Bioavailability of the Common Cold Medicines in Jellies for Oral Administration

Jellies for oral administration have been suggested as alternative dosage forms to conventional tablets for improved palatability and compliances for pediatric and geriatric patients. To evaluate the effect of jelly formulation on the bioavailability of cold medicines, two types of jellies were prepared for a fixed-dose combination of acetaminophen (AAP), chlorpheniramine maleate (CPM), dextromethorphan hydrobromide (DMH), and dl-methylephedrine hydrochloride (MEH). Jelly-S and Jelly-H were fabricated using carrageenan and locust bean gum in the absence and presence of xanthan gum, respectively. In vitro dissolution and in vivo absorption of the four drugs in the jellies were compared with other conventional formulations, a syrup and two types of immediate-release (IR) tablets with different hardness, Tablet-S (15 kPa) and Tablet-H (20 kPa). All the formulations exhibited more than 80% dissolution rate within 2 h even though the syrup, Jelly-S, and Tablet-S showed higher 30-min dissolution compared to Jelly-H and Tablet-H. The dissolution rates from the jellies decreased with increasing pH, which resulted in the slowest dissolution in pH 6.8 compared to the syrup and IR tablets. When administered orally to beagle dogs, all five formulations were determined not to be bioequivalent. However, Jelly-S and Jelly-H showed 0.82–1.05 of the geometric mean ratios (GMRs) of AUC0-t for all four drugs compared to the syrup suggesting comparable absorption. In two IR tablets, GMRs of AUC0-t were in a range of 0.55–0.95 indicating a tendency of lower absorption than the syrup and jellies. In conclusion, jelly can be a patient-centered formulation with comparable bioavailability to syrup.

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Comparative in vitro Dissolution and in vivo Bioavailability of Diflunisal/Naproxen Fixed-Dose Combination Tablets and Concomitant Administration of Diflunisal and Naproxen in Healthy Adult Subjects

Drug Research ◽

10.1055/s-0033-1333768 ◽

2013 ◽

Vol 63 (03) ◽

pp. 150-158 ◽

Cited By ~ 2

Author(s):

S. Helmy ◽

H. El Bedaiwy

Keyword(s):

Healthy Adult ◽

Concomitant Administration ◽

Fixed Dose Combination ◽

In Vitro Dissolution ◽

Fixed Dose ◽

Dose Combination

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Development, Characterization and In Vivo Pharmacokinetic Assessment of Rectal Suppositories Containing Combination Antiretroviral Drugs for HIV Prevention

Pharmaceutics ◽

10.3390/pharmaceutics13081110 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1110

Author(s):

Kunal Jhunjhunwala ◽

Charles W. Dobard ◽

Sunita Sharma ◽

Natalia Makarova ◽

Angela Holder ◽

...

Keyword(s):

Hiv Prevention ◽

Antiretroviral Drugs ◽

Water Soluble ◽

Fixed Dose ◽

Receptive Anal Intercourse ◽

On Demand ◽

Dose Combination ◽

Rectal Suppositories

Receptive anal intercourse (RAI) contributes significantly to HIV acquisition underscoring the need to develop HIV prevention options for populations engaging in RAI practices. We explored the feasibility of formulating rectal suppositories with potent antiviral drugs for on-demand use. A fixed-dose combination of tenofovir (TFV) and elvitegravir (EVG) (40 mg each) was co-formulated in six different suppository bases (three fat- and three water-soluble). Fat-soluble witepsol H15 and water-soluble polyethylene glycol (PEG) based suppositories demonstrated favorable in vitro release and were advanced to assess in vivo pharmacokinetics following rectal administration in macaques. In vivo drug release profiles were similar for both suppository bases. Median concentrations of TFV and EVG detected in rectal fluids at 2 h were 1- and 2-logs higher than the in vitro IC50, respectively; TFV-diphosphate levels in rectal tissues met or exceeded those associated with high efficacy against rectal simian HIV (SHIV) exposure in macaques. Leveraging on these findings, a PEG-based suppository with a lower dose combination of tenofovir alafenamide (TAF) and EVG (8 mg each) was developed and found to achieve similar rectal drug exposures in macaques. This study establishes the utility of rectal suppositories as a promising on-demand strategy for HIV PrEP and supports their clinical development.

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In vitro dissolution method fitted to in vivo absorption profile of rivaroxaban immediate-release tablets applying in silico data

Drug Development and Industrial Pharmacy ◽

10.1080/03639045.2017.1411939 ◽

2017 ◽

Vol 44 (5) ◽

pp. 723-728 ◽

Cited By ~ 1

Author(s):

Nathalie R. Wingert ◽

Natália O. dos Santos ◽

Sarah C. Campanharo ◽

Elisa S. Simon ◽

Nadia M. Volpato ◽

...

Keyword(s):

In Silico ◽

Immediate Release ◽

In Vitro Dissolution ◽

Absorption Profile ◽

Dissolution Method ◽

In Vivo Absorption

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Requirements for Additional Strength Biowaivers for Modified Release Solid Oral Dosage Forms in International Pharmaceutical Regulators Programme Participating Regulators and Organisations: Differences and Commonalities

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps32260 ◽

2021 ◽

Vol 24 ◽

pp. 548-562

Author(s):

Matthias Shona Roost ◽

Henrike Potthast ◽

Chantal Walther ◽

Alfredo García-Arieta ◽

Ivana Abalos ◽

...

Keyword(s):

Immediate Release ◽

Dosage Forms ◽

Oral Dosage ◽

In Vitro Dissolution ◽

Quantitative Composition ◽

Modified Release ◽

Solid Oral Dosage Forms ◽

Oral Dosage Forms

This article describes an overview of waivers of in vivo bioequivalence studies for additional strengths in the context of the registration of modified release generic products and is a follow-up to the recent publication for the immediate release solid oral dosage forms. The current paper is based on a survey among the participating members of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Program (IPRP) regarding this topic. Most jurisdictions consider the extrapolation of bioequivalence results obtained with one (most sensitive) strength of a product series as less straightforward for modified release products than for immediate release products. There is consensus that modified release products should demonstrate bioequivalence not only in the fasted state but also in the fed state, but differences exist regarding the necessity of additional multiple dose studies. Fundamental differences between jurisdictions are revealed regarding requirements on the quantitative composition of different strengths and the differentiation of single and multiple unit dosage forms. Differences in terms of in vitro dissolution requirements are obvious, though these are mostly related to possible additional comparative investigations rather than regarding the need for product-specific methods. As with the requirements for immediate release products, harmonization of the various regulations for modified release products is highly desirable to conduct the appropriate studies from a scientific point of view, thus ensuring therapeutic equivalence.

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Crushed Tablets: Does the Administration of Food Vehicles and Thickened Fluids to Aid Medication Swallowing Alter Drug Release?

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j39w3v ◽

2014 ◽

Vol 17 (2) ◽

pp. 207 ◽

Cited By ~ 26

Author(s):

Yady Juliana Manrique-Torres ◽

Danielle J Lee ◽

Faiza Islam ◽

Lisa M Nissen ◽

Julie A.Y. Cichero ◽

...

Keyword(s):

Drug Release ◽

Orange Juice ◽

Immediate Release ◽

Drug Dissolution ◽

In Vitro Dissolution ◽

Simulated Gastric Fluid ◽

Drug Bioavailability ◽

Thickening Agents

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Evaluation of in vitro dissolution similarity of bisoprolol film-coated tablets based on Weibull modelling using MATLABTM simulation software

World Journal of Advanced Research and Reviews ◽

10.30574/wjarr.2021.10.1.0143 ◽

2021 ◽

Vol 10 (1) ◽

pp. 056-073

Author(s):

Ivana Mitrevska ◽

Hristijan Mickoski ◽

Katerina Brezovska ◽

Aneta Dimitrovska

Keyword(s):

Immediate Release ◽

Simulation Software ◽

In Vitro Dissolution ◽

Accurate Estimation ◽

Mathematical Function ◽

Medicinal Products ◽

Non Linear ◽

Linear Effects

The aim of this study was to compare the in vitro dissolution behaviour of reference (R) and generic-test (T) medicinal products with non-linear effects model. Mathematical function Weibull, was employed as basis for the non-linear effects model, coupled with MATLABTM simulation software to describe the release profile of the active substance. Medicinal products selected for the presented study include immediate-release tablets Concor 10 mg and Bisoprolol 10 mg, which belongs to BCS class 1 of biopharmaceutics classification system. The result from the study indicated that Weibull distribution function coupled with computer-based program is more useful for comparison of the dissolution profiles. This combined approach provides robust and informative results, with accurate estimation on the in vitro performance for the medicinal products and it’s the most suitable tool for prediction of in vivo behaviour of the medicinal product. In summary, we have employed Simulink graphical programming to design our system in a simulation environment.

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Comparative study of different meloxicam generic products with the brand product

Al Mustansiriyah Journal of Pharmaceutical Sciences ◽

10.32947/ajps.19.04.0424 ◽

2019 ◽

pp. 116-124

Keyword(s):

Immediate Release ◽

Generic Product ◽

In Vitro Dissolution ◽

Dissolution Profile ◽

Innovator Product ◽

Similarity Factor ◽

Generic Products ◽

Brand Product

This study aims to evaluate different products of meloxicam Table; Five meloxicam immediate-release generic products (15 mg Tables) were compared with the innovator, reference product, (Mobic®, Boehringer) to find the interchangeable product with the innovator product. Different physical tests were conducted including weight uniformity, thickness, diameter, hardness, friability and disintegration test. In addition, prediction of in-vivo behavior was assessed by measuring the dissolution profile of meloxicam for all the products. Similarity factor (f2) was calculated to compare between the dissolution profile of the generic products with the dissolution profile of innovator product. The results revealed that all the studied products are complied with the British Pharmacopoeia requirements. However, not all of them showed similar in-vitro profile to the brand product. Four out of five generic products, included in this study, showed similarity in dissolution profile to the brand one, which indicates possible bio-equivalency, with the advantages of money saving of using such generic products. One generic product showed similarity factor less than 50, which might give an indication that this generic product is not capable to be bioequivalent with the brand (innovator) product. Overall, this study can be considered an important applicable study that gives an indication about the in-vivo performance of different products. In addition, the study demonstrates the applicability of a simple in-vitro dissolution study as a surrogate way of assessing product bioavailability instead of an expensive and complicated in-vivo bioequivalent study.

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