A review of in vitro and in vivo methods and their correlations to assess mouthfeel of solid 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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β-Cyclodextrin as an excipient in solid oral dosage forms: in vitro and in vivo evaluation of spray-dried diazepam-β-cyclodextrin products

International Journal of Pharmaceutics ◽

10.1016/0378-5173(89)90194-4 ◽

1989 ◽

Vol 51 (3) ◽

pp. 213-223 ◽

Cited By ~ 17

Author(s):

H.P.R. Bootsma ◽

H.W. Frijlink ◽

A. Eissens ◽

J.H. Proost ◽

H. Van Doorne ◽

...

Keyword(s):

Dosage Forms ◽

Oral Dosage ◽

In Vivo Evaluation ◽

Solid Oral Dosage Forms ◽

Oral Dosage Forms ◽

Spray Dried

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In Vitro Studies are Sometimes Better than Conventional Human Pharmacokinetic In Vivo Studies in Assessing Bioequivalence of Immediate-Release Solid Oral Dosage Forms

The AAPS Journal ◽

10.1208/s12248-008-9027-6 ◽

2008 ◽

Vol 10 (2) ◽

pp. 289-299 ◽

Cited By ~ 65

Author(s):

James E. Polli

Keyword(s):

Immediate Release ◽

Dosage Forms ◽

Oral Dosage ◽

In Vivo Studies ◽

Human Pharmacokinetic ◽

Solid Oral Dosage Forms ◽

Oral Dosage Forms ◽

Better Than

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Multi-Analytical Framework to Assess the In Vitro Swallowability of Solid Oral Dosage Forms Targeting Patient Acceptability and Adherence

Pharmaceutics ◽

10.3390/pharmaceutics13030411 ◽

2021 ◽

Vol 13 (3) ◽

pp. 411

Author(s):

Abdul Latif Ershad ◽

Ali Rajabi-Siahboomi ◽

Shahrzad Missaghi ◽

Daniel Kirby ◽

Afzal Rahman Mohammed

Keyword(s):

Hydroxypropyl Methylcellulose ◽

Analytical Framework ◽

Dosage Forms ◽

Oral Dosage ◽

Surface Erosion ◽

World Population ◽

Swallowing Problems ◽

Solid Oral Dosage Forms ◽

Oral Dosage Forms

A lack of effective intervention in addressing patient non-adherence and the acceptability of solid oral dosage forms combined with the clinical consequences of swallowing problems in an ageing world population highlight the need for developing methods to study the swallowability of tablets. Due to the absence of suitable techniques, this study developed various in vitro analytical tools to assess physical properties governing the swallowing process of tablets by mimicking static and dynamic stages of time-independent oral transitioning events. Non-anatomical models with oral mucosa-mimicking surfaces were developed to assess the swallowability of tablets; an SLA 3D printed in vitro oral apparatus derived the coefficient of sliding friction and a friction sledge for a modified tensometer measured the shear adhesion profile. Film coat hydration and in vitro wettability was evaluated using a high-speed recording camera that provided quantitative measurements of micro-thickness changes, simulating static in vivo tablet–mucosa oral processing stages with artificial saliva. In order to ascertain the discriminatory power and validate the multianalytical framework, a range of commonly available tablet coating solutions and new compositions developed in our lab were comparatively evaluated according to a quantitative swallowability index that describes the mathematical relationship between the critical physical forces governing swallowability. This study showed that the absence of a film coat significantly impeded the ease of tablet gliding properties and formed chalky residues caused by immediate tablet surface erosion. Novel gelatin- and λ-carrageenan-based film coats exhibited an enhanced lubricity, lesser resistance to tangential motion, and reduced stickiness than polyvinyl alcohol (PVA)–PEG graft copolymer, hydroxypropyl methylcellulose (HPMC), and PVA-coated tablets; however, Opadry® EZ possessed the lowest friction–adhesion profile at 1.53 a.u., with the lowest work of adhesion profile at 1.28 J/mm2. For the first time, the in vitro analytical framework in this study provides a fast, cost-effective, and repeatable swallowability ranking method to screen the in vitro swallowability of solid oral medicines in an effort to aid formulators and the pharmaceutical industry to develop easy-to-swallow formulations.

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