resistivity reduced from greater than 1×10(13)Ωm to less than 1×10(9)Ωm, and to lower the glass transition temperature (T(g)) of the coating polymer for film forming in the pan coater. The application of liquid plasticizer was followed by spraying charged coating particles using an electrostatic charging gun to enhance the uniform deposition on tablet surface. The coating particles were coalesced into a thin film by curing at an acceptable processing temperature as formation was confirmed by SEM micrographs. The results also show that the optimized dry powder coating process produces tablets with smooth surface, good coating uniformity and release profile that are comparable to that of the tablet cores. The data also suggest that this novel electrostatic dry powder coating technique is an alternative to aqueous- or solvent-based coating process for pharmaceutical products. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  4. 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.

  5. Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

    PubMed

    Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-02-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. 21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...

  7. 21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.863...

  8. 21 CFR 520.420 - Chlorothiazide tablets and boluses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Chlorothiazide tablets and boluses. 520.420 Section 520.420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.420...

  9. 21 CFR 520.1193 - Ivermectin tablets and chewables.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ivermectin tablets and chewables. 520.1193 Section 520.1193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1193 Ivermectin...

  10. 21 CFR 520.420 - Chlorothiazide tablets and boluses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Chlorothiazide tablets and boluses. 520.420 Section 520.420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.420...

  11. 21 CFR 520.310 - Caramiphen ethanedisulfonate and ammonium chloride tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Caramiphen ethanedisulfonate and ammonium chloride tablets. 520.310 Section 520.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...

  12. 21 CFR 520.310 - Caramiphen ethanedisulfonate and ammonium chloride tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Caramiphen ethanedisulfonate and ammonium chloride tablets. 520.310 Section 520.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...

  13. 21 CFR 520.310 - Caramiphen ethanedisulfonate and ammonium chloride tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Caramiphen ethanedisulfonate and ammonium chloride tablets. 520.310 Section 520.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...

  14. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.784 Doxylamine...

  15. 21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.863...

  16. 21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...

  17. 21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...

  18. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.784 Doxylamine...

  19. 21 CFR 520.1157 - Iodinated casein tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Iodinated casein tablets. 520.1157 Section 520.1157 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1157 Iodinated casein...

  20. 21 CFR 520.531 - Cythioate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.531 Cythioate tablets. (a.... (3) Limitations. For oral use in dogs only. Do not use in greyhounds or in animals that are pregnant...

  1. 21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...

  2. 16 CFR 1700.14 - Substances requiring special packaging.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

  3. 16 CFR 1700.14 - Substances requiring special packaging.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

  4. 16 CFR § 1700.14 - Substances requiring special packaging.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

  5. 16 CFR 1700.14 - Substances requiring special packaging.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

  6. 16 CFR 1700.14 - Substances requiring special packaging.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

  7. FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration.

    PubMed

    Perioli, Luana; Ambrogi, Valeria; Pagano, Cinzia; Scuota, Stefania; Rossi, Carlo

    2009-07-30

    Topical administration of the antibacterial metronidazole (MET) represents the most common therapy in the treatment of bacterial vaginosis (BV). The formulations generally available for BV therapy are creams, gels, vaginal lavages and vaginal suppositories. In this study, a new dosage form, containing MET, was developed with the aim to realize vaginal mucoadhesive tablets by including bioadhesive polymers as chitosan (FG90C), polyvinylpyrrolidone (PVPK90) and polycarbophil (PCPAA1), blended in different ratios. All formulations were characterized by studies of DSC, friability, hardness, hydration, mucoadhesion, in vitro release and antibacterial activity. All polymer mixtures employed were used to prepare tablets with the compactness and hardness so as allow the application on vaginal mucosa. FG90C performances improved in particular when mixed to PVPK90 (1:1 ratio). This kind of delivery system is suitable for formulating MET for topical application representing a good alternative to traditional dosage forms for vaginal topical administration.

  8. Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms.

    PubMed

    Gioumouxouzis, Christos I; Chatzitaki, Aikaterini-Theodora; Karavasili, Christina; Katsamenis, Orestis L; Tzetzis, Dimitrios; Mystiridou, Emmanouela; Bouropoulos, Nikolaos; Fatouros, Dimitrios G

    2018-06-14

    Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (μCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.

  9. A Tape Method for Fast Characterization and Identification of Active Pharmaceutical Ingredients in the 2-18 THz Spectral Range

    NASA Astrophysics Data System (ADS)

    Kissi, Eric Ofosu; Bawuah, Prince; Silfsten, Pertti; Peiponen, Kai-Erik

    2015-03-01

    In order to find counterfeit drugs quickly and reliably, we have developed `tape method' a transmission spectroscopic terahertz (THz) measurement technique and compared it with a standard attenuated total reflection (ATR) THz spectroscopic measurement. We used well-known training samples, which include commercial paracetamol and aspirin tablets to check the validity of these two measurement techniques. In this study, the spectral features of some active pharmaceutical ingredients (APIs), such as aspirin and paracetamol are characterized for identification purpose. This work covers a wide THz spectral range namely, 2-18 THz. This proposed simple but novel technique, the tape method, was used for characterizing API and identifying their presence in their dosage forms. By comparing the spectra of the APIs to their dosage forms (powder samples), all distinct fingerprints present in the APIs are also present in their respective dosage forms. The positions of the spectral features obtained with the ATR techniques were akin to that obtained from the tape method. The ATR and the tape method therefore, complement each other. The presence of distinct fingerprints in this spectral range has highlighted the possibility of developing fast THz sensors for the screening of pharmaceuticals. It is worth noting that, the ATR method is applicable to flat faced tablets whereas the tape method is suitable for powders in general (e.g. curved surface tablets that require milling before measurement). Finally, we have demonstrated that ATR techniques can be used to screen counterfeit antimalarial tablets.

  10. A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets.

    PubMed

    Okwuosa, Tochukwu C; Stefaniak, Dominika; Arafat, Basel; Isreb, Abdullah; Wan, Ka-Wai; Alhnan, Mohamed A

    2016-11-01

    The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing. Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus. Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern. Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.

  11. A novel solid dosage form of rifampicin and isoniazid with improved functionality.

    PubMed

    Gohel, Mukesh C; Sarvaiya, Krishnakant G

    2007-08-24

    The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium and to modulate the release of rifampicin in the stomach and isoniazid in the intestine. Gastroretentive tablets of rifampicin (150 mg) were prepared by the wet granulation method using hydroxypropyl methylcellulose, calcium carbonate, and polyethylene glycol 4000. The granules and tablets of rifampicin were characterized. Hard gelatin capsules (size 4) containing a compacted mass of isoniazid (150 mg) and dicalcium phosphate (75 mg) were enteric coated. Two tablets of rifampicin and 1 capsule (size 4) of isoniazid were put into a hard gelatin capsule (size 00). The in vitro drug release and in vitro drug degradation studies were performed. Rifampicin was released over 4 hours by zero-order kinetics from the novel dosage form. More than 90% of isoniazid was released in alkaline medium in 30 minutes. The results of dissolution studies with the US Pharmacopeia XXIII method revealed that a substantial amount of rifampicin was degraded from the immediate release capsule containing rifampicin and isoniazid powder owing to drug accumulation in the dissolution vessel and also to the presence of isoniazid. The degradation of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested (3.6%-4.8% degradation of rifampicin at 4 hours) because of the minimization of physical contact between the 2 drugs and controlled release of rifampicin in acidic medium in the modified Rossett-Rice apparatus. This study concludes that the problem of rifampicin degradation can be alleviated to a certain extent by this novel dosage form.

  12. Buccal Dosage Forms: General Considerations for Pediatric Patients.

    PubMed

    Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O

    2017-02-01

    The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.

  13. Swallowing Tablets and Capsules Increases the Risk of Penetration and Aspiration in Patients with Stroke-Induced Dysphagia.

    PubMed

    Schiele, Julia T; Penner, Heike; Schneider, Hendrik; Quinzler, Renate; Reich, Gabriele; Wezler, Nikolai; Micol, William; Oster, Peter; Haefeli, Walter E

    2015-10-01

    We evaluated the prevalence of difficulties swallowing solid dosage forms in patients with stroke-induced dysphagia and whether swallowing tablets/capsules increases their risk of penetration and aspiration. Concurrently, we explored whether routinely performed assessment tests help identify patients at risk. Using video endoscopy, we evaluated how 52 patients swallowed four different placebos (round, oval, and oblong tablets and a capsule) with texture-modified water (TMW, pudding consistency) and milk and rated their swallowing performance according to the Penetration Aspiration Scale (PAS). Additionally, Daniels Test, Bogenhausener Dysphagiescore, Scandinavian Stroke Scale, Barthel Index, and Tinetti's Mobility Test were conducted. A substantial proportion of the patients experienced severe difficulties swallowing solid oral dosage forms (TMW: 40.4 %, milk: 43.5 %). Compared to the administration of TMW/milk alone, the placebos increased the PAS values in the majority of the patients (TMW: median PAS from 1.5 to 2.0; milk: median PAS from 1.5 to 2.5, each p value <0.0001) and residue values were significantly higher (p < 0.05). Whereas video-endoscopic examination reliably identified patients with difficulties swallowing medication, neither patients' self-evaluation nor one of the routinely performed bedside tests did. Therefore, before video-endoscopic evaluation, many drugs were modified unnecessarily and 20.8 % of these were crushed inadequately, although switching to another dosage form or drug would have been possible. Hence, safety and effectiveness of swallowing tablets and capsules should be evaluated routinely in video-endoscopic examinations, tablets/capsules should rather be provided with TMW than with milk, and the appropriateness of "non per os except medication" orders for dysphagic stroke patients should be questioned.

  14. 21 CFR 520.622c - Diethylcarbamazine citrate chewable tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine citrate chewable tablets. 520.622c Section 520.622c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622c...

  15. 21 CFR 520.763a - Dithiazanine iodide tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dithiazanine iodide tablets. 520.763a Section 520.763a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.763a Dithiazanine...

  16. 21 CFR 520.540c - Dexamethasone chewable tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dexamethasone chewable tablets. 520.540c Section 520.540c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540c...

  17. 21 CFR 520.763a - Dithiazanine iodide tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dithiazanine iodide tablets. 520.763a Section 520.763a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.763a Dithiazanine...

  18. 21 CFR 520.622c - Diethylcarbamazine citrate chewable tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine citrate chewable tablets. 520.622c Section 520.622c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622c...

  19. 21 CFR 520.622a - Diethylcarbamazine citrate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine citrate tablets. 520.622a Section 520.622a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622a...

  20. 21 CFR 520.622a - Diethylcarbamazine citrate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine citrate tablets. 520.622a Section 520.622a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622a...

  1. 21 CFR 520.622a - Diethylcarbamazine citrate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine citrate tablets. 520.622a Section 520.622a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622a...

  2. 21 CFR 520.622c - Diethylcarbamazine citrate chewable tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine citrate chewable tablets. 520.622c Section 520.622c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622c...

  3. 21 CFR 520.540c - Dexamethasone chewable tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dexamethasone chewable tablets. 520.540c Section 520.540c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540c...

  4. 21 CFR 520.622a - Diethylcarbamazine citrate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine citrate tablets. 520.622a Section 520.622a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622a...

  5. 21 CFR 520.763a - Dithiazanine iodide tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dithiazanine iodide tablets. 520.763a Section 520.763a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.763a Dithiazanine...

  6. 21 CFR 520.1196 - Ivermectin and pyrantel pamoate chewable tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ivermectin and pyrantel pamoate chewable tablets. 520.1196 Section 520.1196 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1196...

  7. 21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ivermectin, pyrantel, and praziquantel tablets. 520.1199 Section 520.1199 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1199...

  8. 21 CFR 520.82a - Aminopropazine fumarate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Aminopropazine fumarate tablets. 520.82a Section 520.82a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82a...

  9. 21 CFR 520.1242b - Levamisole hydrochloride tablet or oblet (bolus).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Levamisole hydrochloride tablet or oblet (bolus). 520.1242b Section 520.1242b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...

  10. 21 CFR 520.82a - Aminopropazine fumarate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Aminopropazine fumarate tablets. 520.82a Section 520.82a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82a...

  11. 21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ivermectin, fenbendazole, and praziquantel tablets. 520.1200 Section 520.1200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1200...

  12. 21 CFR 520.622c - Diethylcarbamazine citrate chewable tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine citrate chewable tablets. 520.622c Section 520.622c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622c...

  13. 21 CFR 520.82a - Aminopropazine fumarate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Aminopropazine fumarate tablets. 520.82a Section 520.82a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82a...

  14. 21 CFR 520.763a - Dithiazanine iodide tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Dithiazanine iodide tablets. 520.763a Section 520.763a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.763a Dithiazanine...

  15. 21 CFR 520.540c - Dexamethasone chewable tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dexamethasone chewable tablets. 520.540c Section 520.540c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540c...

  16. INFLUENCE OF TABLET SPLITTING ON CONTENT UNIFORMITY OF LISINOPRIL/ HYDROCHLORTHIAZIDE TABLETS

    PubMed Central

    Vranić, Edina; Uzunović, Alija

    2007-01-01

    Dose-related adverse effects of medications are a major problem in modern medical practice. The “correct” dose, based on drug company guidelines in package inserts, may not be correct for many patients. Tablet splitting or dividing has been an accepted practice for many years as a means of obtaining the prescribed dose of medication. As model tablets for this investigation, two batches of lisinopril-hydrochlorothiazide scored tablets labeled to contain 20/12,5 mg were used. The aim of this study was to establish possible influence of tablet splitting on content uniformity of lisinopril/hydrochlorthiazide tablets. Determination of the content uniformity of lisinopril and hydrochlorthiazide in our batches, was carried out by HPLC method. The results of content uniformity studies for halves of tablets containing combination of lisinopril-hydrochlorthiazide (supposed to contain 50% of stated 20/12,5 mg in the whole tablet) were: 49,60 ±3,29% and 49,29±0,60 % (lisinopril); 50,33±3,50% and 50,69±1,95% (hydrochlorthiazide) for batch I and II, respectively. We can conclude that the results obtained in this study support an option of tablet splitting, which is very important for obtaining the required dosage when a dosage form of the required strength is unavailable, and for better individualization of the therapy PMID:18039191

  17. Modeling picking on pharmaceutical tablets

    NASA Astrophysics Data System (ADS)

    Swaminathan, Shrikant

    Tablets are the most popular solid dosage form in the pharmaceutical industry because they are cheap to manufacture, chemically and mechanically stable and easy to transport and fairly easy to control dosage. Pharmaceutical tableting operations have been around for decades however the process is still not well understood. One of the common problems faced during the production of pharmaceutical tablets by powder compaction is sticking of powder to the punch face, This is known as 'sticking'. A more specialized case of sticking is picking when the powder is pulled away form the compact in the vicinity of debossed features. In the pharmaceutical industry, picking is solved by trial and error which is an expensive, labor intensive and time consuming affair. The objective of this work was to develop, validate, and implement a modeling framework for predicting picking in powder compacts. The model was developed in Abaqus a commercially available finite element package. The resulting model was used to investigate the influence of debossed feature geometry viz. the stroke angle and degree of pre-pick, and, influence of lubricant on picking. (Abstract shortened by ProQuest.).

  18. 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 rights reserved.

  19. Bioavailability of two oral suspension and two oral tablet formulations of acyclovir 400 mg: two single-dose, open-label, randomized, two-period crossover comparisons in healthy Mexican adult subjects.

    PubMed

    Palma-Aguirre, Jose Antonio; Absalón-Reyes, Jose Antonio; Novoa-Heckel, Germán; de Lago, Alberto; Oliva, Iván; Rodríguez, Zulema; González-de la Parra, Mario; Burke-Fraga, Victoria; Namur, Salvador

    2007-06-01

    Acyclovir is an important antiviral drug, used extensively for treatment of herpes simplex and varicella zoster. Six oral generic formulations of acyclovir are available in Mexico; however, a literature search failed to identify data information concerning the bioavailability of these formulations in the Mexican population. The aim of these 2 studies was to compare the bioavailability of 4 oral formulations of acyclovir 400 mg--2 tablet formulations and 2 suspension formulations--with their corresponding listed drug references in Mexico (a list issued by Mexican Health Authorities). Two separate, single-dose, open-label, randomized, 2-period crossover studies were conducted at the Centro de Estudios Científicos y Clínicos Pharma, S.A. de C.V. (clinical unit), Mexico City, Mexico. For each study, a different set of eligible subjects were selected. They included healthy Mexican volunteers of either sex. For each study, subjects were randomly assigned to receive 1 test formulation of acyclovir 400 mg followed by the reference formulation, or vice versa, with a 1-week washout period between doses. After a 12-hour (overnight) fast, subjects received a single 400-mg dose (tablet or 10-mL suspension) of the corresponding formulation. For the analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, and 24 hours after dosing. The formulations were considered bioequivalent if the natural logarithm (ln)-transformed ratios of Cmax and AUC were within the predetermined equivalence range of 80% to 125% and if P

  20. Transit of pharmaceutical dosage forms through the small intestine.

    PubMed Central

    Davis, S S; Hardy, J G; Fara, J W

    1986-01-01

    The gastrointestinal transit of pharmaceutical dosage forms has been measured in 201 studies in normal subjects using gamma scintigraphy. Solutions, small pellets, and single units (matrix tablets and osmotic pumps) were administered with different amounts of food in the stomach, ranging from fasted state to heavy breakfast. Gastric emptying was affected by the nature of the dosage form and the presence of food in the stomach. Solutions and pellets were emptied even when the stomach was in the digestive mode, while single units were retained for long periods of time, depending on the size of the meal. In contrast, measured intestinal transit times were independent of the dosage form and fed state. The small intestinal transit time of about three hours (mean +/- 1 h SEM) has implications for the design of dosage forms for the sustained release of drugs in specific positions in the gastrointestinal tract. PMID:3732895

  1. 21 CFR 520.82b - Aminopropazine fumarate, neomycin sulfate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Aminopropazine fumarate, neomycin sulfate tablets. 520.82b Section 520.82b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82b...

  2. 21 CFR 520.82b - Aminopropazine fumarate, neomycin sulfate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Aminopropazine fumarate, neomycin sulfate tablets. 520.82b Section 520.82b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82b...

  3. 21 CFR 520.82b - Aminopropazine fumarate, neomycin sulfate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Aminopropazine fumarate, neomycin sulfate tablets. 520.82b Section 520.82b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82b...

  4. Hyperspectral techniques in analysis of oral dosage forms.

    PubMed

    Hamilton, Sara J; Lowell, Amanda E; Lodder, Robert A

    2002-10-01

    Pharmaceutical oral dosage forms are used in this paper to test the sensitivity and spatial resolution of hyperspectral imaging instruments. The first experiment tested the hypothesis that a near-infrared (IR) tunable diode-based remote sensing system is capable of monitoring degradation of hard gelatin capsules at a relatively long distance (0.5 km). Spectra from the capsules were used to differentiate among capsules exposed to an atmosphere containing 150 ppb formaldehyde for 0, 2, 4, and 8 h. Robust median-based principal component regression with Bayesian inference was employed for outlier detection. The second experiment tested the hypothesis that near-IR imaging spectrometry of tablets permits the identification and composition of multiple individual tablets to be determined simultaneously. A near-IR camera was used to collect thousands of spectra simultaneously from a field of blister-packaged tablets. The number of tablets that a typical near-IR camera can currently analyze simultaneously was estimated to be approximately 1300. The bootstrap error-adjusted single-sample technique chemometric-imaging algorithm was used to draw probability-density contour plots that revealed tablet composition. The single-capsule analysis provides an indication of how far apart the sample and instrumentation can be and still maintain adequate signal-to-noise ratio (S/N), while the multiple-tablet imaging experiment gives an indication of how many samples can be analyzed simultaneously while maintaining an adequate S/N and pixel coverage on each sample.

  5. 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.

  6. Preparation of delayed release tablet dosage forms by compression coating: effect of coating material on theophylline release.

    PubMed

    El-Malah, Yasser; Nazzal, Sami

    2010-06-01

    In this study, compression-coated tablets were prepared and examined by real-time swelling/erosion analysis and dissolution studies. Of the coating materials, PVP showed no swelling behavior and had no impact on theophylline release. Polyox(®) exhibited swelling behavior of an entangled polymer, which was reflected in its > 14-hour delayed-release profile. Hydroxypropyl methylcellulose (HPMC), which revealed the characteristics of a disentangled polymer, caused a 2-h delay in theophylline release. Based on preliminary texture analysis data, Polyox(®)/PVP blends were used as coating materials to manipulate the onset of drug release from the compression-coated tablets. Of the blends, at a 1:1 ratio, for example, resulted in a burst release after 10 h, which demonstrated the feasibility of preparing delayed release dosage forms by compression coating. Furthermore, it was feasible to predict the dissolution behavior of polymers from their swelling/erosion data, which were generated from texture analysis.

  7. Formulation of medicines for children

    PubMed Central

    Nunn, Tony; Williams, Julie

    2005-01-01

    The development of age-adapted dosage forms and taste-masking of bitter-tasting drugs administered orally for children, are formidable challenges for formulation scientists. Childhood is a period of maturation requiring knowledge of developmental pharmacology to establish dose but the ability of the child to manage different dosage forms and devices also changes. Paediatric formulations must allow accurate administration of the dose to children of widely varying age and weight. Whilst the oral route will be preferred for long term use and the intravenous route for the acutely ill, many of the dosage forms designed for adults, such as oro-dispersible tablets, buccal gels and transdermal patches, would also benefit children if they contained an appropriate paediatric dose. The age at which children can swallow conventional tablets is of great importance for their safety. Liquid medicines are usually recommended for infants and younger dhildren so the ability to mask unpleasant taste with sweeteners and flavours is crucial. More sophisticated formulations such as granules and oro-dispersible tablets may be required but there will be limitations on choice and concentration of excipients. There are many gaps in our knowledge about paediatric formulations and many challenges for the industry if suitable preparations are to be available for all ranges. A CHMP points to consider document is soon to be released. More research and clinical feedback are important because a formulation with poor acceptability may affect compliance, prescribing practice and ultimately commercial viability. PMID:15948931

  8. 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

  9. Advances in development, scale-up and manufacturing of microbicide gels, films, and tablets.

    PubMed

    Garg, Sanjay; Goldman, David; Krumme, Markus; Rohan, Lisa C; Smoot, Stuart; Friend, David R

    2010-12-01

    Vaginal HIV microbicides are topical, self administered products designed to prevent or significantly reduce transmission of HIV infection in women. The earliest microbicide candidates developed have been formulated as coitally dependent (used around the time of sex) gels and creams. All microbicide candidates tested in Phase III clinical trials, so far, have been gel products with non-specific mechanisms of action. However, recently, research is focusing on compounds containing highly potent and specific anti-retrovirals. These specific anti-retrovirals are being formulated as primary dosage forms such as vaginal gels or in alternative dosage forms such as fast dissolve films and tablets. Recent innovations also include development of combination products of highly active antiviral drugs such as reverse transcriptase inhibitors and entry inhibitors, which would theoretically be more effective and would reduce the possibility of drug resistance. In this article, an overview of recent advances in the microbicide gel, film, and tablet formulations and issues pertaining to scale-up, formulation, and evaluation challenges and regulatory guidelines have been presented. This article forms part of a special supplement covering presentations on gels, tablets, and films from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Formulation and process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant.

    PubMed

    Leane, Michael M; Sinclair, Wayne; Qian, Feng; Haddadin, Raja; Brown, Alan; Tobyn, Mike; Dennis, Andrew B

    2013-01-01

    Amorphous forms of poorly soluble drugs are more frequently being incorporated into solid dispersions for administration and extensive research has led to a reasonable understanding of how these dispersions, although still kinetically unstable, improve stability relative to the pure amorphous form. There remains however a paucity of literature describing the effects on such solid dispersions of subsequent processing into solid dosage forms such as tablets. This paper addresses this area by looking at the effects of the addition of common excipients and different manufacturing routes on the stability of a spray-dried dispersion (SDD) of the cannabinoid CB-1 antagonist, ibipinabant. A marked difference in physical stability of tablets was seen with the different fillers with microcrystalline cellulose (MCC) giving the best stability profile. It was found that minimising the number of compression steps led to improved formulation stability with a direct compression process giving the best results. Increased levels of crystallinity were seen in coated tablets most likely due to the exposure of the amorphous matrix to moisture and heat during the coating process. DSIMS analysis of the SDD particles indicated increased levels of polymer on the surface.

  11. Tablet splitting of narrow therapeutic index drugs: a nationwide survey in Taiwan.

    PubMed

    Chou, Chia-Lin; Hsu, Chia-Chen; Chou, Chia-Yu; Chen, Tzeng-Ji; Chou, Li-Fang; Chou, Yueh-Ching

    2015-12-01

    Tablet splitting or pill splitting frequently occurs in daily medical practice. For drugs with special pharmacokinetic characters, such as drugs with narrow therapeutic index (NTI), unequal split tablets might lead to erroneous dose titration and it even cause toxicity. The aim of this study was to investigate the frequency of prescribing split NTI drugs at ambulatory setting in Taiwan. A population-based retrospective study was conducted using the National Health Insurance Research Database in Taiwan. All ambulatory visits were analyzed from the longitudinal cohort datasets of the National Health Insurance Research Database. The details of ambulatory prescriptions containing NTI drugs were extracted by using the claims datasets of one million beneficiaries from National Healthcare Insurance Research Database in 2010 in Taiwan. The analyses were stratified by dosage form, patient age and the number of prescribed tablets in a single dose for each NTI drugs. Main outcome measures Number and distinct dosage forms of available NTI drug items in Taiwan, number of prescriptions involved split NTI drugs, and number of patients received split NTI drugs. A total of 148,548 patients had received 512,398 prescriptions of NTI drugs and 41.8 % (n = 62,121) of patients had received 36.3 % (n = 185,936) of NTI drug prescriptions in form of split tablets. The percentage of splitting was highest in digoxin prescriptions (81.0 %), followed by warfarin (72.0 %). In the elderly patients, split tablets were very prevalent with digoxin (82.4 %) and warfarin (84.5 %). NTI drugs were frequently prescribed to be taken in split forms in Taiwan. Interventions may be needed to provide effective and convenient NTI drug use. Further studies are needed to evaluate the clinical outcome of inappropriate split NTI drugs.

  12. UV Spectrophotometric Method for Estimation of Polypeptide-K in Bulk and Tablet Dosage Forms

    NASA Astrophysics Data System (ADS)

    Kaur, P.; Singh, S. Kumar; Gulati, M.; Vaidya, Y.

    2016-01-01

    An analytical method for estimation of polypeptide-k using UV spectrophotometry has been developed and validated for bulk as well as tablet dosage form. The developed method was validated for linearity, precision, accuracy, specificity, robustness, detection, and quantitation limits. The method has shown good linearity over the range from 100.0 to 300.0 μg/ml with a correlation coefficient of 0.9943. The percentage recovery of 99.88% showed that the method was highly accurate. The precision demonstrated relative standard deviation of less than 2.0%. The LOD and LOQ of the method were found to be 4.4 and 13.33, respectively. The study established that the proposed method is reliable, specific, reproducible, and cost-effective for the determination of polypeptide-k.

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

    PubMed

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

    2017-01-01

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

  14. 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

  15. Electrolyte-stimulated biphasic dissolution profile and stability enhancement for tablets containing drug-polyelectrolyte complexes.

    PubMed

    Kindermann, Christoph; Matthée, Karin; Sievert, Frank; Breitkreutz, Jörg

    2012-10-01

    Recently introduced drug-polyelectrolyte complexes prepared by hot-melt extrusion should be processed to solid dosage forms with tailor-made release properties. Their potential of stability enhancement should be investigated. Milled hot-melt extruded naproxen-EUDRAGIT® E PO polyelectrolyte complexes were subsequently processed to double-layer tablets with varying complex loadings on a rotary-die press. Physicochemical interactions were studied under ICH guideline conditions and using the Gordon-Taylor equation. Sorption and desorption were determined to investigate the influence of moisture and temperature on the complex and related to stability tests under accelerated conditions. Naproxen release from the drug-polyelectrolyte complex is triggered by electrolyte concentration. Depending on the complex loading, phosphate buffer pH 6.8 stimulated a biphasic dissolution profile of the produced double-layer tablets: immediate release from the first layer with 65% loading and prolonged release from the second layer within 24 h (98.5% loading). XRPD patterns proved pseudopolymorphism for tablets containing the pure drug under common storage conditions whereas the drug-complex was stable in the amorphous state. Drug-polyelectrolyte complexes enable tailor-made dissolution profiles of solid dosage forms by electrolyte stimulation and increase stability under common storage conditions.

  16. Melt-processed polymeric cellular dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2015-12-28

    The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.

  17. Preparation of surfactant-free nanoparticles of methacrylic acid copolymers used for film coating.

    PubMed

    Nguyen, Cung An; Konan-Kouakou, Yvette Niamien; Allémann, Eric; Doelker, Eric; Quintanar-Guerrero, David; Fessi, Hatem; Gurny, Robert

    2006-07-28

    The aim of the present study was to prepare surfactant-free pseudolatexes of various methacrylic acid copolymers. These aqueous colloidal dispersions of polymeric materials for oral administration are intended for film coating of solid dosage forms or for direct manufacturing of nanoparticles. Nanoparticulate dispersions were produced by an emulsification-diffusion method involving the use of partially water-miscible solvents and the mutual saturation of the aqueous and organic phases prior to the emulsification in order to reduce the initial thermodynamic instability of the emulsion. Because of the self-emulsifying properties of the methacrylic acid copolymers, it was possible to prepare aqueous dispersions of colloidal size containing up to 30% wt/vol of Eudragit RL, RS, and E using 2-butanone or methyl acetate as partially water-miscible solvents, but without any surfactant. However, in the case of the cationic Eudragit E, protonation of the tertiary amine groups by acidification of the aqueous phase was necessary to improve the emulsion stability in the absence of surfactant and subsequently to prevent droplet coalescence during evaporation. In addition, a pseudolatex of Eudragit E was used to validate the coating properties of the formulation for solid dosage forms. Film-coated tablets of quinidine sulfate showed a transparent glossy continuous film that was firmly attached to the tablet. The dissolution profile of quinidine sulfate from the tablets coated with the Eudragit E pseudolatex was comparable to that of tablets coated with an acetonic solution of Eudragit E. Furthermore, both types of coating ensured similar taste masking. The emulsification-evaporation method used was shown to be appropriate for the preparation of surfactant-free colloidal dispersions of the 3 types of preformed methacrylic acid copolymers; the dispersions can subsequently be used for film coating of solid dosage forms.

  18. 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

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

    PubMed

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

    2014-07-16

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

  20. 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 products. The dehydroepiandrosterone rapid-dissolving tablets investigated in this pilot study were physically and chemically stable during preparation and over six months of storage at 25°C and 60% relative humidity. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  1. Meta-analysis of Magnetic Marker Monitoring Data to Characterize the Movement of Single Unit Dosage Forms Though the Gastrointestinal Tract Under Fed and Fasting Conditions.

    PubMed

    Hénin, Emilie; Bergstrand, Martin; Weitschies, Werner; Karlsson, Mats O

    2016-03-01

    To develop a model predicting movement of non-disintegrating single unit dosage forms (or "tablet") through the gastrointestinal tract and characterizing the effect of food intake, based on Magnetic Marker Monitoring data, allowing real-time location of a magnetically labeled formulation. Five studies including 30 individuals in 94 occasions under 3 food status were considered. The mean residence time (MRT) of the tablet and the effect of food intake in proximal (PS) and distal stomach (DS), small intestine (SI), ascending (AC), transverse (TC) and descending colon (DC) were estimated using a Markov model for probabilities of movement. Under fasting conditions, tablet MRTs were 9.4 min in PS, 10.4 in DS, 246 in SI, 545 in AC, 135 in TC, and 286 in DC. A meal taken simultaneous to tablet intake prolonged tablet MRT to 99 min in PS and to 232 in DS; probability of gastric emptying increased of 89% each hour from 2.25 h after meal. The effect of a gastroileac reflex, caused by a secondary meal, accelerated the transit from terminal SI to AC. This model-based knowledge can be used as a part of mechanism-based models for drug absorption, applied for bottom-up predictions and/or top-down estimation.

  2. Determination of aliskiren in tablet dosage forms by a validated stability-indicating RP-LC method.

    PubMed

    Wrasse-Sangoi, M; Sangoi, M S; Oliveira, P R; Secretti, L T; Rolim, C M B

    2011-02-01

    A reversed-phase liquid chromatography (RP-LC) method is validated for the determination of aliskiren in tablet dosage form. The LC method is carried out on a Waters XBridge C(18) column (150 × 4.6 mm i.d.), maintained at 25°C. The mobile phase consisted of acetonitrile:water (95:5, v/v)/phosphoric acid (25 mM, pH 3.0) (40:60, v/v), run at a flow rate of 1.0 mL/min, with photodiode array detector set at 229 nm. The chromatographic separation is obtained with aliskiren retention time of 3.68 min, and it is linear in the range of 10-300 μg/mL (r = 0.9999). The limits of detection and quantitation are 2.38 and 7.93 μg/mL, respectively. The specificity and stability-indicating capability of the method are proven through degradation studies, which also showed that there is no interference of the formulation excipients, showing that peak is free from any coeluting peak. The method showed adequate precision, with a relative standard deviation (RSD) values lower than 0.92%. Good values of accuracy were also obtained, with a mean value of 99.55%. Experimental design is used during validation to calculate method robustness. The proposed method is applied for the analysis of the tablet dosage forms, contributing to improve the quality control and to assure the therapeutic efficacy.

  3. Warfarin Personalized Dosage: Re-compounding for a More Suitable Therapy and Better Compliance.

    PubMed

    Pellagatti, Tommaso; Ternelli, Marco; Frascio, Davide; Bettini, Ruggero

    2017-01-01

    Warfarin is still the most prescribed oral anticoagulant prescribed for the prophylaxis and treatment of thromboembolic events such as stroke, heart attack, embolism, and deep vein thrombosis. It is administered orally in the form of sodium salt as a tablet with a typical strength of 5 mg. The molecule has a narrow therapeutic index. As a consequence, the dosage must be individualized for each patient based on the patient response in terms of time of coagulation. Thus, warfarin represents an example of a drug whose dose needs to be tailored to individual requirements that are often changing and, therefore, constitute a paramount illustration of personalized medicine. The aim of the present work was to investigate to what extent the manual division of a warfarin tablet by the patient represents an issue in terms of dose accuracy and precision. A second goal was to demonstrate that possible problems stemming from the manual division of the warfarin tablet could be overcome by compounding a solid dosage form (e.g., a capsule) starting from the commercially available warfarin product. The results of the present study put into evidence the great inhomogeneity and discrepancy from the target dose obtained when commercially available warfarin tablets are manually divided in four parts. This represents a potential source of inefficacy of the anticoagulant activity, with increased risk of either bleeding or thromboembolic events. The proposed solution is effective and yet simple and economically affordable, in particular considering the cost of the possible hospitalizations related to therapy failure. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  4. Comparative Application of PLS and PCR Methods to Simultaneous Quantitative Estimation and Simultaneous Dissolution Test of Zidovudine - Lamivudine Tablets.

    PubMed

    Üstündağ, Özgür; Dinç, Erdal; Özdemir, Nurten; Tilkan, M Günseli

    2015-01-01

    In the development strategies of new drug products and generic drug products, the simultaneous in-vitro dissolution behavior of oral dosage formulations is the most important indication for the quantitative estimation of efficiency and biopharmaceutical characteristics of drug substances. This is to force the related field's scientists to improve very powerful analytical methods to get more reliable, precise and accurate results in the quantitative analysis and dissolution testing of drug formulations. In this context, two new chemometric tools, partial least squares (PLS) and principal component regression (PCR) were improved for the simultaneous quantitative estimation and dissolution testing of zidovudine (ZID) and lamivudine (LAM) in a tablet dosage form. The results obtained in this study strongly encourage us to use them for the quality control, the routine analysis and the dissolution test of the marketing tablets containing ZID and LAM drugs.

  5. Magnetic marker monitoring: high resolution real-time tracking of oral solid dosage forms in the gastrointestinal tract.

    PubMed

    Weitschies, Werner; Blume, Henning; Mönnikes, Hubert

    2010-01-01

    Knowledge about the performance of dosage forms in the gastrointestinal tract is essential for the development of new oral delivery systems, as well as for the choice of the optimal formulation technology. Magnetic Marker Monitoring (MMM) is an imaging technology for the investigation of the behaviour of solid oral dosage forms within the gastrointestinal tract, which is based on the labelling of solid dosage forms as a magnetic dipole and determination of the location, orientation and strength of the dipole after oral administration using measurement equipment and localization methods that are established in biomagnetism. MMM enables the investigation of the performance of solid dosage forms in the gastrointestinal tract with a temporal resolution in the range of a few milliseconds and a spatial resolution in 3D in the range of some millimetres. Thereby, MMM provides real-time tracking of dosage forms in the gastrointestinal tract. MMM is also suitable for the determination of dosage form disintegration and for quantitative measurement of in vivo drug release in case of appropriate extended release dosage forms like hydrogel-forming matrix tablets. The combination of MMM with pharmacokinetic measurements (pharmacomagnetography) enables the determination of in vitro-in vivo correlations (IVIC) and the delineation of absorption sites in the gastrointestinal tract. Copyright 2009 Elsevier B.V. All rights reserved.

  6. Determination of azathioprine and its related substances by capillary zone electrophoresis and its application to pharmaceutical dosage forms assay.

    PubMed

    Shafaati, A; Clark, B J

    2000-03-01

    The development of a stability-indicating capillary zone electrophoresis (CZE) method for the determination of the drug azathioprine (AZA) and its related substances in bulk and dosage forms is described. Theophylline was used as an internal standard to improve quantitative results. The method was fully validated in terms of repeatability (n = 10, RSD for migration time and peak area ratio were 0.15% and 0.60%, respectively), reproducibility (n = 5, RSD of peak area ratio was 0.84%), linearity at two ranges of the azathioprine concentration, limits of detection (LOD) and quantitation (LOQ), and robustness. The method was applied for determination of the drug in bulk and a commercial tablet dosage form (recovery 98.3-101.3%) and in powder for injection (recovery 98.7-100.6%). The method was fast and reliable for the analysis of AZA and its related substances in bulk and dosage forms.

  7. Oral drug therapy in elderly with dysphagia: between a rock and a hard place!

    PubMed Central

    Logrippo, Serena; Ricci, Giovanna; Sestili, Matteo; Cespi, Marco; Ferrara, Letizia; Palmieri, Giovanni F; Ganzetti, Roberta; Bonacucina, Giulia; Blasi, Paolo

    2017-01-01

    Demographic indicators forecast that by 2050, the elderly will account for about one-third of the global population. Geriatric patients require a large number of medicines, and in most cases, these products are administered as solid oral solid dosage forms, as they are by far the most common formulations on the market. However, this population tends to suffer difficulties with swallowing. Caregivers in hospital geriatric units routinely compound in solid oral dosage forms for dysphagic patients by crushing the tablets or opening the capsules to facilitate administration. The manipulation of a tablet or a capsule, if not clearly indicated in the product labeling, is an off-label use of the medicine, and must be supported by documented scientific evidence and requires the patient’s informed consent. Compounding of marketed products has been recognized as being responsible for an increased number of adverse events and medical errors. Since extemporaneous compounding is the rule and not the exception in geriatrics departments, the seriousness and scope of issues caused by this daily practice are probably underestimated. In this article, the potential problems associated with the manipulation of authorized solid oral dosage forms are discussed. PMID:28203065

  8. Kinetics of degradation of enalapril maleate in dosage forms.

    PubMed

    Stanisz, Beata

    2004-01-01

    The effect of humidity and temperature on the stability of enalapril maleate (ENA) in tablets have been studied. Tablets with ENA were stored in final packs (blisters) and without final packs in the atmosphere of increased humidity (76.4 % RH) and in the temperature range from 313 K to 333 K (forced degradation test). Degradation of ENA in tablets stored in final packs and without final packs followed the first order reaction model. During this study, the product of hydrolysis of the ester group and intramolecular cyclization have been observed. Thermodynamic parameters (activation energies, enthalpy and entropy) for the decomposition of ENA in tablets were calculated.

  9. Comparative Plasma Exposure of Albendazole after Administration of Rapidly Disintegrating Tablets in Dogs

    PubMed Central

    Castro, Silvina G.; Dib, Alicia; Suarez, Gonzalo; Allemandi, Daniel; Lanusse, Carlos; Sanchez Bruni, Sergio; Palma, Santiago D.

    2013-01-01

    The main objectives of this study were (a) to evaluate the in vitro performance of the rapid disintegration tablets as a way to improve the solid dispersions and (b) to study the in vivo pharmacokinetics of the albendazole modified formulation in dogs. Rapid disintegration of tablets seems to be a key factor for efficiency of solid dispersions with regard to improvement of the albendazole bioavailability. The in vivo assays performed on dogs showed a marked increase in drug plasma exposure when albendazole was given in solid dispersions incorporated into rapid disintegration tablets compared with conventional solid dosage form. PMID:24063016

  10. Terahertz Technology: A Boon to Tablet Analysis

    PubMed Central

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

    2009-01-01

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

  11. Application of instrumental evaluation of color for the pre-formulation and formulation of rabeprazole.

    PubMed

    Rhee, Yun-Seok; Park, Chun-Woong; Shin, Yoon-Sub; Kam, Sung-Hoon; Lee, Kyu-Hyun; Park, Eun-Seok

    2008-02-28

    The aims of this study were to fast screen the compatibility of rabeprazole and excipients using a spectrocolorimeter and to examine the relationship between the color change value and drug contents/drug degradation products in solid dosage forms. The color change values of rabeprazole-excipient mixtures were measured using a spectrocolorimeter, with six tablet formulations compressed using a single-punch instrumental tablet press. The rabeprazole and degradation products contents in the tablets were analyzed using an HPLC method, with the color change values of the tablets measured using spectrocolorimetery for 4 weeks. These experiments indicated that the instrumental evaluation of color was a speedy, simple and useful tool in the determination of the interaction between the drug and excipients, as well as in the formulation of solid dosage forms. The relationships of the % reduced drug contents versus the color change value, and those of the % drug degradation products versus the color change value were exponentially increased in formulations containing zinc stearate. On stress testing, the color change value of rabeprazole was inconsistent with previous reports, as the degradation of rabeprazole can be greatly influenced by humidity as well as temperature. Consequently, these results highlight the potential of color formation in the application of pre-formulation and formulation of drugs.

  12. Formulation and evaluation of non-effervescent floating tablets of losartan potassium.

    PubMed

    Getyala, Anil; Gangadharappa, H V; Prasad, M Sarat Chandra; Reddy, M Praveen Kumar; Kumar, T M Pramod

    2013-10-01

    The aim of the work is to modify the solubility and bioavailability of Losartan potassium, by employing noneffervescent floating drug delivery (tablet dosage forms). Non-effervescent systems are a type of floating drug delivery systems, that have been used to boost the gastric residence and the floatation time in the gastro intestinal tract. The study included formulation of floating tablets using polymers like Chitosan and Karaya gum as matrix forming agents. Accurel(®) MP 1000 was used as floating agent. The tablets were prepared by direct compression technique. FTIR, DSC studies conformed that there was no incompatibility between the polymer and the drug. Tablet preformulation parameters were within the Pharmacopoeial limit. Tablet showed zero lag time, contisnuance of buoyancy for >12 h. The tablet showed good in vitro release. Drug release was through swelling and abided by the gellation mechanism. In vivo X-ray studies depicted that tablets continued to float in the GIT for 12 h. Accelerated stability showed that, tablets were stable for over 6 month. Thus the prepared non-effervescent floating tablet of Losartan potassium can be used for the treatment of hypertension for more than 12 h with single dose administration.

  13. Confectionery-based dose forms.

    PubMed

    Tangso, Kristian J; Ho, Quy Phuong; Boyd, Ben J

    2015-01-01

    Conventional dosage forms such as tablets, capsules and syrups are prescribed in the normal course of practice. However, concerns about patient preferences and market demands have given rise to the exploration of novel unconventional dosage forms. Among these, confectionery-based dose forms have strong potential to overcome compliance problems. This report will review the availability of these unconventional dose forms used in treating the oral cavity and for systemic drug delivery, with a focus on medicated chewing gums, medicated lollipops, and oral bioadhesive devices. The aim is to stimulate increased interest in the opportunities for innovative new products that are available to formulators in this field, particularly for atypical patient populations.

  14. An integrated system for dissolution studies and magnetic resonance imaging of controlled release, polymer-based dosage forms-a tool for quantitative assessment of hydrogel formation processes.

    PubMed

    Kulinowski, Piotr; Dorozyński, Przemysław; Jachowicz, Renata; Weglarz, Władysław P

    2008-11-04

    Controlled release (CR) dosage forms are often based on polymeric matrices, e.g., sustained-release tablets and capsules. It is crucial to visualise and quantify processes of the hydrogel formation during the standard dissolution study. A method for imaging of CR, polymer-based dosage forms during dissolution study in vitro is presented. Imaging was performed in a non-invasive way by means of the magnetic resonance imaging (MRI). This study was designed to simulate in vivo conditions regarding temperature, volume, state and composition of dissolution media. Two formulations of hydrodynamically balanced systems (HBS) were chosen as model CR dosage forms. HBS release active substance in stomach while floating on the surface of the gastric content. Time evolutions of the diffusion region, hydrogel formation region and "dry core" region were obtained during a dissolution study of L-dopa as a model drug in two simulated gastric fluids (i.e. in fed and fasted state). This method seems to be a very promising tool for examining properties of new formulations of CR, polymer-based dosage forms or for comparison of generic and originator dosage forms before carrying out bioequivalence studies.

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

    PubMed

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

    2002-01-01

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

  16. 21 CFR 310.518 - Drug products containing iron or iron salts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... an active ingredient in solid oral dosage form, e.g., tablets or capsules shall meet the following.... (ii) If a drug product is packaged in unit-dose packaging, and if the immediate container bears...

  17. 21 CFR 310.518 - Drug products containing iron or iron salts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... an active ingredient in solid oral dosage form, e.g., tablets or capsules shall meet the following.... (ii) If a drug product is packaged in unit-dose packaging, and if the immediate container bears...

  18. Simultaneous in vitro and in vivo evaluation of both trimethoprim and sulfamethoxazole from certain dosage forms.

    PubMed

    Meshali, M; El-Sabbagh, H; Ghanem, A; Foda, A

    1983-06-01

    The dissolution rates of trimethoprim (T), and sulphamethoxazole (S), from different brands of tablets and suspensions were studied at pH = 1.1 and 7.2. The bioavailabilities of both drugs in humans were studied by the urine excretion method. The dissolution rates were dependent on the pH of the dissolution medium, the solubilities of the drugs at the pH involved, the dosage form and the brand studied. While the dissolution rates of T from all brands studied were consistent with their pH-dependent solubility, those of S were not. The dissolution rates of S from suspensions were found to be equal at pH = 7.2, but different at pH = 1.1. A correlation existed between the dissolution rate of T at pH = 1.1 from tablets and the excretion rate in humans. With S, however, no such correlation was observed at either pH.

  19. [Application of an artificial neural network in the design of sustained-release dosage forms].

    PubMed

    Wei, X H; Wu, J J; Liang, W Q

    2001-09-01

    To use the artificial neural network (ANN) in Matlab 5.1 tool-boxes to predict the formulations of sustained-release tablets. The solubilities of nine drugs and various ratios of HPMC: Dextrin for 63 tablet formulations were used as the ANN model input, and in vitro accumulation released at 6 sampling times were used as output. The ANN model was constructed by selecting the optimal number of iterations (25) and model structure in which there are one hidden layer and five hidden layer nodes. The optimized ANN model was used for prediction of formulation based on desired target in vitro dissolution-time profiles. ANN predicted profiles based on ANN predicted formulations were closely similar to the target profiles. The ANN could be used for predicting the dissolution profiles of sustained release dosage form and for the design of optimal formulation.

  20. Oral drug delivery in personalized medicine: unmet needs and novel approaches.

    PubMed

    Wening, Klaus; Breitkreutz, Jörg

    2011-02-14

    Increasing knowledge into personalized medicine has demonstrated the need for individual dosing. Drug dosage forms are urgently needed enabling an individual therapy, especially for oral drug delivery. This review is focusing on approaches for solid and liquid oral dosage forms for individual dosing. The proposed dosage forms and devices may be distinguished into assembling and partition concepts and have been categorized regarding their applicability, costs, dose flexibility and potential benefits. Opportunities, challenges and further unmet needs are elaborated and critically discussed. Liquid dosage forms can be accurately dosed by novel dropping tubes or oral syringes, but less precisely by dosing spoons and cups. Breaking scored tablets into fragments show major risks such as inaccurate dosing, formation of potent dust and stability issues of the residual segments. Novel approaches are proposed for solid dosage forms enabling a flexible and appropriate therapy such as various dispensers for multiparticulate drug formulations. However, most of the proposals still have to prove their applicability in practice. Promising concepts are the solid dosage pen and drug-loaded oral films which can be cut in individual sections enabling freely selectable doses. Further research and development are required for novel dosage forms and medical devices appropriate for individualized therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Preparation and stability evaluation of extemporaneous oral suspension of valsartan using commercially available tablets.

    PubMed

    Zaid, Abdel Naser; Assali, Mohyeddin; Qaddomi, Aiman; Ghanem, Mashhour; Zaaror, Yara Abu

    2014-01-01

    The aim of this study was to develop an extemporaneous valsartan suspension (80 mg valsartan/5 mL) starting from commercial tablets (80-mg/ tablet). A high-performance liquid chromatographic system was used for the analysis and quantification of valsartan in the samples studied. Samples of valsartan suspension for analysis were prepared as reported by the validated high-performance liquid chromatographic method and the dissolution tests were performed according to the U.S. Food and Drug Administration's method. The high-performance liquid chromatographic assay indicated that the 80-mg/5-mL valsartan suspension was stable for 30 days when stored at long-term and accelerated storage conditions. Valsartan release profile showed that approximately 85% of valsartan dissolved after 10 minutes and, accordingly, the calculation of similarity factor was not necessary. It is possible for the pharmacist to crush valsartan 80-mg tablets and prepare a suspension which has dosage flexibility that can be calculated according to body-surface area, kidney, and liver functions, without affecting the chemical stability of the active ingredient nor its dissolution profile and also have a cost-effective dosage form.

  2. 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.

  3. Investigation of the Sensitivity of Transmission Raman Spectroscopy for Polymorph Detection in Pharmaceutical Tablets.

    PubMed

    Feng, Hanzhou; Bondi, Robert W; Anderson, Carl A; Drennen, James K; Igne, Benoît

    2017-08-01

    Polymorph detection is critical for ensuring pharmaceutical product quality in drug substances exhibiting polymorphism. Conventional analytical techniques such as X-ray powder diffraction and solid-state nuclear magnetic resonance are utilized primarily for characterizing the presence and identity of specific polymorphs in a sample. These techniques have encountered challenges in analyzing the constitution of polymorphs in the presence of other components commonly found in pharmaceutical dosage forms. Laborious sample preparation procedures are usually required to achieve satisfactory data interpretability. There is a need for alternative techniques capable of probing pharmaceutical dosage forms rapidly and nondestructively, which is dictated by the practical requirements of applications such as quality monitoring on production lines or when quantifying product shelf lifetime. The sensitivity of transmission Raman spectroscopy for detecting polymorphs in final tablet cores was investigated in this work. Carbamazepine was chosen as a model drug, polymorph form III is the commercial form, whereas form I is an undesired polymorph that requires effective detection. The concentration of form I in a direct compression tablet formulation containing 20% w/w of carbamazepine, 74.00% w/w of fillers (mannitol and microcrystalline cellulose), and 6% w/w of croscarmellose sodium, silicon dioxide, and magnesium stearate was estimated using transmission Raman spectroscopy. Quantitative models were generated and optimized using multivariate regression and data preprocessing. Prediction uncertainty was estimated for each validation sample by accounting for all the main variables contributing to the prediction. Multivariate detection limits were calculated based on statistical hypothesis testing. The transmission Raman spectroscopic model had an absolute prediction error of 0.241% w/w for the independent validation set. The method detection limit was estimated at 1.31% w/w. The results demonstrated that transmission Raman spectroscopy is a sensitive tool for polymorphs detection in pharmaceutical tablets.

  4. Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form.

    PubMed

    Haznar-Garbacz, Dorota; Kaminska, Ewa; Zakowiecki, Daniel; Lachmann, Marek; Kaminski, Kamil; Garbacz, Grzegorz; Dorożyński, Przemysław; Kulinowski, Piotr

    2018-02-01

    The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.

  5. Compilation of a near-infrared library for the construction of quantitative models of amoxicillin and potassium clavulanate oral dosage forms

    NASA Astrophysics Data System (ADS)

    Zou, Wen-bo; Chong, Xiao-meng; Wang, Yan; Hu, Chang-qin

    2018-05-01

    The accuracy of NIR quantitative models depends on calibration samples with concentration variability. Conventional sample collecting methods have some shortcomings especially the time-consuming which remains a bottleneck in the application of NIR models for Process Analytical Technology (PAT) control. A study was performed to solve the problem of sample selection collection for construction of NIR quantitative models. Amoxicillin and potassium clavulanate oral dosage forms were used as examples. The aim was to find a normal approach to rapidly construct NIR quantitative models using an NIR spectral library based on the idea of a universal model [2021]. The NIR spectral library of amoxicillin and potassium clavulanate oral dosage forms was defined and consisted of spectra of 377 batches of samples produced by 26 domestic pharmaceutical companies, including tablets, dispersible tablets, chewable tablets, oral suspensions, and granules. The correlation coefficient (rT) was used to indicate the similarities of the spectra. The samples’ calibration sets were selected from a spectral library according to the median rT of the samples to be analyzed. The rT of the samples selected was close to the median rT. The difference in rT of those samples was 1.0% to 1.5%. We concluded that sample selection is not a problem when constructing NIR quantitative models using a spectral library versus conventional methods of determining universal models. The sample spectra with a suitable concentration range in the NIR models were collected quickly. In addition, the models constructed through this method were more easily targeted.

  6. Analysis of clonazepam in a tablet dosage form using smallbore HPLC.

    PubMed

    Spell, J C; Stewart, J T

    1998-11-01

    A stability indicating, reversed phase high-performance liquid chromatographic method utilizing a smallbore HPLC column has been developed for the determination of clonazepam in a commercial tablet dosage form. The use of a small bore column results in a substantial solvent savings, as well as a greater mass sensitivity, especially in the identification of degradation peaks in a chromatogram. The method involves ultraviolet detection at 254 nm and utilized a 150 x 3.0 mm i.d. column packed with 3 microm octyldecylsilane particles with a mobile phase of water methanol acetonitrile (40:30:30, v/v/v) at a flow rate of 400 microl min(-1) at ambient temperature, with and without the use of 1,2-dichlorobenzene as the internal standard. The current USP method for the analysis of clonazepam using a 300 x 3.9 mm i.d. conventional octyldecylsilane column was utilized as a comparison to the smallbore method. The retention times for clonazepam and the internal standard on the 3.0 mm i.d. column were 4.0 and 12.5 min, respectively. The intra- and interday RSDs on the 3.0 mm i.d. column were < 0.55% (n =4) using the internal standard, and < 0.19% (n = 4) without the internal standard at the lower limit of the standard curve, 50 microg ml(-1) and had a limit of detection of 24 ng ml(-1). The assay using the 3.0 mm i.d. column was shown to be suitable for measuring clonazepam in a tablet dosage form.

  7. Dissolution of solid dosage form. II. Equations for the dissolution of nondisintegrating tablet under the sink condition.

    PubMed

    Yonezawa, Y; Shirakura, K; Otsuka, A; Sunada, H

    1991-03-01

    An equation for dissolution from the whole surface of a nondisintegrating single component tablet under the sink condition was derived. Also, equations for several dissolution manners of the tablet under the sink condition were derived in the postulation of the dominant dissolution rate constant which determines the dissolution manner. The applicability or validity of these equations were examined by the dissolution measurements with nondisintegrating single component tablets. About one-tenth the amount of the amount needed to saturate the solution was used to prepare a tablet, and dissolution measurements were carried out with the tablet whose flat or side surface was masked with an adhesive tape in accordance with the conditions for derivation of equations. Among the derived equations, dissolution from the whole surface of a tablet was expressed by a form similar to the cube root law equation for particles. Hence, a single component tablet compressed by the use of a suitable amount was thought to behave like a single crystal. Also, equations derived for several dissolution manners were thought to be applicable for the dissolution of a nonspherical particle and crystal concerning the crystal's habit and its dissolution property, and the extended applicability was examined by converting the crystal into a simplified or idealized form, i.e., rectangle or plate.

  8. 3D inkjet printing of tablets exploiting bespoke complex geometries for controlled and tuneable drug release.

    PubMed

    Kyobula, Mary; Adedeji, Aremu; Alexander, Morgan R; Saleh, Ehab; Wildman, Ricky; Ashcroft, Ian; Gellert, Paul R; Roberts, Clive J

    2017-09-10

    A hot melt 3D inkjet printing method with the potential to manufacture formulations in complex and adaptable geometries for the controlled loading and release of medicines is presented. This first use of a precisely controlled solvent free inkjet printing to produce drug loaded solid dosage forms is demonstrated using a naturally derived FDA approved material (beeswax) as the drug carrier and fenofibrate as the drug. Tablets with bespoke geometries (honeycomb architecture) were fabricated. The honeycomb architecture was modified by control of the honeycomb cell size, and hence surface area to enable control of drug release profiles without the need to alter the formulation. Analysis of the formed tablets showed the drug to be evenly distributed within the beeswax at the bulk scale with evidence of some localization at the micron scale. An analytical model utilizing a Fickian description of diffusion was developed to allow the prediction of drug release. A comparison of experimental and predicted drug release data revealed that in addition to surface area, other factors such as the cell diameter in the case of the honeycomb geometry and material wettability must be considered in practical dosage form design. This information when combined with the range of achievable geometries could allow the bespoke production of optimized personalised medicines for a variety of delivery vehicles in addition to tablets, such as medical devices for example. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Formulation and optimisation of raft-forming chewable tablets containing H2 antagonist

    PubMed Central

    Prajapati, Shailesh T; Mehta, Anant P; Modhia, Ishan P; Patel, Chhagan N

    2012-01-01

    Purpose: The purpose of this research work was to formulate raft-forming chewable tablets of H2 antagonist (Famotidine) using a raft-forming agent along with an antacid- and gas-generating agent. Materials and Methods: Tablets were prepared by wet granulation and evaluated for raft strength, acid neutralisation capacity, weight variation, % drug content, thickness, hardness, friability and in vitro drug release. Various raft-forming agents were used in preliminary screening. A 23 full-factorial design was used in the present study for optimisation. The amount of sodium alginate, amount of calcium carbonate and amount sodium bicarbonate were selected as independent variables. Raft strength, acid neutralisation capacity and drug release at 30 min were selected as responses. Results: Tablets containing sodium alginate were having maximum raft strength as compared with other raft-forming agents. Acid neutralisation capacity and in vitro drug release of all factorial batches were found to be satisfactory. The F5 batch was optimised based on maximum raft strength and good acid neutralisation capacity. Drug–excipient compatibility study showed no interaction between the drug and excipients. Stability study of the optimised formulation showed that the tablets were stable at accelerated environmental conditions. Conclusion: It was concluded that raft-forming chewable tablets prepared using an optimum amount of sodium alginate, calcium carbonate and sodium bicarbonate could be an efficient dosage form in the treatment of gastro oesophageal reflux disease. PMID:23580933

  10. Formulation and optimisation of raft-forming chewable tablets containing H2 antagonist.

    PubMed

    Prajapati, Shailesh T; Mehta, Anant P; Modhia, Ishan P; Patel, Chhagan N

    2012-10-01

    The purpose of this research work was to formulate raft-forming chewable tablets of H2 antagonist (Famotidine) using a raft-forming agent along with an antacid- and gas-generating agent. Tablets were prepared by wet granulation and evaluated for raft strength, acid neutralisation capacity, weight variation, % drug content, thickness, hardness, friability and in vitro drug release. Various raft-forming agents were used in preliminary screening. A 2(3) full-factorial design was used in the present study for optimisation. The amount of sodium alginate, amount of calcium carbonate and amount sodium bicarbonate were selected as independent variables. Raft strength, acid neutralisation capacity and drug release at 30 min were selected as responses. Tablets containing sodium alginate were having maximum raft strength as compared with other raft-forming agents. Acid neutralisation capacity and in vitro drug release of all factorial batches were found to be satisfactory. The F5 batch was optimised based on maximum raft strength and good acid neutralisation capacity. Drug-excipient compatibility study showed no interaction between the drug and excipients. Stability study of the optimised formulation showed that the tablets were stable at accelerated environmental conditions. It was concluded that raft-forming chewable tablets prepared using an optimum amount of sodium alginate, calcium carbonate and sodium bicarbonate could be an efficient dosage form in the treatment of gastro oesophageal reflux disease.

  11. Two release rates from monolithic carboxymethyl starch tablets: formulation, characterization, and in vitro/in vivo evaluation.

    PubMed

    Le, Tien Canh; Mateescu, Mircea Alexandru

    2017-08-01

    Most of non-steroidal anti-inflammatory drugs (NSAIDs) including ibuprofen at more than 1200 mg/day may generate gastrointestinal and cardiovascular side effects. Bilayer or multiparticulate devices have been developed for controlled release in order to prevent undesired side effects. A new "two release rate (2RR) monolithic tablets" approach is now proposed for controlled release of poorly soluble drugs, particularly NSAIDs. Ibuprofen was used as model drug. This concept is based on a calcium carboxymethyl-starch (CaCMS) complex as a novel, low-cost excipient for monolithic dosage forms easy to manufacture by direct compaction. The in vitro dissolution from CaCMS formulations (tablets containing 400 or 600 mg active principle) showed two distinct release rates: (i) an initial fast release (for 30 min in simulated gastric fluid) of about 200 mg ibuprofen, an amount similar to the dosage of conventional immediate-release form (Motrin® 200 mg), and (ii) a slow release of remaining about 200 or 400 mg for a period of 12 h. A preliminary in vivo study (beagle dogs) showed pharmacokinetic parameters of one single controlled-release dosage of ibuprofen (400 mg) formulated with CaCMS, near equivalence with multiple doses (three tablets of 200 mg ibuprofen) of conventional Motrin®. A marked reduction (with 33%) of administered dose (400 instead 600 mg) was achieved by the new formulation with equivalent therapeutic effects. This dose reduction may be beneficial and is expected to minimize side damage risks. Although the present study was limited to NSAIDs, the 2RR concept can be applied for other drugs, particularly for subjects unable to follow frequent administrations.

  12. Photocurable poly(ethylene glycol) as a bioink for the inkjet 3D pharming of hydrophobic drugs.

    PubMed

    Acosta-Vélez, Giovanny F; Zhu, Timothy Z; Linsley, Chase S; Wu, Benjamin M

    2018-04-26

    Binder jetting and material extrusion are the two most common additive manufacturing techniques used to create pharmaceutical tablets. However, their versatility is limited since the powder component is present throughout the dosage forms fabricated by binder jet 3D printing and material extrusion 3D printing requires high operating temperatures. Conversely, material jetting allows for compositional control at a voxel level and can dispense material at room temperature. Unfortunately, there are a limited number of materials that are both printable and biocompatible. Therefore, the aim of this study was to engineer photocurable bioinks that are suitable for hydrophobic active pharmaceutical ingredients and have rapid gelation times upon visible light exposure. The resulting bioinks were comprised of poly(ethylene glycol) diacrylate (250 Da) as the crosslinkable monomer, Eosin Y as the photoinitiator, and methoxide-poly(ethylene glycol)-amine as the coinitiator. Additionally, poly(ethylene glycol) (200 Da) was added as a plasticizer to modulate the drug release profiles, and Naproxen was used as the model drug due to its high hydrophobicity. Various bioink formulations were dispensed into the bottom half of blank preform tablets - made via direct compression - using a piezoelectric nozzle, photopolymerized, and capped with the top half of the preform tablet to complete the pharmaceutical dosage form. Results from the release studies showed that drug release can be modulated by both the percent of poly(ethylene glycol) diacrylate in the formulation and the light exposure time used to cure the bioinks. These bioinks have the potential to expand the library of materials available for creating pharmaceutical tablets via inkjet printing with personalized drug dosages. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Raman spectroscopy for the analytical quality control of low-dose break-scored tablets.

    PubMed

    Gómez, Diego A; Coello, Jordi; Maspoch, Santiago

    2016-05-30

    Quality control of solid dosage forms involves the analysis of end products according to well-defined criteria, including the assessment of the uniformity of dosage units (UDU). However, in the case of break-scored tablets, given that tablet splitting is widespread as a means to adjust doses, the uniform distribution of the active pharmaceutical ingredient (API) in all the possible fractions of the tablet must be assessed. A general procedure to accomplish with both issues, using Raman spectroscopy, is presented. It is based on the acquisition of a collection of spectra in different regions of the tablet, that later can be selected to determine the amount of API in the potential fractions that can result after splitting. The procedure has been applied to two commercial products, Sintrom 1 and Sintrom 4, with API (acenocoumarol) mass proportion of 2% and 0.7% respectively. Partial Least Squares (PLS) calibration models were constructed for the quantification of acenocoumarol in whole tablets using HPLC as a reference analytical method. Once validated, the calibration models were used to determine the API content in the different potential fragments of the scored Sintrom 4 tablets. Fragment mass measurements were also performed to estimate the range of masses of the halves and quarters that could result after tablet splitting. The results show that Raman spectroscopy can be an alternative analytical procedure to assess the uniformity of content, both in whole tablets as in its potential fragments, and that Sintrom 4 tablets can be perfectly split in halves, but some cautions have to be taken when considering the fragmentation in quarters. A practical alternative to the use of UDU test for the assessment of tablet fragments is proposed. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. [Consideration of drug absorption in customizing drug therapy].

    PubMed

    Walter-Sack, I; Haefeli, W E

    2000-09-01

    The rate and extent of drug absorption from the small intestine are related to the release of the active ingredient from a dosage form, its solubility in the liquid phase of gastrointestinal contents, and the transport of the dissolved compound or the intact dosage form from the stomach into the duodenum. With pharmaceutical preparations releasing the active compound within the stomach, and enteric-coated "micro"-formulations (micropellets), gastric emptying is possible during the interdigestive and the digestive period. Potential differences of drug absorption between fasting administration and intake during the digestive period are unpredictable, because they are related to the release characteristics of the dosage form. However, larger enteric-coated preparations like tablets can leave the stomach only with a phase 3 contraction of fasting motility; intake during the digestive period will result in gastric retention of this type of dosage form until all food has left the stomach and fasting motility is restored. Consequently the onset of drug absorption is delayed. This interaction between food and large enteric-coated dosage forms is predictable from pyloric function in relation to the gastric motility. As it occurs regularly, it can be taken into account when prescribing enteric-coated dosage forms. If concomitant intake of food and enteric-coated drugs is unavoidable, but a rapid onset of drug absorption is necessary, micropellets are the dosage form of choice. When the therapeutic effect is insufficient, drug dosage form and timing of drug administration should be checked before prescribing a different active compound.

  15. An investigation into moisture barrier film coating efficacy and its relevance to drug stability in solid dosage forms.

    PubMed

    Mwesigwa, Enosh; Basit, Abdul W

    2016-01-30

    Barrier coatings are frequently employed on solid oral dosage forms under the assumption that they prevent moisture sorption into tablet cores thereby averting premature degradation of moisture-sensitive active ingredients. However, the efficacy of moisture barrier coatings remains unproven and they may actually accelerate degradation. This study aimed to investigate the barrier performance of four coating systems following application onto a low hygroscopic tablet formulation containing aspirin as a model moisture sensitive drug. Tablets were prepared by direct compaction and coated with aqueous dispersions of Eudragit(®) L30 D-55, Eudragit(®) EPO, Opadry(®) AMB and Sepifilm(®) LP at the vendors' recommended weight gains. Moisture uptake was studied by dynamic vapor sorption at 0 and 75% RH (25°C). Accelerated stability studies were undertaken at 75% RH/25°C for 90 days and HPLC assay was used to determine aspirin content. Uncoated tablet cores equilibrated rapidly and took up very little water (0.09%). The mean water uptake for coated cores was higher than for the uncoated formulation and varied as follows: 0.19% (Eudragit(®) L30 D-55), 0.35% (Opadry(®) AMB), 0.49% (Sepifilm(®) LP) and 0.76% (Eudragit(®) EPO). The level of aspirin decreased in all the samples such that by the time the study was terminated, the mean aspirin recovered was as follows: uncoated cores 80.0%; Eudragit® L30 D-55 coated cores 78.8%; Opadry(®) AMB coated cores 76.2%, Sepifilm(®) LP coated cores 76.0% and Eudragit(®) EPO coated samples 66.5%. From these results, it is concluded that the efficacy of moisture barrier polymer coatings on low hygroscopic cores is limited, and application of these coatings can, instead, enhance drug degradation in solid dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Applications of Natural Polymeric Materials in Solid Oral Modified-Release Dosage Forms.

    PubMed

    Li, Liang; Zhang, Xin; Gu, Xiangqin; Mao, Shirui

    2015-01-01

    Solid oral modified-release dosage forms provide numerous advantages for drug delivery compared to dosage forms where the drugs are released and absorbed rapidly following ingestion. Natural polymers are of particular interest as drug carriers due to their good safety profile, biocompatibility, biodegradability, and rich sources. This review described the current applications of important natural polymers, such as chitosan, alginate, pectin, guar gum, and xanthan gum, in solid oral modified-release dosage forms. It was shown that natural polymers have been widely used to fabricate solid oral modified-release dosage forms such as matrix tablets, pellets and beads, and especially oral drug delivery systems such as gastroretentive and colon drug delivery systems. Moreover, chemical modifications could overcome the shortcomings associated with the use of natural polymers, and the combination of two or more polymers presented further advantages compared with that of single polymer. In conclusion, natural polymers and modified natural polymers have promising applications in solid oral modified-release dosage forms. However, commercial products based on them are still limited. To accelerate the application of natural polymers in commercial products, in vivo behavior of natural polymers-based solid oral modified-release dosage forms should be deeply investigated, and meanwhile quality of the natural polymers should be controlled strictly, and the influence of formulation and process parameters need to be understood intensively.

  17. Quantitative surface topography assessment of directly compressed and roller compacted tablet cores using photometric stereo image analysis.

    PubMed

    Allesø, Morten; Holm, Per; Carstensen, Jens Michael; Holm, René

    2016-05-25

    Surface topography, in the context of surface smoothness/roughness, was investigated by the use of an image analysis technique, MultiRay™, related to photometric stereo, on different tablet batches manufactured either by direct compression or roller compaction. In the present study, oblique illumination of the tablet (darkfield) was considered and the area of cracks and pores in the surface was used as a measure of tablet surface topography; the higher a value, the rougher the surface. The investigations demonstrated a high precision of the proposed technique, which was able to rapidly (within milliseconds) and quantitatively measure the obtained surface topography of the produced tablets. Compaction history, in the form of applied roll force and tablet punch pressure, was also reflected in the measured smoothness of the tablet surfaces. Generally it was found that a higher degree of plastic deformation of the microcrystalline cellulose resulted in a smoother tablet surface. This altogether demonstrated that the technique provides the pharmaceutical developer with a reliable, quantitative response parameter for visual appearance of solid dosage forms, which may be used for process and ultimately product optimization. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. How do formulation and process parameters impact blend and unit dose uniformity? Further analysis of the product quality research institute blend uniformity working group industry survey.

    PubMed

    Hancock, Bruno C; Garcia-Munoz, Salvador

    2013-03-01

    Responses from the second Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) survey of industry have been reanalyzed to identify potential links between formulation and processing variables and the measured uniformity of blends and unit dosage forms. As expected, the variability of the blend potency and tablet potency data increased with a decrease in the loading of the active pharmaceutical ingredient (API). There was also an inverse relationship between the nominal strength of the unit dose and the blend uniformity data. The data from the PQRI industry survey do not support the commonly held viewpoint that granulation processes are necessary to create and sustain tablet and capsule formulations with a high degree of API uniformity. There was no correlation between the blend or tablet potency variability and the type of process used to manufacture the product. Although it is commonly believed that direct compression processes should be avoided for low API loading formulations because of blend and tablet content uniformity concerns, the data for direct compression processes reported by the respondents to the PQRI survey suggest that such processes are being used routinely to manufacture solid dosage forms of acceptable quality even when the drug loading is quite low. Copyright © 2012 Wiley Periodicals, Inc.

  19. The influence of averaging procedure on the accuracy of IVIVC predictions: immediate release dosage form case study.

    PubMed

    Ostrowski, Michalł; Wilkowska, Ewa; Baczek, Tomasz

    2010-12-01

    In vivo-in vitro correlation (IVIVC) is an effective tool to predict absorption behavior of active substances from pharmaceutical dosage forms. The model for immediate release dosage form containing amoxicillin was used in the presented study to check if the calculation method of absorption profiles can influence final results achieved. The comparison showed that an averaging of individual absorption profiles performed by Wagner-Nelson (WN) conversion method can lead to lose the discrimination properties of the model. The approach considering individual plasma concentration versus time profiles enabled to average absorption profiles prior WN conversion. In turn, that enabled to find differences between dispersible tablets and capsules. It was concluded that in the case of immediate release dosage form, the decision to use averaging method should be based on an individual situation; however, it seems that the influence of such a procedure on the discrimination properties of the model is then more significant. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  20. Modeling of in-use stability for tablets and powders in bottles.

    PubMed

    Waterman, Kenneth C; Chen, Lili; Waterman, Philip; MacDonald, Bruce C; Monahan, Andrew P; Scrivens, Garry

    2016-10-01

    A model is presented for determining the time when an active pharmaceutical ingredient in tablets/powders will remain within its specification limits during an in-use period; that is, when a heat-induction sealed bottle is opened for fixed time periods and where tablets are removed at fixed time points. This model combines the Accelerated Stability Assessment Program to determine the impact on degradation rates of relative humidity (RH) with calculations of the RH as a function of time for the dosage forms under in-use conditions. These calculations, in a conservative approach, assume that the air inside bottles with broached heat-induction seals completely exchanges with the external environment during periods when the bottle remains open. The solid dosages are assumed to sorb water at estimable rates during these openings. When bottles are capped, the moisture vapor transmission rate can be estimated to determine the changing RH inside the bottles between opening events. The impact of silica gel desiccants can also be included in the modeling.

  1. Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

    PubMed

    Dadey, Eric

    Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

  2. Formulation, Characterization and Physicochemical Evaluation of Ranitidine Effervescent Tablets

    PubMed Central

    Aslani, Abolfazl; Jahangiri, Hajar

    2013-01-01

    Purpose: The aim of this study was to design, formulate and physicochemically evaluate effervescent ranitidine hydrochloride (HCl) tablets since they are easily administered while the elderly and children sometimes have difficulties in swallowing oral dosage forms. Methods: Effervescent ranitidine HCl tablets were prepared in a dosage of 300 mg by fusion and direct compression methods. The powder blend and granule mixture were evaluated for various pre-compression characteristics, such as angle of repose, compressibility index, mean particle size and Hausner's ratio. The tablets were evaluated for post-compression features including weight variation, hardness, friability, drug content, dissolution time, carbon dioxide content, effervescence time, pH, content uniformity and water content. Effervescent systems with appropriate pre and post-compression qualities dissolved rapidly in water were selected as the best formulations. Results: The results showed that the flowability of fusion method is more than that of direct compression and the F5 and F6 formulations of 300 mg tablets were selected as the best formulations because of their physicochemical characteristics. Conclusion: In this study, citric acid, sodium bicarbonate and sweeteners (including mannitol, sucrose and aspartame) were selected. Aspartame, mint and orange flavors were more effective for masking the bitter taste of ranitidine. The fusion method is the best alternative in terms of physicochemical and physical properties. PMID:24312854

  3. Vigabatrin pediatric dosing information for refractory complex partial seizures: results from a population dose-response analysis.

    PubMed

    Nielsen, Jace C; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G; Wesche, David L

    2014-12-01

    We predicted vigabatrin dosages for adjunctive therapy for pediatric patients with refractory complex partial seizures (rCPS) that would produce efficacy comparable to that observed for approved adult dosages. A dose-response model related seizure-count data to vigabatrin dosage to identify dosages for pediatric rCPS patients. Seizure-count data were obtained from three pediatric and two adult rCPS clinical trials. Dosages were predicted for oral solution and tablet formulations. Predicted oral solution dosages to achieve efficacy comparable to that of a 1 g/day adult dosage were 350 and 450 mg/day for patients with body weight ranges 10-15 and >15-20 kg, respectively. Predicted oral solution dosages for efficacy comparable to a 3 g/day adult dosage were 1,050 and 1,300 mg/day for weight ranges 10-15 and >15-20 kg, respectively. Predicted tablet dosage for efficacy comparable to a 1 g/day adult dosage was 500 mg/day for weight ranges 25-60 kg. Predicted tablet dosage for efficacy comparable to a 3 g/day adult dosage was 2,000 mg for weight ranges 25-60 kg. Vigabatrin dosages were identified for pediatric rCPS patients with body weights ≥10 kg. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  4. Physicochemical characterisation of fluids and soft foods frequently mixed with oral drug formulations prior to administration to children.

    PubMed

    Kersten, E; Barry, A; Klein, S

    2016-03-01

    Oral drug administration to children poses specific pharmaceutical challenges that are often not seen to the same extent in adults, and whose occurrence may also be age dependent. When an age-appropriate dosage form is not available, manipulation of adult dosage forms (e.g., splitting and crushing of tablets or opening of capsules) has been reported as a means to facilitate administration to children. To enhance swallowability and/or mask an unpleasant taste of the dosage form to be administered, crushed/split tablets or the contents of capsules are often mixed with food or drinks or suspended in a vehicle prior to administration. However, it seems that the risks and benefits of an approach whereby the dosage form is modified prior to administration in this manner are everything but clear. The aim of the present study was to gain an overview of the physicochemical properties of a number of fluids, soft foods and suspension vehicles that are commonly reported to be mixed with oral medications before administration to children to improve patient acceptability. For this purpose, physicochemical parameters of 15 different fluids, soft foods and suspension vehicles were measured. These included pH, buffer capacity, osmolality, surface tension and viscosity. Results of the study clearly show the differences in physicochemical properties of the test candidates. It is thus obvious that the type of fluid/food mixed with a drug product before administration may have a significant impact on bioavailability of the drug administered. Therefore, a risk-based assessment of such practices considering API properties, formulation features and physicochemical properties of the fluids and foods intended to be co-administered with the dosage form, in conjunction with the anatomical and physiological maturity of the gastro-intestinal tract in the intended paediatric population, should be an essential part of paediatric oral formulation development.

  5. Gastric emptying of enteric-coated tablets

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

    Park, H.M.; Chernish, S.M.; Rosenek, B.D.

    1984-03-01

    To evaluate the gastric emptying time of pharmaceutical dosage forms in a clinical setting, a relatively simple dual-radionuclide technique was developed. Placebo tablets of six different combinations of shape and size were labeled with indium-111 DTPA and enteric coated. Six volunteers participated in a single-blind and crossover study. Tablets were given in the morning of a fasting stomach with 6 oz of water containing /sup 99m/Tc pertechnetate and continuously observed with a gamma camera. A scintigraph was obtained each minute. The results suggested that the size, shape, or volume of the tablet used in this study had no significant effectmore » in the rate of gastric emptying. The tablets emptied erratically and unpredictably, depending upon their time of arrival in the stomach in relation to the occurrence of interdigestive myoelectric contractions. The method described is a relatively simple and accurate technique to allow one to follow the gastric emptying of tablets.« less

  6. 3D Printed "Starmix" Drug Loaded Dosage Forms for Paediatric Applications.

    PubMed

    Scoutaris, Nicolaos; Ross, Steven A; Douroumis, Dennis

    2018-01-16

    Three- dimensional (3D) printing has received significant attention as a manufacturing process for pharmaceutical dosage forms. In this study, we used Fusion Deposition Modelling (FDM) in order to print "candy - like" formulations by imitating Starmix® sweets to prepare paediatric medicines with enhanced palatability. Hot melt extrusion processing (HME) was coupled with FDM to prepare extruded filaments of indomethacin (IND), hypromellose acetate succinate (HPMCAS) and polyethylene glycol (PEG) formulations and subsequently feed them in the 3D printer. The shapes of the Starmix® objects were printed in the form of a heart, ring, bottle, ring, bear and lion. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infra-red Spectroscopy (FT-IR) and confocal Raman analysis were used to assess the drug - excipient interactions and the content uniformity. Physicochemical analysis showed the presence of molecularly dispersed IND in the printed tablets. In vivo taste masking evaluation demonstrated excellent masking of the drug bitterness. The printed forms were evaluated for drug dissolution and showed immediate IND release independently of the printed shape, within 60 min. 3D printing was used successfully to process drug loaded filaments for the development of paediatric printed tablets in the form of Starmix® designs.

  7. Ease of opening of blistered solid dosage forms in a senior citizens target group.

    PubMed

    Braun-Münker, Myriam; Ecker, Felix

    2016-10-30

    Blisters differing in design and handling are established as packaging material for solid dosage forms. The ease of opening of blisters influences application and patient's compliance. In this study the influence of visibility and movability of solid dosage forms in blister packaging on both, easy opening and patient's satisfaction, were investigated by target group testing according to ONR CEN/TS 15945. For each testing 20 participants in the age of 65-80 years were recruited randomly. They opened the blisters on realistic terms without any auxiliary devices. Video documentation of the hands' movements was recorded to analyze the opening procedure. To show the influence of visibility of the dosage form in the blister, capsules size 1 were packed in transparent and opaque blisters. A moderate influence of the visibility on both, the ease of opening and patient satisfaction, was observed. A second study dealt with the movability of solid dosage forms in blisters. Therefore, three different sizes of tablets with similar shapes were packed in identical cavities. Limited movability was found as major criterion on effectiveness and effectivity of opening as well as on satisfaction with the opening procedure. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Bioavailability of an extemporaneous suspension of propafenone made from tablets.

    PubMed

    Olguín, Hugo Juárez; Pérez, Carmen Flores; Pérez, Janett Flores; Mendiola, Blanca Ramírez; Portugal, Miriam Carrasco; Chávez, Jesús Bobadilla

    2006-07-01

    Propafenone is an effective antiarrhythmic agent used in children, while in Mexico no specific formulation for children is available, which causes errors in adequate dosage. The aim of this study was to determine the bioavailability of a suspension prepared extemporaneously using commercial tablets of propafenone. The bioavailability was determined in two groups of rabbits (n = 8): the first group received a single intravenous dose of 2 mg/kg of propafenone; the second was orally administered an extemporaneous suspension of propafenone prepared from commercial tablets. Blood samples were drawn at several times during the next 24 h and analysed by HPLC to determine drug levels. The extemporaneous suspension was tested previously with satisfactory results regarding physicochemical and microbiologic stability. The area under the curve (AUC) for the i.v. route was 5600.6 ng/ml.h and for oral administration the AUC was 3327.6 ng/ml.h. The bioavailability was calculated at 59.41%. These results are consistent with previous reports for solid dosage forms. The propafenone suspension prepared extemporaneously using commercial tablets is bioavailable using an animal model; nevertheless, it is necessary to carry out human studies either in volunteers or in patients to confirm these results.

  9. Electrochemical Studies on Minoxidil and Its Determination in Tablets by Differential-Pulse Polarography.

    DTIC Science & Technology

    1984-01-16

    AD-R76 981 ELECTROCHEMICAL STUDIES ON MINOXIDIL AND ITS j/j IDETERMINATION IN TABLETS BY..(U) UTAH UNIV SALT LAKE AS CITY DEPT OF CHEMISTRY L...INSTRUCTIONES 2. QVT CCESSIN ". 3 krCIPII-.,n I CATALOG Numtnk 22 ’TTE(d.t8v . TYPE OF R4EPORT a PERIOD COEd Electrochemical Studies on Minoxidil and... minoxidil in pharmaceutical dosage forms. The extracting . solvent was methani and the supporting electrolyte was 1.0 N sulphuric acid. L. An excellent

  10. Analysis of Counterfeit Coated Tablets and Multi-Layer Packaging Materials Using Infrared Microspectroscopic Imaging.

    PubMed

    Winner, Taryn L; Lanzarotta, Adam; Sommer, André J

    2016-06-01

    An effective method for detecting and characterizing counterfeit finished dosage forms and packaging materials is described in this study. Using attenuated total internal reflection Fourier transform infrared spectroscopic imaging, suspect tablet coating and core formulations as well as multi-layered foil safety seals, bottle labels, and cigarette tear tapes were analyzed and compared directly with those of a stored authentic product. The approach was effective for obtaining molecular information from structures as small as 6 μm.

  11. Development of modified-release dosage forms containing loratadine and pseudoephedrine sulfate.

    PubMed

    Sznitowska, Małgorzata; Cal, Krzysztof; Kupiec, Katarzyna

    2004-12-01

    Pseudoephedrine sulfate (PES) is a short-acting sympathomimetic amine and decongestant. Loratadine (L) is a long-acting antihistamine, H1 blocker. These drugs administered together provide relief from a whole range of rhinitis (hay fever) symptoms. Combination of both drugs is available in the form of sugar-coated modified-release tablets Clarinase (Schering-Plough). In this product, 5 mg of L and 60 mg of PES is present in the sugar-coating layer ready for an immediate release, and the rest of PES (60 mg) is incorporated in the extended-release core of the tablet. This enables fast as well as prolonged release of PES over 6-8 h. Because the sugar coating technologies are troublesome and rarely used nowadays, the aim of this study was to develop alternative oral dosage forms containing L (5 mg) and PES (120 mg). It was assumed that, similarly to the original product, the total dose of L and the half dose of PES should be released during 1 h and the remaining dose of PES ought to be gradually released for up to 8 h.

  12. 3D-micro-patterned fibrous dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2018-03-01

    At present, the most prevalent pharmaceutical dosage forms, the orally-delivered immediate-release tablets and capsules, are porous, granular solids. They disintegrate into their constituent particulates upon ingestion to release drug rapidly. The design, development, and manufacture of such granular solids, however, is inefficient due to difficulties associated with the unpredictable inter-particle interactions. Therefore, to achieve more predictable dosage form properties and processing, we have recently introduced melt-processed polymeric cellular dosage forms. The cellular forms disintegrated and released drug rapidly if the cells were predominantly interconnected. Preparation of interconnected cells, however, relies on the coalescence of gas bubbles in the melt, which is unpredictable. In the present work, therefore, new melt-processed fibrous dosage forms with contiguous void space are presented. The dosage forms are prepared by melt extrusion of the drug-excipient mixture followed by patterning the fibrous extrudate on a moving surface. It is demonstrated that the resulting fibrous structures are fully predictable by the extruder nozzle diameter and the motion of the surface. Furthermore, drug release experiments show that the disintegration time of the fibrous forms prepared in this work is of the order of that of the corresponding single fibers. The thin fibers of polyethylene glycol (excipient) and acetaminophen (drug) in turn disintegrate in a time proportional to the fiber radius and well within immediate-release specification. Finally, models of dosage form disintegration and drug release by single fibers and fibrous dosage forms are developed. It is found that drug release from fibrous forms is predictable by the physico-chemical properties of the excipient and such microstructural parameters as the fiber radius, the inter-fiber spacing, and the volume fraction of water-soluble excipient in the fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Improving the drug release of Naproxen Sodium tablets by preparing granules and tablets with a preferred mixing ratio of hydrates.

    PubMed

    Bär, David; Debus, Heiko; Grune, Christian; Tosch, Stephan; Fischer, Wolfgang; Mäder, Karsten; Imming, Peter

    2017-12-01

    Naproxen is a typical and well-known analgesic classified as non-steroidal anti-inflammatory drug (NSAID) and is commercialized as tablets or liquid-filled capsules. Naproxen is typically used asa sodium salt because of its better processability compared to Naproxen free acid. This entails hygroscopicity and gives rise to the existence of four different hydrates, which show polymorphic and pseudopolymorphic properties. Solid dosage forms containing Naproxen Sodium often have to be processed in an applicable dosage form by granulation and tablet compression. During granulation, Naproxen Sodium will be in contact with water and is exposed to the drop and rise in temperature and to mechanical stress. The result could be a mixture of different hydrates of Naproxen Sodium. This study showed that a modified designed fluid bed granulation was not affected by differences in the mixing ratio of hydrates when using different water contents after spraying and at the end with the finished granules. Here, X-ray diffraction combined with Rietveld refinement was used to analyze the ratio of the hydrates and its identity. All granulation batches showed a large amount of Naproxen Sodium Monohydrate (>87%) and no differences could be observed during tablet compression. Quantities of other hydrates were negligibly small. Furthermore, this study also demonstrated the influence of tablet compression by transforming the hydrates of the granules. In addition to Naproxen Sodium Monohydrate, a large quantity of amorphous structures has also been found. Rietveld evaluation combined with the preliminary studies of the raw hydrates provided conclusions on the drug release of the tablets containing hydrates of Naproxen Sodium which were influenced by tablet compression. Fast drug release was obtained when a maximum water content of about 21% was used after spraying during granulation, independently of the final water content of the finished granules. A maximum water content of less than 21% after spraying yielded a high quantity of amorphous components after tablet compression and thus worsened the drug release. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 21 CFR 520.246 - Butorphanol tartrate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....246 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.246 Butorphanol... associated with inflammatory conditions of the upper respiratory tract. (3) Limitations. For oral use in dogs...

  15. 21 CFR 520.246 - Butorphanol tartrate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....246 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.246 Butorphanol... associated with inflammatory conditions of the upper respiratory tract. (3) Limitations. For oral use in dogs...

  16. 21 CFR 520.90b - Ampicillin trihydrate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....90b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.90b Ampicillin... 5 days, stop treatment, reevaluate diagnosis, and change therapy. (2) Indications for use. Oral...

  17. 21 CFR 520.246 - Butorphanol tartrate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....246 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.246 Butorphanol... associated with inflammatory conditions of the upper respiratory tract. (3) Limitations. For oral use in dogs...

  18. 21 CFR 520.90b - Ampicillin trihydrate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....90b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.90b Ampicillin... 5 days, stop treatment, reevaluate diagnosis, and change therapy. (2) Indications for use. Oral...

  19. 21 CFR 520.1157 - Iodinated casein tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....1157 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1157 Iodinated casein... alopecia, scaliness of the skin surface, loss of hair, seborrhea, thickening of the skin, hyperpigmentation...

  20. 21 CFR 520.1157 - Iodinated casein tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....1157 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1157 Iodinated casein... alopecia, scaliness of the skin surface, loss of hair, seborrhea, thickening of the skin, hyperpigmentation...

  1. The practice and clinical implications of tablet splitting in international health

    PubMed Central

    Elliott, Ivo; Mayxay, Mayfong; Yeuichaixong, Sengchanh; Lee, Sue J; Newton, Paul N

    2014-01-01

    Objective Tablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed. Methods We selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded. Results Five of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets. Conclusion These findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended. PMID:24702766

  2. An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

    PubMed

    Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

    2015-04-30

    Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Visualization and Non-Destructive Quantification of Inkjet-Printed Pharmaceuticals on Different Substrates Using Raman Spectroscopy and Raman Chemical Imaging.

    PubMed

    Edinger, Magnus; Bar-Shalom, Daniel; Rantanen, Jukka; Genina, Natalja

    2017-05-01

    The purpose of this study was to investigate the applicability of Raman spectroscopy for visualization and quantification of inkjet-printed pharmaceuticals. Haloperidol was used as a model active pharmaceutical ingredient (API), and a printable ink base containing lactic acid and ethanol was developed. Inkjet printing technology was used to apply haloperidol ink onto three different substrates. Custom-made inorganic compacts and dry foam, as well as marketed paracetamol tablets were used as the substrates. Therapeutic personalized doses were printed by using one to ten printing rounds on the substrates. The haloperidol content in the finished dosage forms were determined by high-performance liquid chromatography (HPLC). The distribution of the haloperidol on the dosage forms were visualized using Raman chemical imaging combined with principal components analysis (PCA). Raman spectroscopy combined with modeling by partial least squares (PLS) regression was used for establishment of a quantitative model of the haloperidol content in the printed dosage forms. A good prediction of the haloperidol content was achieved for the inorganic compacts, while a slightly poorer prediction was observed for the paracetamol tablets. It was not possible to quantify haloperidol on the dry foam due to the low and varying density of the substrate. Raman spectroscopy is a useful tool for visualization and quality control of inkjet printed personalized medicine.

  4. Development and Validation of UV-Visible Spectrophotometric Method for Simultaneous Determination of Eperisone and Paracetamol in Solid Dosage Form.

    PubMed

    Khanage, Shantaram Gajanan; Mohite, Popat Baban; Jadhav, Sandeep

    2013-01-01

    Eperisone Hydrochloride (EPE) is a potent new generation antispasmodic drug which is used in the treatment of moderate to severe pain in combination with Paracetamol (PAR). Both drugs are available in tablet dosage form in combination with a dose of 50 mg for EPE and 325 mg PAR respectively. The method is based upon Q-absorption ratio method for the simultaneous determination of the EPE and PAR. Absorption ratio method is used for the ratio of the absorption at two selected wavelength one of which is the iso-absorptive point and other being the λmax of one of the two components. EPE and PAR shows their iso-absorptive point at 260 nm in methanol, the second wavelength used is 249 nm which is the λmax of PAR in methanol. The linearity was obtained in the concentration range of 5-25 μg/mL for EPE and 2-10 μg/mL for PAR. The proposed method was effectively applied to tablet dosage form for estimation of both drugs. The accuracy and reproducibility results are close to 100% with 2% RSD. RESULTS of the analysis were validated statistically and found to be satisfactory. The results of proposed method have been validated as per ICH guidelines. A simple, precise and economical spectrophotometric method has been developed for the estimation of EPE and PAR in pharmaceutical formulation.

  5. Quality by design I: Application of failure mode effect analysis (FMEA) and Plackett-Burman design of experiments in the identification of "main factors" in the formulation and process design space for roller-compacted ciprofloxacin hydrochloride immediate-release tablets.

    PubMed

    Fahmy, Raafat; Kona, Ravikanth; Dandu, Ramesh; Xie, Walter; Claycamp, Gregg; Hoag, Stephen W

    2012-12-01

    As outlined in the ICH Q8(R2) guidance, identifying the critical quality attributes (CQA) is a crucial part of dosage form development; however, the number of possible formulation and processing factors that could influence the manufacturing of a pharmaceutical dosage form is enormous obviating formal study of all possible parameters and their interactions. Thus, the objective of this study is to examine how quality risk management can be used to prioritize the number of experiments needed to identify the CQA, while still maintaining an acceptable product risk profile. To conduct the study, immediate-release ciprofloxacin tablets manufactured via roller compaction were used as a prototype system. Granules were manufactured using an Alexanderwerk WP120 roller compactor and tablets were compressed on a Stokes B2 tablet press. In the early stages of development, prior knowledge was systematically incorporated into the risk assessment using failure mode and effect analysis (FMEA). The factors identified using FMEA were then followed by a quantitative assessed using a Plackett-Burman screening design. Results show that by using prior experience, literature data, and preformulation data the number of experiments could be reduced to an acceptable level, and the use of FMEA and screening designs such as the Plackett Burman can rationally guide the process of reducing the number experiments to a manageable level.

  6. Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2016-07-25

    At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. Copyright © 2016. Published by Elsevier B.V.

  7. Microbiological assay for the analysis of certain macrolides in pharmaceutical dosage forms.

    PubMed

    Mahmoudi, A; Fourar, R E-A; Boukhechem, M S; Zarkout, S

    2015-08-01

    Clarithromycin (CLA) and roxithromycin (ROX) are macrolide antibiotics with an expanded spectrum of activity that are commercially available as tablets. A microbiological assay, applying the cylinder-plate method and using a strain of Micrococcus luteus ATCC 9341 as test organism, has been used and validated for the quantification of two macrolide drugs; CLA and ROX in pure and pharmaceutical formulations. The validation of the proposed method was carried out for linearity, precision, accuracy and specificity. The linear dynamic ranges were from 0.1 to 0.5μg/mL for both compounds. Logarithmic calibration curve was obtained for each macrolide (r>0.989) with statistically equal slopes varying from 3.275 to 4.038, and a percentage relative standard deviation in the range of 0.24-0.92%. Moreover, the method was applied successfully for the assay of the studied drugs in pharmaceutical tablet dosage forms. Recovery from standard addition experiments in commercial products was 94.71-96.91% regarding clarithromycin and 93.94-98.12% regarding roxithromycin, with a precision (%RSD) 1.32-2.11%. Accordingly, this microbiological assay can be used for routine quality control analysis of titled drugs in tablet formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. [Technological and pharmacotherapeutic properties of selected drugs with modified release of diclofenac sodium].

    PubMed

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

    2012-01-01

    Diclofenac and its sodium salt is one of the best-known and popular therapeutic agents from the group of NSAIDs used in medicine in many various pharmaceutical forms. Therapeutic products containing diclofenac sodium salt in doses of 100 mg and 75 mg with a qualitatively and quantitatively diversified share of excipients and a variable dosage form of the drug (solid capsules, tablets with modified release) were subjected to technological and pharmaceutical analysis. The effect of solid formulation components of polymer character making the core and the coating of the pharmaceutical form of therapeutic products on the disintegration time and pharmaceutical availability in pharmacopoeial receptor fluids was estimated. Market therapeutic products with diclofenac sodium in doses of 75 mg and 100 mg, technological analysis of the drug dosage form was conducted, disintegration time of solid oral dosage forms of the drug with diclofenac sodium salt was examined and research on pharmaceutical availability of diclofenac sodium salt from tested therapeutic products was conducted using the acid phase and the buffer phase according to the FP standards for delayed release enteral dosage forms. The experimental data was supplemented with the statistical analysis. There are three formulations in the form of solid capsules and one formulation in the form of a coated tablet. All therapeutic products bear features of a dosage form of modified release of diclofenac sodium salt, frequently of a delayed release formula in the duodenum or the small intestine with regard to the limitation of typical undesirable effects after taking NSAIDs. Considerable diversity between solid capsules and the tablet with modified release during disintegration or hydration and swelling has been observed. In the environment of a receptor fluid--purified water (pH = 7) the capsule Dicloberl retard disintegrates at the fastest rate in 5,49 minutes, and then in the order: DicloDuo 75 mg--8,13 minutes and Olfen 100 SR--11,27 minutes. The hydration degree of gelatin walls of capsules depends on the pH of the receptor fluid. The availability of diclofenac sodium salt in given receptor fluids confirms the fact of significant connection of clinical effectiveness of the tested pharmaceutical forms with the activity of hydrogen ions (pH) of the environment in which there are therapeutic products, and excipients used for making the pharmaceutical phase. Tested therapeutic products with diclofenac sodium salt are differentiated by the type of a dosage form. Dicloberl retard contains the minimally indispensable number of simple, commonly used excipients. The research on the disintegration time may only be related to the products Dicloberl retard, Olfen 100 SR and DicloDuo 75 mg treating it as the time of deformation and disintegration of a capsule. In all three types of receptor fluids, the capsule Dicloberl retard has the fastest disintegration rate. The "acid phase" demonstrated stability of the products with a slight dissolution of diclofenac sodium salt on the level 1,3-4,18% of the Q release coefficient. In the environment of artificial intestinal juice, Dicloberl retard is more effective releasing larger amounts of diclofenac sodium salt during 4 hours of exposition (differences from 10% to 14% of the Q release coefficient).

  9. Relative Bioavailability of Scopolamine Dosage Forms and Interaction with Dextroamphetamine

    NASA Technical Reports Server (NTRS)

    Boyd, Jason L.; Du, Brian; Vaksman, Zalman; Locke, James P.; Putcha, Lakshmi

    2007-01-01

    The NASA Reduced Gravity Office (RGO) uses scopolamine (SCOP) and in combination with dextoamphetamine (DEX) to manage motion sickness symptoms during parabolic flights. The medications are dispensed as custom dosage forms as gelatin capsules. Anecdotal evidence of efficacy suggests that these formulations are unreliable and less efficacious for the treatment of motion sickness. We estimated bioavailability of four different oral formulations used by NASA for the treatment of motion sickness. Twelve healthy, non-smoking subjects between 21and 48 years of age received four treatments on separate days in a randomized fashion; the treatments were 0.8 mg SCOP alone as tablet, 0.8 mg SCOP alone in gel cap, 0.8 mg SCOP and 10 mg DEX as tablets, and 0.8 mg SCOP and 10 mg DEX in gel cap. After each treatment, blood, saliva, and urine samples were collected at scheduled time intervals for 24 h after dosing. Bioavailability and pharmacokinetic parameters were calculated and compared using ANOVA. After administration of SCOP tablets alone, maximum concentration (C(sub max)) and time for maximum concentration (t(sub max)) were 0.26 plus or minus 0.04 ng/mL and 0.71 plus or minus 0.02 h, respectively; volume of distribution, and clearance were 47.6 plus or minus 4.72 L/kg and 23.0 plus or minus 4.58 L/h/kg, respectively. SCOP t(sub max) after administration as gelcaps was significantly longer than that with tablets (1.04 h, p less than 0.05), but no significant differences in other pharmacokinetic parameters of SCOP were observed between the two dosage forms. When coadministered with DEX, the area underneath the concentration versus time curve (AUC) of SCOP was significantly reduced to 0.61 plus or minus 0.09 and 0.64 plus or minus 0.11 ng (raised dot) h/mL after administration as a tablet or gelcap formulation, respectively; SCOP C(sub max) was lower after coadministration with DEX, this difference, however, was not statistically significant. Delayed absorption with gelcaps coupled with reduced bioavailability with DEX coadministration may have resulted in the observed treatment failure with some of these formulations. This could result from failure to reach minimum effective concentrations after treatment with gelcap formulations before parabolic flights. A new nomogram for dosing is proposed for treatment with SCOP gelcaps or SCOP-DEX combination.

  10. 21 CFR 520.309 - Carprofen.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Carprofen. 520.309 Section 520.309 Food and Drugs..., AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.309 Carprofen. (a) Specifications. (1) Each caplet contains 25, 75, or 100 milligrams (mg) carprofen. (2) Each chewable tablet contains 25, 75...

  11. Tabletted microspheres containing Cynara scolymus (var. Spinoso sardo) extract for the preparation of controlled release nutraceutical matrices.

    PubMed

    Gavini, E; Alamanni, M C; Cossu, M; Giunchedi, P

    2005-08-01

    Controlled release dosage forms based on tabletted microspheres containing fresh artichoke Cynara scolymus extract were performed for the oral administration of a nutritional supplement. Microspheres were prepared using a spray-drying technique; lactose or hypromellose have been chosen as excipients. Microspheres were characterized in terms of encapsulated extract content, size and morphology. Qualitative and quantitative composition of the extract before and after the spray process was determined. Compressed matrices (tablets) were prepared by direct compression of the spray-dried microspheres. In vitro release tests of microparticles and tablets prepared were carried out in both acidic and neutral media. Spray-drying is a good method to prepare microspheres containing the artichoke extract. The microspheres encapsulate an amount of extract close to the theoretical value. Particle size analyses indicate that the microparticles have dvs of approximately 6-7 microm. Electronic microscopy observations reveal that particles based on lactose have spherical shape and particles containing hypromellose are almost collapsed. The hydroalcoholic extract is stable to the microsphere production process: its polyphenolic composition (qualitative and quantitative) did not change after spraying. In vitro release studies show that microparticles characterized by a quick polyphenolic release both in acidic and neutral media due to the high water solubility of the carrier lactose. On the contrary, microspheres based hypromellose release only 20% of the loaded extract at pH 1.2 in 2 h and the total amount of polyphenols is released only after about further 6 h at pH 6.8. Matrices prepared tabletting lactose microspheres and hypromellose microparticles in the weight ratio 1:1 show a slow release rate, that lasts approximately 24 h. This one-a-day sustained release formulation containing Cynara scolymus extract could be proposed as a nutraceutical controlled release dosage form for oral administration.

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

    PubMed Central

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

    2011-01-01

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

  13. Oral delivery of medications to companion animals: palatability considerations.

    PubMed

    Thombre, Avinash G

    2004-06-23

    There is an increased need for highly palatable solid oral dosage forms for companion animals, which are voluntarily accepted by the dog or cat, either from a feeding bowl or from the outstretched hand of the pet owner. Such dosage forms represent an emerging trend in companion animal formulations with major impact on medical needs such as convenience and compliance, particularly for chronically administered medications, and on marketing needs such as product differentiation. This review focuses on the science of taste, food and flavor preferences of dogs and cats, and palatability testing, in the context of applying these principles to the development of an oral palatable tablet for companion animals.

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

    PubMed

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

    2016-08-01

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

  15. 21 CFR 520.2280 - Sulfamethizole and methenamine mandelate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfamethizole and methenamine mandelate tablets... Sulfamethizole and methenamine mandelate tablets. (a) Specifications. Each tablet contains 250 milligrams of... urethra and bladder. (2) It is administered at a dosage level of one tablet for each 20 pounds of body...

  16. Pharmacokinetics of three formulations of ondansetron hydrochloride in healthy volunteers: 24-mg oral tablet, rectal suppository, and i.v. infusion.

    PubMed

    VanDenBerg, C M; Kazmi, Y; Stewart, J; Weidler, D J; Tenjarla, S N; Ward, E S; Jann, M W

    2000-06-01

    The absolute bioavailability and pharmacokinetics of three formulations of ondansetron hydrochloride 24 mg--an oral tablet, an intravenous solution, and an extemporaneous rectal suppository--were studied. Twelve healthy, nonsmoking volunteers (six men and six women) were given ondansetron in a study with a three-way cross-over design. All subjects received each dosage form on the same day in the following order: oral tablet, rectal suppository, and intravenous infusion. Administrations were separated by one week. Blood sampling times varied, depending on the administration route. Mean absolute bioavailability for the oral tablet and the rectal suppository differed significantly. Absorption of ondansetron was prolonged when it was administered as the rectal suppository. Absolute bioavailability for the 24-mg tablet was similar to that for other tablet strengths in previous studies. All subjects completed the study without significant adverse effects. Absorption of ondansetron from the rectal suppository was prolonged compared with the oral tablet and the i.v. infusion. Bioavailability for the 24-mg suppository formulation was considerably lower than for the 24-mg tablet.

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

    PubMed Central

    Shah, Kifayat Ullah; Khan, Gul Majid

    2012-01-01

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

  18. 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.

  19. 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.

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

    PubMed Central

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

    2011-01-01

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

  1. 21 CFR 520.1447 - Milbemycin oxime, lufenuron, and praziquantel tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...) Amount. 0.5 mg milbemycin oxime, 10 mg lufenuron, and 5 mg of praziquantel per kilogram of body weight, once a month. (ii) Indications for use. For the prevention of heartworm disease caused by Dirofilaria...

  2. 21 CFR 520.1447 - Milbemycin oxime, lufenuron, and praziquantel tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...) Amount. 0.5 mg milbemycin oxime, 10 mg lufenuron, and 5 mg of praziquantel per kilogram of body weight, once a month. (ii) Indications for use. For the prevention of heartworm disease caused by Dirofilaria...

  3. 21 CFR 520.1447 - Milbemycin oxime, lufenuron, and praziquantel tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...) Amount. 0.5 mg milbemycin oxime, 10 mg lufenuron, and 5 mg of praziquantel per kilogram of body weight, once a month. (ii) Indications for use. For the prevention of heartworm disease caused by Dirofilaria...

  4. 21 CFR 201.122 - Drugs for processing, repacking, or manufacturing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs for processing, repacking, or manufacturing... for processing, repacking, or manufacturing. A drug in a bulk package, except tablets, capsules, or... manufacturing, processing, or repacking”; and if in substantially all dosage forms in which it may be dispensed...

  5. 76 FR 12563 - Oral Dosage Form New Animal Drugs; Spinosad and Milbemycin Oxime

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-08

    ... spinosad and milbemycin oxime in dogs for the treatment and prevention of flea infestations and for the... and milbemycin oxime) Chewable Tablets in dogs for the treatment and prevention of flea infestations... chapter. (c) Conditions of use in dogs--(1) Amount. Administer once a month at a [[Page 12564

  6. Simultaneous Determination of Ursodeoxycholic Acid and Chenodeoxycholic Acid in Pharmaceutical Dosage Form by HPLC-UV Detection.

    PubMed

    Khairy, Mostafa A; Mansour, Fotouh R

    2017-01-01

    A reversed-phase HPLC method was developed for the simultaneous determination of ursodeoxycholic acid (UDCA) and the epimeric isomer, chenodeoxycholic acid (CDCA), in their synthetic mixtures and in tablet dosage form. The proposed HPLC method uses a C18 column and mobile phase consisting of an acetonitrile-phosphate buffer mixture (pH 2.3, 100 mM; 50 + 50, v/v) at a flow rate of 2.0 mL/min with UV detection at 210 nm. The method was validated according to the International Conference on Harmonization guidelines; and linearity, range, accuracy, precision, robustness, and system suitability were studied. The LOD and LOQ were also calculated and found to be 1.23 and 3.73 μg/mL for UDCA and 0.83 and 2.52 μg/mL for CDCA, respectively. The method was adapted for UHPLC, in which baseline separation was achieved in <2.5 min. The assay results of Ursomix tablets by the developed method were statistically compared with those obtained by the reference method using t- and F-tests, and no significant differences were observed.

  7. Derivative Spectrophotometric Method for Estimation of Antiretroviral Drugs in Fixed Dose Combinations

    PubMed Central

    P.B., Mohite; R.B., Pandhare; S.G., Khanage

    2012-01-01

    Purpose: Lamivudine is cytosine and zidovudine is cytidine and is used as an antiretroviral agents. Both drugs are available in tablet dosage forms with a dose of 150 mg for LAM and 300 mg ZID respectively. Method: The method employed is based on first order derivative spectroscopy. Wavelengths 279 nm and 300 nm were selected for the estimation of the Lamovudine and Zidovudine respectively by taking the first order derivative spectra. The conc. of both drugs was determined by proposed method. The results of analysis have been validated statistically and by recovery studies as per ICH guidelines. Result: Both the drugs obey Beer’s law in the concentration range 10-50 μg mL-1,for LAM and ZID; with regression 0.9998 and 0.9999, intercept – 0.0677 and – 0.0043 and slope 0.0457 and 0.0391 for LAM and ZID, respectively.The accuracy and reproducibility results are close to 100% with 2% RSD. Conclusion: A simple, accurate, precise, sensitive and economical procedures for simultaneous estimation of Lamovudine and Zidovudine in tablet dosage form have been developed. PMID:24312779

  8. Comparative Studies on the Dissolution Profiles of Oral Ibuprofen Suspension and Commercial Tablets using Biopharmaceutical Classification System Criteria

    PubMed Central

    Rivera-Leyva, J. C.; García-Flores, M.; Valladares-Méndez, A.; Orozco-Castellanos, L. M.; Martínez-Alfaro, M.

    2012-01-01

    In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest. PMID:23626386

  9. Formulation and evaluation of floating tablet of H2-receptor antagonist.

    PubMed

    Kesarla, Rajesh S; Vora, Pratik Ashwinbhai; Sridhar, B K; Patel, Gunvant; Omri, Abdelwahab

    2015-01-01

    Conventional sustained dosage form of ranitidine hydrochloride (HCl) does not prevent frequent administration due to its degradation in colonic media and limited absorption in the upper part of GIT. Ranitidine HCl floating tablet was formulated with sublimation method to overcome the stated problem. Compatibility study for screening potential excipients was carried out using Fourier transform infrared spectroscopy (FT-IR) and differential scanning chromatography (DSC). Selected excipients were further evaluated for optimizing the formulation. Preliminary screening of binder, polymer and sublimating material was based on hardness and drug release, drug release with release kinetics and floating lag time with total floatation time, respectively. Selected excipients were subjected to 3(2) factorial design with polymer and sublimating material as independent factors. Matrix tablets were obtained by using 16/32" flat-faced beveled edges punches followed by sublimation. FT-IR and DSC indicated no significant incompatibility with selected excipients. Klucel-LF, POLYOX WSR N 60 K and l-menthol were selected as binder, polymer and sublimating material, respectively, for factorial design batches after preliminary screening. From the factorial design batches, optimum concentration to release the drug within 12 h was found to be 420 mg of POLYOX and 40 mg of l-menthol. Stability studies indicated the formulation as stable. Ranitidine HCl matrix floating tablets were formulated to release 90% of drug in stomach within 12 h. Hence, release of the drug could be sustained within narrow absorption site. Moreover, the dosage form was found to be floating within a fraction of second independent of the pH of media ensuring a robust formulation.

  10. Review of bilayer tablet technology.

    PubMed

    Abebe, Admassu; Akseli, Ilgaz; Sprockel, Omar; Kottala, Niranjan; Cuitiño, Alberto M

    2014-01-30

    Therapeutic strategies based on oral delivery of bilayer (and multilayer) tablets are gaining more acceptance among brand and generic products due to a confluence of factors including advanced delivery strategies, patient compliance and combination therapy. Successful manufacturing of these ever more complex systems needs to overcome a series of challenges from formulation design to tablet press monitoring and control. This article provides an overview of the state-of-the-art of bilayer tablet technology, highlighting the main benefits of this type of oral dosage forms while providing a description of current challenges and advances toward improving manufacturing practices and product quality. Several aspects relevant to bilayer tablet manufacturing are addressed including material properties, lubrication, layer ordering, layer thickness, layer weight control, as well as first and final compression forces. A section is also devoted to bilayer tablet characterization that present additional complexities associated with interfaces between layers. The available features of the manufacturing equipment for bilayer tablet production are also described indicating the different strategies for sensing and controls offered by bilayer tablet press manufacturers. Finally, a roadmap for bilayer tablet manufacturing is advanced as a guideline to formulation design and selection of process parameters and equipment. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Amoxicillin/clavulanic acid (875/125): bioequivalence of a novel Solutab tablet and rationale for a twice-daily dosing regimen.

    PubMed

    Sourgens, H; Bertola, M A; Verschoor, J S C; Kuipers, M; Rayer, B

    2004-03-01

    A new amoxicillin/clavulanic acid tablet formulation (Solutab tablet, Forcid Solutab) containing amoxicillin/clavulanic acid (875/125) has been developed. The aim of the present study was to demonstrate bioequivalence between the new tablet formulation (test), taken as an intact tablet and after prior dispersal, versus the originator product viz. Augmentan film-coated tablet (875/125) used as reference. The study was performed in 48 healthy volunteers according to an open, single-dose, crossover design. Bioequivalence was demonstrated using Cmax and AUC(0-infinity) as primary parameters of evaluation for both amoxicillin and clavulanic acid with 90% confidence intervals of the ratios Solutab tablet/Augmentan within the range of 0.8-1.25. The duration of the plasma concentration exceeding the amoxicillin minimal inhibitory concentration (MICs) was calculated using individual plasma concentration-time curves and compartmental analysis. The data showed that the bioavailability characteristics of the test tablet, taken intact or in dispersed form, and the reference tablets were very similar. The analysis, moreover, also confirmed the appropriateness of using a b.i.d. dosage regimen for both formulations, taking into account the pharmacodynamic breakpoint values for some major pathogens.

  12. EVALUATION OF CASES WITH THE USAGE OF COMMERCIALLY AVAILABLE TABLETS IN THE PEDIATRIC FORMULA.

    PubMed

    Kuriata, Elżbieta; Sawicki, Wiesław

    2015-01-01

    Lack of availability, of either the medicinal product intended to be used for children, or such in a dose which is fitting for the individual child's needs, results in physicians administering medicines meant for the adult. The target of the thesis was to evaluate the cases with the usage of commercially avaible conventional tablet-formulated medicinal products intended for the adult in the pediatric formula. The subjects of the evaluation were the form of the pediatric drug, prepared from commercially available tablets and capsules, as well as the legitimacy of their usage in the treatment of the pediatric population. One hundred and fifty-four prescriptions filled in community pharmacies of Warminsko-Mazurskie Voivodeship in 2011 were chosen. A total of 5805 divided powders in starch capsules were prepared. The prescribing practice included 6 groups of manufactured medicinal products in the form of conventional tablets, containing as follows: anti-hypertensive medicines (ACE inhibitors--enalapril, captopril, ramipril, loop diuretics--furosemide, potassium sparing diuretics--spironolactone, β-adrenolytics--propranolol, α- and β-adrenolytics--carvedilol), medicines for heart failure (foxglove glycosides--digoxin, methyldigoxin), anti-clotting medicines (acetylsalicylic acid), peristalsis stimulating agents (metoclopramide), antibacterial medicines (furagin), and dopaminergic (carbidopa-levodopa). The only compounded forms ordered by the physicians were divided powders for an internal use. Starch capsules for powder preparation provided the only 'package' for the dose of the compounded powder, which after pouring, solving or suspending in water was administered to children. Such a shift of the form, between an oral tablet and divided powder for an internal use, did not cause a change in the method of administration. The information on indications and the way of dosage for children, inserted in the Summary of Product Characteristics, enables the administration which follows the registered indications, despite the shortage of an appropriate dose in the pharmaceutical market. In contrast, an absence of the information regarding the indications and a dosage for children in the Summary of Product Characteristic, results in an off-label administration, in case of a child.

  13. 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.

  14. Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms.

    PubMed

    Lin, Zhongqiang; Zhou, Deliang; Hoag, Stephen; Qiu, Yihong

    2016-03-01

    Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory guidance should be reevaluated to assure consistent safety and efficacy among different strengths.

  15. [Levitra (oral dispersible tablet)--an innovative drug for the treatment of patients with erectile dysfunction].

    PubMed

    Korneev, I A

    2013-01-01

    The arsenal of professionals providing assistance to men with erectile dysfunction includes a new, mouth dissolving dosage form of the vardenafil--levitra ODT. This form is effective, safe, and has a higher bioavailability as compared to vardenafil in the form of coated tablets. POTENT I and POTENT II studies revealed that levitra ODT equally successfully corrects erectile dysfunction in men younger and older than 65 years regardless of concomitant diseases and metabolic disorders: hypertension, diabetes, dyslipidemia. In addition, it was found that this drug helped to successfully carry out sexual intercourse in the first 15 minutes after dosing in 62.5% of patients. This allows to widely recommend levitra ODT for the treatment of erectile dysfunction in young men and older men.

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

    PubMed

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

    2003-10-01

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

  17. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2016-06-01

    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

    PubMed

    Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

    This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the world. Tablets are often split to modify dose strength, make swallowing easier, and reduce cost to the consumer. To better address product quality for this widely used practice, the U.S. Food and Drug Administration (FDA) published a Guidance for Industry that addresses tablet splitting. The guidance provides testing criteria for scored tablets, which is a part of the FDA review process for drugs. The model drugs selected for this study were amlodipine and gabapentin, which have different sizes, shapes, and tablet scores. Whole and split amlodipine tablets were tested for drug content because of a concern that the low-dose strength may cause greater variability. Whole and split gabapentin tablets were tested for weight variation because of their higher dosage strength of 600 mg. All whole tablets met the acceptance criteria for the Uniformity of Dosage Units based on the guidance recommendations. When unscored amlodipine tablets were split by a splitter, all formulations did not meet the acceptance criteria. When fully scored gabapentin tablets were split by hand and by splitter, they met the acceptance criteria. The findings of this FDA study indicated physical characteristics such as size, shape, and tablet score can affect the uniformity of split tablets. © PDA, Inc. 2016.

  19. Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, part II: extension to describe performance of solid dosage forms.

    PubMed

    Thelen, Kirstin; Coboeken, Katrin; Willmann, Stefan; Dressman, Jennifer B; Lippert, Jörg

    2012-03-01

    The physiological absorption model presented in part I of this work is now extended to account for dosage-form-dependent gastrointestinal (GI) transit as well as disintegration and dissolution processes of various immediate-release and modified-release dosage forms. Empirical functions of the Weibull type were fitted to experimental in vitro dissolution profiles of solid dosage forms for eight test compounds (aciclovir, caffeine, cimetidine, diclofenac, furosemide, paracetamol, phenobarbital, and theophylline). The Weibull functions were then implemented into the model to predict mean plasma concentration-time profiles of the various dosage forms. On the basis of these dissolution functions, pharmacokinetics (PK) of six model drugs was predicted well. In the case of diclofenac, deviations between predicted and observed plasma concentrations were attributable to the large variability in gastric emptying time of the enteric-coated tablets. Likewise, oral PK of furosemide was found to be predominantly governed by the gastric emptying patterns. It is concluded that the revised model for GI transit and absorption was successfully integrated with dissolution functions of the Weibull type, enabling prediction of in vivo PK profiles from in vitro dissolution data. It facilitates a comparative analysis of the parameters contributing to oral drug absorption and is thus a powerful tool for formulation design. Copyright © 2011 Wiley Periodicals, Inc.

  20. [Pharmaceutical counseling of non-conventional dosage forms concerning the health-literacy and the patient adherence in public medication dispensing -Questionnaire surveys in Hungarian community pharmacies.

    PubMed

    Somogyi, O; Zelko, R

    Although the non-conventional dosage forms (e.g. modified release per oral systems or transdermal patches) have more significant advantages than other conventional dosage forms, the pa- tients have to apply them correctly in their home medicine using to reach the effective and safe therapy. A guideline of relevant application instructions contribute to development of an effective pharmaceutical counseling in community pharmacies. The counseling and advices can improve the patients' knowledge concerning application rules of different new dosage forms (health- literacy) with patient adherence. Finally it will result more effective and safer therapies. The aim of our Hungarian questionnaire surveys was to explore the patients' drug application habits or application errors and improve special verbal counseling of mentioned non-conventional dosage forms in community pharmacies. Understandable patient information leaflets were developed about application rules and besides the levels of patients' reading comprehension was evaluated in case of the leaflet of medicinal patches. The results show that a properly developed text is useful for the majority of patients but they need the verbal explanation as well, moreover there is a demand for the verbal counseling in community pharmacies. The most common application errors were explored and the most effective instructions or application rules were collected for the pharmacists and patients concerning the modified release tablets or capsules and transdermal patches.

  1. Issues impacting therapeutic outcomes in pediatric patients: an overview.

    PubMed

    Kalra, Atin; Goindi, Shishu

    2014-01-01

    The quest for achieving optimal therapeutic outcomes in pediatric patients has evaded the healthcare professionals for long and often lack of child specific dosage forms and the associated events that follow with it have been considered to be major contributor towards suboptimal outcomes. Consequently, there have been sustained efforts over the years to address this issue with the enactment of legislations like Best Pharmaceutical for Children Act (BPCA), Pediatric Research Equity Act (PREA) and Pediatric Regulation by European Union (EU) to incentivise the participation of pharmaceutical industry towards development of child friendly dosage forms. Initiatives taken in past by organisations like World Health Organisation (WHO) and Drugs for Neglected Diseases Initiative (DNDi) to spur the development of child friendly dosage forms has helped to address issues pertaining to management of Human Immunodeficiency Virus (HIV) and malaria in pediatric patients. Present efforts aimed at developing child friendly dosage forms include oro-dispersible platforms including thin films and mini-tablets. Despite these leaps and advancements in developing better dosage forms for children, lower therapeutic outcomes in pediatric patients continue to remain an unresolved issue because of detrimental effects of additional factors such as parents understanding of label instructions and complexities involved in executing pediatric clinical studies thus requiring a concerted effort from pharmaceutical companies, academic researchers, parents and healthcare providers to work for better treatment outcomes in children.

  2. 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.

  3. Towards more reliable automated multi-dose dispensing: retrospective follow-up study on medication dose errors and product defects.

    PubMed

    Palttala, Iida; Heinämäki, Jyrki; Honkanen, Outi; Suominen, Risto; Antikainen, Osmo; Hirvonen, Jouni; Yliruusi, Jouko

    2013-03-01

    To date, little is known on applicability of different types of pharmaceutical dosage forms in an automated high-speed multi-dose dispensing process. The purpose of the present study was to identify and further investigate various process-induced and/or product-related limitations associated with multi-dose dispensing process. The rates of product defects and dose dispensing errors in automated multi-dose dispensing were retrospectively investigated during a 6-months follow-up period. The study was based on the analysis of process data of totally nine automated high-speed multi-dose dispensing systems. Special attention was paid to the dependence of multi-dose dispensing errors/product defects and pharmaceutical tablet properties (such as shape, dimensions, weight, scored lines, coatings, etc.) to profile the most suitable forms of tablets for automated dose dispensing systems. The relationship between the risk of errors in dose dispensing and tablet characteristics were visualized by creating a principal component analysis (PCA) model for the outcome of dispensed tablets. The two most common process-induced failures identified in the multi-dose dispensing are predisposal of tablet defects and unexpected product transitions in the medication cassette (dose dispensing error). The tablet defects are product-dependent failures, while the tablet transitions are dependent on automated multi-dose dispensing systems used. The occurrence of tablet defects is approximately twice as common as tablet transitions. Optimal tablet preparation for the high-speed multi-dose dispensing would be a round-shaped, relatively small/middle-sized, film-coated tablet without any scored line. Commercial tablet products can be profiled and classified based on their suitability to a high-speed multi-dose dispensing process.

  4. Nano/micro/meso scale interactions in mechanics of pharmaceutical solid dosage forms

    NASA Astrophysics Data System (ADS)

    Akseli, Ilgaz

    Oral administration in form tablets has been the most common method for delivering drug to the human systemic blood circulation accurately and reproducibly due to its established manufacturing methods and reliability as well as cost. The mechanical criteria for a successful powder-to-tablet processing are good flowability, compressibility and compactibility that are closely related to the mechanical and adhesion properties of the particles and particle strength. In this thesis, air-coupled acoustic and ultrasonic techniques are presented and demonstrated as noncontact and nondestructive methods for physical (mechanical) integrity monitoring and mechanical characterization of tablets. A testing and characterization experimental platform for defect detection, coating thickness and mechanical property determination of tablets was also developed. The presented air-coupled technique was based on the analysis of the transient vibrational responses of a tablet in both temporal and spectral domains. The contact ultrasonic technique was based on the analysis of the propagation speed of an acoustic pulse launched into a tablet and its reflection from the coat-core interface of the tablet. In defect monitoring, the ultimate objective is to separate defective tablets from nominal ones. In the case of characterization, to extract the coating layer thicknesses and mechanical properties of the tablets from a subset of the measured resonance frequencies, an iterative computational procedure was demonstrated. In the compaction monitoring experiments, an instrumented punch and a cylindrical die were employed to extract the elasticity properties of tablets during compaction. To study the effect of compaction kinetics on tablet properties and defect, finite element analyses of single layer and bilayer tablets were performed. A noncontact work-of-adhesion technique was also demonstrated to determine the work-of-adhesion of pharmaceutical powder particles.

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

    PubMed

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

    2010-12-01

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

  6. 21 CFR 101.17 - Food labeling warning, notice, and safe handling statements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... any other labeling. (e) Dietary supplements containing iron or iron salts. (1) The labeling of any dietary supplement in solid oral dosage form (e.g., tablets or capsules) that contains iron or iron salts... concentrating and inhaling the contents can be harmful or fatal. (2) The warning required by paragraph (b)(1) of...

  7. 21 CFR 101.17 - Food labeling warning, notice, and safe handling statements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... any other labeling. (e) Dietary supplements containing iron or iron salts. (1) The labeling of any dietary supplement in solid oral dosage form (e.g., tablets or capsules) that contains iron or iron salts... concentrating and inhaling the contents can be harmful or fatal. (2) The warning required by paragraph (b)(1) of...

  8. 21 CFR 101.17 - Food labeling warning, notice, and safe handling statements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... any other labeling. (e) Dietary supplements containing iron or iron salts. (1) The labeling of any dietary supplement in solid oral dosage form (e.g., tablets or capsules) that contains iron or iron salts... concentrating and inhaling the contents can be harmful or fatal. (2) The warning required by paragraph (b)(1) of...

  9. Spectrophotometric methods for the determination of benazepril hydrochloride in its single and multi-component dosage forms.

    PubMed

    El-Yazbi, F A; Abdine, H H; Shaalan, R A

    1999-06-01

    Three sensitive and accurate methods are presented for the determination of benazepril in its dosage forms. The first method uses derivative spectrophotometry to resolve the interference due to formulation matrix. The second method depends on the color formed by the reaction of the drug with bromocresol green (BCG). The third one utilizes the reaction of benazepril, after alkaline hydrolysis, with 3-methylbenzothialozone (MBTH) hydrazone where the produced color is measured at 593 nm. The latter method was extended to develop a stability-indicating method for this drug. Moreover, the derivative method was applied for the determination of benazepril in its combination with hydrochlorothiazide. The proposed methods were applied for the analysis of benazepril in the pure form and in tablets. The coefficient of variation was less than 2%.

  10. OPTIMIZATION OF FUROSEMIDE LIQUISOLID TABLETS PREPARATION PROCESS LEADING TO THEIR MASS AND SIZE REDUCTION.

    PubMed

    Kurek, Mateusz; Woyna-Orlewicz, Krzysztof; Khalid, Mohammad Hassan; Jachowicz, Renata

    2016-09-01

    The great number of drug substances currently used in solid oral dosage forms is characterized by poor water solubility. Therefore, various methods of dissolution rate enhancement are an important topic of research interest in modem drug technology. The purpose of this study was to enhance the furosemide dissolution rate from liquisolid tablets while maintaining an acceptable size and mass. Two types of dibasic calcium phosphate (Fujicalin®/Emcompress®) and microcrystalline cellulose (Vivapur® 102/Vivapur® 12) were used as carriers and magnesium aluminometasilicate (Neusilin® US2) was used as a coating material. The flowable liquid retention potential for those excipients was tested by measuring the angle of slide. To evaluate the impact of used excipients on tablet properties fourteen tablet formulations were prepared. It was found that LS2 tablets containing spherically granulated dibasic calcium phosphate and magnesium aluminometasilicate exhibit the best dissolution profile and mechanical properties while tablets composed only with Neusilin® US2 was characterized by the smallest size and mass with preserved good mechanical properties and furosemide dissolution.

  11. Simultaneous determination of gatifloxacin and ambroxol hydrochloride from tablet dosage form using reversed-phase high performance liquid chromatography.

    PubMed

    Shahed, Mirza; Nanda, Rabindra; Dehghan, Muhammad Hassan; Nasreen, Huda; Feroz, Shaikh

    2008-05-01

    A reversed-phase high performance liquid chromatography (HPLC) method was developed, validated, and used for the quantitative determination of gatifloxacin (GA) and ambroxol hydrochloride (AM), from its tablet dosage form. Chromatographic separation was performed on a HiQ Sil C18 column (250 mm x 4.6 mm, 5 microm), with a mobile phase comprising of a mixture of 0.01 mol/L potassium dihydrogen orthophosphate buffer and acetonitrile (70 : 30, v/v), and pH adjusted to 3 with orthophosphoric acid, at a flow rate of 1 mL/min, with detection at 247 nm. Separation was completed in less than 10 min. As per International Conference on Harmonisation (ICH) guidelines the method was validated for linearity, accuracy, precision, limit of quantitation, limit of detection, and robustness. Linearity of GA was found to be in the range of 10 -60 microg/mL and that for AM was found to be 5 - 30 microg/mL. The correlation coefficients were 0.999 6 and 0.999 3 for GA and AM respectively. The results of the tablet analysis (n = 5) were found to be 99.94% with +/- 0.25% standard deviation (SD) and 99.98% with +/- 0.36% SD for GA and AM respectively. Percent recovery of GA was found to be 99.92% - 100.02% and that of AM was 99.86% - 100.16%. The assay experiment shows that the method is free from interference of excipients. This demonstrates that the developed HPLC method is simple, linear, precise, and accurate, and can be conveniently adopted for the routine quality control analysis of the tablet.

  12. 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.

  13. Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders.

    PubMed

    Grymonpré, W; Verstraete, G; Vanhoorne, V; Remon, J P; De Beer, T; Vervaet, C

    2018-03-01

    The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all critical sources of variability which could affect this granulation technique. The purpose of this study was to provide an in-depth analysis of the continuous TSMG process in order to expose the critical process parameters (CPP) and elucidate the impact of process and formulation parameters on the critical quality attributes (CQA) of granules and tablets during continuous TSMG. A first part of the study dealt with the screening of various amorphous polymers as binder for producing high-dosed melt granules of two model drug (i.e. acetaminophen and hydrochlorothiazide). The second part of this study described a quality-by-design (QbD) approach for melt granulation of hydrochlorothiazide in order to thoroughly evaluate TSMG, milling and tableting stage of the continuous TSMG line. Using amorphous polymeric binders resulted in melt granules with high milling efficiency due to their brittle behaviour without producing excessive amounts of fines, providing high granule yields with low friability. Therefore, it makes them extremely suitable for further downstream processing. One of the most important CPP during TSMG with polymeric binders was the granulation-torque, which - in case of polymers with high T g - increased during longer granulation runs to critical levels endangering the continuous process flow. However, by optimizing both screw speed and throughput or changing to polymeric binders with lower T g it was possible to significantly reduce this risk. This research paper highlighted that TSMG must be considered as a viable option during formulation development of solid oral dosage forms based on the robustness of the CQA of both melt granules and tablets. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Stability of amlodipine besylate in two liquid dosage forms.

    PubMed

    Nahata, M C; Morosco, R S; Hipple, T F

    1999-01-01

    To determine the stability of amlodipine besylate in two liquid dosage forms under refrigeration and at room temperature. Commercially available amlodipine tablets (Norvasc-Pfizer) were used to prepare two suspensions: one in extemporaneously prepared 1% methylcellulose in syrup (1:1), and another in equal volumes of commercially available OraPlus/OraSweet. Each suspension containing amlodipine 1 mg/mL was stored in 10 plastic prescription bottles; 5 were stored at 4 degrees C and 5 at 25 degrees C. Samples were collected immediately after preparation (day 0) and on days 7, 14, 28, 42, 56, 70, and 91. Amlodipine concentration was measured by stability-indicating HPLC method (n = 15). Research laboratory at Children's Hospital. Physical and chemical stability (> 90% of the initial concentration) of amlodipine in the two extemporaneously prepared suspensions during storage in plastic prescription bottles at 4 degrees C and 25 degrees C. Observed mean concentrations exceeded 90% of the initial concentrations in both suspensions for 91 days at 4 degrees C and 56 days at 25 degrees C. No noticeable change in physical appearance or odor was observed; pH changed slightly in the methylcellulose-containing formulation stored at 25 degrees C. Amlodipine was stable in two suspensions when stored in plastic prescription bottles for 91 days at 4 degrees C or 56 days at 25 degrees C. These formulations may be considered for pediatric or elderly patients who are unable to swallow tablets. The liquid dosage form would also permit accurate administration of amlodipine doses to infants and young children based on their body weight.

  15. Simultaneous Estimation of Amlodipine Besilate and Olmesartan Medoxomil in Pharmaceutical Dosage Form

    PubMed Central

    Wankhede, S. B.; Wadkar, S. B.; Raka, K. C.; Chitlange, S. S.

    2009-01-01

    Two UV Spectrophotometric and one reverse phase high performance liquid chromatography methods have been developed for the simultaneous estimation of amlodipine besilate and olmesartan medoxomil in tablet dosage form. First UV spectrophotometric method was a determination using the simultaneous equation method at 237.5 nm and 255.5 nm over the concentration range 10-50 μg/ml and 10-50 μg/ml, for amlodipine besilate and olmesartan medoxomil with accuracy 100.09%, and 100.22% respectively. Second UV spectrophotometric method was a determination using the area under curve method at 242.5-232.5 nm and 260.5-250.5 nm over the concentration range of 10-50 μg/ml and 10-50 μg/ml, for amlodipine besilate and olmesartan medoxomil with accuracy 100.10%, and 100.48%, respectively. In reverse phase high performance liquid chromatography analysis carried out using 0.05M potassuim dihydrogen phosphate buffer:acetonitrile (50:50 v/v) as the mobile phase and Kromasil C18 (4.6 mm i.d.×250 mm) column as the stationery phase with detection wavelength of 238 nm. Flow rate was 1.0 ml/min. Retention time for amlodipine besilate and olmesartan medoxomil were 3.69 and 5.36 min, respectively. Linearity was obtained in the concentration range of 4-20 μg/ml and 10-50 μg/ml for amlodipine besilate and olmesartan medoxomil, respectively. Proposed methods can be used for the estimation of amlodipine besilate and olmesartan medoxomil in tablet dosage form provided all the validation parameters are met. PMID:20502580

  16. Sensitive inexpensive spectrophotometric and spectrofluorimetric analysis of ezogabine, levetiracetam and topiramate in tablet formulations using Hantzsch condensation reaction

    NASA Astrophysics Data System (ADS)

    Ibrahim, F. A.; El-Yazbi, A. F.; Wagih, M. M.; Barary, M. A.

    2017-09-01

    Two highly sensitive, simple and selective spectrophotometric and spectrofluorimetric assays have been investigated for the analysis of ezogabine, levetiracetam and topiramate in their pure and in pharmaceutical dosage forms. The suggested methods depend on the condensation of the primary amino-groups in the three drugs with acetylacetone and formaldehyde according to Hantzsch reaction yielding highly fluorescent yellow colored dihydropyridine derivatives. The reaction products of ezogabine, levetiracetam and topiramate were measured spectrophotometrically at 418, 390 and 380 nm or spectrofluorimetrically at λem/ex of 495/425 nm, 490/415 nm and 488/410 nm, respectively. Various experimental conditions have been carefully studied to maximize the reaction yield. At the optimum reaction conditions, the calibration curves were rectilinear over the concentration ranges of 8-25, 60-180 and 80-200 μg/mL spectrophotometrically and 0.02-0.2, 0.2-1.2 and 0.2-1.5 μg/mL spectrofluorimetrically for ezogabine, levetiracetam and topiramate, respectively with good correlation coefficients. The suggested methods were applied successfully for the analysis of ezogabine, levetiracetam and topiramate in their commercial tablets with high percentage recoveries and negligible interference from various excipients in pharmaceutical dosage forms. The results were statistically analyzed and showed the absence of any significant difference between both developed and published methods. The procedures were validated and evaluated by the ICH guidelines revealing good reproducibility and accuracy. Therefore, the two proposed methods may be considered of high interest for practical and reliable analysis of ezogabine, levetiracetam and topiramate in pharmaceutical dosage forms.

  17. A New Rapid and Sensitive Stability-Indicating UPLC Assay Method for Tolterodine Tartrate: Application in Pharmaceuticals, Human Plasma and Urine Samples.

    PubMed

    Yanamandra, Ramesh; Vadla, Chandra Sekhar; Puppala, Umamaheshwar; Patro, Balaram; Murthy, Yellajyosula L N; Ramaiah, Parimi Atchuta

    2012-01-01

    A new rapid, simple, sensitive, selective and accurate reversed-phase stability-indicating Ultra Performance Liquid Chromatography (RP-UPLC) technique was developed for the assay of Tolterodine Tartrate in pharmaceutical dosage form, human plasma and urine samples. The developed UPLC method is superior in technology to conventional HPLC with respect to speed, solvent consumption, resolution and cost of analysis. Chromatographic run time was 6 min in reversed-phase mode and ultraviolet detection was carried out at 220 nm for quantification. Efficient separation was achieved for all the degradants of Tolterodine Tartrate on BEH C18 sub-2-μm Acquity UPLC column using Trifluoroacetic acid and acetonitrile as organic solvent in a linear gradient program. The active pharmaceutical ingredient was extracted from tablet dosage form using a mixture of acetonitrile and water as diluent. The calibration graphs were linear and the method showed excellent recoveries for bulk and tablet dosage form. The test solution was found to be stable for 40 days when stored in the refrigerator between 2 and 8 °C. The developed UPLC method was validated and meets the requirements delineated by the International Conference on Harmonization (ICH) guidelines with respect to linearity, accuracy, precision, specificity and robustness. The intra-day and inter-day variation was found be less than 1%. The method was reproducible and selective for the estimation of Tolterodine Tartrate. Because the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one.

  18. A New Rapid and Sensitive Stability-Indicating UPLC Assay Method for Tolterodine Tartrate: Application in Pharmaceuticals, Human Plasma and Urine Samples

    PubMed Central

    Yanamandra, Ramesh; Vadla, Chandra Sekhar; Puppala, Umamaheshwar; Patro, Balaram; Murthy, Yellajyosula. L. N.; Ramaiah, Parimi Atchuta

    2012-01-01

    A new rapid, simple, sensitive, selective and accurate reversed-phase stability-indicating Ultra Performance Liquid Chromatography (RP-UPLC) technique was developed for the assay of Tolterodine Tartrate in pharmaceutical dosage form, human plasma and urine samples. The developed UPLC method is superior in technology to conventional HPLC with respect to speed, solvent consumption, resolution and cost of analysis. Chromatographic run time was 6 min in reversed-phase mode and ultraviolet detection was carried out at 220 nm for quantification. Efficient separation was achieved for all the degradants of Tolterodine Tartrate on BEH C18 sub-2-μm Acquity UPLC column using Trifluoroacetic acid and acetonitrile as organic solvent in a linear gradient program. The active pharmaceutical ingredient was extracted from tablet dosage form using a mixture of acetonitrile and water as diluent. The calibration graphs were linear and the method showed excellent recoveries for bulk and tablet dosage form. The test solution was found to be stable for 40 days when stored in the refrigerator between 2 and 8 °C. The developed UPLC method was validated and meets the requirements delineated by the International Conference on Harmonization (ICH) guidelines with respect to linearity, accuracy, precision, specificity and robustness. The intra-day and inter-day variation was found be less than 1%. The method was reproducible and selective for the estimation of Tolterodine Tartrate. Because the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one. PMID:22396907

  19. Evaluation of accelerated stability test conditions for medicated chewing gums.

    PubMed

    Maggi, Lauretta; Conte, Ubaldo; Nhamias, Alain; Grenier, Pascal; Vergnault, Guy

    2013-10-01

    The overall stability of medicated chewing gums is investigated under different storage conditions. Active substances with different chemical stabilities in solid state are chosen as model drugs. The dosage form is a three layer tablet obtained by direct compression. The gum core contains the active ingredient while the external layers are formulated to prevent gum adhesion to the punches of the tableting machine. Two accelerated test conditions (40°C/75% RH and 30°C/65% RH) are performed for 6 months. Furthermore, a long-term stability test at room conditions is conducted to verify the predictability of the results obtained from the stress tests. Some drugs are stable in all the conditions tested, but other drugs, generally considered stable in solid dosage forms, have shown relevant stability problems particularly when stress test conditions are applied to this particular semi-solid dosage forms. For less stable drugs, the stress conditions of 40°C/75% RH are not always predictable of chewing gum stability at room temperature and may produce false negative; intermediate conditions, 30°C/65% RH, are more predictive for this purpose, the results of drug content found after 6 months at intermediate stress conditions and 12 months at room conditions are generally comparable. But the results obtained show that only long-term conditions stability tests gave consistent results. During aging, the semi solid nature of the gum base itself, may also influence the drug delivery rate during chewing and great attention should be given also to the dissolution stability.

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

    PubMed

    Guguloth, Mohan; Bomma, Ramesh; Veerabrahma, Kishan

    2011-01-01

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

  1. [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 aminophylline solution. These results suggest that the press-coated aminophylline tablet (with the timed-release characteristic) offers a promising forms of theophylline chronotherapy for asthma.

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

    PubMed

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

    2016-05-30

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

  3. [Comparative pharmacokinetics of paracetamol in humans following single oral and rectal administration (author's transl)].

    PubMed

    Liedtke, R; Berner, G; Haase, W; Nicolai, W; Staab, R; Wagener, H H

    1979-01-01

    The pharmacokinetic behaviour of N-acetyl-p-aminophenol (paracetamol) after single dose applications of 500 mg and 1000 mg dosages in the form of liquids, tablets and suppositories was compared. The estimation of the pharmacokinetic constants by a simultaneous curve fitting with a direct search procedure, based on an open two-compartment model, showed for the liquid as well as for the tablet formulation a good conformable and dosage proportional behaviour of the relative bioavailability. In opposite to the oral application, the suppositories had a significantly reduced invasion kinetics with a comparable elimination kinetics characterized by a lowering of Cmax and an increase of Tmax-values with comparable AUCs. The calculation of collapse-coefficients showed, with the exception of one suppository formulation, for all administrations a pharmacokinetic behaviour deviating from an open one-compartment model. The clinical consequences resulting from the pharmacokinetic behaviour of the different galenic formulations and routes of administrations are discussed.

  4. First derivative spectrophotometric determination of granisetron hydrochloride in presence of its hydrolytic products and preservative and application to pharmaceutical preparations.

    PubMed

    Hewala, Ismail I; Bedair, Mona M; Shousha, Sherif M

    2013-04-01

    Granisetron is a selective 5-HT3 receptor antagonist used in prevention and treatment of chemotherapy-induced nausea and vomiting. The drug is available in tablet dosage form and parenteral dosage form containing benzyl alcohol as a preservative. The main route of degradation of granisetron is through hydrolysis. The present work describes the development of a simple, rapid, and reliable first derivative spectrophotometric method for the determination of granisetron in presence of its hydrolytic products as well as the formulations adjuvant and benzyl alcohol. The method is based on the measurement of the first derivative response of granisetron at 290 nm where the interference of the hydrolytic products, the co-formulated adjuvant and benzyl alcohol is completely eliminated. The proposed method was validated with respect to specificity, linearity, selectivity, accuracy, precision, robustness, detection, and quantification limits. Regression analysis showed good correlation between the first derivative response and the concentration of granisetron over a range of 8-16 μg ml(-1) . Statistical analysis proved the accuracy of the proposed method compared with a reference stability indicating high performance liquid chromatography method. The described method was successfully applied to the determination of granisetron in different batches of tablets and ampoules. The assay results obtained in this study strongly encourage us to apply the validated method for the quality control and routine analysis of tablets and parenteral preparations containing granisetron. Copyright © 2012 John Wiley & Sons, Ltd.

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

    PubMed

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

    2008-01-01

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

  6. A Fast and Validated Reversed-Phase HPLC Method for Simultaneous Determination of Simvastatin, Atorvastatin, Telmisartan and Irbesartan in Bulk Drugs and Tablet Formulations

    PubMed Central

    Alhazmi, Hassan A.; Alnami, Ahmed M.; Arishi, Mohammed A. A.; Alameer, Raad K.; Al Bratty, Mohammed; Rehman, Zia ur; Javed, Sadique A.; Arbab, Ismail A.

    2017-01-01

    The aim of this study was to develop and validate a fast and simple reversed-phase HPLC method for simultaneous determination of four cardiovascular agents—atorvastatin, simvastatin, telmisartan and irbesartan in bulk drugs and tablet oral dosage forms. The chromatographic separation was accomplished by using Symmetry C18 column (75 mm × 4.6 mm; 3.5 μ) with a mobile phase consisting of ammonium acetate buffer (10 mM; pH 4.0) and acetonitrile in a ratio 40:60 v/v. Flow rate was maintained at 1 mL/min up to 3.5 min, and then suddenly changed to 2 mL/min till the end of the run (7.5 min). The data was acquired using ultraviolet detector monitored at 220 nm. The method was validated for linearity, precision, accuracy and specificity. The developed method has shown excellent linearity (R2 > 0.999) over the concentration range of 1–16 µg/mL. The limits of detection (LODs) and limits of quantification (LOQs) were in the range of 0.189–0.190 and 0.603–0.630 µg/mL, respectively. Inter-day and intra-day accuracy and precision data were recorded in the acceptable limits. The new method has successfully been applied for quantification of all four drugs in their tablet dosage forms with percent recovery within 100 ± 2%. PMID:29257120

  7. Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing.

    PubMed

    Goyanes, Alvaro; Chang, Hanah; Sedough, Daniel; Hatton, Grace B; Wang, Jie; Buanz, Asma; Gaisford, Simon; Basit, Abdul W

    2015-12-30

    The aim of this work was to explore the feasibility of using fused deposition modelling (FDM) 3D printing (3DP) technology with hot melt extrusion (HME) and fluid bed coating to fabricate modified-release budesonide dosage forms. Budesonide was sucessfully loaded into polyvinyl alcohol filaments using HME. The filaments were engineered into capsule-shaped tablets (caplets) containing 9mg budesonide using a FDM 3D printer; the caplets were then overcoated with a layer of enteric polymer. The final printed formulation was tested in a dynamic dissolution bicarbonate buffer system, and two commercial budesonide products, Cortiment® (Uceris®) and Entocort®, were also investigated for comparison. Budesonide release from the Entocort® formulation was rapid in conditions of the upper small intestine while release from the Cortiment® product was more delayed and very slow. In contrast, the new 3D printed caplet formulation started to release in the mid-small intestine but release then continued in a sustained manner throughout the distal intestine and colon. This work has demonstrated the potential of combining FDM 3DP with established pharmaceutical processes, including HME and film coating, to fabricate modified release oral dosage forms. Copyright © 2015. Published by Elsevier B.V.

  8. The use of Hibiscus esculentus (Okra) gum in sustaining the release of propranolol hydrochloride in a solid oral dosage form.

    PubMed

    Zaharuddin, Nurul Dhania; Noordin, Mohamed Ibrahim; Kadivar, Ali

    2014-01-01

    The effectiveness of Okra gum in sustaining the release of propranolol hydrochloride in a tablet was studied. Okra gum was extracted from the pods of Hibiscus esculentus using acetone as a drying agent. Dried Okra gum was made into powder form and its physical and chemical characteristics such as solubility, pH, moisture content, viscosity, morphology study using SEM, infrared study using FTIR, crystallinity study using XRD, and thermal study using DSC and TGA were carried out. The powder was used in the preparation of tablet using granulation and compression methods. Propranolol hydrochloride was used as a model drug and the activity of Okra gum as a binder was compared by preparing tablets using a synthetic and a semisynthetic binder which are hydroxylmethylpropyl cellulose (HPMC) and sodium alginate, respectively. Evaluation of drug release kinetics that was attained from dissolution studies showed that Okra gum retarded the release up to 24 hours and exhibited the longest release as compared to HPMC and sodium alginate. The tensile and crushing strength of tablets was also evaluated by conducting hardness and friability tests. Okra gum was observed to produce tablets with the highest hardness value and lowest friability. Hence, Okra gum was testified as an effective adjuvant to produce favourable sustained release tablets with strong tensile and crushing strength.

  9. The Use of Hibiscus esculentus (Okra) Gum in Sustaining the Release of Propranolol Hydrochloride in a Solid Oral Dosage Form

    PubMed Central

    Noordin, Mohamed Ibrahim; Kadivar, Ali

    2014-01-01

    The effectiveness of Okra gum in sustaining the release of propranolol hydrochloride in a tablet was studied. Okra gum was extracted from the pods of Hibiscus esculentus using acetone as a drying agent. Dried Okra gum was made into powder form and its physical and chemical characteristics such as solubility, pH, moisture content, viscosity, morphology study using SEM, infrared study using FTIR, crystallinity study using XRD, and thermal study using DSC and TGA were carried out. The powder was used in the preparation of tablet using granulation and compression methods. Propranolol hydrochloride was used as a model drug and the activity of Okra gum as a binder was compared by preparing tablets using a synthetic and a semisynthetic binder which are hydroxylmethylpropyl cellulose (HPMC) and sodium alginate, respectively. Evaluation of drug release kinetics that was attained from dissolution studies showed that Okra gum retarded the release up to 24 hours and exhibited the longest release as compared to HPMC and sodium alginate. The tensile and crushing strength of tablets was also evaluated by conducting hardness and friability tests. Okra gum was observed to produce tablets with the highest hardness value and lowest friability. Hence, Okra gum was testified as an effective adjuvant to produce favourable sustained release tablets with strong tensile and crushing strength. PMID:24678512

  10. X-ray powder diffractometry of intact film coated tablets--an approach to monitor the physical form of the active pharmaceutical ingredient during processing and storage.

    PubMed

    Yamada, Hiroyuki; Suryanarayanan, Raj

    2007-08-01

    The antiviral compound, 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl)ester (MCC-478), can exist in several anhydrous polymorphic forms and also as a hemihydrate. The XRD patterns of the tablets, containing each form of the active pharmaceutical ingredient (API), revealed at least one peak unique to each form. A semiquantitative microdiffractometric method was developed to nondestructively characterize the physical form of the API in intact film-coated tablets. This was accomplished even though the weight fraction of the API was <0.2 and that of mannitol, a highly crystalline excipient, was approximately 0.6. The method was used to determine the effect of aqueous film-coating process on the physical form of the API. The final dosage form was also monitored following storage at 40 degrees C/75% RH for 6 months. There was no phase transformation of the API either due to the film-coating process or following accelerated storage. This technique has potential utility not only for process control during manufacture, but also for the quality control of the final product. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

  11. Development and evaluation of a monolithic floating dosage form for furosemide.

    PubMed

    Menon, A; Ritschel, W A; Sakr, A

    1994-02-01

    The poor bioavailability of orally dosed furosemide (60%), a weakly acidic drug, is due to the presence of a biological window comprised of the upper gastrointestinal tract. The purpose of the present study was to develop and optimize in vitro a monolithic modified-release dosage form (MMR) for furosemide with increased gastric residence time and to evaluate the in vivo performance of the dosage form. The principle of floatation was used to restrict the MMR to the stomach. A two-factor three-level full factorial experimental design was employed for formulation development. A flow-through cell was designed to evaluate in vitro dissolution parameters. Quadratic regression models indicated the polymer viscosity and polymer:drug ratio to be significant (p < 0.05) formulation factors in determining the duration of buoyancy and the release profile. Statistical optimization using response surface methodology with certain physiological constraints relating to gastric emptying time predicted an optimal MMR. In vivo evaluation of the optimized MMR in beagle dogs resulted in a significant increase (p < 0.05) in the absolute bioavailability for the MMR dosage form (42.9%) as compared to the commercially available tablet (33.4%) and enteric product (29.5%). Significant in vitro/in vivo correlations (p < 0.05) were obtained for the MMR using deconvolution analysis normalized for bioavailability. The floating dosage form was found to be a feasible approach in delivering furosemide to the upper gastrointestinal tract to maximize drug absorption.

  12. The topological pressure-temperature phase diagram of fluoxetine nitrate: monotropy unexpectedly turning into enantiotropy

    NASA Astrophysics Data System (ADS)

    Céolin, René; Rietveld, Ivo B.

    2017-04-01

    The phase behavior of pharmaceuticals is important for regulatory requirements and dosage form development. Racemic fluoxetine nitrate possesses two crystalline forms for which initial measurements indicated that they have a monotropic relationship with form I the only stable form. By constructing the topological pressure-temperature phase diagram, it has been shown that unexpectedly form II has a stable domain in the phase diagram and can be easily obtained by heating and grinding. The pressure necessary to obtain form II is only 11 MPa, which is much lower than most pressure used for tableting in the pharmaceutical industry.

  13. The development of carbamazepine-succinic acid cocrystal tablet formulations with improved in vitro and in vivo performance.

    PubMed

    Ullah, Majeed; Hussain, Izhar; Sun, Changquan Calvin

    2016-01-01

    The use of soluble cocrystal for delivering drugs with low solubility, although a potentially effective approach, often suffers the problem of rapid disproportionation during dissolution, which negates the solubility advantages offered by the cocrystal. This necessitates their robust stabilization in order for successful use in a tablet dosage form. The cocrystal between carbamezepine and succinic acid (CBZ-SUC) exhibits a higher aqueous solubility than its dihydrate, which is the stable form of CBZ in water. Using this model system, we demonstrate an efficient and material-sparing tablet formulation screening approach enabled by intrinsic dissolution rate measurements. Three tablet formulations capable of stabilizing the cocrystal both under accelerated condition of 40 °C and 75% RH and during dissolution were developed using three different polymers, Soluplus® (F1), Kollidon VA/64 (F2) and Hydroxypropyl methyl cellulose acetate succinate (F3). When compared to a marketed product, Epitol® 200 mg tablets (F0), drug release after 60 min from formulations F1 (∼82%), F2 (∼95%) and F3 (∼95%) was all higher than that from Epitol® (79%) in a modified simulated intestinal fluid. Studies in albino rabbits show correspondingly better bioavailability of F1-F3 than Epitol.

  14. Preparation and evaluation of novel metronidazole sustained release and floating matrix tablets.

    PubMed

    Asnaashari, Solmaz; Khoei, Nazaninossadat Seyed; Zarrintan, Mohammad Hosein; Adibkia, Khosro; Javadzadeh, Yousef

    2011-08-01

    In the present study, metronidazole was used for preparing floating dosage forms that are designed to retain in the stomach for a long time and have developed as a drug delivery system for better eradication of Helicobacter Pylori in peptic ulcer diseases. For this means, various formulations were designed using multi-factorial design. HPMC, psyllium and carbopol in different concentrations were used as floating agents, and sodium bicarbonate was added as a gas-forming agent. Hardness, friability, drug loading, floating ability and release profiles as well as kinetics of release were assessed. Formulations containing HPMC as filler showed prolonged lag times for buoyancy. Adding psyllium to these formulations had reduced relative lag times. Overall, selected formulations were able to float immediately and showed buoyancy for at least 8?h. Meanwhile, sustained profiles of drug release were also obtained. Kinetically, among the 10 assessed models, the release pattern of metronidazole from the tablets fitted best to Power law, Weibull and Higuchi models in respect overall to mean percentage error values of 3.8, 4.73 and 5.77, respectively, for calcium carbonate-based tablets and, 2.95, 6.39 and 3.9, respectively, for calcium silicate-based tablets. In general, these systems can float in the gastric condition and control the drug release from the tablets.

  15. General public knowledge, preferred dosage forms, and beliefs toward medicines in western Saudi Arabia.

    PubMed

    Alhaddad, Mahmoud S; Abdallah, Qasem M; Alshakhsheer, Sami M; Alosaimi, Salman B; Althmali, Ahmed R; Alahmari, Solaiman A

    2014-06-01

    To measure general public knowledge, source of knowledge, preferred dosage forms, and beliefs toward medicines. A cross-sectional study design using convenience-sampling technique was used. A pre-validated questionnaire was designed and distributed to the general public through face-to-face interviews. All data were analyzed, and p-values less than 0.05 were considered significant. The study took place in the Clinical Pharmacy Department, Taif University, Taif, Kingdom of Saudi Arabia between August 2012 and February 2013 RESULTS: Nine hundred participants successfully responded to this study. Males represented two-thirds of the respondents (66.8%). In addition, 52% of respondents were of high education level. Modern (74.2%) and alternative medicines (88.7%) were understood by most respondents. Tablets (69.6%) and capsules (37.6%) represented the highest preferred dosage forms. In addition, physicians (66.6%) and pharmacists (46.2%) were the main sources of information regarding medicines. In terms of beliefs, respondents showed wrong beliefs in many statements used in this study. There is a need to improve public knowledge and beliefs toward medicines as well as utilizing public preferred dosage forms. In addition, pharmacists should play a major role in these programs since they are experts on medicines and play a more active role in patient education and counseling.

  16. Amorphization within the tablet: Using microwave irradiation to form a glass solution in situ.

    PubMed

    Doreth, Maria; Hussein, Murtadha Abdul; Priemel, Petra A; Grohganz, Holger; Holm, René; Lopez de Diego, Heidi; Rades, Thomas; Löbmann, Korbinian

    2017-03-15

    In situ amorphization is a concept that allows to amorphize a given drug in its final dosage form right before administration. Hence, this approach can potentially be used to circumvent recrystallization issues that other amorphous formulation approaches are facing during storage. In this study, the feasibility of microwave irradiation to prepare amorphous solid dispersions (glass solutions) in situ was investigated. Indomethacin (IND) and polyvinylpyrrolidone K12 (PVP) were tableted at a 1:2 (w/w) ratio. In order to study the influence of moisture content and energy input on the degree of amorphization, tablet formulations were stored at different relative humidity (32, 43 and 54% RH) and subsequently microwaved using nine different power-time combinations up to a maximum energy input of 90kJ. XRPD results showed that up to 80% (w/w) of IND could be amorphized within the tablet. mDSC measurements revealed that with increasing microwaving power and time, the fractions of crystalline IND and amorphous PVP reduced, whereas the amount of in situ formed IND-PVP glass solution increased. Intrinsic dissolution showed that the dissolution rate of the microwaved solid dispersion was similar to that of a quench cooled, fully amorphous glass solution even though the microwaved samples contained residual crystalline IND. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Improving the hardness of dry granulated tablets containing sodium lauryl sulfate.

    PubMed

    Moore, Francis; Okelo, Geoffrey; Colón, Ivelisse; Kushner, Joseph

    2010-11-15

    The impact of the addition of a wetting agent, the surfactant sodium lauryl sulfate (SLS), on the tablet hardness of a dry granulated, solid oral dosage form was investigated. In three batches, SLS was added concurrently with: (1) a poorly soluble, highly hydrophobic active pharmaceutical ingredient (API) and the other excipients prior to the initial blending step, (2) magnesium stearate prior to roller compaction, or (3) magnesium stearate prior to tableting. A fourth batch, which did not contain SLS, served as a control. The maximum hardness of 100 mg, 1/4″-SRC tablets for the four batches--SLS added initially, prior to roller compaction, prior to tableting, and no SLS--were 61±3, 71±3, 89±5, and 86±3N, respectively, suggesting reduced processing of SLS improves tablet hardness by ∼50%. Dissolution of the tablets in 900 ml of simulated gastric fluid with paddles at 75 rpm showed that: (1) there was no impact on the insertion point of SLS into the process on API dissolution, and (2) that the presence of SLS improved dissolution by 5% compared to the control tablets. Adding SLS just prior to tableting can improve tablet hardness and yield similar dissolution performance relative to SLS addition prior to the initial blending step. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Mini-tablets versus pellets as promising multiparticulate modified release delivery systems for highly soluble drugs.

    PubMed

    Gaber, Dina M; Nafee, Noha; Abdallah, Osama Y

    2015-07-05

    Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkably higher coating thickness was required for pellets to provide equivalent retardation. Ethyl cellulose in the core ensured faster release due to polymer migration to the surface and pore formation in the coat. mini-tablets showed higher stability to pellets upon storage. Industrially speaking, mini-tablets proved to be superior to pellets in terms of manufacturing, product quality and economical aspects. Results point out the urgent need for standardized evaluation procedures for mini-tablets. Copyright © 2015. Published by Elsevier B.V.

  19. Toward predicting tensile strength of pharmaceutical tablets by ultrasound measurement in continuous manufacturing.

    PubMed

    Razavi, Sonia M; Callegari, Gerardo; Drazer, German; Cuitiño, Alberto M

    2016-06-30

    An ultrasound measurement system was employed as a non-destructive method to evaluate its reliability in predicting the tensile strength of tablets and investigate the benefits of incorporating it in a continuous line, manufacturing solid dosage forms. Tablets containing lactose, acetaminophen, and magnesium stearate were manufactured continuously and in batches. The effect of two processing parameters, compaction force and level of shear strain were examined. Young's modulus and tensile strength of tablets were obtained by ultrasound and diametrical mechanical testing, respectively. It was found that as the blend was exposed to increasing levels of shear strain, the speed of sound in the tablets decreased and the tablets became both softer and mechanically weaker. Moreover, the results indicate that two separate tablet material properties (e.g., relative density and Young's modulus) are necessary in order to predict tensile strength. A strategy for hardness prediction is proposed that uses the existing models for Young's modulus and tensile strength of porous materials. Ultrasound testing was found to be very sensitive in differentiating tablets with similar formulation but produced under different processing conditions (e.g., different level of shear strain), thus, providing a fast, and non-destructive method for hardness prediction that could be incorporated to a continuous manufacturing process. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Formulation and evaluation of different floating tablets containing metronidazole to target stomach.

    PubMed

    Loh, Zhiao C; Elkordy, Amal A

    2015-01-01

    The purpose of this study is to formulate and develop tablets dosage form containing Metronidazole which has swelling and floating properties as a gastroretentive controlled-release drug delivery system to improve drug bioavailability. Fifteen different formulations of effervescence-forming floating systems were designed using HPMC K15M, xanthan gum, co-povidone, Eudragit® RL PO, pluronic® F-127 and/or polypropylene foam powder as swelling agents and sodium bicarbonate with/ without citric acid as gas-forming agents at different compositions. Six out of these 15 formulations which have satisfactory tablet floating behaviour were further studied with the incorporation of Metronidazole. The tablets were evaluated based on tablet physicochemical properties, floating behaviour, swelling ability and drug dissolution studies which were carried out using 0.1M HCl at 37°C for 8 hours. Furthermore, evaluation of the powder mixtures using Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscope (SEM) were investigated. Most of the tablets show good physicochemical properties except for F11 which contains pluronic® F-127 as its release-retarding matrix-forming polymer. Other formulations show high swelling capacity, ability to float for at least 8 hours in vitro and have sustained drug release characteristics. Data obtained indicated that F3 which contains HPMC (12.5%w/w), xanthan gum (25%w/w), co-povidone (12.5%w/w) and sodium bicarbonate (31.7%w/w) is a suitable formulation with short floating lag time, good floating behaviour and sustained drug release for at least 8 hours in vitro with a zero order kinetic. Combinations of HPMC K15M and xanthan gum as swelling agents show synergistic effect in retarding drug release and are suitable in providing the most sustained drug release system.

  1. [Divisibility of warfarin and fluindione tablets tested in elderly patients and their family circle].

    PubMed

    Pautas, Eric; Despres, Jérémie; Peyron, Isabelle; Golmard, Jean-Louis; Grange, Jennifer; Koenig, Nelly; Gouronnec, Adeline; Mitha, Nathalie; Siguret, Virginie; Gouin-Thibault, Isabelle

    2011-06-01

    Vitamin K antagonist tablets are often split to fractionate the dose by elderly patients. We performed a study in order to assess the divisibility of one dosage strength of score-lined warfarin and of score-lined fluindione. Due to a recent change in the pharmaceutical form of fluindione in order to improve the divisibility, the study was performed over 2 different periods (with the « old » and with the « new » pharmaceutical form). In each period, 10 patients mean aged 82 years, 10 relatives, 10 nurses, 10 medical doctors) were asked to split in half warfarin tablets (W2 1(st) period et W2 2(d) period) and fluindione tablets (F2 et F'2), and to split fluindione tablets into 4 fragments (F4 et F'4). The first end-point was the accuracy of splitting estimated by the difference between the real and the expected weight of fragmented tablets. The statistical analysis was performed using an ANOVA test with 2 variables, subject and drug. The difference between the 2 periods were analyzed using an ANOVA test with 2 variables, subject and period. Over the 2 periods, the differences between real and expected weight were of 4.65% for W2 1(st) phase, 9.48% for F2, 15.35% for F4, 5.56% for W2 2(d )period, 4.30% for F'2, and 6.98% for F'4. The quality of splitting was statistically poorer in the elderly patient group compared to other subjects. This study was not design to assess the clinical relevance (bleeding or thromboembolism) or the anticoagulation control of the variations in drug mass due to inappropriate splitting of tablets. However, split form of drugs should be prescribe with caution to elderly patients.

  2. Characterization of the coating and tablet core roughness by means of 3D optical coherence tomography.

    PubMed

    Markl, Daniel; Wahl, Patrick; Pichler, Heinz; Sacher, Stephan; Khinast, Johannes G

    2018-01-30

    This study demonstrates the use of optical coherence tomography (OCT) to simultaneously characterize the roughness of the tablet core and coating of pharmaceutical tablets. OCT is a high resolution non-destructive and contactless imaging methodology to characterize structural properties of solid dosage forms. Besides measuring the coating thickness, it also facilitates the analysis of the tablet core and coating roughness. An automated data evaluation algorithm extracts information about coating thickness, as well as tablet core and coating roughness. Samples removed periodically from a pan coating process were investigated, on the basis of thickness and profile maps of the tablet core and coating computed from about 480,000 depth measurements (i.e., 3D data) per sample. This data enables the calculation of the root mean square deviation, the skewness and the kurtosis of the assessed profiles. Analyzing these roughness parameters revealed that, for the given coating formulation, small valleys in the tablet core are filled with coating, whereas coarse features of the tablet core are still visible on the final film-coated tablet. Moreover, the impact of the tablet core roughness on the coating thickness is analyzed by correlating the tablet core profile and the coating thickness map. The presented measurement method and processing could be in the future transferred to in-line OCT measurements, to investigate core and coating roughness during the production of film-coated tablets. Copyright © 2017. Published by Elsevier B.V.

  3. Mucoadhesive Microparticles in a Rapidly Dissolving Tablet for Sustained Drug Delivery to the Eye

    PubMed Central

    Choy, Young Bin; Patel, Samirkumar R.; Park, Jung-Hwan; McCarey, Bernard E.; Edelhauser, Henry F.

    2011-01-01

    Purpose. To test the hypothesis that mucoadhesive microparticles formulated in a rapidly dissolving tablet can achieve sustained drug delivery to the eye. Methods. Mucoadhesive microparticles, smaller than 5 μm were fabricated with poly(lactic-co-glycolic acid) and poly(ethylene glycol) as a core material and mucoadhesion promoter, respectively, and encapsulated pilocarpine as a model drug. These microparticles were embedded in a poly(vinyl alcohol) matrix to form a dry tablet designed to reduce rapid clearance of the microparticles on initial application to the eye. Results. This in vitro drug release study exhibited that for all formulations, approximately 90% of pilocarpine was released during the first 10 minutes, and the remaining 10% was released slowly for 3 hours. In vivo mucoadhesion test on the rabbit eye indicated that mucoadhesive microparticles adhered significantly better to the preocular surface than other formulations. To assess the pharmacodynamics, the most prolonged pilocarpine-induced pupil constriction was observed in rabbit eyes in vivo using a tablet with mucoadhesive microparticles; it lasted up to 330 minutes. Conclusions. The authors conclude that mucoadhesive microparticles formulated into a dry dosage form is a promising system for sustained drug delivery to the eye. PMID:21245405

  4. Multi-unit dosage formulations of theophylline for controlled release applications.

    PubMed

    Uhumwangho, Michael U; Okor, Roland S

    2007-01-01

    The study was carried out to investigate the drug release profiles of multi-unit dosage formulations of theophylline consisting of both the fast and slow release components in a unit dose. The fast release component consisted of conventional granules of theophylline formed by mixing the drug powder with starch mucilage (20% w/v) while the slow release component consisted of wax granulations of theophylline formed by triturating the drug powder with a melted Carnauba wax (drug:wax ratio, 4:1). The granules were either filled into capsules or tabletted. In the study design, the drug release characteristics of the individual fast or slow release particles were first determined separately and then mixed in various proportions for the purpose of optimizing the drug release profiles. The evaluating parameters were the prompt release in the first 1 h (mp), the maximum release (m infinity) and the time to attain it (t infinity). Total drug content in each capsule or tablet was 300 mg and two of such were used in dissolution studies. The release kinetics and hence the release mechanism was confirmed by measuring the linear regression coefficient (R2 values) of the release data. The release kinetics was generally most consistent with the Higuchi square root of time relationship (R2 = 0.95). indicating a diffusion-controlled mechanism. The mp (mg) and t infinity (h) values for capsules and tablets of the conventional granules were (420 mg, 3 h) and (348 mg, 5 h), respectively, while for the capsules and tablets of the wax granulations mp and t infinity values were (228 mg, 9 h) and (156 mg, 12 h), respectively, indicating that a combination of wax granulation and tableting markedly retarded drug release. In the multi-unit dose formulations where the conventional and wax granulations were mixed in the ratios 2:1, 1:1 and 1:2 (conventional: matrix), the m infinity and t infinity values for the capsules were (378 mg, 6 h), (326 mg, 6 h) and (272 mg, 7 h), reSpectively. The corresponding values of m infinity and t infinity for the tablets were (240 mg, 9 h), (180 mg, 11 h) and (128 mg, 12 h) against the set target (200 mg, 12 h). The indication is that tableting rather than encapsulation can more effectively control drug release from the systems.

  5. Analytical Method Development and Validation for the Simultaneous Estimation of Abacavir and Lamivudine by Reversed-phase High-performance Liquid Chromatography in Bulk and Tablet Dosage Forms.

    PubMed

    Raees Ahmad, Sufiyan Ahmad; Patil, Lalit; Mohammed Usman, Mohammed Rageeb; Imran, Mohammad; Akhtar, Rashid

    2018-01-01

    A simple rapid, accurate, precise, and reproducible validated reverse phase high performance liquid chromatography (HPLC) method was developed for the determination of Abacavir (ABAC) and Lamivudine (LAMI) in bulk and tablet dosage forms. The quantification was carried out using Symmetry Premsil C18 (250 mm × 4.6 mm, 5 μm) column run in isocratic way using mobile phase comprising methanol: water (0.05% orthophosphoric acid with pH 3) 83:17 v/v and a detection wavelength of 245 nm and injection volume of 20 μl, with a flow rate of 1 ml/min. In the developed method, the retention times of ABAC and LAMI were found to be 3.5 min and 7.4 min, respectively. The method was validated in terms of linearity, precision, accuracy, limits of detection, limits of quantitation, and robustness in accordance with the International Conference on Harmonization guidelines. The assay of the proposed method was found to be 99% - 101%. The recovery studies were also carried out and mean % recovery was found to be 99% - 101%. The % relative standard deviation from reproducibility was found to be <2%. The proposed method was statistically evaluated and can be applied for routine quality control analysis of ABAC and LAMI in bulk and in tablet dosage form. Attempts were made to develop RP-HPLC method for simultaneous estimation of Abacavir and Lamivudine for the RP-HPLC method. The developed method was validated according to the ICH guidelines. The linearity, precision, range, robustness were within the limits as specified by the ICH guidelines. Hence the method was found to be simple, accurate, precise, economic and reproducible. So the proposed methods can be used for the routine quality control analysis of Abacavir and Lamivudine in bulk drug as well as in formulations. Abbreviations Used: HPLC: High-performance liquid chromatography, UV: Ultraviolet, ICH: International Conference on Harmonization, ABAC: Abacavir, LAMI: Lamivudine, HIV: Human immunodeficiency virus, AIDS: Acquired immunodeficiency syndrome, NRTI: Nucleoside reverse transcriptase inhibitors, ARV: Antiretroviral, RSD: Relative standard deviation, RT: Retention time, SD: Standard deviation.

  6. Near-Infrared Spatially Resolved Spectroscopy for Tablet Quality Determination.

    PubMed

    Igne, Benoît; Talwar, Sameer; Feng, Hanzhou; Drennen, James K; Anderson, Carl A

    2015-12-01

    Near-infrared (NIR) spectroscopy has become a well-established tool for the characterization of solid oral dosage forms manufacturing processes and finished products. In this work, the utility of a traditional single-point NIR measurement was compared with that of a spatially resolved spectroscopic (SRS) measurement for the determination of tablet assay. Experimental designs were used to create samples that allowed for calibration models to be developed and tested on both instruments. Samples possessing a poor distribution of ingredients (highly heterogeneous) were prepared by under-blending constituents prior to compaction to compare the analytical capabilities of the two NIR methods. The results indicate that SRS can provide spatial information that is usually obtainable only through imaging experiments for the determination of local heterogeneity and detection of abnormal tablets that would not be detected with single-point spectroscopy, thus complementing traditional NIR measurement systems for in-line, and in real-time tablet analysis. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. Fast disintegrating tablets: Opportunity in drug delivery system

    PubMed Central

    Parkash, Ved; Maan, Saurabh; Deepika; Yadav, Shiv Kumar; Hemlata; Jogpal, Vikas

    2011-01-01

    Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Oral drug delivery remains the preferred route for administration of various drugs. Recent developments in the technology have prompted scientists to develop FDTs with improved patient compliance and convenience. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. FDTs are solid unit dosage forms, which disintegrate or dissolve rapidly in the mouth without chewing and water. FDTs or orally disintegrating tablets provide an advantage particularly for pediatric and geriatric populations who have difficulty in swallowing conventional tablets and capsules. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray drying and use of disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and dissolution are also discussed. PMID:22247889

  8. 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.

  9. Manufacturing Amorphous Solid Dispersions with a Tailored Amount of Crystallized API for Biopharmaceutical Testing.

    PubMed

    Theil, Frank; Milsmann, Johanna; Anantharaman, Sankaran; van Lishaut, Holger

    2018-05-07

    The preparation of an amorphous solid dispersion (ASD) by dissolving a poorly water-soluble active pharmaceutical ingredient (API) in a polymer matrix can improve the bioavailability by orders of magnitude. Crystallization of the API in the ASD, though, is an inherent threat for bioavailability. Commonly, the impact of crystalline API on the drug release of the dosage form is studied with samples containing spiked crystallinity. These spiked samples possess implicit differences compared to native crystalline samples, regarding size and spatial distribution of the crystals as well as their molecular environment. In this study, we demonstrate that it is possible to grow defined amounts of crystalline API in solid dosage forms, which enables us to study the biopharmaceutical impact of actual crystallization. For this purpose, we studied the crystal growth in fenofibrate tablets over time under an elevated moisture using transmission Raman spectroscopy (TRS). As a nondestructive method to assess API crystallinity in ASD formulations, TRS enables the monitoring of crystal growth in individual dosage forms. Once the kinetic trace of the crystal growth for a certain environmental condition is determined, this method can be used to produce samples with defined amounts of crystallized API. To investigate the biopharmaceutical impact of crystallized API, non-QC dissolution methods were used, designed to identify differences between the various amounts of crystalline materials present. The drug release in the samples manufactured in this fashion was compared to that of samples with spiked crystallinity. In this study, we present for the first time a method for targeted crystallization of amorphous tablets to simulate crystallized ASDs. This methodology is a valuable tool to generate model systems for biopharmaceutical studies on the impact of crystallinity on the bioavailability.

  10. High-throughput prediction of tablet weight and trimethoprim content of compound sulfamethoxazole tablets for controlling the uniformity of dosage units by NIR.

    PubMed

    Dong, Yanhong; Li, Juan; Zhong, Xiaoxiao; Cao, Liya; Luo, Yang; Fan, Qi

    2016-04-15

    This paper establishes a novel method to simultaneously predict the tablet weight (TW) and trimethoprim (TMP) content of compound sulfamethoxazole tablets (SMZCO) by near infrared (NIR) spectroscopy with partial least squares (PLS) regression for controlling the uniformity of dosage units (UODU). The NIR spectra for 257 samples were measured using the optimized parameter values and pretreated using the optimized chemometric techniques. After the outliers were ignored, two PLS models for predicting TW and TMP content were respectively established by using the selected spectral sub-ranges and the reference values. The TW model reaches the correlation coefficient of calibration (R(c)) 0.9543 and the TMP content model has the R(c) 0.9205. The experimental results indicate that this strategy expands the NIR application in controlling UODU, especially in the high-throughput and rapid analysis of TWs and contents of the compound pharmaceutical tablets, and may be an important complement to the common NIR on-line analytical method for pharmaceutical tablets. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Dose uniformity of scored and unscored tablets: Application of the FDA Tablet Scoring Guidance for Industry.

    PubMed

    Ciavarella, Anthony; Khan, Mansoor; Gupta, Abhay; Faustino, Patrick

    2016-06-20

    This FDA laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5-2.1 standard deviation (SD) of the % label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3-9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting "can affect how much drug is present in the split tablet and available for absorption" as stated in the guidance (1). Copyright © 2016, Parenteral Drug Association.

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

    PubMed

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

    2014-08-01

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

  13. Quantitative analysis of visible surface defect risk in tablets during film coating using terahertz pulsed imaging.

    PubMed

    Niwa, Masahiro; Hiraishi, Yasuhiro

    2014-01-30

    Tablets are the most common form of solid oral dosage produced by pharmaceutical industries. There are several challenges to successful and consistent tablet manufacturing. One well-known quality issue is visible surface defects, which generally occur due to insufficient physical strength, causing breakage or abrasion during processing, packaging, or shipping. Techniques that allow quantitative evaluation of surface strength and the risk of surface defect would greatly aid in quality control. Here terahertz pulsed imaging (TPI) was employed to evaluate the surface properties of core tablets with visible surface defects of varying severity after film coating. Other analytical methods, such as tensile strength measurements, friability testing, and scanning electron microscopy (SEM), were used to validate TPI results. Tensile strength and friability provided no information on visible surface defect risk, whereas the TPI-derived unique parameter terahertz electric field peak strength (TEFPS) provided spatial distribution of surface density/roughness information on core tablets, which helped in estimating tablet abrasion risk prior to film coating and predicting the location of the defects. TPI also revealed the relationship between surface strength and blending condition and is a nondestructive, quantitative approach to aid formulation development and quality control that can reduce visible surface defect risk in tablets. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. 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.

  15. 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.

  16. Application of 13C NMR cross-polarization inversion recovery experiments for the analysis of solid dosage forms.

    PubMed

    Pisklak, Dariusz Maciej; Zielińska-Pisklak, Monika; Szeleszczuk, Łukasz

    2016-11-20

    Solid-state nuclear magnetic resonance (ssNMR) is a powerful and unique method for analyzing solid forms of the active pharmaceutical ingredients (APIs) directly in their original formulations. Unfortunately, despite their wide range of application, the ssNMR experiments often suffer from low sensitivity and peaks overlapping between API and excipients. To overcome these limitations, the crosspolarization inversion recovery method was successfully used. The differences in the spin-lattice relaxation time constants for hydrogen atoms T1(H) between API and excipients were employed in order to separate and discriminate their peaks in ssNMR spectra as well as to increase the intensity of API signals in low-dose formulations. The versatility of this method was demonstrated by different examples, including the excipients mixture and commercial solid dosage forms (e.g. granules and tablets). Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Validated spectrofluorimetric method for determination of two phosphodiesterase inhibitors tadalafil and vardenafil in pharmaceutical preparations and spiked human plasma.

    PubMed

    Abu El-Enin, Mohammed Abu Bakr; Al-Ghaffar Hammouda, Mohammed El-Sayed Abd; El-Sherbiny, Dina Tawfik; El-Wasseef, Dalia Rashad; El-Ashry, Saadia Mahmoud

    2016-02-01

    A valid, sensitive and rapid spectrofluorimetric method has been developed and validated for determination of both tadalafil (TAD) and vardenafil (VAR) either in their pure form, in their tablet dosage forms or spiked in human plasma. This method is based on measurement of the native fluorescence of both drugs in acetonitrile at λem 330 and 470 nm after excitation at 280 and 275 nm for tadalafil and vardenafil, respectively. Linear relationships were obtained over the concentration range 4-40 and 10-250 ng/mL with a minimum detection of 1 and 3 ng/mL for tadalafil and vardenafil, respectively. Various experimental parameters affecting the fluorescence intensity were carefully studied and optimized. The developed method was applied successfully for the determination of tadalafil and vardenafil in bulk drugs and tablet dosage forms. Moreover, the high sensitivity of the proposed method permitted their determination in spiked human plasma. The developed method was validated in terms of specificity, linearity, lower limit of quantification (LOQ), lower limit of detection (LOD), precision and accuracy. The mean recoveries of the analytes in pharmaceutical preparations were in agreement with those obtained from the comparison methods, as revealed by statistical analysis of the obtained results using Student's t-test and the variance ratio F-test. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Quantitative analysis of crystalline pharmaceuticals in powders and tablets by a pattern-fitting procedure using X-ray powder diffraction data.

    PubMed

    Yamamura, S; Momose, Y

    2001-01-16

    A pattern-fitting procedure for quantitative analysis of crystalline pharmaceuticals in solid dosage forms using X-ray powder diffraction data is described. This method is based on a procedure for pattern-fitting in crystal structure refinement, and observed X-ray scattering intensities were fitted to analytical expressions including some fitting parameters, i.e. scale factor, peak positions, peak widths and degree of preferred orientation of the crystallites. All fitting parameters were optimized by the non-linear least-squares procedure. Then the weight fraction of each component was determined from the optimized scale factors. In the present study, well-crystallized binary systems, zinc oxide-zinc sulfide (ZnO-ZnS) and salicylic acid-benzoic acid (SA-BA), were used as the samples. In analysis of the ZnO-ZnS system, the weight fraction of ZnO or ZnS could be determined quantitatively in the range of 5-95% in the case of both powders and tablets. In analysis of the SA-BA systems, the weight fraction of SA or BA could be determined quantitatively in the range of 20-80% in the case of both powders and tablets. Quantitative analysis applying this pattern-fitting procedure showed better reproducibility than other X-ray methods based on the linear or integral intensities of particular diffraction peaks. Analysis using this pattern-fitting procedure also has the advantage that the preferred orientation of the crystallites in solid dosage forms can be also determined in the course of quantitative analysis.

  19. Higher Strength Lanthanum Carbonate Provides Serum Phosphorus Control With a Low Tablet Burden and Is Preferred by Patients and Physicians: A Multicenter Study

    PubMed Central

    Mehrotra, Rajnish; Martin, Kevin J.; Fishbane, Steven; Sprague, Stuart M.; Zeig, Steven; Anger, Michael

    2008-01-01

    Background and objectives: Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d. Design, setting, participants, & measurements: This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with ≤3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B. Results: At the end of week 4, 54% of patients achieved serum phosphorus control at dosages ≤3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication. Conclusions: Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden. PMID:18579668

  20. 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

  1. Physical and Chemical Stability of Mycophenolate Mofetil (MMF) Suspension Prepared at the Hospital

    PubMed Central

    Fahimi, Fanak; Baniasadi, Shadi; Mortazavi, Seyed Alireza; Dehghan, Hanie; Zarghi, Afshin

    2012-01-01

    To evaluate the physical and chemical stability of a suspension of mycophenolate mofetil (MMF) prepared in the hospital from commercially available MMF capsules and tablets. Extemporaneous pharmacy was used as a feasible method in this experimental study to prepare suspension form of MMF. Suspension formulations were prepared from both tablets and capsules forms of MMF. Thereafter the stability parameters such as pH, microbial control, thermal and physical stability and particle sizes were evaluated. The amount of MMF, in the suspension was measured at various time points by HPLC. The HPLC method showed that concentration of suspensions prepared from tablets and capsules were 49 mg/mL and 50 mg/mL at time 0, respectively. The effective amount of suspensions prepared from capsules was 101% at time 0, 100% after 7 days, 98% after 14 days, and less than 70% after 28 days. According to the obtained results in this study, capsule-based suspension was stable for as long as 14 days at 5°C. This formulation appears to be clinically acceptable and provides a convenient dosage form for pediatric patients and for adults during the early postoperative period. PMID:24250439

  2. Discrete element method (DEM) simulations of stratified sampling during solid dosage form manufacturing.

    PubMed

    Hancock, Bruno C; Ketterhagen, William R

    2011-10-14

    Discrete element model (DEM) simulations of the discharge of powders from hoppers under gravity were analyzed to provide estimates of dosage form content uniformity during the manufacture of solid dosage forms (tablets and capsules). For a system that exhibits moderate segregation the effects of sample size, number, and location within the batch were determined. The various sampling approaches were compared to current best-practices for sampling described in the Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) guidelines. Sampling uniformly across the discharge process gave the most accurate results with respect to identifying segregation trends. Sigmoidal sampling (as recommended in the PQRI BUWG guidelines) tended to overestimate potential segregation issues, whereas truncated sampling (common in industrial practice) tended to underestimate them. The size of the sample had a major effect on the absolute potency RSD. The number of sampling locations (10 vs. 20) had very little effect on the trends in the data, and the number of samples analyzed at each location (1 vs. 3 vs. 7) had only a small effect for the sampling conditions examined. The results of this work provide greater understanding of the effect of different sampling approaches on the measured content uniformity of real dosage forms, and can help to guide the choice of appropriate sampling protocols. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Formulations of Amlodipine: A Review

    PubMed Central

    Ahsan, Syed Furqan; Khan, Marium Fatima

    2016-01-01

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

  4. Development of multiple-unit pellet system tablets by employing the SeDeM expert diagram system I: pellets with different sizes.

    PubMed

    Hamman, Hannlie; Hamman, Josias; Wessels, Anita; Scholtz, Jacques; Steenekamp, Jan Harm

    2017-07-03

    Multiple-unit pellet systems (MUPS) provide several pharmacokinetic and pharmacodynamic advantages over single-unit dosage forms, however, compression of pellets into MUPS tablets present certain challenges. Although the SeDeM Expert Diagram System (SeDeM EDS) was originally developed to provide information about the most appropriate excipient and the minimum amount thereof that is required for producing direct compressible tablets, this study investigated the possibility to apply the SeDeM EDS in the production of MUPS tablets. In addition, the effect of pellet size (i.e. 0.5, 1.0, 1.5, 2.0, and 2.5 mm) on SeDeM EDS predictions regarding the MUPS tablet formulations was investigated. The compressibility incidence factor values were below the acceptable value (i.e. 5.00) for all the pellet sizes. Kollidon ® VA 64 was identified as the most appropriate excipient to improve compressibility. The compression indices, namely, the parameter index (IP), parametric profile index (IPP), and good compression index (GCI) indicated that acceptable MUPS tablets could be produced from the final pellet-excipient blends based on predictions from the SeDeM EDS. These MUPS tablets complied with specifications for friability, hardness, and mass variation. The SeDeM EDS system is therefore applicable to assist in the formulation of acceptable MUPS tablets.

  5. Experimental analysis of tablet properties for discrete element modeling of an active coating process.

    PubMed

    Just, Sarah; Toschkoff, Gregor; Funke, Adrian; Djuric, Dejan; Scharrer, Georg; Khinast, Johannes; Knop, Klaus; Kleinebudde, Peter

    2013-03-01

    Coating of solid dosage forms is an important unit operation in the pharmaceutical industry. In recent years, numerical simulations of drug manufacturing processes have been gaining interest as process analytical technology tools. The discrete element method (DEM) in particular is suitable to model tablet-coating processes. For the development of accurate simulations, information on the material properties of the tablets is required. In this study, the mechanical parameters Young's modulus, coefficient of restitution (CoR), and coefficients of friction (CoF) of gastrointestinal therapeutic systems (GITS) and of active-coated GITS were measured experimentally. The dynamic angle of repose of these tablets in a drum coater was investigated to revise the CoF. The resulting values were used as input data in DEM simulations to compare simulation and experiment. A mean value of Young's modulus of 31.9 MPa was determined by the uniaxial compression test. The CoR was found to be 0.78. For both tablet-steel and tablet-tablet friction, active-coated GITS showed a higher CoF compared with GITS. According to the values of the dynamic angle of repose, the CoF was adjusted to obtain consistent tablet motion in the simulation and in the experiment. On the basis of this experimental characterization, mechanical parameters are integrated into DEM simulation programs to perform numerical analysis of coating processes.

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

    PubMed

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

    2013-01-01

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

  7. 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.

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

    PubMed Central

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

    2013-01-01

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

  9. Women's preferences for vaginal antimicrobial contraceptives. III. Choice of a formulation, applicator, and packaging.

    PubMed

    Hardy, E; Jiménez, A L; de Pádua, K S; Zaneveld, L J

    1998-10-01

    Novel vaginal formulations are under development to combat the increasing incidence of sexually transmitted diseases, including AIDS, and also unplanned pregnancies. A study was performed to determine women's preferences for different dosage forms (gel, cream, ovule/suppository, film, foam, tablet), width, length, and color of an applicator, and various types of packages. The study was conducted in Campinas, Brazil. A total of 635 women were interviewed, including both adolescents and adults and low and middle-high socioeconomic groups. The large majority of the women preferred a gel over a cream; both were preferred over the other methods. When asked which method they would not use, the film was most frequently identified, followed by the tablet and ovule. The primary reasons for selecting a particular dosage form were ease of use, absence of odor or the presence of a pleasant one, absence of color, and insertion with an applicator. The major reasons for not using a method were discomfort, "plastic" appearance, distrust of effectiveness, difficulty with insertion, messiness, and rigidity/hardness. The majority of the women liked the applicator shown. The prefilled single dose applicator was by far the preferred packaging. This information should aid in the development of consumer-friendly, vaginal formulations.

  10. Transmission FTIR derivative spectroscopy for estimation of furosemide in raw material and tablet dosage form

    PubMed Central

    Gallignani, Máximo; Rondón, Rebeca A.; Ovalles, José F.; Brunetto, María R.

    2014-01-01

    A Fourier transform infrared derivative spectroscopy (FTIR-DS) method has been developed for determining furosemide (FUR) in pharmaceutical solid dosage form. The method involves the extraction of FUR from tablets with N,N-dimethylformamide by sonication and direct measurement in liquid phase mode using a reduced path length cell. In general, the spectra were measured in transmission mode and the equipment was configured to collect a spectrum at 4 cm−1 resolution and a 13 s collection time (10 scans co-added). The spectra were collected between 1400 cm−1 and 450 cm−1. Derivative spectroscopy was used for data processing and quantitative measurement using the peak area of the second order spectrum of the major spectral band found at 1165 cm−1 (SO2 stretching of FUR) with baseline correction. The method fulfilled most validation requirements in the 2 mg/mL and 20 mg/mL range, with a 0.9998 coefficient of determination obtained by simple calibration model, and a general coefficient of variation <2%. The mean recovery for the proposed assay method resulted within the (100±3)% over the 80%–120% range of the target concentration. The results agree with a pharmacopoeial method and, therefore, could be considered interchangeable. PMID:26579407

  11. 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.

  12. Stability of extemporaneously prepared rufinamide oral suspensions.

    PubMed

    Hutchinson, David J; Liou, Yayin; Best, Robert; Zhao, Fang

    2010-03-01

    Rufinamide is an oral antiepileptic drug indicated for adjunctive therapy in treating generalized seizures associated with Lennox-Gastaut syndrome. Currently, rufinamide is available as 200-mg and 400-mg tablets. A liquid dosage form does not exist at the present time. Lack of a suspension formulation may present an administration problem for many children and adults who are unable to swallow tablets. The availability of a liquid dosage form will provide an easy and accurate way to measure and administer the medication. To determine the stability of both sugar-containing and sugar-free rufinamide suspensions over a 90-day period. A suspension of rufinamide 40 mg/mL was prepared by grinding twelve 400-mg tablets of rufinamide tablets in a glass mortar. Sixty milliliters of Ora-Plus and 60 mL of either Ora-Sweet or Ora-Sweet SF (sugar free) were mixed and added to the powder to make a final volume of 120 mL. Three identical samples of each formulation were prepared and placed in 60-mL amber plastic bottles and were stored at room temperature. A 1-mL sample was withdrawn from each of the 6 bottles with a micropipette immediately after preparation and at 7, 14, 28, 56, and 90 days. After further dilution to an expected concentration of 0.4 mg/mL, the samples were assayed using high-performance liquid chromatography. Stability was defined as the retention of at least 90% of the initial concentration. At least 90% of the initial rufinamide concentration remained throughout the 90-day study period in both preparations. There were no detectable changes in color, odor, taste, and pH and no visible microbial growth. Extemporaneously compounded suspensions of rufinamide 40 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet or Ora-Sweet SF were stable for at least 90 days when stored in 59-mL amber polypropylene plastic bottles at room temperature.

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

    PubMed

    Mikac, Urša; Kristl, Julijana; Baumgartner, Saša

    2011-05-01

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

  14. 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

  15. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

    PubMed Central

    Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

    2015-01-01

    The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. PMID:25678774

  16. Alternative Manufacturing Concepts for Solid Oral Dosage Forms From Drug Nanosuspensions Using Fluid Dispensing and Forced Drying Technology.

    PubMed

    Bonhoeffer, Bastian; Kwade, Arno; Juhnke, Michael

    2018-03-01

    Flexible manufacturing technologies for solid oral dosage forms with a continuous adjustability of the manufactured dose strength are of interest for applications in personalized medicine. This study explored the feasibility of using microvalve technology for the manufacturing of different solid oral dosage form concepts. Hard gelatin capsules filled with excipients, placebo tablets, and polymer films, placed in hard gelatin capsules after drying, were considered as substrates. For each concept, a basic understanding of relevant formulation parameters and their impact on dissolution behavior has been established. Suitable matrix formers, present either on the substrate or directly in the drug nanosuspension, proved to be essential to prevent nanoparticle agglomeration of the drug nanoparticles and to ensure a fast dissolution behavior. Furthermore, convection and radiation drying methods were investigated for the fast drying of drug nanosuspensions dispensed onto polymer films, which were then placed in hard gelatin capsules. Changes in morphology and in drug and matrix former distribution were observed for increasing drying intensity. However, even fast drying times below 1 min could be realized, while maintaining the nanoparticulate drug structure and a good dissolution behavior. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  17. Improvement of enalapril maleate chemical stability by high shear melting granulation.

    PubMed

    de Oliveira, Ana Paula Montandon; Cunha, Talita Amorim; Serpa, Raphael Caixeta; Taveira, Stephânia Fleury; Lima, Eliana Martins; Almeida Diniz, Danielle Guimarães; de Freitas, Luis Alexandre Pedro; Marreto, Ricardo Neves

    2014-09-18

    Abstract Enalapril maleate is a widely used drug, which is chemically unstable when mixed with excipients resulting in enalaprilat and diketopiperazine as the main degradation products. The preparation of enalapril sodium salt has been used to improve drug stability in solid dosage forms; however, product rejection is observed when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. In this study, granules were prepared by melting granulation using stearic acid or glyceryl monostearate, with a view to developing more stable enalapril maleate solid dosage forms. The granules were prepared in a laboratory-scale high shear mixer and compressed in a rotary machine. Size distribution, flow properties, in vitro drug release and enalapril maleate chemical stability were evaluated and compared with data obtained from tablets prepared without hydrophobic binders. All formulations showed good physical properties and immediate drug release. The greatest improvement in the enalapril maleate stability was observed in formulations containing stearic acid. This study showed that hot melting granulation could be successfully used to prepare enalapril maleate granules which could substitute the in situ formation of enalapril sodium salt, since they provided better enalapril stability in solid dosage forms.

  18. 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.

  19. Application of terahertz pulse imaging as PAT tool for non-destructive evaluation of film-coated tablets under different manufacturing conditions.

    PubMed

    Dohi, Masafumi; Momose, Wataru; Yoshino, Hiroyuki; Hara, Yuko; Yamashita, Kazunari; Hakomori, Tadashi; Sato, Shusaku; Terada, Katsuhide

    2016-02-05

    Film-coated tablets (FCTs) are a popular solid dosage form in pharmaceutical industry. Manufacturing conditions during the film-coating process affect the properties of the film layer, which might result in critical quality problems. Here, we analyzed the properties of the film layer using a non-destructive approach with terahertz pulsed imaging (TPI). Hydrophilic tablets that become distended upon water absorption were used as core tablets and coated with film under different manufacturing conditions. TPI-derived parameters such as film thickness (FT), film surface reflectance (FSR), and interface density difference (IDD) between the film layer and core tablet were affected by manufacturing conditions and influenced critical quality attributes of FCTs. Relative standard deviation of FSR within tablets correlated well with surface roughness. Tensile strength could be predicted in a non-destructive manner using the multivariate regression equation to estimate the core tablet density by film layer density and IDD. The absolute value of IDD (Lateral) correlated with the risk of cracking on the lateral film layer when stored in a high-humidity environment. Further, in-process control was proposed for this value during the film-coating process, which will enable a feedback control system to be applied to process parameters and reduced risk of cracking without a stability test. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. On the role of API in determining porosity, pore structure and bulk modulus of the skeletal material in pharmaceutical tablets formed with MCC as sole excipient.

    PubMed

    Ridgway, Cathy; Bawuah, Prince; Markl, Daniel; Zeitler, J Axel; Ketolainen, Jarkko; Peiponen, Kai-Erik; Gane, Patrick

    2017-06-30

    The physical properties and mechanical integrity of pharmaceutical tablets are of major importance when loading with active pharmaceutical ingredient(s) (API) in order to ensure ease of processing, control of dosage and stability during transportation and handling prior to patient consumption. The interaction between API and excipient, acting as functional extender and binder, however, is little understood in this context. The API indomethacin is combined in this study with microcrystalline cellulose (MCC) at increasing loading levels. Tablets from the defined API/MCC ratios are made under conditions of controlled porosity and tablet thickness, resulting from different compression conditions, and thus compaction levels. Mercury intrusion porosimetry is used to establish the accessible pore volume, pore size distribution and, adopting the observed region of elastic intrusion-extrusion at high pressure, an elastic bulk modulus of the skeletal material is recorded. Porosity values are compared to previously published values derived from terahertz (THz) refractive index data obtained from exactly the same tablet sample sets. It is shown that the elastic bulk modulus is dependent on API wt% loading under constant tablet preparation conditions delivering equal dimensions and porosity. The findings are considered of novel value in respect to establishing consistency of tablet production and optimisation of physical properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. 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.

  2. 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.

  3. Design, Formulation, and Physicochemical Evaluation of Montelukast Orally Disintegrating Tablet

    PubMed Central

    Aslani, Abolfazl; Beigi, Maryam

    2016-01-01

    Background: Orally disintegrating tablets (ODTs) are a modern form of tablets that when placed in the oral cavity, disperses rapidly. These tablets have advantages, particularly good applications for children and old patients who have a complication in chewing or swallowing solid dosage forms. The aim of this study was to design, formulate, and evaluate the physicochemical properties of 5 mg montelukast ODTs for the prevention of asthma and seasonal allergies. Methods: Formulations were prepared with different amounts of super disintegrating agents and effervescent bases as disintegrant agents. Flowability and compressibility of mixed powders were evaluated. The prepared formulations were tested for hardness, thickness, friability, weight variation, drug content, wetting time, disintegration time, dissolution study, and moisture uptake studies. Results: The compressibility index and angle of repose were in the range of 15.87%–23.43% and 32.93–34.65, respectively. Hardness, thickness, friability, wetting time, and content uniformity of formulations were in the range of 33.7–37.1 N, 3.00–3.81 mm, 0.27%–0.43%, 31–50 s and 96.28%–99.90%, respectively. Disintegration time of the tablets prepared with super disintegrating agents, effervescent bases, and combination of two were in the range of 30–50, more than 60 and 20–36 s, respectively. Conclusions: Mixture of powders and tablets passed all the specified tests. The results showed formulations prepared by super disintegrating agents and super disintegrating agents with effervescent bases had shorter disintegration time compared to formulations with effervescent bases alone. PMID:27857833

  4. 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.

  5. Oral desmopressin in central diabetes insipidus.

    PubMed Central

    Westgren, U; Wittström, C; Harris, A S

    1986-01-01

    Seven paediatric patients with central diabetes insipidus were studied in an open dose ranging study in hospital followed by a six month study on an outpatient basis to assess the efficacy and safety of peroral administration of DDAVP (desmopressin) tablets. In the dose ranging study a dose dependent antidiuretic response was observed. The response to 12.5-50 mcg was, however, less effective in correcting baseline polyuria than were doses of 100 mcg and above. Patients were discharged from hospital on a preliminary dosage regimen ranging from 100 to 400 mcg three times daily. After an initial adjustment in dosage in three patients at one week follow up, all patients were stabilised on treatment with tablets and reported an adequate water turnover at six months. As with the intranasal route of administration dosage requirements varied from patient to patient, and a dose range rather than standard doses were required. A significant correlation, however, was found for the relation between previous intranasal and present oral daily dosage. No adverse reactions were reported. No clinically significant changes were noted in blood chemistry and urinalysis. All patients expressed a preference for the oral over existing intranasal treatment. Treatment with tablets offers a beneficial alternative to the intranasal route, particularly in patients with chronic rhinitis or impaired vision. PMID:3963868

  6. Applicability of UV laser-induced solid-state fluorescence spectroscopy for characterization of solid dosage forms.

    PubMed

    Woltmann, Eva; Meyer, Hans; Weigel, Diana; Pritzke, Heinz; Posch, Tjorben N; Kler, Pablo A; Schürmann, Klaus; Roscher, Jörg; Huhn, Carolin

    2014-10-01

    High production output of solid pharmaceutical formulations requires fast methods to ensure their quality. Likewise, fast analytical procedures are required in forensic sciences, for example at customs, to substantiate an initial suspicion. We here present the design and the optimization of an instrumental setup for rapid and non-invasive characterization of tablets by laser-induced fluorescence spectroscopy (with a UV-laser (λ ex = 266 nm) as excitation source) in reflection geometry. The setup was first validated with regard to repeatability, bleaching phenomena, and sensitivity. The effect on the spectra by the physical and chemical properties of the samples, e.g. their hardness, homogeneity, chemical composition, and granule grain size of the uncompressed material, using a series of tablets, manufactured in accordance with design of experiments, was investigated. Investigation of tablets with regard to homogeneity, especially, is extremely important in pharmaceutical production processes. We demonstrate that multiplicative scatter correction is an appropriate tool for data preprocessing of fluorescence spectra. Tablets with different physical and chemical characteristics can be discriminated well from their fluorescence spectra by subjecting the results to principal component analysis.

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

    PubMed

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

    2012-05-01

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

  8. Asymmetric flow field-flow fractionation (AF4) for the quantification of nanoparticle release from tablets during dissolution testing.

    PubMed

    Engel, A; Plöger, M; Mulac, D; Langer, K

    2014-01-30

    Nanoparticles composed of poly(DL-lactide-co-glycolide) (PLGA) represent promising colloidal drug carriers for improved drug targeting. Although most research activities are focused on intravenous application of these carriers the peroral administration is described to improve bioavailability of poorly soluble drugs. Based on these insights the manuscript describes a model tablet formulation for PLGA-nanoparticles and especially its analytical characterisation with regard to a nanosized drug carrier. Besides physico-chemical tablet characterisation according to pharmacopoeias the main goal of the study was the development of a suitable analytical method for the quantification of nanoparticle release from tablets. An analytical flow field-flow fractionation (AF4) method was established and validated which enables determination of nanoparticle content in solid dosage forms as well as quantification of particle release during dissolution testing. For particle detection a multi-angle light scattering (MALS) detector was coupled to the AF4-system. After dissolution testing, the presence of unaltered PLGA-nanoparticles was successfully proved by dynamic light scattering and scanning electron microscopy. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Simultaneous determination of related substances of telmisartan and hydrochlorothiazide in tablet dosage form by using reversed phase high performance liquid chromatographic method

    PubMed Central

    Mukhopadhyay, Sutirtho; Kadam, Kiran; Sawant, Laxman; Nachane, Dhanashree; Pandita, Nancy

    2011-01-01

    Objective: Telmisartan is a potent, long-lasting, nonpeptide antagonist of the angiotensin II type-1 (AT1) receptor that is indicated for the treatment of essential hypertension. Hydrochlorothiazide is a widely prescribed diuretic and it is indicated for the treatment of edema, control of essential hypertension and management of diabetes insipidus. In the current article a new, accurate, sensitive, precise, rapid, reversed phase high performance liquid chromatography (RP-HPLC) method was developed for determination of related substances of Telmisartan and Hydrochlorthiazide in tablet dosage form. Materials and Methods: Simultaneous determination of related substances was performed on Kromasil C18 analytical column (250 × 4.6 mm; 5μm pertical size) column at 40°C employing a gradient elution. Mobile phase consisting of solvent A (solution containing 2.0 g of potassium dihydrogen phosphate anhydrous and 1.04 g of Sodium 1- Hexane sulphonic acid monohydrate per liter of water, adjusted to pH 3.0 with orthophosphoric acid) and solvent B (mixture of Acetonitrile: Methanol in the ratio 80:20 v/v) was used at a flow rate of 1.0 ml min–1. UV detection was performed at 270 nm. Results: During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. Conclusions: HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. It may find application for the routine analysis of the related substances of both Telmisartan and Hydrochlorthiazide in this combination tablets. PMID:21966158

  10. Ion beam analysis and PD-MS as new analytical tools for quality control of pharmaceuticals: comparative study from fluphenazine in solid dosage forms.

    PubMed

    Nsouli, Bilal; Bejjani, Alice; Negra, Serge Della; Gardon, Alain; Thomas, Jean-Paul

    2010-09-01

    In order to evaluate the potential of accelerator based analytical techniques ((particle induced X-ray emission (PIXE), particle induced gamma-ray emission (PIGE), and particle desorption mass spectrometry (PD-MS)) for the analysis of commercial pharmaceutical products in their solid dosage form, the fluphenazine drug has been taken as a representative example. It is demonstrated that PIXE and PIGE are by far the best choice for quantification of the active ingredient (AI) (certification with 7% precision) from the reactions induced on its specific heteroatoms fluorine and sulfur using pellets made from original tablets. Since heteroatoms cannot be present in all types of drugs, the PD-MS technique, which makes easily the distinction between AI(s) and excipients, has been evaluated for the same material. It is shown that the quantification of AI is obtained via the detection of its protonated molecule. However, calibration curves have to be made from the secondary ion yield variations since matrix effects of various nature are characteristics of such mixtures of heterogeneous materials (including deposits from soluble components). From the analysis of solid tablets, (either transformed into pellets and even as received), it is strongly suggested that the physical state of the grains in the mixture is a crucial parameter in the ion emission and accordingly for the calibration curves. As a result of our specific (but not optimized) conditions the resulting precision is <17% with an almost linear range extending from 0.04 to 7.87 mg of AI in a tablet made under the manufacturer conditions (the commercial drug product is labeled at 5 mg).

  11. Simulation of roller compaction with subsequent tableting and characterization of lactose and microcrystalline cellulose.

    PubMed

    Hein, Stephanie; Picker-Freyer, Katharina M; Langridge, John

    2008-01-01

    Tablets are by far the most common solid oral dosage forms, and many drugs need to be granulated before they can be tableted. Increasingly roller compaction is being used as a dry granulation technique; however it is a very time and material intensive method. Thus some mini roller compactors and simulations of the roller compaction process have been developed as a means of studying the technique at small scale. An important factor in the selection of materials for roller compaction is their ability to be recompressed into tablets after the initial roller compaction and milling steps. In this paper the roller compaction process was simulated on the basis of some models by Gereg and Cappola (2002) and Zinchuk et al. (2004). An eccentric tableting machine was used to make compacts from alpha-lactose monohydrate, anhydrous beta-lactose, spray-dried lactose and microcrystalline cellulose at different maximum relative densities (rho rel,max 0.6-0.9). These compacts were milled immediately to granules with a rotary granulator. The properties of the granules were analyzed and compared to the properties of the original powders. These granules and powders were then tableted at different maximum relative densities (rho rel,max 0.75-0.95) and their properties including elastic recovery, crushing force and 3D-model were analyzed. The properties of the tablets made from the granules were compared to the properties of the tablets made from the powders to determine which excipients are most suitable for the roller compaction process. The study showed that anhydrous beta-lactose is the preferred form of lactose for use in roller compaction since compaction did not affect tablet crushing force to a large extent. With the simulation of roller compaction process one is able to find qualified materials for use in roller compaction without the necessity of a great deal of material and time.

  12. Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology.

    PubMed

    Mohammed, Noorullah Naqvi; Majumdar, Soumyajit; Singh, Abhilasha; Deng, Weibin; Murthy, Narasimha S; Pinto, Elanor; Tewari, Divya; Durig, Thomas; Repka, Michael A

    2012-12-01

    The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.

  13. Efficacy of three formulations of diflubenzuron, an insect growth regulator, against Culex quinquefasciatus Say, the vector of Bancroftian filariasis in India

    PubMed Central

    Sadanandane, C.; Doss, P. S. Boopathi; Jambulingam, P.

    2012-01-01

    Background & objectives: Insect growth regulators (IGRs) offer alternatives to conventional chemical larvicides that pose problem of resistance and environmental safety. However, only a limited number of IGRs have been approved for use in mosquito control. In the present study, two new formulations of the IGR diflubenzuron, 2 per cent granular (GR) and 2 per cent tablet (DT) were tested for its efficacy against Culex quinquefasciatus, in comparison to its 25 per cent wettable powder (WP) formulation. Methods: The WP, GR and DT formulations were tested in cesspits, street drains and abandoned wells each at four dosages, 25, 50, 75 and 100 g ai/ha. Additionally, the DT formulation was tested at a higher dosage of 1 tablet/m2 (equal to 400 g ai/ha). Results: The WP and GR formulations yielded >80 per cent inhibition of adult emergence (IE) for 7-10 days in cesspits, 4-7 days in street drains and 7-21 days in abandoned wells at all dosages tested. The DT formulation was effective only at higher dosage 100 g ai/ha and or 1 tablet/m2 for 7-15 days at all habitats. Interpretation & conclusions: The trial showed that the dosage 25 g ai/ha of 25 per cent WP could be the field dosage for cesspits and wells, and 50 g ai/ha for drains, to be applied at weekly intervals. The dosages 25, 50 and 100 g ai/ha of 2 per cent GR could be the field dosages for application in cesspits at weekly intervals, in abandoned wells every three weeks and in drains at weekly intervals, respectively. Diflubenzuron 25 per cent WP and 2 per cent GR could be used for larval control of Cx. quinquefasciatus under integrated vector management programme. PMID:23287125

  14. 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.

  15. Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system.

    PubMed

    Haseeb, Muhammad Tahir; Hussain, Muhammad Ajaz; Bashir, Sajid; Ashraf, Muhammad Umer; Ahmad, Naveed

    2017-03-01

    Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach. Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material. Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM. LSH tablets exhibited dynamic swelling-deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets. The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion. These finding indicates that LSH holds potential to be developed as sustained release material for tablet.

  16. Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms.

    PubMed

    Debotton, Nir; Dahan, Arik

    2017-01-01

    Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products. © 2016 Wiley Periodicals, Inc.

  17. Quality of anthelminthic medicines available in Jimma Ethiopia.

    PubMed

    Belew, Sileshi; Suleman, Sultan; Wynendaele, Evelien; D'Hondt, Matthias; Kosgei, Anne; Duchateau, Luc; De Spiegeleer, Bart

    2018-01-01

    Soil-transmitted helminthiasis and schistosomiasis are major public health problems in Ethiopia. Mass deworming of at-risk population using a single dose administration of 400mg albendazole (ABZ) or 500mg mebendazole (MBZ) for treatment of common intestinal worms and 40mg of praziquantel (PZQ) per kg body weight for treatment of schistosomiasis is one of the strategies recommended by World Health Organization (WHO) in order to control the morbidity of soil-transmitted helminthiasis and schistosomiasis. Since storage condition, climate, way of transportation and distribution route could all affect the quality of medicines, regular assessment by surveys is very critical to ensure the therapeutic outcome, to minimize risk of toxicity to the patient and resistance of parasites. Therefore, this study was conducted to assess the pharmaceutical quality of ABZ, MBZ and PZQ tablet brands commonly available in Jimma town (south west Ethiopia). Retail pharmacies (n=10) operating in Jimma town were selected using simple random sampling method. Samples of anthelminthic medicines available in the selected pharmacies were collected. Sample information was recorded and encompassed trade name, active ingredient name, manufacturer's name and full address, labeled medicine strength, dosage form, number of units per container, dosage statement, batch/lot number, manufacturing and expiry dates, storage information and presence of leaflets/package insert. Moreover, a first visual inspection was performed encompassing uniformity of color, uniformity of size, breaks, cracks, splits, embedded surface spots or visual contaminations. Finally, physico-chemical quality attributes investigated encompassed mass uniformity, quantity of active pharmaceutical ingredient (API), disintegration and dissolution, all following Pharmacopoeial test methods The physical characteristics of dosage form, packaging and labeling information of all samples complied with criteria given in the WHO checklists. The mass uniformity of tablets of each brand of ABZ, MBZ and PZQ complied with the pharmacopoeial specification limits, i.e no more than 2 individual masses >5% of average tablet weight, and none deviate by more than 10%. The quantity of APIs in all investigated tablet brands were within the 90-110% label claim (l.c.) limits, ranging between 95.05 and 110.09% l.c. Disintegration times were in line with the pharmacopoeial specification limit for immediate release (IR) tablets, ranging between 0.5 and 13min. However, the dissolution results (mean±SD, n=6) of one ABZ brand (i.e. Wormin ® , Q=59.21±0.99% at 30min) and two PZQ brands (i.e. Bermoxel ® , Q=63.43%±0.7 and Distocide ® , Q=62.43%±1.67, at 75min) showed poor dissolution, failing the United States Pharmacopoeia (USP) dissolution specification limit. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Pharmacokinetic equivalence of a levothyroxine sodium soft capsule manufactured using the new food and drug administration potency guidelines in healthy volunteers under fasting conditions.

    PubMed

    Colucci, Philippe; D'Angelo, Pina; Mautone, Giuseppe; Scarsi, Claudia; Ducharme, Murray P

    2011-06-01

    To assess the pharmacokinetic equivalence of a new soft capsule formulation of levothyroxine versus a marketed reference product and to assess the soft capsule formulated with stricter potency guidelines versus the capsule before the implementation of the new potency rule. Two single-dose randomized two-way crossover pharmacokinetic equivalence studies and one dosage form proportionality single-dose study comparing low, medium, and high strengths of the new formulation. All three studies were performed in a clinical setting. Participants were healthy male and female adult subjects with normal levothyroxine levels. A total of 90 subjects participated in the three studies. Pharmacokinetic parameters were calculated on baseline- adjusted concentrations. The first pharmacokinetic equivalence study compared the levothyroxine sodium soft capsule formulation (Tirosint) with the reference Synthroid tablets and the two products were considered bioequivalent. The dosage form proportionality study compared the 50-, 100-, and 150-μg test capsules strengths dosed at the same level (600 μg) and all three strengths were considered equivalent when given at the same dosage. The last study compared the test capsule used in the first two studies with a new capsule formulation following the new potency guideline (±5%) set forward by the Food and Drug Administration and the two capsules were considered bioequivalent. Doses were well tolerated by subjects in all three studies with no serious adverse events reported. The levothyroxine soft capsule formulated with the stricter new potency guideline set forward by the Food and Drug Administration met equivalence criteria in terms of rate and extent of exposure under fasting conditions to the reference tablet formulation. Clinical doses of the capsule formulation can be given using any combination of the commercialized strengths.

  19. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-04-27

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

  2. Application of three-dimensional printing for colon targeted drug delivery systems

    PubMed Central

    Charbe, Nitin B.; McCarron, Paul A.; Lane, Majella E.; Tambuwala, Murtaza M.

    2017-01-01

    Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems. PMID:28929046

  3. Application of three-dimensional printing for colon targeted drug delivery systems.

    PubMed

    Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M

    2017-01-01

    Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.

  4. 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.

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

    PubMed

    Jagdale, Swati C; Pawar, Chandrakala R

    2014-01-01

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

  6. Stability-indicating RP-HPLC Method for the Simultaneous Determination of Sitagliptin and Simvastatin in Tablets

    PubMed Central

    Ramalingam, P.; Bhaskar, V. Udaya; Reddy, Y. Padmanabha; Kumar, K. Vinod

    2014-01-01

    A new stability-indicating high-performance liquid chromatographic method for simultaneous analysis of sitagliptin and simvastatin in pharmaceutical dosage form was developed and validated. The mobile phase consisted of methanol and water (70:30, v/v) with 0.2 % of n-heptane sulfonic acid adjusted to pH 3.0 with ortho phosphoric acid was used. Retentions of sitagliptin and simvastatin were 4.3 min and 30.4 min, respectively with a flow rate of 1 ml/min on C8 (Qualisil BDS, 250×4.6 mm, 5 μ). Eluents were detected at 253 nm using photodiode diode array detector. The linear regression analysis data for the linearity plot showed correlation coefficient values of 0.9998 and 0.9993 for sitagliptin and simvastatin, with respective concentration ranges of 20-150 μg/ml and 8-60 μg/ml. The relative standard deviation for inter-day precision was lower than 2.0%. The assay of sitagliptin and simvastatin was determined in tablet dosage form was found to be within limits. Both drugs were subjected to a variety of stress conditions such as acidic, basic, oxidation, photolytic, neutral and thermal stress in order to achieve adequate degradation. Results revealed that considerable degradation was found in all stress conditions except oxidative degradations. The method has proven specificity for stability indicating assay method. PMID:25425754

  7. A Simple and Specific Stability- Indicating RP-HPLC Method for Routine Assay of Adefovir Dipivoxil in Bulk and Tablet Dosage Form.

    PubMed

    Darsazan, Bahar; Shafaati, Alireza; Mortazavi, Seyed Alireza; Zarghi, Afshin

    2017-01-01

    A simple and reliable stability-indicating RP-HPLC method was developed and validated for analysis of adefovir dipivoxil (ADV).The chromatographic separation was performed on a C 18 column using a mixture of acetonitrile-citrate buffer (10 mM at pH 5.2) 36:64 (%v/v) as mobile phase, at a flow rate of 1.5 mL/min. Detection was carried out at 260 nm and a sharp peak was obtained for ADV at a retention time of 5.8 ± 0.01 min. No interferences were observed from its stress degradation products. The method was validated according to the international guidelines. Linear regression analysis of data for the calibration plot showed a linear relationship between peak area and concentration over the range of 0.5-16 μg/mL; the regression coefficient was 0.9999and the linear regression equation was y = 24844x-2941.3. The detection (LOD) and quantification (LOQ) limits were 0.12 and 0.35 μg/mL, respectively. The results proved the method was fast (analysis time less than 7 min), precise, reproducible, and accurate for analysis of ADV over a wide range of concentration. The proposed specific method was used for routine quantification of ADV in pharmaceutical bulk and a tablet dosage form.

  8. Characterization of new functionalized calcium carbonate-polycaprolactone composite material for application in geometry-constrained drug release formulation development.

    PubMed

    Wagner-Hattler, Leonie; Schoelkopf, Joachim; Huwyler, Jörg; Puchkov, Maxim

    2017-10-01

    A new mineral-polymer composite (FCC-PCL) performance was assessed to produce complex geometries to aid in development of controlled release tablet formulations. The mechanical characteristics of a developed material such as compactibility, compressibility and elastoplastic deformation were measured. The results and comparative analysis versus other common excipients suggest efficient formation of a complex, stable and impermeable geometries for constrained drug release modifications under compression. The performance of the proposed composite material has been tested by compacting it into a geometrically altered tablet (Tablet-In-Cup, TIC) and the drug release was compared to commercially available product. The TIC device exhibited a uniform surface, showed high physical stability, and showed absence of friability. FCC-PCL composite had good binding properties and good compactibility. It was possible to reveal an enhanced plasticity characteristic of a new material which was not present in the individual components. The presented FCC-PCL composite mixture has the potential to become a successful tool to formulate controlled-release dosage solid forms.

  9. 21 CFR 520.2330 - Sulfisoxazole tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... (a) Specifications. Each tablet contains 260 milligrams (4 grains) of sulfisoxazole. (b) Sponsor. See... orally per 4 pounds of body weight. 1 1 These conditions are NAS/NRC reviewed and deemed effective... sulfisoxazole. 1 (3) Limitations. Repeat dosage at 24-hour intervals until 2 to 3 days after disappearance of...

  10. 21 CFR 520.2330 - Sulfisoxazole tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... (a) Specifications. Each tablet contains 260 milligrams (4 grains) of sulfisoxazole. (b) Sponsor. See... orally per 4 pounds of body weight. 1 1 These conditions are NAS/NRC reviewed and deemed effective... sulfisoxazole. 1 (3) Limitations. Repeat dosage at 24-hour intervals until 2 to 3 days after disappearance of...

  11. 21 CFR 520.2330 - Sulfisoxazole tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... (a) Specifications. Each tablet contains 260 milligrams (4 grains) of sulfisoxazole. (b) Sponsor. See... orally per 4 pounds of body weight. 1 1 These conditions are NAS/NRC reviewed and deemed effective... sulfisoxazole. 1 (3) Limitations. Repeat dosage at 24-hour intervals until 2 to 3 days after disappearance of...

  12. 21 CFR 520.2330 - Sulfisoxazole tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... (a) Specifications. Each tablet contains 260 milligrams (4 grains) of sulfisoxazole. (b) Sponsor. See... orally per 4 pounds of body weight. 1 1 These conditions are NAS/NRC reviewed and deemed effective... sulfisoxazole. 1 (3) Limitations. Repeat dosage at 24-hour intervals until 2 to 3 days after disappearance of...

  13. Valsartan.

    PubMed

    Ardiana, Febry; Suciati; Indrayanto, Gunawan

    2015-01-01

    Valsartan is an antihypertensive drug which selectively inhibits angiotensin receptor type II. Generally, valsartan is available as film-coated tablets. This review summarizes thermal analysis, spectroscopy characteristics (UV, IR, MS, and NMR), polymorphism forms, impurities, and related compounds of valsartan. The methods of analysis of valsartan in pharmaceutical dosage forms and in biological fluids using spectrophotometer, CE, TLC, and HPLC methods are discussed in details. Both official and nonofficial methods are described. It is recommended to use LC-MS method for analyzing valsartan in complex matrices such as biological fluids and herbal preparations; in this case, MRM is preferred than SIM method. © 2015 Elsevier Inc. All rights reserved.

  14. [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.

  15. 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

  16. 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.

  17. The effect of food on gastrointestinal (GI) transit of sustained-release ibuprofen tablets as evaluated by gamma scintigraphy

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

    Borin, M.T.; Khare, S.; Beihn, R.M.

    1990-03-01

    The GI transit of radiolabeled sustained-release ibuprofen 800-mg tablets in eight healthy, fed volunteers was monitored using external gamma scintigraphy. Ibuprofen serum concentrations were determined from blood samples drawn over 36 hr following dosing. Sustained-release ibuprofen tablets containing 0.18% of 170Er2O3 (greater than 96% 170Er) in the bulk formulation were manufactured under pilot-scale conditions and were radiolabeled utilizing a neutron activation procedure which converted stable 170Er to radioactive 171Er (t1/2 = 7.5 hr). At the time of dosing, each tablet contained 50 mu Ci of 171Er. Dosage form position were reported at various time intervals. In five subjects the sustained-releasemore » tablet remained in the stomach and eroded slowly over 7-12 hr, resulting in gradual increases in small bowel radioactivity. In the remaining three subjects, the intact tablet was ejected from the stomach and a gastric residence time of approximately 4 hr was measured. This is in marked contrast to a previous study conducted in fasted volunteers in which gastric retention time ranged from 10 to 60 min. Differences in GI transit between fed and fasted volunteers had little effect on ibuprofen bioavailability. AUC and Tmax were unaltered and Cmax was increased by 24%, which is in agreement with results from a previous, crossover-design food effect study.« less

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

    PubMed Central

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

    2013-01-01

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

  19. Evaluation of the impact of sodium lauryl sulfate source variability on solid oral dosage form development.

    PubMed

    Qiang, Dongmei; Gunn, Jocelyn A; Schultz, Leon; Li, Z Jane

    2010-12-01

    The objective of this study was to investigate the effects of sodium lauryl sulfate (SLS) from different sources on solubilization/wetting, granulation process, and tablet dissolution of BILR 355 and the potential causes. The particle size distribution, morphology, and thermal behaviors of two pharmaceutical grades of SLS from Spectrum and Cognis were characterized. The surface tension and drug solubility in SLS solutions were measured. The BILR 355 tablets were prepared by a wet granulation process and the dissolution was evaluated. The critical micelle concentration was lower for Spectrum SLS, which resulted in a higher BILR 355 solubility. During wet granulation, less water was required to reach the same end point using Spectrum than Cognis SLS. In general, BILR 355 tablets prepared with Spectrum SLS showed a higher dissolution than the tablets containing Cognis SLS. Micronization of SLS achieved the same improved tablet dissolution as micronized active pharmaceutical ingredient. The observed differences in wetting and solubilization were likely due to the different impurity levels in SLS from two sources. This study demonstrated that SLS from different sources could have significant impact on wet granulation process and dissolution. Therefore, it is critical to evaluate SLS properties from different suppliers, and then identify optimal formulation and process parameters to ensure robustness of drug product manufacture process and performance.

  20. 3D printing of tablets using inkjet with UV photoinitiation.

    PubMed

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

    2017-08-30

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

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

    PubMed

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

    2017-03-01

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

  2. 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.

  3. Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

    PubMed

    Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

    2016-08-01

    The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

  4. In Vitro Drug Release After Crushing: Evaluation of Xtampza® ER and Other ER Opioid Formulations.

    PubMed

    Mayock, Stephen P; Saim, Said; Fleming, Alison B

    2017-12-01

    Extended-release (ER) opioids are associated with high rates of abuse. Recreational opioid users often manipulate ER formulations to achieve a high plasma concentration in a short amount of time, resulting in a more rapid and intense high. Patients may also manipulate ER tablets to facilitate swallowing, without recognizing that manipulation could increase release rate. The goal of this study was to assess the ability of oxycodone DETERx (Xtampza ® ER, Collegium Pharmaceutical, Inc., Canton, MA, USA) and other commercially available ER opioid formulations with and without physicochemical abuse-deterrent characteristics to be manipulated by crushing in an in vitro setting. In vitro dissolution techniques were used to compare the opioid release from a variety of ER opioid formulations. Dissolution was assessed for intact and crushed dosage forms. Opioid release was quantified using high-performance liquid chromatography. Intact formulations exhibited drug release rates characteristic of 12- or 24-h dosage forms. After crushing using commonly available household tools, only Xtampza ER maintained ER of opioid. Xtampza ER maintained its ER characteristics after crushing, unlike many other commercially available opioid formulations, including some formulated with abuse-deterrent properties. As such, Xtampza ER may be less appealing to abusers and offer a margin of safety for patients who manipulate dosage forms to facilitate swallowing.

  5. Particle Engineering of Excipients for Direct Compression: Understanding the Role of Material Properties.

    PubMed

    Mangal, Sharad; Meiser, Felix; Morton, David; Larson, Ian

    2015-01-01

    Tablets represent the preferred and most commonly dispensed pharmaceutical dosage form for administering active pharmaceutical ingredients (APIs). Minimizing the cost of goods and improving manufacturing output efficiency has motivated companies to use direct compression as a preferred method of tablet manufacturing. Excipients dictate the success of direct compression, notably by optimizing powder formulation compactability and flow, thus there has been a surge in creating excipients specifically designed to meet these needs for direct compression. Greater scientific understanding of tablet manufacturing coupled with effective application of the principles of material science and particle engineering has resulted in a number of improved direct compression excipients. Despite this, significant practical disadvantages of direct compression remain relative to granulation, and this is partly due to the limitations of direct compression excipients. For instance, in formulating high-dose APIs, a much higher level of excipient is required relative to wet or dry granulation and so tablets are much bigger. Creating excipients to enable direct compression of high-dose APIs requires the knowledge of the relationship between fundamental material properties and excipient functionalities. In this paper, we review the current understanding of the relationship between fundamental material properties and excipient functionality for direct compression.

  6. Pricing of multiple dosage prescription medications: an analysis of the Ontario Drug Benefit Formulary.

    PubMed

    Lexchin, Joel

    2009-07-01

    This paper investigates the pricing strategy (perfect flat pricing, perfect monotonic pricing, intermediate) used for multiple dosage medications listed in the Ontario Drug Benefit Formulary. All multiple dosage solid medications containing a single active ingredient newly listed in the Ontario Drug Benefit Formulary between 1996 and 2005 were identified. The relationship between price and dosage was calculated using a previously developed method. Seventy-three multiple dosage medications were introduced. Where medications were equivalent to existing ones in most cases companies followed the pricing strategy used by therapeutically equivalent drugs already in the formulary. Where there were no equivalent products companies did not adopt any particular pricing strategy. There was no difference in the way that companies priced scored tablets versus unscored tablets and capsules or in the way that they priced drugs that had objective measurements of efficacy/effectiveness, for example blood pressure, versus those that did not have these measurements. When Monotonic pricing is used it leads to higher expenditures whereas flat pricing results in lower expenditures and offers more predictability in expenditures. Provincial governments should consider requiring flat pricing in return for formulary listing.

  7. An examination of the prescription and dispensing of medicines by Western herbal therapists: a national survey in Australia.

    PubMed

    Casey, M G; Adams, J; Sibbritt, D

    2007-03-01

    To describe the patterns of prescription and dispensing of herbal medicines employed by Western herbal practitioners in Australia. A national postal survey sent to all full members of the National Herbalist Association of Australia (NHAA). Nationwide clinics of professional herbal practitioners in Australia. Measures of medicinal use were collected including aspects of prescription, formulation, dispensing and preparation forms of medicines used. The practitioners were asked if they dispensed their own medicines, about the form of herbal preparations used, aspects of formulation and dosages. The predominant prescription by most Western herbal practitioners in Australia is individualised herbal formulae rather than the use of single herbs. Traditional preparations of herbals such as teas and powders are used but liquid herbal extracts are most commonly dispensed. These liquid medicines are in the form of highly concentrated fluid extracts in ratios of 1:1 or 1:2, herb material to liquid. Pre-formulated tablets or capsules made by herbal manufacturers are being incorporated into modern practice but most prescriptions are individualised liquid formulae prepared and dispensed, from the clinic dispensary, after patient consultation. In addition to internal prescriptions, topical creams, pessaries, douches, gargles, eyebaths and poultices or washes are still incorporated into treatments. Although there is variation in used dosage ranges, the predominant system is that of pharmacologically active doses of highly concentrated fluid extracts. The professional prescription of Western herbal medicines is different to commercial usage. As opposed to pre-formulated tablets, or use of single herbals, the vast majority of Western herbalists in Australia construct individualised herbal formulations for their patients after consultation. The preferred form of administration of these prescriptions is as highly concentrated liquid herbal extracts in pharmacologically active doses.

  8. Compression-induced crystallization of amorphous indomethacin in tablets: characterization of spatial heterogeneity by two-dimensional X-ray diffractometry.

    PubMed

    Thakral, Naveen K; Mohapatra, Sarat; Stephenson, Gregory A; Suryanarayanan, Raj

    2015-01-05

    Tablets of amorphous indomethacin were compressed at 10, 25, 50, or 100 MPa using either an unlubricated or a lubricated die and stored individually at 35 °C in sealed Mylar pouches. At selected time points, tablets were analyzed by two-dimensional X-ray diffractometry (2D-XRD), which enabled us to profile the extent of drug crystallization in tablets, in both the radial and axial directions. To evaluate the role of lubricant, magnesium stearate was used as "internal" and/or "external" lubricant. Indomethacin crystallization propensity increased as a function of compression pressure, with 100 MPa pressure causing crystallization immediately after compression (detected using synchrotron radiation). However, the drug crystallization was not uniform throughout the tablets. In unlubricated systems, pronounced crystallization at the radial surface could be attributed to die wall friction. The tablet core remained substantially amorphous, irrespective of the compression pressure. Lubrication of the die wall with magnesium stearate, as external lubricant, dramatically decreased drug crystallization at the radial surface. The spatial heterogeneity in drug crystallization, as a function of formulation composition and compression pressure, was systematically investigated. When formulating amorphous systems as tablets, the potential for compression induced crystallization warrants careful consideration. Very low levels of crystallization on the tablet surface, while profoundly affecting product performance (decrease in dissolution rate), may not be readily detected by conventional analytical techniques. Early detection of crystallization could be pivotal in the successful design of a dosage form where, in order to obtain the desired bioavailability, the drug may be in a high energy state. Specialized X-ray diffractometric techniques (2D; use of high intensity synchrotron radiation) enabled detection of very low levels of drug crystallization and revealed the heterogeneity in crystallization within the tablet.

  9. Development and in vitro evaluation of mesalamine delayed release pellets and tableted reservoir-type pellets.

    PubMed

    Bendas, Ehab R; Christensen, J Mark; Ayres, James W

    2010-04-01

    The basic objective of this study was to develop a novel technique that aids in compaction of coated pellets into tablets and obtain a release pattern from compressed pellets resembling the same pattern before compression. Multi-unit dosage forms of mesalamine targeted to the colon were formulated by extrusion-spheronization, and then coated with Eudragit S (30%). These pellets were filled into gelatin capsules or further formulated and compressed into tablets. Tablets for colonic delivery of mesalamine were prepared by mixing the coated beads with cushioning agents like stearic acid and Explotab, or by applying an additional coat of gelatin (4% weight gain) onto the Eudragit S coated pellets, and then compressing into tablets (tableted reservoir-type pellets). Then additional coating of the tablets prepared by the coating technique was applied utilizing Eudragit L 100-55 (5% weight gain). This technique provides additive protection for the coated beads to withstand the compression force during tableting. Excellent in vitro dissolution results were obtained, which were comparable to the results of the release of mesalamine from uncompressed beads filled in capsules. Mesalamine release from the capsules was 0.3% after 2 hours in gastric pH, 0.37% was released after an additional 1 hour in pH 6, and 89% was released after 1.5 hours in colonic pH 7.2. Various formulation and process parameters have to be optimized in order to obtain tableted reservoir-type pellets having the same release properties as the uncompressed pellets. The coating technique delays the release of mesalamine until the beads reach the terminal ileum and colon. Once released in the colon, mesalamine is minimally absorbed and can act locally to treat ulcerative colitis.

  10. 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.

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

    PubMed

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

    2016-05-02

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

  12. ColoPulse tablets perform comparably in healthy volunteers and Crohn's patients and show no influence of food and time of food intake on bioavailability.

    PubMed

    Maurer, J M; Schellekens, R C A; van Rieke, H M; Stellaard, F; Wutzke, K D; Buurman, D J; Dijkstra, G; Woerdenbag, H J; Frijlink, H W; Kosterink, J G W

    2013-12-28

    ColoPulse tablets are an innovative development in the field of oral drug delivery and are characterized by a colon-specific release. Until now ColoPulse dosage forms (only capsules) have been studied in healthy volunteers having a standardized breakfast three hours after administration but not in specific patient groups and not with a shorter interval between administration and breakfast. Information on bioavailability and release characteristics of ColoPulse tablets in Crohn's patients and the influence of food and time of food intake is a prerequisite to properly design future clinical studies with active substances in these patients. In the current cross-over study bioavailability and drug release characteristics of ColoPulse tablets were compared in healthy volunteers and in Crohn's patients in remission. Furthermore the influence of food and time of food intake on the in vivo drug release behavior of ColoPulse tablets was investigated. In this study the dual label isotope strategy was used which means that a ColoPulse tablet containing (13)C-urea and an uncoated, immediate release tablet containing (15)N2-urea were taken simultaneously. Breath and urine samples were collected during the test day for isotope analysis. The appearance of the stable isotopes in breath and/or urine provides information on the site of release from the dosage form, release characteristics and bioavailability. Both tablets were administered on two different days in a cross-over design: the first day with a breakfast (non-standardized) one hour after administration and the second day with a standardized breakfast three hours after administration of the tablets. There was no difference in instructions for administration between both days. Results of 16 healthy volunteers and 14 Crohn's patients were evaluated. At least 86% (51 out of 59) of all ColoPulse tablets administered in this study released their contents at the desired intestinal region. There was no significant difference in bioavailability between healthy volunteers and Crohn's patients on both days (day 1 75.8% vs 90.2%, p=0.070 and day 2 83.4% vs 91.4%, p=0.265). There was also no significant influence of food and time of food intake on bioavailability in healthy volunteers (75.8% and 83.4%, p=0.077) and in Crohn's patients (90.2% and 91.4%, p=0.618) when day 1 and day 2 were compared. Release characteristics did not significantly differ between healthy volunteers and Crohn's patients. However, food and time of food intake had some, clinically non-relevant, influence on the release characteristics within both groups which is in line with the fact that food affects gastro-intestinal transit times. This study shows that ColoPulse tablets enable the site-specific delivery of drugs or other compounds (e.g. diagnostics) deep in the ileo-colonic region of the intestine of Crohn's patients in a comparable amount and rate as in healthy volunteers. Food and time of food intake had no relevant influence on bioavailability. In conclusion ColoPulse delivery systems are promising and deserve further research for local therapy with immunosuppressive drugs in Crohn's patients in the near future. © 2013.

  13. Analytical Enantio-Separation of Linagliptin in Linagliptin and Metformin HCl Dosage Forms by Applying Two-Level Factorial Design.

    PubMed

    Jadhav, Sushant B; Mane, Rahul M; Narayanan, Kalyanraman L; Bhosale, Popatrao N

    2016-10-17

    A novel, stability indicating, reverse phase high-performance liquid chromatography (RP-HPLC) method was developed to determine the S -isomer of linagliptin (LGP) in linagliptin and metformin hydrochloride (MET HCl) tablets (LGP-MET HCl) by implementing design of experiment (DoE), i.e., two-level, full factorial design (2³ + 3 centre points = 11 experiments) to understand the critical method parameters (CMP) and its relation with the critical method attribute (CMA), and to ensure robustness of the method. The separation of the S -isomer, LGP and MET HCl in the presence of their impurities was achieved on Chiralpak ® IA-3 ( Amylose tris (3, 5-dimethylphenylcarbamate ), immobilized on 3 µm silica gel) stationary phase (250 × 4.6 mm, 3 µm) using isocratic elution and detector wavelength at 225 nm with a flow rate of 0.5 mL·min -1 , an injection volume of 10 µL with a sample cooler (5 °C) and column oven temperature of 25 °C. Ethanol:Methanol:Monoethanolamine (EtOH:MeOH:MEA) in the ratio of 60:40:0.2 v / v / v was used as a mobile phase. The developed method was validated in accordance with international council for harmonisation (ICH) guidelines and was applied for the estimation of the S -isomer of LGP in LGP-MET HCl tablets. The same method also can be extended for the estimation of the S -isomer in LGP dosage forms.

  14. Stability-indicating method for simultaneous estimation of olmesartan medoxomile, amlodipine besylate and hydrochlorothiazide by RP-HPLC in tablet dosage form.

    PubMed

    Jain, P S; Patel, M K; Gorle, A P; Chaudhari, A J; Surana, S J

    2012-09-01

    A simple, specific, accurate and precise stability-indicating reversed-phase high-performance liquid chromatographic method was developed for simultaneous estimation of olmesartan medoxomile (OLME), amlodipine besylate (AMLO) and hydrochlorothiazide (HCTZ) in tablet dosage form. The method was developed using an RP C18 base deactivated silica column (250 × 4.6 mm, 5 µm) with a mobile phase consisting of triethylamine (pH 3.0) adjusted with orthophosphoric acid (A) and acetonitrile (B), with a timed gradient program of T/%B: 0/30, 7/70, 8/30, 10/30 with a flow rate of 1.4 mL/min. Ultraviolet detection was used at 236 nm. The retention times for OLME, AMLO and HCTZ were found to be 6.72, 4.28 and 2.30, respectively. The proposed method was validated for precision, accuracy, linearity, range, robustness, ruggedness and force degradation study. The calibration curves of OLME, AMLO and HCTZ were linear over the range of 50-150, 12.5-37.5 and 31-93 µg/mL, respectively. The method was found to be sensitive. The limits of detection of OLME, AMLO and HCTZ were determined 0.19, 0.16 and 0.22 µg/mL and limits of quantification of OLME, AMLO and HCTZ were determined 0.57, 0.49 and 0.66, respectively. Forced degradation study was performed according to International Conference on Harmonization guidelines.

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

    PubMed Central

    Jagdale, Swati C.; Pawar, Chandrakala R.

    2014-01-01

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

  16. Templates of patient brochures for the preparation, administration and safe-handling of oral chemotherapy.

    PubMed

    Siden, Rivka; Kem, Ravie; Ostrenga, Andrew; Nicksy, Darcy; Bernhardt, Brooke; Bartholomew, Joy

    2014-06-01

    The increased use of oral chemotherapy for the treatment of cancer introduces new challenges for patients and caregivers. Among them are the ability to swallow oral solid dosage forms, the proper administration of the agents and the safe-handling of chemotherapeutic drugs in the home. Since these drugs are hazardous, proper preparation, administration, and disposition introduces a variety of safety issues. The increased toxicity of these drugs coupled with complicated dosing regimens and the occasional need to dilute the drug or measure a liquid dosage form require careful instruction of the patient and/or caregivers. The purpose of this project was to create templates for writing patient instruction brochures. A group of clinicians specializing in oncology from several institutions in the United States and Canada met through a series of conference calls. The group included pharmacists with a specialty in pediatric oncology, investigational drug pharmacists, and an oncology nurse practitioner. National guidelines and practices at each institution were used for the creation of templates to be used in developing templates for medication and formulation-specific instruction brochures. The group developed six templates. The templates ranged in scope from instructions on the administration of intact tablets or capsules to directions on opening capsules or crushing tablets and mixing the content with foods or liquids. Thirty-three drug-specific brochures were developed using the templates. Templates of patient brochures and drug-specific brochures on the safe handling of chemotherapy in the home can be created using a collaborative, multi-institutional approach.

  17. Recent advances in small molecule drug delivery.

    PubMed

    Kidane, Argaw; Bhatt, Padmanabh P

    2005-08-01

    The majority of new drugs, and new drug products, being developed and marketed by the pharmaceutical industry are small molecules. Oral administration remains the most common route of delivering such drugs, typically in the form of immediate-release tablets or capsules. While the immediate-release dosage forms dominate the market today, more specialized and rationalized products incorporating the concepts of drug delivery are being developed to overcome the physicochemical, physiological and pharmacological challenges inherent with the drugs, and to improve the treatment regimens for the patients. Today, these specialized concepts are increasingly being applied to first-generation products and not just products intended for the life cycle management of the franchise.

  18. 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

  19. Comparison studies on the percolation thresholds of binary mixture tablets containing excipients of plastic/brittle and plastic/plastic deformation properties.

    PubMed

    Amin, Mohd C I; Fell, John T

    2004-01-01

    Percolation theory has been used with great interest in understanding the design and characterization of dosage forms. In this study, work has been carried out to investigate the behavior of binary mixture tablets containing excipients of similar and different deformation properties. The binary mixture tablets were prepared by direct compression using lactose, polyvinyl chloride (PVC), Eudragit RS 100, and microcrystalline cellulose (MCC). The application of percolation theory on the relationships between compactibility, Pmax, or compression susceptibility (compressibility), gamma, and mixture compositions reveals the presence of percolation thresholds even for mixtures of similar deformation properties. The results showed that all mixture compositions exhibited at least one discreet change in the slope, which was referred to as the percolation threshold. The PVC/Eudragit RS100 mixture compositions showed significant percolation threshold at 80% (w/w) PVC loading. Two percolation thresholds were observed from a series of binary mixtures containing similar plastic deformation materials (PVC/MCC). The percolation thresholds were determined at 20% (w/w) and 80% (w/w) PVC loading. These are areas where one of the components percolates throughout the system and the properties of the tablets are expected to experience a sudden change. Experimental results, however, showed that total disruption of the tablet physical properties at the specified percolation thresholds can be observed for PVC/lactose mixtures at 20-30% (w/w) loading while only minor changes in the tablets' strength for PVC/MCC or PVC/Eudragit RS 100 mixtures were observed.

  20. Tableting properties of silica aerogel and other silicates.

    PubMed

    Hentzschel, C M; Alnaief, M; Smirnova, I; Sakmann, A; Leopold, C S

    2012-04-01

    In solid oral dosage forms silicates are commonly used as glidants in low concentration. However, due to their large specific surface area, silicates may also be used as carrier materials for drugs. Moreover, silicates allow amorphisation of drugs by co-grinding or processing with supercritical fluids. The aim of this study was to investigate the physical and the tableting properties of Silica Aerogel (special type of silica with an extremely large specific surface area), Neusilin(®) US2 (magnesium aluminometasilicate), Florite(®) (calcium silicate) and Aerosil(®) 200 (colloidal silica). Powder blends of Avicel(®) PH102 (microcrystalline cellulose) and different amounts of the respective silicate were compacted and analyzed for their tabletability (tensile strength vs. compaction pressure) as well as their Heckel plot. With Neusilin(®) the tabletability appeared to be independent of the silicate concentration, whereas with Florite(®) an increasing silicate concentration led to a higher tensile strength. In contrast, the addition of Silica Aerogel and Aerosil(®) resulted in a decrease of the tensile strength. With Aerosil(®) a maximum tolerable concentration of 20% [w/w] was determined. Plastic deformation of all powder blends decreased with increasing silicate concentration. This effect was most pronounced with Aerosil(®) and least with Florite(®). Tablets with acceptable tensile strength were obtained with all plain silicates except for Aerosil(®). Therefore, these silicates may be used in tablet formulations, e.g. as carrier materials for liquid or amorphous drugs.

  1. Development and Validation of a Rapid RP-UPLC Method for the Simultaneous Estimation of Bambuterol Hydrochloride and Montelukast Sodium from Tablets

    PubMed Central

    Yanamandra, R.; Vadla, C. S.; Puppala, U. M.; Patro, B.; Murthy, Y. L. N.; Parimi, A. R.

    2012-01-01

    A rapid, simple, sensitive and selective analytical method was developed by using reverse phase ultra performance liquid chromatographic technique for the simultaneous estimation of bambuterol hydrochloride and montelukast sodium in combined tablet dosage form. The developed method is superior in technology to conventional high performance liquid chromatography with respect to speed, resolution, solvent consumption, time, and cost of analysis. Elution time for the separation was 6 min and ultra violet detection was carried out at 210 nm. Efficient separation was achieved on BEH C18 sub-2-μm Acquity UPLC column using 0.025% (v/v) trifluoro acetic acid in water and acetonitrile as organic solvent in a linear gradient program. Resolutions between bambuterol hydrochloride and montelukast sodium were found to be more than 31. The active pharmaceutical ingredient was extracted from tablet dosage from using a mixture of methanol, acetonitrile and water as diluent. The calibration graphs were linear for bambuterol hydrochloride and montelukast sodium in the range of 6.25-37.5 μg/ml. The percentage recoveries for bambuterol hydrochloride and montelukast sodium were found to be in the range of 99.1-100.0% and 98.0-101.6%, respectively. The test solution was found to be stable for 7 days when stored in the refrigerator between 2-8°. Developed UPLC method was validated as per International Conference on Harmonization specifications for method validation. This method can be successfully employed for simultaneous estimation of bambuterol hydrochloride and montelukast sodium in bulk drugs and formulations. PMID:23325991

  2. Emerging technologies for the non-invasive characterization of physical-mechanical properties of tablets.

    PubMed

    Dave, Vivek S; Shahin, Hend I; Youngren-Ortiz, Susanne R; Chougule, Mahavir B; Haware, Rahul V

    2017-10-30

    The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate and efficient characterization of these properties is critical for successful development and manufacturing of a robust tablets. These properties are mainly analyzed and monitored with traditional pharmacopeial and non-pharmacopeial methods. Such methods are associated with several challenges such as lack of spatial resolution, efficiency, or sample-sparing attributes. Recent advances in technology, design, instrumentation, and software have led to the emergence of newer techniques for non-invasive characterization of physical-mechanical properties of tablets. These techniques include near infrared spectroscopy, Raman spectroscopy, X-ray microtomography, nuclear magnetic resonance (NMR) imaging, terahertz pulsed imaging, laser-induced breakdown spectroscopy, and various acoustic- and thermal-based techniques. Such state-of-the-art techniques are currently applied at various stages of development and manufacturing of tablets at industrial scale. Each technique has specific advantages or challenges with respect to operational efficiency and cost, compared to traditional analytical methods. Currently, most of these techniques are used as secondary analytical tools to support the traditional methods in characterizing or monitoring tablet quality attributes. Therefore, further development in the instrumentation and software, and studies on the applications are necessary for their adoption in routine analysis and monitoring of tablet physical-mechanical properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Influence of formulation parameters on dissolution rate enhancement of glyburide using liquisolid technique.

    PubMed

    Singh, Sachin Kumar; Srinivasan, K K; Gowthamarajan, K; Prakash, Dev; Gaikwad, Narayan B; Singare, Dhananjay S

    2012-08-01

    The aim of this study was to investigate the use of liquisolid technique in improving the dissolution of glyburide in a solid dosage form. This study was designed to evaluate the effects of different formulation variables, i.e. type of non-volatile liquid vehicles and drug concentrations, on drug dissolution rates. The liquisolid tablets were formulated with Propylene glycol, as liquid vehicle. Microcrystalline cellulose was used as a carrier material, silica as a coating material and croscaremellose as a disintegrant. In vitro drug dissolution profiles of the liquisolid formulations were studied and compared with direct compressed non-micronized and micronized tablets of glyburide using USP II, paddle apparatus at 50 rpm for 60 min using 900 ml of 0.05 M Phosphate Buffer, pH 7.5. The stability studies showed that the dissolution profiles of liquisolid tablets prepared with propylene glycol were not affected by ageing significantly, as f2 value found between aged and fresh samples was 51.92. Differential scanning calorimetry revealed that the drug has got solubilized in the liquid vehicle. This was further supported by the powder X-ray diffraction studies of pure drug and the liquisolid powder system. It can be concluded that it is possible to load poorly soluble drug into liquisolid tablets by addition of PVP to the liquid vehicle. This is valuable for the preparation of liquisolid tablets of poorly soluble drugs. The liquisolid tablets prepared with PVP showed a remarkably improved dissolution rate in comparison with DC tablet and other formulations.

  4. Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form.

    PubMed

    Suganthi, A; John, Sofiya; Ravi, T K

    2008-01-01

    A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75+/-0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form.

  5. Validation of UV spectrophotometric methods for the determination of dothiepin hydrochloride in pharmaceutical dosage form and stress degradation studies

    NASA Astrophysics Data System (ADS)

    Abdulrahman, Sameer A. M.; Basavaiah, K.; Cijo, M. X.; Vinay, K. B.

    2012-11-01

    Spectrophotometric methods have been developed for the determination of dothiepin hydrochloride (DOTH) in both pure and tablet dosage form and their limits of detection and quantification have been evaluated. The methods are based on the measurement of the absorbance of a DOTH solution either in 0.1 N HCl at 229 nm (method A) or in methanol at 231 nm (method B). Beer's law is obeyed over a concentration range of 1-16 μg/ml DOTH for both methods. Molar absorptivity values are calculated to be 2.48 × 104 and 2.42 × 104 l/(mol × cm) with Sandell sensitivity values of 0.0134 and 0.0137 μg/cm2 for methods A and B, respectively. The degradation behavior of DOTH was investigated under different stress conditions such as acid hydrolysis, alkaline hydrolysis, water hydrolysis, oxidation, dry heat treatment, and UV-degradation. The drug undergoes significant degradation under oxidative conditions only.

  6. A pragmatic approach for engineering porous mannitol and mechanistic evaluation of particle performance.

    PubMed

    Al-Khattawi, Ali; Koner, Jasdip; Rue, Peter; Kirby, Dan; Perrie, Yvonne; Rajabi-Siahboomi, Ali; Mohammed, Afzal R

    2015-08-01

    The importance of mannitol has increased recently as an emerging diluent for orodispersible dosage forms. The study aims to prepare spray dried mannitol retaining high porosity and mechanical strength for the development of orally disintegrating tablets (ODTs). Aqueous feed of d-mannitol (10% w/v) comprising ammonium bicarbonate, NH4HCO3 (5% w/v) as pore former was spray dried at inlet temperature of 110-170°C. Compacts were prepared at 151MPa and characterized for porosity, hardness and disintegration time. Particle morphology and drying mechanisms were studied using thermal (HSM, DSC and TGA) and polymorphic (XRD) methods. Tablet porosity increased from 0.20±0.002 for pure mannitol to 0.53±0.03 using fabricated porous mannitol. Disintegration time dropped by 50-77% from 135±5.29s for pure mannitol to 75.33±2.52-31.67±1.53s for mannitol 110-170°C. Hardness increased by 150% at 110°C (258.67±28.89N) and 30% at 150°C (152.70±10.58N) compared to pure mannitol tablets (104.17±1.70N). Increasing inlet temperature resulted in reducing tablet hardness due to generation of 'micro-sponge'-like particles exhibiting significant elastic recovery. Impact of mannitol polymorphism on plasticity/elasticity cannot be ruled out as a mixture of α and β polymorphs formed upon spray drying. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. 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.

  8. Assessment of levothyroxine sodium bioavailability: recommendations for an improved methodology based on the pooled analysis of eight identically designed trials with 396 drug exposures.

    PubMed

    Walter-Sack, Ingeborg; Clanget, Christof; Ding, Reinhard; Goeggelmann, Christoph; Hinke, Vera; Lang, Matthias; Pfeilschifter, Johannes; Tayrouz, Yorki; Wegscheider, Karl

    2004-01-01

    Assessment of dosage form performance in delivering endogenous compounds, such as hormones, in vivo requires a specific approach. Assessment of relative bioavailability of levothyroxine sodium (L-T4) from eight solid preparations, compared with a liquid formulation, by using pharmacological doses, and critical evaluation of trial methodology based on the pooled analysis of individual data. Eight open-label, randomised, single-dose, crossover phase I studies using eight solid L-T4 dosage forms (25, 50, 75, 100, 125, 150, 175, 200 microg per tablet; administered total doses 600, 625 or 700 microg) and a liquid formulation; assessment of relative bioavailability by 90% confidence intervals for the relative area under the concentration-time curve (AUC) of total thyroxine (TT4), i.e. protein-bound plus free thyroxine, calculated by using the recommended log AUC four-way analysis of variance models for crossover designs. For the pooled analysis, general linear models were applied to assess the validity of model assumptions, to identify potential sources of effect modification, to discuss alternative modelling approaches with respect to endogenous hormone secretion and to give recommendations for future designs and sample sizes. One hundred and sixty-nine healthy males; 29 of these individuals participating in two studies. Single oral doses of L-T4 tablets and the liquid formulation administered after fasting, separated by at least 6 weeks; a total of 396 drug exposures. TT4 AUC from 0 to 48 hours and peak plasma concentration with and without baseline correction. Each study demonstrated equivalence of the tablets to the drinking solution, independent of the chosen analysis model. Sequence effects that could devalidate the chosen crossover approach were not found. Period effects with changing directions that could best be explained by seasonal variation were detected. While the pre-specified method of baseline correction of simply subtracting individual time-zero TT4 values was disadvantageous, the analysis of total AUC could be improved considerably by covariate adjustment for baseline TT4. With this approach, sample sizes could have been substantially reduced or, alternatively, the recommended equivalence ranges could be reduced to +/-6%. Using a single pharmacological dose of L-T4 in two-period crossover designs is a safe and reliable procedure to assess L-T4 dosage form performance. With an adequate statistical modelling approach, the design is efficient and allows general conclusions with moderate sample sizes.

  9. Validated spectrofluorimetric method for the determination of carbamazepine in pharmaceutical dosage forms after reaction with 4-chloro-7--nitrobenzo-2-oxa-1,3-diazole (NBD-Cl).

    PubMed

    Walash, Mohammed I; El-Enany, Nahed; Askar, Hanany

    2015-11-01

    A sensitive and simple spectrofluorimetric method has been developed and validated for the determination of the anti-epileptic drug carbamazepine (CBZ) in its dosage forms. The method was based on a nucleophilic substitution reaction of CBZ with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer (pH 9) to form a highly fluorescent derivative that was measured at 530 nm after excitation at 460 nm. Factors affecting the formation of the reaction product were studied and optimized, and the reaction mechanism was postulated. The fluorescence-concentration plot is rectilinear over the range of 0.6-8 µg/mL with limit of detection of 0.06 µg/mL and limit of quantitation of 0.19 µg/mL. The method was applied to the analysis of commercial tablets and the results were in good agreement with those obtained using the reference method. Validation of the analytical procedures was evaluated according to ICH guidelines. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Impact of the digital revolution on the future of pharmaceutical formulation science.

    PubMed

    Leuenberger, Hans; Leuenberger, Michael N

    2016-05-25

    The ongoing digital revolution is no longer limited to the application of apps on the smart phone for daily needs but starts to affect also our professional life in formulation science. The software platform F-CAD (Formulation-Computer Aided Design) of CINCAP can be used to develop and test in silico capsule and tablet formulations. Such an approach allows the pharmaceutical industry to adopt the workflow of the automotive and aircraft industry. Thus, the first prototype of the drug delivery vehicle is prepared virtually by mimicking the composition (particle size distribution of the active drug substance and of the excipients within the tablet) and the process such as direct compression to obtain a defined porosity. The software is based on a cellular automaton (CA) process mimicking the dissolution profile of the capsule or tablet formulation. To take account of the type of dissolution equipment and all SOPs (Standard Operation Procedures) such as a single punch press to manufacture the tablet, a calibration of the F-CAD dissolution profile of the virtual tablet is needed. Thus, the virtual tablet becomes a copy of the real tablet. This statement is valid for all tablets manufactured within the same formulation design space. For this reason, it is important to define already for Clinical Phase I the formulation design space and to work only within this formulation design space consisting of the composition and the processes during all the Clinical Phases. Thus, it is not recommended to start with a simple capsule formulation as service dosage form and to change later to a market ready tablet formulation. The availability of F-CAD is a necessary, but not a sufficient condition to implement the workflow of the automotive and aircraft industry for developing and testing drug delivery vehicles. For a successful implementation of the new workflow, a harmonization of the equipment and the processes between the development and manufacturing departments is a must. In this context, the clinical samples for Clinical Phases I and II should be prepared with a mechanical simulator of the high-speed rotary press used for large batches for Clinical Phases III & IV. If not, the problem of working practically and virtually in different formulation design spaces will remain causing worldwide annually billion of $ losses according to the study of Benson and MacCabe. The harmonization of equipment and processes needs a close cooperation between the industrial pharmacist and the pharmaceutical engineer. In addition, Virtual Equipment Simulators (VESs) of small and large scale equipment for training and computer assisted scale-up would be desirable. A lean and intelligent management information and documentation system will improve the connectivity between the different work stations. Thus, in future, it may be possible to rent at low costs F-CAD as an IT (Information Technology) platform based on a cloud computing solution. By the adoption of the workflow of the automotive and aircraft industry significant savings, a reduced time to market, a lower attrition rate, and a much higher quality of the final marketed dosage form can be achieved. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Formulation Development of Spherical Crystal Agglomerates of Itraconazole for Preparation of Directly Compressible Tablets with Enhanced Bioavailability.

    PubMed

    Fadke, Janki; Desai, Jagruti; Thakkar, Hetal

    2015-12-01

    The objective of the present work was to formulate tablet dosage form of itraconazole with enhanced bioavailability. Spherical crystal agglomerates (SCA) of itraconazole prepared by quasi emulsification solvent diffusion method using Soluplus and polyethylene glycol 4000 (PEG 4000) showed increased solubility (540 μg/ml) in 0.1 N hydrochloric acid as compared to pure drug (12 μg/ml). A Fourier transform infrared (FTIR) study indicated compatibility of drug with the excipients. The developed SCA were spherical with smooth surface having an average size of 412 μm. The significantly improved micromeritic properties compared to the plain drug suggested its suitability for direct compression. The antifungal activity of itraconazole was retained in the SCA form as evidenced from the results of the disc diffusion method. The optimized SCA formulation could be easily compressed into tablet with desirable characteristics of hardness (5 kg/cm(2)) and disintegration time (6.3 min). The in vitro dissolution studies showed significant difference in the dissolution profiles of pure drug (21%) and SCA formulation (85%) which was even greater than that of marketed preparation (75%). In vivo pharmacokinetic showed significant enhancement in C max and AUC0-t with relative bioavailability of 225%. The SCA formulation seems to be promising for enhancement of oral bioavailability of itraconazole.

  12. New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials.

    PubMed

    Gottwald-Hostalek, Ulrike; Uhl, Wolfgang; Wolna, Peter; Kahaly, George J

    2017-02-01

    Small levothyroxine (L-T4) dose changes can lead to significant clinical effects. To ensure thyroid hormone levels are safely maintained, authorities are increasingly adopting stricter potency specifications for L-T4, the most stringent of these being 95-105% of the labeled dose over the whole shelf-life. Levothyroxine sodium (Euthyrox, Eutirox, Lévothyrox ) has been reformulated, and two studies performed, to ensure bioequivalence to the currently marketed formulation and dosage form proportionality of the new formulation. The bioequivalence study was an open-label, randomized, single-dose, two-period, two-sequence crossover comparing the highest dosage strengths of the currently marketed and the new L-T4 formulation at a total dose of 600 μg. The dosage form proportionality study was an open-label, randomized, three-period, six-sequence crossover, comparing 50 μg, 100 μg, and 200 μg L-T4 tablets, at a total dose of 600 μg. Blood samples were taken at predefined time intervals. Primary outcomes were area under the curve (AUC) and maximum concentration (C max ) of thyroxine (T4) in plasma. In the bioequivalence study, comparing the T4 profiles for the new and current formulation of L-T4, the geometric least square mean ratio of the baseline-adjusted AUC 0-72,adj was 99.3% (90% confidence interval [CI]: 95.6-103.2) and the C max,adj was 101.7% (90% CI: 98.8-104.6). Bioequivalence was established if the 90% CI lay within the predefined 0.9-1.11 limits. In the dosage form proportionality study, pairwise comparisons ranged from 99.3% to 104.8%, and all 95% CIs were within the predefined CI range (0.8-1.25): the three dose strengths were dosage form proportional. The new formulation of L-T4 meets the most stringent potency specification guidelines, and has been demonstrated to be bioequivalent to the current formulation and to show dosage form proportionality. The new formulation will enable patients to receive a dose fine tuned to their medical needs, contributing to improved safety in the use of L-T4.

  13. Acceptability of different oral formulations in infants and preschool children

    PubMed Central

    van Riet-Nales, Diana A; de Neef, Barbara J; Schobben, Alfred F A M; Ferreira, José A; Egberts, Toine C G; Rademaker, Catharine M A

    2013-01-01

    Objective Liquid medicines are easy to swallow. However, they may have disadvantages, such as a bad taste or refrigerated storage conditions. These disadvantages may be avoided by the use of oral solid medicines, such as powders or tablets. The aim of this study was to investigate the acceptability of and preference among four oral formulations in domiciliary infants and preschool children in The Netherlands. Methods Parents administered four oral placebo dosage forms that were aimed at a neutral taste, at home, to their child (1–4 years of age) twice on one day following a randomised cross-over design: small (4 mm) tablet, powder, suspension and syrup. They were asked to report the child's acceptability by a score on a 10 cm visual analogue scale (VAS score) and by the result of the intake. At the end of the study, they were asked to report the preference of the child and themselves. Results 183 children were included and 148 children were evaluated. The data revealed a period/cross-over effect. The estimate of the mean VAS score was significantly higher for the tablet than for the suspension (tablet 9.39/9.01; powder 8.84/8.20, suspension 8.26/7.90, syrup 8.35/8.19; data day 1/all days). The estimate of the mean number of intakes fully swallowed was significantly higher for the tablet than for the other formulations (all p values <0.05). Children and parents preferred the tablet and syrup over the suspension and the suspension over the powder (all p values <0.05). Conclusions All formulations were well accepted. The tablets were the best accepted formulation; the tablets and syrup the most preferred. Trial Registration number ISRCTN63138435. PMID:23853004

  14. Tablet Splitting of Antiepileptic Drugs in Pediatric Epilepsy: Potential Effect on Plasma Drug Concentrations.

    PubMed

    Nidanapu, Ravi Prasad; Rajan, Sundaram; Mahadevan, Subramanian; Gitanjali, Batmanabane

    2016-12-01

    Tablet splitting is the process of dividing a tablet into portions to obtain a prescribed dose of medication. Very few studies have investigated whether split parts of a tablet deliver the expected amount of drug to patients. Our objectives were to evaluate the split parts of adult-dose tablet formulations for percentage of weight deviation, weight uniformity, weight loss, drug content, and the content uniformity of four antiepileptic drugs (AEDs) prescribed to pediatric patients. We also measured AED plasma concentrations in the children. We chose to study first-line AEDs (phenytoin sodium [PHE], sodium valproate [SVA], carbamazepine, and phenobarbitone) as they are routinely prescribed in India. We asked caregivers to perform the same splitting process they follow in their homes on three whole tablets during their routine visit to the outpatient department. After caregivers split the tablets, we studied the weight and content of the split parts. We also used high-performance liquid chromatography to study plasma drug concentrations in children who had received split AEDs for at least 4 months. A total of 168 caregivers participated in the study, and we analyzed 1098 split tablet parts. In total, 539 (49.0 %) split parts were above the specified limit of the 2010 Indian Pharmacopeia (IP) acceptable percentage weight deviation (PHE 169 [48.8 %], SVA 187 [51.9 %], carbamazepine 56 [41.1 %], phenobarbitone 127 [49.6 %]); 456 (41.5 %) split parts were outside the proxy IP specification for drug content (PHE 135 [39.0 %], SVA 140 [38.8 %], carbamazepine 51 [37.5 %], phenobarbitone 130 [50.7 %]), and 253 split parts were outside the acceptable content uniformity range of <85 % and >115 % (PHE 85 [24.5 %], SVA 98 [27.2 %], carbamazepine 14 [10.2 %], phenobarbitone 56 [21.8 %]). In total, 130 (72.2 %) patients had plasma drug concentrations outside the therapeutic range (PHE 36 [72.0 %], SVA 39 [78.0 %], carbamazepine 34 [68.0 %], phenobarbitone 21 [70.0 %]). Splitting adult-dosage formulations of AEDs results in patients not receiving the optimal dose. Plasma drug concentrations are also not optimal. Pediatric dosage formulations should be preferred to splitting adult-dosage formulations in pediatric epilepsy.

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2016-01-01

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

  17. Safe and effective pharmacotherapy in infants and preschool children: importance of formulation aspects

    PubMed Central

    van Riet-Nales, Diana A; Schobben, Alfred F A M; Vromans, Herman; Egberts, Toine C G; Rademaker, Carin M A

    2016-01-01

    Safe and effective paediatric pharmacotherapy requires careful evaluation of the type of drug substance, the necessary dose and the age-appropriateness of the formulation. Generally, the younger the child, the more the attention that is required. For decades, there has been a general lack of (authorised) formulations that children are able to and willing to take. Moreover, little was known on the impact of pharmaceutical aspects on the age-appropriateness of a paediatric medicine. As a result of legislative incentives, such knowledge is increasingly becoming available. It has become evident that rapidly dissolving tablets with a diameter of 2 mm (mini-tablets) can be used in preterm neonates and non-rapidly dissolving 2 mm mini-tablets in infants from 6 months of age. In addition, uncoated 4 mm mini-tablets can be used in infants from the age of 1 year. Also, there is some evidence that children prefer mini-tablets over a powder, suspension or syrup. Other novel types of age-appropriate oral formulations such as orodispersible films may further add to the treatment possibilities. This review provides an overview of the current knowledge on oral formulations for infants and preschool children, the advantages and disadvantages of the different types of dosage forms and the age groups by which these can likely be used. PMID:26979250

  18. Sample Size for Tablet Compression and Capsule Filling Events During Process Validation.

    PubMed

    Charoo, Naseem Ahmad; Durivage, Mark; Rahman, Ziyaur; Ayad, Mohamad Haitham

    2017-12-01

    During solid dosage form manufacturing, the uniformity of dosage units (UDU) is ensured by testing samples at 2 stages, that is, blend stage and tablet compression or capsule/powder filling stage. The aim of this work is to propose a sample size selection approach based on quality risk management principles for process performance qualification (PPQ) and continued process verification (CPV) stages by linking UDU to potential formulation and process risk factors. Bayes success run theorem appeared to be the most appropriate approach among various methods considered in this work for computing sample size for PPQ. The sample sizes for high-risk (reliability level of 99%), medium-risk (reliability level of 95%), and low-risk factors (reliability level of 90%) were estimated to be 299, 59, and 29, respectively. Risk-based assignment of reliability levels was supported by the fact that at low defect rate, the confidence to detect out-of-specification units would decrease which must be supplemented with an increase in sample size to enhance the confidence in estimation. Based on level of knowledge acquired during PPQ and the level of knowledge further required to comprehend process, sample size for CPV was calculated using Bayesian statistics to accomplish reduced sampling design for CPV. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Chemometrics-assisted spectrophotometric green method for correcting interferences in biowaiver studies: Application to assay and dissolution profiling study of donepezil hydrochloride tablets

    NASA Astrophysics Data System (ADS)

    Korany, Mohamed A.; Mahgoub, Hoda; Haggag, Rim S.; Ragab, Marwa A. A.; Elmallah, Osama A.

    2018-06-01

    A green, simple and cost effective chemometric UV-Vis spectrophotometric method has been developed and validated for correcting interferences that arise during conducting biowaiver studies. Chemometric manipulation has been done for enhancing the results of direct absorbance, resulting from very low concentrations (high incidence of background noise interference) of earlier points in the dissolution timing in case of dissolution profile using first and second derivative (D1 & D2) methods and their corresponding Fourier function convoluted methods (D1/FF& D2/FF). The method applied for biowaiver study of Donepezil Hydrochloride (DH) as a representative model was done by comparing two different dosage forms containing 5 mg DH per tablet as an application of a developed chemometric method for correcting interferences as well as for the assay and dissolution testing in its tablet dosage form. The results showed that first derivative technique can be used for enhancement of the data in case of low concentration range of DH (1-8 μg mL-1) in the three different pH dissolution media which were used to estimate the low drug concentrations dissolved at the early points in the biowaiver study. Furthermore, the results showed similarity in phosphate buffer pH 6.8 and dissimilarity in the other 2 pH media. The method was validated according to ICH guidelines and USP monograph for both assays (HCl of pH 1.2) and dissolution study in 3 pH media (HCl of pH 1.2, acetate buffer of pH 4.5 and phosphate buffer of pH 6.8). Finally, the assessment of the method greenness was done using two different assessment techniques: National Environmental Method Index label and Eco scale methods. Both techniques ascertained the greenness of the proposed method.

  20. Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use

    PubMed Central

    Rawas-Qalaji, Mutasem; Simons, Keith J.

    2018-01-01

    Epinephrine is a life-saving treatment in anaphylaxis. In community settings, a first-aid dose of epinephrine is injected from an auto-injector (EAI). Needle phobia highly contributes to EAI underuse, leading to fatalities—especially in children. A novel rapidly-disintegrating sublingual tablet (RDST) of epinephrine was developed in our laboratory as a potential alternative dosage form. The aim of this study was to evaluate the sublingual bioavailability of epinephrine 30 mg as a potential pediatric dose incorporated in our novel taste-masked RDST in comparison with intramuscular (IM) epinephrine 0.15 mg from EAI, the recommended and only available dosage form for children in community settings. We studied the rate and extent of epinephrine absorption in our validated rabbit model (n = 5) using a cross-over design. The positive control was IM epinephrine 0.15 mg from an EpiPen Jr®. The negative control was a placebo RDST. Tablets were placed under the tongue for 2 min. Blood samples were collected at frequent intervals and epinephrine concentrations were measured using HPLC with electrochemical detection. The mean ± SEM maximum plasma concentration (Cmax) of 16.7 ± 1.9 ng/mL at peak time (Tmax) of 21 min after sublingual epinephrine 30 mg did not differ significantly (p > 0.05) from the Cmax of 18.8 ± 1.9 ng/mL at a Tmax of 36 min after IM epinephrine 0.15 mg. The Cmax of both doses was significantly higher than the Cmax of 7.5 ± 1.7 ng/mL of endogenous epinephrine after placebo. These taste-masked RDSTs containing a 30 mg dose of epinephrine have the potential to be used as an easy-to-carry, palatable, non-invasive treatment for anaphylactic episodes for children in community settings. PMID:29439456

  1. Chemometrics-assisted spectrophotometric green method for correcting interferences in biowaiver studies: Application to assay and dissolution profiling study of donepezil hydrochloride tablets.

    PubMed

    Korany, Mohamed A; Mahgoub, Hoda; Haggag, Rim S; Ragab, Marwa A A; Elmallah, Osama A

    2018-06-15

    A green, simple and cost effective chemometric UV-Vis spectrophotometric method has been developed and validated for correcting interferences that arise during conducting biowaiver studies. Chemometric manipulation has been done for enhancing the results of direct absorbance, resulting from very low concentrations (high incidence of background noise interference) of earlier points in the dissolution timing in case of dissolution profile using first and second derivative (D1 & D2) methods and their corresponding Fourier function convoluted methods (D1/FF& D2/FF). The method applied for biowaiver study of Donepezil Hydrochloride (DH) as a representative model was done by comparing two different dosage forms containing 5mg DH per tablet as an application of a developed chemometric method for correcting interferences as well as for the assay and dissolution testing in its tablet dosage form. The results showed that first derivative technique can be used for enhancement of the data in case of low concentration range of DH (1-8μgmL -1 ) in the three different pH dissolution media which were used to estimate the low drug concentrations dissolved at the early points in the biowaiver study. Furthermore, the results showed similarity in phosphate buffer pH6.8 and dissimilarity in the other 2pH media. The method was validated according to ICH guidelines and USP monograph for both assays (HCl of pH1.2) and dissolution study in 3pH media (HCl of pH1.2, acetate buffer of pH4.5 and phosphate buffer of pH6.8). Finally, the assessment of the method greenness was done using two different assessment techniques: National Environmental Method Index label and Eco scale methods. Both techniques ascertained the greenness of the proposed method. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Development and validation of a discriminating in vitro dissolution method for a poorly soluble drug, olmesartan medoxomil: comparison between commercial tablets.

    PubMed

    Bajerski, Lisiane; Rossi, Rochele Cassanta; Dias, Carolina Lupi; Bergold, Ana Maria; Fröehlich, Pedro Eduardo

    2010-06-01

    A dissolution test for tablets containing 40 mg of olmesartan medoxomil (OLM) was developed and validated using both LC-UV and UV methods. After evaluation of the sink condition, dissolution medium, and stability of the drug, the method was validated using USP apparatus 2, 50 rpm rotation speed, and 900 ml of deaerated H(2)O + 0.5% sodium lauryl sulfate (w/v) at pH 6.8 (adjusted with 18% phosphoric acid) as the dissolution medium. The model-independent method using difference factor (f(1)) and similarity factor (f(2)), model-dependent method, and dissolution efficiency were employed to compare dissolution profiles. The kinetic parameters of drug release were also investigated. The obtained results provided adequate dissolution profiles. The developed dissolution test was validated according to international guidelines. Since there is no monograph for this drug in tablets, the dissolution method presented here can be used as a quality control test for OLM in this dosage form, especially in a batch to batch evaluation.

  3. Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol.

    PubMed

    Kaialy, Waseem; Khan, Usman; Mawlud, Shadan

    2016-08-20

    Mannitol is a pharmaceutical excipient that is receiving increased popularity in solid dosage forms. The aim of this study was to provide comparative evaluation on the effect of mannitol concentration on the physicochemical, mechanical, and pharmaceutical properties of lyophilised mannitol. The results showed that the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol powders are strong functions of mannitol concentration. By decreasing mannitol concentration, the true density, bulk density, cohesivity, flowability, netcharge-to-mass ratio, and relative degree of crystallinity of LM were decreased, whereas the breakability, size distribution, and size homogeneity of lyophilised mannitol particles were increased. The mechanical properties of lyophilised mannitol tablets improved with decreasing mannitol concentration. The use of lyophilised mannitol has profoundly improved the dissolution rate of indomethacin from tablets in comparison to commercial mannitol. This improvement exhibited an increasing trend with decreasing mannitol concentration. In conclusion, mannitols lyophilised from lower concentrations are more desirable in tableting than mannitols from higher concentrations due to their better mechanical and dissolution properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Basics of Compounding: 3D Printing--Pharmacy Applications, Part 1.

    PubMed

    Allen, Loyd V

    2017-01-01

    Three-dimensional printing quickly became a standard tool in the automotive, aerospace, and consumer goods industries and, recently, has begun gaining traction in pharmaceutical manufacturing. 3D printing has steadily grown, introducing a new element into dosage form development, and has received a boost with U.S. Food and Drug Administration (FDA) approval of the 3D-printed orodispersible tablet, Spritam (levetiracetam). This part 1 of a 3-part article introduces 3D printing and its application to pharmacy. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  5. Brand versus generic dispensing trend for ciprofloxacin 500 mg, levofloxacin 500 mg, and moxifloxacin 400 mg (oral dosage forms) among pharmacies of Karachi, Pakistan.

    PubMed

    Zehra, Fatima; Naqvi, Atta Abbas; Tasneem, Sumbul; Ahmad, Rizwan; Ahmad, Niyaz; Shamsi, Adnan Zia; Asghar, Naqiya Ali; Khan, Ghufran Ullah

    2017-01-01

    Pakistan spends 0.7% of its gross domestic product on health. The public sector health-care system provides services to 22% of population thus paving the way for a dominant private sector. Patients in Pakistan mostly pay their medical expenses directly, and 64% of the health expenditures are borne by the household. Expenditure on medicine constitutes 43% of the total household expenditure. A quantitative cross-sectional study was conducted in Karachi, Pakistan, for a month. It was aimed at gathering response from different pharmacies to understand the brand versus generic dispensing trend of ciprofloxacin 500 mg, levofloxacin 500 mg, and moxifloxacin 400 mg oral dosage forms. The study employed convenience sampling and used a survey checklist. The data gathered was entered in SPSS version 22. The mean price per tablet for ciprofloxacin brand and generic was reported at Pakistani Rupees (PKR) 48.44 and PKR 26.85, respectively. The trend for dispensing ciprofloxacin highlighted a split in the market between brand (51%) and generic (49%). For levofloxacin brand and generic, the price per tablet was reported at PKR 36.50 and PKR 36.15 respectively, and despite same price, the market was dominated by generic levofloxacin (92%). Due to a price difference between brand and generic moxifloxacin, i.e., PKR 129.44 and PKR 71.91, respectively, the market was mostly occupied by the generic form (75%). Pricing mechanism must be revisited, and the authorities should take stern actions against any illegitimate price hike. The surging burden of drug expenditure on poorer sections of the society must be addressed by the government on an urgent basis.

  6. Drug delivery systems with modified release for systemic and biophase bioavailability.

    PubMed

    Leucuta, Sorin E

    2012-11-01

    This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

  7. Spectrophotometric Methods for Simultaneous Determination of Sofosbuvir and Ledipasvir (HARVONI Tablet): Comparative Study with Two Generic Products.

    PubMed

    Abo-Talib, Nisreen F; El-Ghobashy, Mohamed R; Tammam, Marwa H

    2017-07-01

    Sofosbuvir and ledipasvir are the first drugs in a combination pill to treat chronic hepatitis C virus. Simple, sensitive, and rapid spectrophotometric methods are presented for the determination of sofosbuvir and ledipasvir in their combined dosage form. These methods were based on direct measurement of ledipasvir at 333 nm (due to the lack of interference of sofosbuvir) over a concentration range of 4.0-14.0 µg/mL, with a mean recovery of 100.78 ± 0.64%. Sofosbuvir was determined, without prior separation, by third-derivative values at 281 nm; derivative ratio values at 265.8 nm utilizing 5.0 µg/mL ledipasvir as a divisor; the ratio difference method using values at 270 and 250 nm using 5.0 µg/mL ledipasvir as a divisor; and the ratio subtraction method using values at 261 nm. These methods were found to be linear for sofosbuvir over a concentration range of 5.0-35.0 µg/mL. The suggested methods were validated according to International Conference on Harmonization guidelines. Statistical analysis of the results showed no significant difference between the proposed methods and the manufacturer's LC method of determination with respect to accuracy and precision. These methods were used to compare the equivalence of an innovator drug dosage form and two generic drug dosage forms of the same strength.

  8. A Validated Stability Indicating RP-HPLC Method for the Determination of Emtricitabine, Tenofovir Disoproxil Fumarate, Elvitegravir and Cobicistat in Pharmaceutical Dosage Form

    PubMed Central

    Runja, Chinnalalaiah; Ravi Kumar, Pigili; Avanapu, Srinivasa Rao

    2016-01-01

    A new simple, rapid stability indicating assay method has been developed and validated for the determination of emtricitabine, tenofovir disoproxil fumarate, elvitegravir and cobicistat using reverse-phase high-performance liquid chromatography in their pharmaceutical dosage form. The chromatographic separation was performed on an ODS column (250 × 4.6 mm, 5 µm) using mobile phase A (potassium dihydrogen orthophosphate, pH adjusted to 2.5) and mobile phase B (acetonitrile) in the ratio of 55:45% v/v at a flow rate of 1 mL/min. The analytes were detected at 250 nm. The method was found to be linear in the concentration range of 2–12 µg/mL for EMT, 3–18 µg/mL for TNDF, 1.5–9 µg/mL for ELV and COB, with the coefficient value (R2) of >0.9990. The accuracy was measured via recovery studies and found to be acceptable, and the percentage recoveries were found in the range of 99.93–100.08 ± 0.5%. Forced degradation studies were also conducted, and the drugs were subjected to various stress conditions such as acid hydrolysis, base hydrolysis, oxidative, photolytic and thermal degradation. The proposed method was successfully validated and applied for the quantitative estimation of these drugs in both bulk and tablet dosage forms. PMID:26865655

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

    NASA Astrophysics Data System (ADS)

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

    2018-02-01

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

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

    PubMed

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

    2010-05-01

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

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

    PubMed

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

    2013-01-01

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

  12. Cost implication of irrational prescribing of chloroquine in Lagos State general hospitals.

    PubMed

    Aina, Bolajoko A; Tayo, Fola; Taylor, Ogori

    2008-02-01

    A major share of the hospital budget is spent on drugs. Irrational use of these drugs is a waste of financial and human resources that could have been deployed for another use within the hospital setting especially in cases where such drugs are provided free to patients. Also there is increased morbidity and progression of severity with irrational use. The objective of this study was to determine the irrational use of chloroquine and the subsequent cost implications in Lagos State general hospitals. A retrospective study period of one year (January to December, 2000) was selected. A total of 18,781 prescription forms of "Free Eko Malaria" were sampled for children and adults from all the Lagos State general hospitals. Drug costs in each prescription form were identified. Cost effectiveness analysis of chloroquine tablet and intramuscular injection was undertaken. The average cost of medicine per prescription was 132.071 ($1.03) which should have been 94.22 ($0.73) if prescribed rationally. The total cost of prescriptions for malaria under study was 2,480,425.00 ($19,348.09). About 68% {(1,679,444.00) ($13,100.19)} of the total cost was lost to irrational prescribing. This is a waste of scarce resources. When the prescriptions were differentiated into the different dosage forms prescribed, the prescriptions containing intramuscular injections only had over 90% of the cost lost to irrational prescribing. Cost effectiveness analysis showed that chloroquine tablet was 17 times more cost effective than chloroquine injection (intramuscular) from a health care system perspective while it was 14 times more cost effective from a patient perspective. There is waste of scarce resources with irrational dispensing of drugs and these resources could have been deployed to other uses or areas within the hospitals. The tablet chloroquine was more cost effective than injection chloroquine (intramuscular). Increasing the cost of tablets, decreasing effectiveness of tablets, decreasing the cost of injections and increasing the effectiveness of injections did not change the cost effectiveness conclusion.

  13. Evaluating bioequivalence of meloxicam tablets: is in-vitro dissolution test overdiscriminating?

    PubMed

    Jin, Chan; Zhao, Chenyao; Shen, Dachao; Dong, Wenxiang; Liu, Hongzhuo; He, Zhonggui

    2018-02-01

    The aim of the study was to assess the impact of the differences in dissolution profiles of meloxicam tablets on the in-vivo bioavailability parameters after oral administration. Compare in-vitro dissolution testing in the recommended media to evaluate in-vivo bioequivalence outcomes for the Biopharmaceutics Classification System Class II weak acidic drugs. Nine Beagle dogs received a single oral administration of each formulation (7.5 mg) in a three-way crossover design. The dissolution of meloxicam from both test products showed marked differences with that from the reference tablet in pH 1.0, 4.5 and 6.8 media at 50 or 75 rpm. Both formulations exhibiting slow or fast dissolution were then compared with the reference product for in-vivo bioequivalence study. Both products were bioequivalent with the reference tablet in either extent or rate of oral absorption. It indicated that the dissolution profiles which discriminated between the formulations in vitro did not accurately predict the in-vivo bioequivalence outcomes. Comparative dissolution profiles using similarity factor (f 2 ) in the recommended media should be relaxed to fulfil the requirements for the development, scale-up and postapproval changes to immediate release oral solid dosage forms of meloxicam. © 2017 Royal Pharmaceutical Society.

  14. Co-Processed Chitin-Mannitol as a New Excipient for Oro-Dispersible Tablets

    PubMed Central

    Daraghmeh, Nidal; Chowdhry, Babur Z.; Leharne, Stephen A.; Al Omari, Mahmoud M. H.; Badwan, Adnan A.

    2015-01-01

    This study describes the preparation, characterization and performance of a novel excipient for use in oro-dispersible tablets (ODT). The excipient (Cop–CM) consists of chitin and mannitol. The excipient with optimal physicochemical properties was obtained at a chitin: mannitol ratio of 2:8 (w/w) and produced by roll compaction (RC). Differential scanning calorimetry (DSC), Fourier transform-Infrared (FT-IR), X-ray powder diffraction (XRPD) and scanning electron microscope (SEM) techniques were used to characterize Cop–CM, in addition to characterization of its powder and ODT dosage form. The effect of particle size distribution of Cop–CM was investigated and found to have no significant influence on the overall tablet physical properties. The compressibility parameter (a) for Cop–CM was calculated from a Kawakita plot and found to be higher (0.661) than that of mannitol (0.576) due to the presence of the highly compressible chitin (0.818). Montelukast sodium and domperidone ODTs produced, using Cop–CM, displayed excellent physicochemical properties. The exceptional binding, fast wetting and superdisintegration properties of Cop–CM, in comparison with commercially available co-processed ODT excipients, results in a unique multifunctional base which can successfully be used in the formulation of oro-dispersible and fast immediate release tablets. PMID:25830680

  15. 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.

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

    PubMed

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

    2015-07-15

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

  17. Ultrasound-assisted powder-coating technique to improve content uniformity of low-dose solid dosage forms.

    PubMed

    Genina, Natalja; Räikkönen, Heikki; Antikainen, Osmo; Heinämäki, Jyrki; Yliruusi, Jouko

    2010-09-01

    An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium phosphate, producing a uniform drug layer on the particle surfaces. It was possible to regulate the amount of API in the treated powder. The thickness of the API layer on the surface of the MCC particles increased near linearly as the number of coating cycles increased, allowing a precise control of the drug content. The tablets (n = 950) prepared from the coated powder showed significantly improved weight and content uniformity in comparison with the reference tablets compressed from a physical binary powder mixture. This was due to the coated formulation remaining uniform during the entire tabletting process, whereas the physical mixture of the powders was subject to segregation. In conclusion, the ultrasound-assisted technique presented here is an effective tool for homogeneous drug coating of powders of irregular particle shape and broad particle size distribution, improving content uniformity of low-dose API in tablets, and consequently, ensuring the safe delivery of a potent active substance to patients.

  18. Three different spectrophotometric methods manipulating ratio spectra for determination of binary mixture of Amlodipine and Atorvastatin

    NASA Astrophysics Data System (ADS)

    Darwish, Hany W.; Hassan, Said A.; Salem, Maissa Y.; El-Zeiny, Badr A.

    2011-12-01

    Three simple, specific, accurate and precise spectrophotometric methods manipulating ratio spectra are developed for the simultaneous determination of Amlodipine besylate (AM) and Atorvastatin calcium (AT) in tablet dosage forms. The first method is first derivative of the ratio spectra ( 1DD), the second is ratio subtraction and the third is the method of mean centering of ratio spectra. The calibration curve is linear over the concentration range of 3-40 and 8-32 μg/ml for AM and AT, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and they are applied to commercial pharmaceutical preparation of the subjected drugs. Standard deviation is <1.5 in the assay of raw materials and tablets. Methods are validated as per ICH guidelines and accuracy, precision, repeatability and robustness are found to be within the acceptable limit.

  19. [Hemostatic and analgesic effect of Gonghuan Zhixue Tablet on mice].

    PubMed

    Fu, Ling-Mei; You, Zhao-Ling; Lei, Lei; Wen, Le-Xi; Chen, Huan-Ming

    2004-03-01

    To explore the hemostatic and analgesic effect of Gonghuan Zhixue Tablet (GHZXT) on mice and to produce experimental evidence for exploiting new drug for endometrorrhagia caused by Cu-intrauterine contraceptive device (Cu-IUD). Compared with 6-aminocaproic acid and notoginseng, the effects of GHZXT on clotting and bleeding time of mice with capillary method and severed tail were investigated; and compared with aspirin, the analgesic effects of GHZXT on mice were investigated with hot plate and torsive body method. The clotting time of mice was remarkably shortened with a rising of the dosage of GHZXT and the difference between each therapeutic group and distilled water group was remarkable. As compared with distilled water group, the bleeding time of each dosage group of GHZXT was obviously shortened; and each dosage of GHZXT could prolong the time of pain reaction to hot plate and decrease the degree of torsive body of the mice. Pharmacological experiment has proved that GHZXT has evident hemostatic and analgesic function.

  20. Medication Errors in Patients with Enteral Feeding Tubes in the Intensive Care Unit.

    PubMed

    Sohrevardi, Seyed Mojtaba; Jarahzadeh, Mohammad Hossein; Mirzaei, Ehsan; Mirjalili, Mahtabalsadat; Tafti, Arefeh Dehghani; Heydari, Behrooz

    2017-01-01

    Most patients admitted to Intensive Care Units (ICU) have problems in using oral medication or ingesting solid forms of drugs. Selecting the most suitable dosage form in such patients is a challenge. The current study was conducted to assess the frequency and types of errors of oral medication administration in patients with enteral feeding tubes or suffering swallowing problems. A cross-sectional study was performed in the ICU of Shahid Sadoughi Hospital, Yazd, Iran. Patients were assessed for the incidence and types of medication errors occurring in the process of preparation and administration of oral medicines. Ninety-four patients were involved in this study and 10,250 administrations were observed. Totally, 4753 errors occurred among the studied patients. The most commonly used drugs were pantoprazole tablet, piracetam syrup, and losartan tablet. A total of 128 different types of drugs and nine different oral pharmaceutical preparations were prescribed for the patients. Forty-one (35.34%) out of 116 different solid drugs (except effervescent tablets and powders) could be substituted by liquid or injectable forms. The most common error was the wrong time of administration. Errors of wrong dose preparation and administration accounted for 24.04% and 25.31% of all errors, respectively. In this study, at least three-fourth of the patients experienced medication errors. The occurrence of these errors can greatly impair the quality of the patients' pharmacotherapy, and more attention should be paid to this issue.

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

    PubMed

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

    1998-01-02

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

  2. Synchrotron Radiation Microcomputed Tomography Guided Chromatographic Analysis for Displaying the Material Distribution in Tablets.

    PubMed

    Zhang, Liu; Wu, Li; Wang, Caifen; Zhang, Guoqing; Yu, Lin; Li, Haiyan; Maharjan, Abi; Tang, Yan; He, Dunwei; York, Peter; Sun, Huimin; Yin, Xianzhen; Zhang, Jiwen; Sun, Lixin

    2018-03-06

    One unusual and challenging scientific field that has received only cursory attention to date is the three-dimensional (3D) microstructure and spatial distribution of drug(s) and formulation materials in solid dosage forms. This study aims to provide deeper insight into the relationships between the microstructure of multiple-unit pellet system (MUPS) tablets and the spatial distribution of the active pharmaceutical ingredient (API) and excipients to facilitate the design of quantitative models for drug delivery systems. Synchrotron radiation X-ray microcomputed tomography (SR-μCT) was established as a 3D structure elucidation technique, which, in conjunction with liquid chromatography coupled to mass spectrometry (LC-MS) or liquid chromatography with evaporative light-scattering detector (LC-ELSD) enables chemical analysis of tablets. On the basis of the specific interior construction of theophylline MUPS tablets, the spatial distribution of materials was acquired by quantifying microregion samples that had been validated by SR-μCT for their locations in the MUPS tablets. The 3D structure of the MUPS tablets was catalogued as three structural domains: a matrix layer (ML), a protective cushion layer (PCL), and pellets (PL). Compared with the components in the ML, components in the PL had a larger proportion of theophylline, sucrose, and diethyl phthalate and a smaller proportion of lactose and sodium lauryl sulfate, whereas glyceryl monostearate was found to account for a large portion of the PCL. Microstructural characterization-guided zonal chemical determination represents a new approach for quality assessment and the development of drug delivery systems with in-depth insight into their constituent layers on a new scale.

  3. 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.

  4. Simultaneous Determination of Miconazole Nitrate and Metronidazole in Different Pharmaceutical Dosage Forms by Gas Chromatography and Flame Ionization Detector (GC-FID).

    PubMed

    Ashour, Safwan; Kattan, Nuha

    2010-03-01

    A simple, rapid and precise gas chromatographic method has been developed for the simultaneous determination of miconazole nitrate (MIZ) and metronidazole (MNZ) in tablets and ovules, using a capillary column AE.SE-54 (15 m × 0.53 mm, i.d.) and nitrogen as a carrier gas at a flow rate of 9 mL min(-1). The oven temperature was programmed at 140°C for 3 min, with a rise of 40°C min(-1) up to 180°C (held for 2 min) and then increased to a final temperature of 250°C. The injector and detector port temperatures were maintained at 260°C. Detection was carried out using flame ionization detector. Results of assay and recovery studies were statistically evaluated for its accuracy and precision. The retention times were about 3.50 and 12.90 min for MNZ and MIZ, respectively. Linearity ranges were 50.0-6030.0 and 62.5-2000.0 μg mL(-1) for MNZ and MIZ, with limit of detection values of 2.5 and 3.1 μg mL(-1), respectively. Correlation coefficients (R(2)) of the regression equations were greater than 0.999 in all cases. No interference from any components of pharmaceutical dosage forms or degradation products was observed. According to the validation results, the proposed method was found to be specific, accurate, precise and could be applied to the simultaneous quantitative analysis of MIZ and MNZ in tablets and ovules.

  5. An innovative validated spectrofluorimetric method for determination of Lisinopril in presence of hydrochlorothiazide; application to content uniformity testing

    NASA Astrophysics Data System (ADS)

    Derayea, Sayed M.; Badr El-din, Khalid M.; Mohammed, Fatma F.

    2018-01-01

    A new sensitive and discriminating spectrofluorimetric method has been developed and validated for determination of Lisinopril, one of the angiotensin converting enzyme inhibitors, in its pure bulk form and pharmaceutical tablets. The reaction of Lisinopril with ethylacetoacetate and formaldehyde in acidic buffered medium (pH 3.8) has yielded a pale yellow product that exhibited a high fluorescence measured at 438 nm after excitation at 350 nm. All the experimental parameters affecting the formation and stability of the produced fluorophore were carefully investigated and optimized to give the maximum sensitivity. The fluorescence intensity was directly proportional to the drug concentration in the range of 0.5-4.5 μg/mL with a limit of detection equal to 0.16 μg/mL. The method was successfully applied in the analysis of the commercially available pharmaceutical tablets containing the single drug or its binary mixtures with Hydrochlorothiazide. Furthermore, the developed procedure was adapted for studying the content uniformity test of some dosage forms containing the cited drug.

  6. Continuous wavelet transforms for the simultaneous quantitative analysis and dissolution testing of lamivudine-zidovudine tablets.

    PubMed

    Dinç, Erdal; Özdemir, Nurten; Üstündağ, Özgür; Tilkan, Müşerref Günseli

    2013-01-01

    Dissolution testing has a very vital importance for a quality control test and prediction of the in vivo behavior of the oral dosage formulation. This requires the use of a powerful analytical method to get reliable, accurate and precise results for the dissolution experiments. In this context, new signal processing approaches, continuous wavelet transforms (CWTs) were improved for the simultaneous quantitative estimation and dissolution testing of lamivudine (LAM) and zidovudine (ZID) in a tablet dosage form. The CWT approaches are based on the application of the continuous wavelet functions to the absorption spectra-data vectors of LAM and ZID in the wavelet domain. After applying many wavelet functions, the families consisting of Mexican hat wavelet with the scaling factor a=256, Symlets wavelet with the scaling factor a=512 and the order of 5 and Daubechies wavelet at the scale factor a=450 and the order of 10 were found to be suitable for the quantitative determination of the mentioned drugs. These wavelet applications were named as mexh-CWT, sym5-CWT and db10-CWT methods. Calibration graphs for LAM and ZID in the working range of 2.0-50.0 µg/mL and 2.0-60.0 µg/mL were obtained measuring the mexh-CWT, sym5-CWT and db10-CWT amplitudes at the wavelength points corresponding to zero crossing points. The validity and applicability of the improved mexh-CWT, sym5-CWT and db10-CWT approaches was carried out by the analysis of the synthetic mixtures containing the analyzed drugs. Simultaneous determination of LAM and ZID in tablets was accomplished by the proposed CWT methods and their dissolution profiles were graphically explored.

  7. 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.

  8. 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

  9. Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets.

    PubMed

    Sadia, Muzna; Sośnicka, Agata; Arafat, Basel; Isreb, Abdullah; Ahmed, Waqar; Kelarakis, Antonios; Alhnan, Mohamed A

    2016-11-20

    This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Physical stability and recrystallization kinetics of amorphous ibipinabant drug product by fourier transform raman spectroscopy.

    PubMed

    Sinclair, Wayne; Leane, Michael; Clarke, Graham; Dennis, Andrew; Tobyn, Mike; Timmins, Peter

    2011-11-01

    The solid-state physical stability and recrystallization kinetics during storage stability are described for an amorphous solid dispersed drug substance, ibipinabant, at a low concentration (1.0%, w/w) in a solid oral dosage form (tablet). The recrystallization behavior of the amorphous ibipinabant-polyvinylpyrrolidone solid dispersion in the tablet product was characterized by Fourier transform (FT) Raman spectroscopy. A partial least-square analysis used for multivariate calibration based on Raman spectra was developed and validated to detect less than 5% (w/w) of the crystalline form (equivalent to less than 0.05% of the total mass of the tablet). The method provided reliable and highly accurate predictive crystallinity assessments after exposure to a variety of stability storage conditions. It was determined that exposure to moisture had a significant impact on the crystallinity of amorphous ibipinabant. The information provided by the method has potential utility for predictive physical stability assessments. Dissolution testing demonstrated that the predicted crystallinity had a direct correlation with this physical property of the drug product. Recrystallization kinetics was measured using FT Raman spectroscopy for the solid dispersion from the tablet product stored at controlled temperature and relative humidity. The measurements were evaluated by application of the Johnson-Mehl-Avrami (JMA) kinetic model to determine recrystallization rate constants and Avrami exponent (n = 2). The analysis showed that the JMA equation could describe the process very well, and indicated that the recrystallization kinetics observed was a two-step process with an induction period (nucleation) followed by rod-like crystal growth. Copyright © 2011 Wiley-Liss, Inc.

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

    PubMed Central

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

    2016-01-01

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

  12. Evaluation of Marbofloxacin in Beagle Dogs After Oral Dosing: Preclinical Safety Evaluation and Comparative Pharmacokinetics of Two Different Tablets

    PubMed Central

    Lei, Zhixin; Liu, Qianying; Yang, Bing; Khaliq, Haseeb; Ahmed, Saeed; Fan, Bowen; Cao, Jiyue; He, Qigai

    2018-01-01

    The current study evaluates a tested marbofloxacin tablet (MBT) (Petsen), in terms of bioavailability and pharmacokinetics (PK) in a comparison of the commercialized and standard tablet (Marbocyl) in beagle dogs. Four different bacterial species were selected for the determination of the minimal inhibitory concentration (MIC) against marbofloxacin (MBF). Target animal safety studies were conducted with a wide spectrum of dosages of Petsen. Pharmacokinetics and bioavailability of Petsen were observed after the oral administration of a recommended dosage of 2 mg/kg. The MIC90 of MBF against Staphylococcus aureus, Escherichia coli, Pasteurella multocida, and Streptococcus were 2.00, 4.00, 0.25, and 0.50 μg/ml, respectively. These results showed that the MBT has an expected antimicrobial activity in vitro. The main parameters of t1/2β, Clb, AUC0−∞, Cmax, and Ke were 22.14 h, 0.15 L/h, 13.27 μg.h/ml, 0.95 μg/ml, 0.09 h−1, and 16.47 h, 0.14 L/h, 14.10 μg.h/ml, 0.97 μg/ml, 0.11 h−1 after the orally administrated Petsen and Marbocyl, while no biologically significant changes and toxicological significance have been found by their comparison. These findings indicate that the Petsen had a slow elimination, high bioavailability and kinetically similar to the commercialized Marbocyl. Furthermore, no statistically significant differences were distinguished on the continuous gradient dosages of 2, 6, and 10 mg/kg in the term of the clinical presentation. The present study results displayed that the tested MBT (Petsen) was safe, with limited toxicity, which was similar to the commercialized tablet (Marbocyl), could provide an alternative MBT as a veterinary medicine in beagle dogs. PMID:29692725

  13. A level A in vitro/in vivo correlation in fasted and fed states using different methods: applied to solid immediate release oral dosage form.

    PubMed

    Souliman, Sabah; Blanquet, Stéphanie; Beyssac, Eric; Cardot, Jean-Michel

    2006-01-01

    The first purpose of this study was to simulate the impact of food intake on drug release and absorption in vivo using a novel in vitro system which mimics the gastro-intestinal (GI) tract in man. The drug studied was acetaminophen in the form of immediate release (IR) tablets. The second purpose was to establish a level A in vitro/in vivo correlation that could predict the bioavailability of a drug instead of using difficult, time-consuming and expensive in vivo bioequivalence studies. The artificial digestive system was used to estimate the availability of acetaminophen IR tablets for absorption in fasted and fed states. The same study was performed in vivo under similar conditions. A comparison study was carried out between the classical and the novel methods to estimate the efficacy of the new in vitro system to simulate the influence of food on drug release and absorption in vivo. A level A in vitro/in vivo correlation was established with a correlation coefficient of 0.9128 and 0.9984 in the fasted and fed states, respectively. Compared to USP II method, the novel in vitro model demonstrated a high level of efficacy in mimicking the behaviour of acetaminophen IR tablets in vivo in fasted and fed states.

  14. Novel platens to measure the hardness of a pentagonal shaped tablet.

    PubMed

    Malladi, Jaya; Sidik, Kurex; Wu, Sutan; McCann, Ryan; Dougherty, Jeffrey; Parab, Prakash; Carragher, Thomas

    2017-03-01

    Tablet hardness, a measure of the breaking force of a tablet, is based on numerous factors. These include the shape of the tablet and the mode of the application of force. For instance, when a pentagonal-shaped tablet was tested with a traditional hardness tester with flat platens, there was a large variation in hardness measurements. This was due to the propensity of vertices of the tablet to crush, referred to as an "improper break". This article describes a novel approach to measure the hardness of pentagonal-shaped tablets using modified platens. The modified platens have more uniform loading than flat platens. This is because they reduce loading on the vertex of the pentagon and apply forces on tablet edges to generate reproducible tablet fracture. The robustness of modified platens was assessed using a series of studies, which included feasibility and Gauge Repeatability & Reproducibility (R&R) studies. A key finding was that improper breaks, generated frequently with a traditional hardness tester using flat platens, were eliminated. The Gauge R&R study revealed that the tablets tested with novel platens generated consistent values in hardness measurements, independent of batch, hardness level, and day of testing, operator and tablet dosage strength.

  15. Recent progress in continuous and semi-continuous processing of solid oral dosage forms: a review.

    PubMed

    Teżyk, Michał; Milanowski, Bartłomiej; Ernst, Andrzej; Lulek, Janina

    2016-08-01

    Continuous processing is an innovative production concept well known and successfully used in other industries for many years. The modern pharmaceutical industry is facing the challenge of transition from a traditional manufacturing approach based on batch-wise production to a continuous manufacturing model. The aim of this article is to present technological progress in manufacturing based on continuous and semi-continuous processing of the solid oral dosage forms. Single unit processes possessing an alternative processing pathway to batch-wise technology or, with some modification, an altered approach that may run continuously, and are thus able to seamlessly switch to continuous manufacturing are briefly presented. Furthermore, the concept of semi-continuous processing is discussed. Subsequently, more sophisticated production systems created by coupling single unit processes and comprising all the steps of production, from powder to final dosage form, were reviewed. Finally, attempts of end-to-end production approach, meaning the linking of continuous synthesis of API from intermediates with the production of final dosage form, are described. There are a growing number of scientific articles showing an increasing interest in changing the approach to the production of pharmaceuticals in recent years. Numerous scientific publications are a source of information on the progress of knowledge and achievements of continuous processing. These works often deal with issues of how to modify or replace the unit processes in order to enable seamlessly switching them into continuous processing. A growing number of research papers concentrate on integrated continuous manufacturing lines in which the production concept of "from powder to tablet" is realized. Four main domains are under investigation: influence of process parameters on intermediates or final dosage forms properties, implementation of process analytical tools, control-managing system responsible for keeping continuous materials flow through the whole manufacturing process and the development of new computational methods to assess or simulate these new manufacturing techniques. The attempt to connect the primary and secondary production steps proves that development of continuously operating lines is possible. A mind-set change is needed to be able to face, and fully assess, the advantages and disadvantages of switching from batch to continuous mode production.

  16. A Stability Indicating HPLC Method for the Determination of Fluvoxamine in Pharmaceutical Dosage Forms.

    PubMed

    Souri, Effat; Donyayi, Hassan; Khaniha, Reza Ahmad; Barazandeh Tehrani, Maliheh

    2015-01-01

    Fluvoxamine maleate is a selective serotonin reuptake inhibitor, which is used for the treatment of different types of depressive disorders. In the present study, a stability indicating HPLC method was developed and validated for the determination of fluvoxamine maleate. The chromatographic separation was carried out using a Nova-Pak CN column and a mixture of K2HPO4 50 mM (pH 7.0) and acetonitrile (60: 40, v/v) as the mobile phase. Target compounds were detected using a UV detector set at 235 nm. The developed method was linear over the concentration range of 1-80 μg/ml with acceptable precision (CV values < 2.0%) and accuracy (error values < 1.6%). The degradation studies showed that fluvoxamine maleate is relatively unstable under acidic, basic and oxidative conditions and also when exposed to UV radiation. On the other hand, the bulk powder of fluvoxamine maleate was relatively stable when exposed to visible light or heat. The proposed method was successfully applied for the determination of active ingredient of fluvoxamine dosage form without any interference from tablet excipients.

  17. 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.

  18. Statistical Considerations Concerning Dissimilar Regulatory Requirements for Dissolution Similarity Assessment. The Example of Immediate-Release Dosage Forms.

    PubMed

    Jasińska-Stroschein, Magdalena; Kurczewska, Urszula; Orszulak-Michalak, Daria

    2017-05-01

    When performing in vitro dissolution testing, especially in the area of biowaivers, it is necessary to follow regulatory guidelines to minimize the risk of an unsafe or ineffective product being approved. The present study examines model-independent and model-dependent methods of comparing dissolution profiles based on various compared and contrasted international guidelines. Dissolution profiles for immediate release solid oral dosage forms were generated. The test material comprised tablets containing several substances, with at least 85% of the labeled amount dissolved within 15 min, 20-30 min, or 45 min. Dissolution profile similarity can vary with regard to the following criteria: time point selection (including the last time point), coefficient of variation, and statistical method selection. Variation between regulatory guidance and statistical methods can raise methodological questions and result potentially in a different outcome when reporting dissolution profile testing. The harmonization of existing guidelines would address existing problems concerning the interpretation of regulatory recommendations and research findings. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form

    PubMed Central

    Suganthi, A.; John, Sofiya; Ravi, T. K.

    2008-01-01

    A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75±0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form. PMID:20046748

  20. Zein as a Pharmaceutical Excipient in Oral Solid Dosage Forms: State of the Art and Future Perspectives.

    PubMed

    Berardi, Alberto; Bisharat, Lorina; AlKhatib, Hatim S; Cespi, Marco

    2018-05-07

    Zein is the main storage protein of corn and it has several industrial applications. Mainly in the last 10-15 years, zein has emerged as a potential pharmaceutical excipient with unique features. Zein is a natural, biocompatible and biodegradable material produced from renewable sources. It is insoluble, yet due to its amphiphilic nature, it has self-assembling properties, which have been exploited for the formation of micromicroparticle and nanoparticle and films. Moreover, zein can hydrate so it has been used in swellable matrices for controlled drug release. Other pharmaceutical applications of zein in oral drug delivery include its incorporation in solid dispersions of poorly soluble drugs and in colonic drug delivery systems. This review describes the features of zein significant for its use as a pharmaceutical excipient for oral drug delivery, and it summaries the literature relevant to macroscopic zein-based oral dosage forms, i.e. tablets, capsules, beads and powders. Particular attention is paid to the most novel formulations and applications of zein. Moreover, gaps of knowledge as well as possible venues for future investigations on zein are highlighted.

  1. Validation of an ultra-fast UPLC-UV method for the separation of antituberculosis tablets.

    PubMed

    Nguyen, Dao T-T; Guillarme, Davy; Rudaz, Serge; Veuthey, Jean-Luc

    2008-04-01

    A simple method using ultra performance LC (UPLC) coupled with UV detection was developed and validated for the determination of antituberculosis drugs in combined dosage form, i. e. isoniazid (ISN), pyrazinamide (PYR) and rifampicin (RIF). Drugs were separated on a short column (2.1 mm x 50 mm) packed with 1.7 mum particles, using an elution gradient procedure. At 30 degrees C, less than 2 min was necessary for the complete separation of the three antituberculosis drugs, while the original USP method was performed in 15 min. Further improvements were obtained with the combination of UPLC and high temperature (up to 90 degrees C), namely HT-UPLC, which allows the application of higher mobile phase flow rates. Therefore, the separation of ISN, PYR and RIF was performed in less than 1 min. After validation (selectivity, trueness, precision and accuracy), both methods (UPLC and HT-UPLC) have proven suitable for the routine quality control analysis of antituberculosis drugs in combined dosage form. Additionally, a large number of samples per day can be analysed due to the short analysis times.

  2. Semi-quantitative prediction of a multiple API solid dosage form with a combination of vibrational spectroscopy methods.

    PubMed

    Hertrampf, A; Sousa, R M; Menezes, J C; Herdling, T

    2016-05-30

    Quality control (QC) in the pharmaceutical industry is a key activity in ensuring medicines have the required quality, safety and efficacy for their intended use. QC departments at pharmaceutical companies are responsible for all release testing of final products but also all incoming raw materials. Near-infrared spectroscopy (NIRS) and Raman spectroscopy are important techniques for fast and accurate identification and qualification of pharmaceutical samples. Tablets containing two different active pharmaceutical ingredients (API) [bisoprolol, hydrochlorothiazide] in different commercially available dosages were analysed using Raman- and NIR Spectroscopy. The goal was to define multivariate models based on each vibrational spectroscopy to discriminate between different dosages (identity) and predict their dosage (semi-quantitative). Furthermore the combination of spectroscopic techniques was investigated. Therefore, two different multiblock techniques based on PLS have been applied: multiblock PLS (MB-PLS) and sequential-orthogonalised PLS (SO-PLS). NIRS showed better results compared to Raman spectroscopy for both identification and quantitation. The multiblock techniques investigated showed that each spectroscopy contains information not present or captured with the other spectroscopic technique, thus demonstrating that there is a potential benefit in their combined use for both identification and quantitation purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Industrial Applications of Terahertz Imaging

    NASA Astrophysics Data System (ADS)

    Zeitler, J. Axel; Shen, Yao-Chun

    This chapter gives a concise overview of potential industrial applications for terahertz imaging that have been reported over the past decade with a discussion of the major advantages and limitations of each approach. In the second half of the chapter we discuss in more detail how terahertz imaging can be used to investigate the microstructure of pharmaceutical dosage forms. A particular focus in this context is the nondestructive measurement of the coating thickness of polymer coated tablets, both by means of high resolution offline imaging in research and development as well as for in-line quality control during production.

  4. PAT-tools for process control in pharmaceutical film coating applications.

    PubMed

    Knop, Klaus; Kleinebudde, Peter

    2013-12-05

    Recent development of analytical techniques to monitor the coating process of pharmaceutical solid dosage forms such as pellets and tablets are described. The progress from off- or at-line measurements to on- or in-line applications is shown for the spectroscopic methods near infrared (NIR) and Raman spectroscopy as well as for terahertz pulsed imaging (TPI) and image analysis. The common goal of all these methods is to control or at least to monitor the coating process and/or to estimate the coating end point through timely measurements. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. A Stability-Indicating HPLC Method for the Determination of Memantine Hydrochloride in Dosage Forms through Derivatization with 1-Fluoro-2,4-dinitrobenzene

    PubMed Central

    Jalalizadeh, Hassan; Raei, Mahdi; Tafti, Razieh Fallah; Farsam, Hassan; Kebriaeezadeh, Abbas; Souri, Effat

    2014-01-01

    Memantine is chemically a tricyclic amine and is used for Parkinson’s disease and movement disorders. Although several HPLC methods with different derivatization reagents have been developed for the determination of memantine in biological fluids, there are some complications which limit the use of these methods in routine analysis of memantine in in vitro tests. We established a simple, sensitive, precise, and accurate HPLC method for the quantification of memantine in dosage forms. Pre-column derivatization of memantine was performed with 1-fluoro-2,4-dinitrobenzene and the reaction product was separated on a Nova-Pak C18 column. A mixture of acetonitrile and sodium dihydrogenphosphate (pH 2.5; 0.05 M) (70: 30, v/v) was used as the mobile phase. UV detection was performed at 360 nm. Forced degradation studies were performed on a powdered tablet sample of memantine hydro-chloride using acidic (0.1 M hydrochloric acid), basic (0.1 M sodium hydroxide), oxidative (10% hydrogen peroxide), thermal (105°C), photolytic, and humidity conditions. Good linearity (r2=0.999) was obtained over the range of 1–12 μg mL−1 of memantine hydrochloride with acceptable within-day and between-day precision values in the range of 0.05–0.95%. The proposed method was used for the assay determination and dissolution rate study of memantine dosage forms with excellent specificity. PMID:24959398

  6. Determination of Verapamil HCl in Pharmaceutical Preparations by a Fluorescent Nano Probe Based on CdTe/CdS/ZnS Quantum Dots

    PubMed Central

    Muhammad, Sohail; Xu, Guanhong; Wei, Fangdi; Ma, Yujie; Ma, Yunsu; Song, Yueyue; Shi, Menglan; Xu, Xiaoman; Cen, Yao; Hu, Qin

    2017-01-01

    An analytical technique based on fluorescence quenching of CdTe/CdS/ZnS quantum dots (QDs) was developed to quantify verapamil in commercially available preparations. Various reaction parameters were optimized and the method developed was validated. One way analysis of variance (ANOVA) and post hoc tests at a 5% significance level were performed to justify the significance of the variation in observations. The linear range of the verapamil concentration was 0.25–5 µg/mL while the limit of detection was 20 µg/mL. Recovery and relative standard deviations were not more than ±10% of the actual amount and <5.9%, respectively. Foreign materials, common metal ions and pharmaceutical excipients of dosage forms caused little interference. To verify the application of the analytical method, the quantity of verapamil in commercially available dosage forms was measured. Verapamil content in the tablets and injections was not more than ±10% of the stated amount and it conformed to the specifications of both the British and the United States pharmacopoeias. In the case of statistical analysis, p-value was <0.05 in almost all levels of all parameters except for the optimized level of system. It can be concluded from the results that the designed method is simple, reliable, cost effective, selective, rapid and sensitive enough to be used for quantitative measurement of the verapamil HCl in dosage forms for quality control purposes. PMID:29084166

  7. Influence of Geometry on the Drug Release Profiles of Stereolithographic (SLA) 3D-Printed Tablets.

    PubMed

    Martinez, Pamela Robles; Goyanes, Alvaro; Basit, Abdul W; Gaisford, Simon

    2018-06-08

    Additive manufacturing (3D printing) permits the fabrication of tablets in shapes unattainable by powder compaction, and so the effects of geometry on drug release behavior is easily assessed. Here, tablets (printlets) comprising of paracetamol dispersed in polyethylene glycol were printed using stereolithographic 3D printing. A number of geometric shapes were produced (cube, disc, pyramid, sphere and torus) with either constant surface area (SA) or constant surface area/volume ratio (SA/V). Dissolution testing showed that printlets with constant SA/V ratio released drug at the same rate, while those with constant SA released drug at different rates. A series of tori with increasing SA/V ratio (from 0.5 to 2.4) were printed, and it was found that dissolution rate increased as the SA/V ratio increased. The data show that printlets can be fabricated in multiple shapes and that dissolution performance can be maintained if the SA/V ratio is constant or that dissolution performance of printlets can be fine-tuned by varying SA/V ratio. The results suggest that 3D printing is therefore a suitable manufacturing method for personalized dosage forms.

  8. Latent variable modeling to analyze the effects of process parameters on the dissolution of paracetamol tablet

    PubMed Central

    Sun, Fei; Xu, Bing; Zhang, Yi; Dai, Shengyun; Shi, Xinyuan; Qiao, Yanjiang

    2017-01-01

    ABSTRACT The dissolution is one of the critical quality attributes (CQAs) of oral solid dosage forms because it relates to the absorption of drug. In this paper, the influence of raw materials, granules and process parameters on the dissolution of paracetamol tablet was analyzed using latent variable modeling methods. The variability in raw materials and granules was understood based on the principle component analysis (PCA), respectively. A multi-block partial least squares (MBPLS) model was used to determine the critical factors affecting the dissolution. The results showed that the binder amount, the post granulation time, the API content in granule, the fill depth and the punch tip separation distance were the critical factors with variable importance in the projection (VIP) values larger than 1. The importance of each unit of the whole process was also ranked using the block importance in the projection (BIP) index. It was concluded that latent variable models (LVMs) were very useful tools to extract information from the available data and improve the understanding on dissolution behavior of paracetamol tablet. The obtained LVMs were also helpful to propose the process design space and to design control strategies in the further research. PMID:27689242

  9. Formulation and optimization of fast dissolving intraoral drug delivery system for clobazam using response surface methodology

    PubMed Central

    Bala, Rajni; Khanna, Sushil; Pawar, Pravin K.

    2013-01-01

    Clobazam is a newer 1,5-benzodiazepine used for the treatment of epilepsy. It is better tolerated and less sedating than other benzodiazepines. Absorption of the drug can be impacted by oral fast dissolving dosage form; this may have implications for epilepsy in pediatrics and those having difficulty in swallowing tablets/capsules resulting in improved patient compliance. The purpose of the present investigation was to formulate and optimize clobazam oro-dissolving tablets by direct compression method using response surface methodology (RSM). Oro-dispersible tablets of clobazam were prepared by direct compression method using crospovidone (2-6%) as a superdisintegrant, microcrystalline cellulose (MCC) (20-40%) was used as diluents along with directly compressible mannitol to enhance mouth feel. A 32 full factorial design was applied to investigate the combined effect of two formulation variables: amount of crospovidone and MCC over the independent variables disintegration time, wetting time and percent drug release. Disintegration time showed by all formulations was found to be in the range of 24.3-193 s based on evaluation parameters the formulation containing 6% of crospovidone and 30% of MCC showed promising performance against all other formulations. The results demonstrated that the RSM could efficiently be applied for the formulation of clobazam oro-dispersible tablets; therefore, constitute an advance in the management of epileptic attacks. PMID:24083203

  10. Using Computational Fluid Dynamics to Compare Shear Rate and Turbulence in the TIM-Automated Gastric Compartment With USP Apparatus II.

    PubMed

    Hopgood, Matthew; Reynolds, Gavin; Barker, Richard

    2018-03-30

    We use computational fluid dynamics to compare the shear rate and turbulence in an advanced in vitro gastric model (TIMagc) during its simulation of fasted state Migrating Motor Complex phases I and II, with the United States Pharmacopeia paddle dissolution apparatus II (USPII). A specific focus is placed on how shear rate in these apparatus affects erosion-based solid oral dosage forms. The study finds that tablet surface shear rates in TIMagc are strongly time dependant and fluctuate between 0.001 and 360 s -1 . In USPII, tablet surface shear rates are approximately constant for a given paddle speed and increase linearly from 9 s -1 to 36 s -1 as the paddle speed is increased from 25 to 100 rpm. A strong linear relationship is observed between tablet surface shear rate and tablet erosion rate in USPII, whereas TIMagc shows highly variable behavior. The flow regimes present in each apparatus are compared to in vivo predictions using Reynolds number analysis. Reynolds numbers for flow in TIMagc lie predominantly within the predicted in vivo bounds (0.01-30), whereas Reynolds numbers for flow in USPII lie above the predicted upper bound when operating with paddle speeds as low as 25 rpm (33). Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Mechanistic study of the azithromycin dosage-form-dependent food effect.

    PubMed

    Curatolo, William; Foulds, George; Labadie, Robert

    2010-07-01

    Azithromycin capsules are known to exhibit a negative food effect, manifest as a decrease in azithromycin bioavailability in the fed state. Azithromycin tablets are known to be bioequivalent to capsules in the fasted state, but do not exhibit a food effect. In the present study, the involvement of gastric degradation of azithromycin to des-cladinose azithromycin (DCA) has been investigated as a possible mechanism for the observed capsule food effect. Healthy volunteers were dosed with azithromycin tablets and capsules, fasted and fed, in a four-way randomized crossover study. Serum levels of DCA were measured as a function of time post-dose. Natural log-transformed PK parameters were statistically analyzed using an ANOVA model appropriate for the study design. When capsules were dosed to fed subjects, the systemic AUC for DCA was 243% of the value observed after fasted-state dosing, and the DCA C(max) was 270% of the value observed after fasted-state dosing. When azithromycin tablets were dosed in the fasted and fed states, there was no significant difference in systemic DCA. Gastric degradation of azithromycin to DCA is the likely mechanism for the observed negative food effect observed for azithromycin capsules. This effect is not observed for tablets. These observations suggest that azithromycin capsules exhibit slow and/or delayed disintegration in the fed stomach, resulting in extended gastric residence and degradation of a portion of the gastrically retained azithromycin.

  12. Comparative in vivo mucoadhesion studies of thiomer formulations using magnetic resonance imaging and fluorescence detection.

    PubMed

    Albrecht, K; Greindl, M; Kremser, C; Wolf, C; Debbage, P; Bernkop-Schnürch, A

    2006-09-28

    The aim of this study was to compare different oral delivery systems based on the thiolated polymer polycarbophil-cysteine (PCP-Cys) and to provide evidence for the validity of the hypothesis that unhydrated polymers provide better mucoadhesion in vivo. To achieve dry polymer application, a new, experimental dosage form named Eutex (made of Eudragit L100-55 and latex) capsule has been developed. Magnetic resonance imaging was used to localize the point of release of the thiolated polymer from the application forms via the positive magnetic resonance signal from a gadolinium complex (Gd-DTPA). In vivo mucoadhesion was determined by ascertaining the residence time of the fluorescence-tagged thiomer on intestinal mucosa after 3 h. Results showed that in comparison to conventional application forms the Eutex capsules led to 1.9-fold higher mucoadhesive properties of PCP-Cys when compared to application with a conventional enteric-coated capsule, and to 1.4-fold higher mucoadhesion when compared to administration with an enteric-coated tablet of the thiomer. The findings of this study should contribute to the understanding of mucoadhesion and mucoadhesion influencing parameters in vivo and should therefore be of considerable interest for the development of future mucoadhesive oral drug delivery dosage forms.

  13. 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 multi-functionality of ARG as filler, binder and disintegrant for directly compressed tablets. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Single dose sublingual testosterone and oral sildenafil vs. a dual route/dual release fixed dose combination tablet: a pharmacokinetic comparison

    PubMed Central

    van Rooij, Kim; de Leede, Leo; Frijlink, Henderik W.; Koppeschaar, Hans P. F.; Olivier, Berend; Tuiten, Adriaan

    2016-01-01

    Aim The aim was to compare the pharmacokinetic profiles of two formulations of a combination drug product containing 0.5 mg testosterone and 50 mg sildenafil for female sexual interest/arousal disorder. The prototype (formulation 1) consists of a testosterone solution for sublingual administration and a sildenafil tablet that is administered 2.5 h later. The dual route/dual release fixed dose combination tablet (formulation 2) employs a sublingual and an oral route for systemic uptake. This tablet has an inner core of sildenafil with a polymeric time delay coating and an outer polymeric coating containing testosterone. It was designed to increase dosing practicality and decrease potential temporal non‐adherence through circumventing the relatively complex temporal dosing scheme. Methods Twelve healthy premenopausal subjects received both formulations randomly on separate days. Blood was sampled frequently to determine the pharmacokinetics of free testosterone, total testosterone, dihydrotestosterone, sildenafil and N‐desmethyl‐sildenafil. Results Formulation 2 had a higher maximum concentration (C max) for testosterone, 8.06 ng ml–1 (95% confidence interval [CI] 6.84, 9.28) and higher area under the plasma concentration–time curve (AUC), 7.69 ng ml–1 h (95% CI 6.22, 9.16) than formulation 1, 5.66 ng ml–1 (95% CI 4.63, 6.69) and 5.12 ng ml–1 h (95% CI 4.51, 5.73), respectively. Formulation 2 had a lower C max for sildenafil, 173 ng ml–1 (95% CI 126, 220) and a lower AUC, 476 ng ml–1 h (95% CI 401, 551) than formulation 1, 268 ng ml–1 (95% CI 188, 348) and 577 ng ml–1 h (95% CI 462, 692), respectively. Formulation 2 released sildenafil after 2.75 h (95% CI 2.40, 3.10). Conclusions The dual route/dual release fixed dose combination tablet fulfilled its design criteria and is considered suitable for further clinical testing. What is Already Known about this Subject Female sexual interest/arousal disorder (FSIAD) is a significant problem impacting psychological well‐being, but the pharmacotherapeutic options for this problem are lacking.The combined, on‐demand, sublingual administration of low dose sublingual testosterone and oral administration of sildenafil is a novel pharmacotherapeutic option under development for FSIAD.In proof‐of‐concept trials, these compounds were successfully administered via different dosage forms (sublingual and oral) at different time points (separated by 2.5 h) because of their markedly different pharmacokinetic–pharmacodynamic profiles. For future larger scale studies and the clinical practice, this raises obvious adherence issues. What this Study Adds A newly developed dual route/dual release fixed dose combination tablet containing testosterone and sildenafil mimics the pharmacokinetic profile of these components when they are administered as different dosage forms, 2.5 h apart.This combination tablet is a suitable final pharmaceutical drug product that will be used in future studies. PMID:26804967

  15. 21 CFR 520.1341 - Megestrol acetate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the postponement of estrus and the alleviation of false pregnancy. (2) It is administered orally... false pregnancy, 1 milligram per pound of body weight per day for 8 days. (3) Full dosage regimen must...

  16. Effects of food on a gastrically degraded drug: azithromycin fast-dissolving gelatin capsules and HPMC capsules.

    PubMed

    Curatolo, William; Liu, Ping; Johnson, Barbara A; Hausberger, Angela; Quan, Ernest; Vendola, Thomas; Vatsaraj, Neha; Foulds, George; Vincent, John; Chandra, Richa

    2011-07-01

    Commercial azithromycin gelatin capsules (Zithromax®) are known to be bioequivalent to commercial azithromycin tablets (Zithromax®) when dosed in the fasted state. These capsules exhibit a reduced bioavailability when dosed in the fed state, while tablets do not. This gelatin capsule negative food effect was previously proposed to be due to slow and/or delayed capsule disintegration in the fed stomach, resulting in extended exposure of the drug to gastric acid, leading to degradation to des-cladinose-azithromycin (DCA). Azithromycin gelatin capsules were formulated with "superdisintegrants" to provide fast-dissolving capsules, and HPMC capsule shells were substituted for gelatin capsule shells, in an effort to eliminate the food effect. Healthy volunteers were dosed with these dosage forms under fasted and fed conditions; pharmacokinetics were evaluated. DCA pharmacokinetics were also evaluated for the HPMC capsule subjects. In vitro disintegration of azithromycin HPMC capsules in media containing food was evaluated and compared with commercial tablets and commercial gelatin capsules. When the two fast-dissolving capsule formulations were dosed to fed subjects, the azithromycin AUC was 38.9% and 52.1% lower than after fasted-state dosing. When HPMC capsules were dosed to fed subjects, the azithromycin AUC was 65.5% lower than after fasted-state dosing. For HPMC capsules, the absolute fasting-state to fed-state decrease in azithromycin AUC (on a molar basis) was similar to the increase in DCA AUC. In vitro capsule disintegration studies revealed extended disintegration times for commercial azithromycin gelatin capsules and HPMC capsules in media containing the liquid foods milk and Ensure®. Interaction of azithromycin gelatin and HPMC capsules with food results in slowed disintegration in vitro and decreased bioavailability in vivo. Concurrent measurement of serum azithromycin and the acid-degradation product DCA demonstrates that the loss of azithromycin bioavailability in the fed state is largely (and probably entirely) due to gastric degradation to DCA. Capsules can provide a useful and elegant dosage form for almost all drugs, but may result in a negative food effect for drugs as acid-labile as azithromycin.

  17. A new, rapid, stability-indicating UPLC method for separation and determination of impurities in amlodipine besylate, valsartan and hydrochlorothiazide in their combined tablet dosage form.

    PubMed

    Vojta, Jiří; Jedlička, Aleš; Coufal, Pavel; Janečková, Lucie

    2015-05-10

    A new rapid stability-indicating UPLC method for separation and determination of impurities in amlodipine besylate, valsartan and hydrochlorothiazide in their combined tablet dosage form was developed. The separation of Ph. Eur. related substances of amlodipine besylate (A, B, D, E, F, G), hydrochlorothiazide (A, B, C), valsartan (B, C), two other valsartan impurities (S)-2-(N-{[2'-cyanobiphenyl-4-yl]methyl}pentanamido)-3-methylbutanoic acid and (S)-3-methyl-2-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methylamino}butanoic acid and several unknown impurities was achieved by reversed phase liquid chromatography with UV detection. The detection wavelengths were set as follows: 225nm for valsartan, its impurities and for the impurity D of amlodipine, 271nm for hydrochlorothiazide and its impurities and 360nm for amlodipine and its impurities except for impurity D. Zorbax Eclipse C8 RRHD (100mm×3.0mm, 1.8μm) was used as a separation column and the analytes were eluted within 11min by a programmed gradient mixture of 0.01M phosphate buffer pH 2.5 and acetonitrile. The method was successfully validated in accordance to the International Conference of Harmonization (ICH) guidelines for amlodipine besylate and its impurity D, valsartan and its impurity C and hydrochlorothiazide and its impurities A, B and C. The triple-combined tablets were exposed to thermal, higher humidity, acid, alkaline, oxidative and photolytic stress conditions. Stressed samples were analyzed by the proposed method. All the significant degradation products and impurities were satisfactory separated from each other and from the principal peaks of drug substances. The peak purity test complied for peaks of amlodipine, valsartan and hydrochlorothiazide in all the stressed samples and indicated no co-elution of degradation products. The method was found to be precise, linear, accurate, sensitive, specific, robust and stability-indicating and could be used as a routine purity test method for amlodipine besylate, valsartan, hydrochlorothiazide and their pharmaceutical combinations. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2017-09-28

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

  19. Development of validated stability indicating assay method for simultaneous estimation of metformin hydrochloride and vildagliptin by RP-HPLC.

    PubMed

    Satheeshkumar, N; Pradeepkumar, M; Shanthikumar, S; Rao, V J

    2014-03-01

    A simple, precise and stability-indicating HPLC method was developed and validated for the simultaneous determination of metformin hydrochloride (MET) and vildagliptin (VLG) in pharmaceutical dosage forms. The method involves use of easily available inexpensive laboratory reagents. The separation was achieved on Grace Cyano column (250 mm×4.6 mm) 5 µm with isocratic flow. The mobile phase was pumped at a flow rate of 1.0 mL/min, consisted of 25 mM ammonium bicarbonate buffer and acetonitrile (65:35, v/v). The UV detection was carried out at 207 nm. A linear response was observed over the concentration range of 25-125 µg/mL for MET and 50-250 µg/mL for VLG respectively. Limit of detection and limit of quantification for MET were 0.36 µg/mL and 1.22 µg/mL, and for VLG were 0.75 µg/mL and 2.51 µg/mL respectively. The method was successfully validated in accordance to ICH guidelines acceptance criteria for specificity, linearity, accuracy, precision, robustness, and system suitability. Individual drugs (MET and VLG) were exposed to thermal, photolytic, hydrolytic and oxidative stress conditions. The resultant stressed samples were analyzed by the proposed method. The method gave high resolution among the degradation products and the analytes. The peak purity of analyte peak in the stressed samples was confirmed by photo diode array detector. The proposed method was successfully applied for the quantitative analysis of MET and VLG in tablet dosage form, which will help to improve quality control and contribute to stability studies of pharmaceutical tablets containing these drugs. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Purity, adulteration and price of drugs bought on-line versus off-line in the Netherlands.

    PubMed

    van der Gouwe, Daan; Brunt, Tibor M; van Laar, Margriet; van der Pol, Peggy

    2017-04-01

    On-line drug markets flourish and consumers have high expectations of on-line quality and drug value. The aim of this study was to (i) describe on-line drug purchases and (ii) compare on-line with off-line purchased drugs regarding purity, adulteration and price. Comparison of laboratory analyses of 32 663 drug consumer samples (stimulants and hallucinogens) purchased between January 2013 and January 2016, 928 of which were bought on-line. The Netherlands. Primary outcome measures were (i) the percentage of samples purchased on-line and (ii) the chemical purity of powders (or dosage per tablet); adulteration; and the price per gram, blotter or tablet of drugs bought on-line compared with drugs bought off-line. The proportion of drug samples purchased on-line increased from 1.4% in 2013 to 4.1% in 2015. The frequency varied widely, from a maximum of 6% for controlled, traditional substances [ecstasy tablets, 3,4-methylenedioxy-methamphetamine (MDMA) powder, amphetamine powder, cocaine powder, 4-bromo-2,5-dimethoxyphenethylamine (2C-B) and lysergic acid diethylamide (LSD)] to more than a third for new psychoactive substances (NPS) [4-fluoroamphetamine (4-FA), 5/6-(2-aminopropyl)benzofuran (5/6-APB) and methoxetamine (MXE)]. There were no large differences in drug purity, yet small but statistically significant differences were found for 4-FA (on-line 59% versus off-line 52% purity for 4-FA on average, P = 0.001), MDMA powders (45 versus 61% purity for MDMA, P = 0.02), 2C-B tablets (21 versus 10 mg 2C-B/tablet dosage, P = 0.49) and ecstasy tablets (131 versus 121 mg MDMA/tablet dosage, P = 0.05). The proportion of adulterated samples purchased on-line and off-line did not differ, except for 4-FA powder, being less adulterated on-line (χ 2  = 8.3; P < 0.02). Drug prices were mainly higher on-line, ranging for various drugs from 10 to 23% higher than that of drugs purchased off-line (six of 10 substances: P < 0.05). Dutch drug users increasingly purchase drugs on-line: new psychoactive substances in particular. Purity and adulteration do not vary considerably between drugs purchased on-line and off-line for most substances, while on-line prices are mostly higher than off-line prices. © 2016 Society for the Study of Addiction.

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