Summary Workshop Report: Bioequivalence, Biopharmaceutics Classification System, and Beyond

Polli, James E.; Abrahamsson, Bertil; Yu, Lawrence X.; Amidon, Gordon L.; Baldoni, John; Cook, Jack; Fackler, Paul; Hartauer, Kerry J.; Johnston, Gordon; Krill, Steve L.; Lipper, Robert A.; Malick, Waseem; Shah, Vinod P.; Sun, Duxin; Winkle, Helen; Wu, Yunhui; Zhang, Hua

doi:10.1208/s12248-008-9040-9

Cited by 54 publications

(41 citation statements)

References 12 publications

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“…In this regard, the US Food and Drug Administration (FDA) currently allows biowaivers for BCS class I (highly soluble and highly permeable) drugs formulated in immediate release, rapidly dissolving drug products (2). Since the publication of the FDA Guidance on BCS in 2000, however, there has been continued interest in the possible extension of BCS-based biowaivers, particularly for class III drugs that exhibit high solubility and low permeability (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Impact of Osmotically Active Excipients on Bioavailability and Bioequivalence of BCS Class III Drugs

Chen

Sadrieh

2013

AAPS J

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Section: Introductionmentioning

confidence: 99%

Impact of Osmotically Active Excipients on Bioavailability and Bioequivalence of BCS Class III Drugs

Chen

Sadrieh

2013

AAPS J

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“…For BCS class III drugs, further studies are required before analyzing the possibility of biowaiving ER formulations of these drugs (65) or generic ER formulations of BCS class I drugs. However, we propose that under a deep case-specific analysis, biowaiving of ER of BCS class I drug formulations may be possible through customized DPC tests or by PT.…”

Section: Discussionmentioning

confidence: 99%

Statistical Comparison of Dissolution Profiles to Predict the Bioequivalence of Extended Release Formulations

Gómez-Mantilla

Schaefer

Casabó

et al. 2014

AAPS J

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Abstract. Appropriate setting of dissolution specification of extended release (ER) formulations should include precise definition of a multidimensional space of complex definition and interpretation, including limits in dissolution parameters, lag time (t-lag), variability, and goodness of fit. This study aimed to set dissolution specifications of ER by developing drug-specific dissolution profile comparison tests (DPC tests) that are able to detect differences in release profiles between ER formulations that represent a lack of bioequivalence (BE). Dissolution profiles of test formulations were simulated using the Weibull and Hill models. Differential equations based in vivo-in vitro correlation (IVIVC) models were used to simulate plasma concentrations. BE trial simulations were employed to find the formulations likely to be declared bioequivalent and nonbioequivalent (BE space). Customization of DPC tests was made by adjusting the delta of a recently described tolerated difference test (TDT) or the limits of rejection of f2. Drug k a (especially if k a is small), formulation lag time (t-lag), the number of subjects included in the BE studies, and the number of sampled time points in the DPC test were the factors that affected the most these setups of dissolution specifications. Another recently described DPC test, permutation test (PT), showed excellent statistical power. All the formulations declared as similar with PT were also bioequivalent. Similar case-specific studies may support the biowaiving of ER drug formulations based on customized DPC tests.

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“…When evaluating P eff data, one must first define the borderline for the low/high-permeability class membership; the completely absorbed β-blocker metoprolol is a widely used and acceptable marker for this purpose (3,33,34). However, as can be seen in Fig.…”

Section: Discussionmentioning

confidence: 99%

Regional-Dependent Intestinal Permeability and BCS Classification: Elucidation of pH-Related Complexity in Rats Using Pseudoephedrine

Fairstein

Swissa

Dahan

2013

AAPS J

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Abstract. Based on its lower Log P value relative to metoprolol, a marker for the low/high-permeability (P eff ) class boundary, pseudoephedrine was provisionally classified as BCS low-permeability compound. On the other hand, following oral administration, pseudoephedrine fraction dose absorbed (F abs ) and systemic bioavailability approaches 100%. This represents a challenge to the generally recognized P eff -F abs correlation. The purpose of this study was to elucidate the underlying mechanisms behind the confusion in pseudoephedrine's BCS classification. Pseudoephedrine's BCS solubility class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Pseudoephedrine was found to be unequivocally a high-solubility compound. All of the permeability studies revealed similar phenomenon; at any given intestinal segment/pH, the permeability of metoprolol was higher than that of pseudoephedrine, however, as the intestinal region becomes progressively distal, and the pH gradually increases, pseudoephedrine's permeability rises above that of metoprolol in the former segment. This unique permeability pattern likely explains pseudoephedrine's complete absorption. In conclusion, pseudoephedrine is a BCS Class I compound; no discrepancy between P eff and F abs is involved in its absorption. Rather, it reflects the complexity behind P eff when considering the whole of the intestine. We propose to allow high-permeability classification to drugs with P eff that matches/exceeds the low/high class benchmark anywhere throughout the intestinal tract and not restricted necessarily to the jejunum.

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Summary Workshop Report: Bioequivalence, Biopharmaceutics Classification System, and Beyond

Cited by 54 publications

References 12 publications

Impact of Osmotically Active Excipients on Bioavailability and Bioequivalence of BCS Class III Drugs

Impact of Osmotically Active Excipients on Bioavailability and Bioequivalence of BCS Class III Drugs

Statistical Comparison of Dissolution Profiles to Predict the Bioequivalence of Extended Release Formulations

Regional-Dependent Intestinal Permeability and BCS Classification: Elucidation of pH-Related Complexity in Rats Using Pseudoephedrine

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