Biowaiver extension potential to BCS Class III high solubility-low permeability drugs: Bridging evidence for metformin immediate-release tablet

Ching Ling Cheng, Lawrence X. Yu, Hwei Ling Lee, Chyun Yu Yang, Chang Sha Lue, Chen Hsi Chou

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

The biopharmaceutics classification system (BCS) allows biowaiver for rapid dissolving immediate-release (IR) products of Class I drugs (high solubility and high permeability). The possibility of extending biowaivers to Class III high solubility and low permeability drugs is currently under scrutiny. In vivo bioequivalence data of different formulations of Class III drugs would support such an extension. The objective of this work was to demonstrate the bioequivalence of two marketed IR tablet products of a Class III drug, metformin hydrochloride, that are rapidly dissolving and have similar in vitro dissolution profiles. The effect of race on the systemic exposure of metformin was also explored. A randomized, open-label, two-period crossover study was conducted in 12 healthy Chinese male volunteers. Each subject received a single-dose of 500 mg of each product after an overnight fasting. The plasma concentrations of metformin were followed for 24 h. No significant formulation effect was found for the bioequivalence metrics: areas under concentration-time curve (AUC0-t, AUC0-∞) and maximal concentration (Cmax). The 90% confidence intervals for the ratio of means were found within the acceptance range of 80-125% for the log-transformed data. Based on these results, it was concluded that the two IR products are bioequivalent. The pharmacokinetic parameters of metformin in Chinese for both products were similar and were in good agreement with those reported for metformin IR tablets in other ethnic populations. This study serves as an example for supporting biowaiver for BCS Class III drugs.

Original languageEnglish
Pages (from-to)297-304
Number of pages8
JournalEuropean Journal of Pharmaceutical Sciences
Volume22
Issue number4
DOIs
Publication statusPublished - 2004 Jul 1

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Biopharmaceutics
Metformin
Solubility
Tablets
Permeability
Therapeutic Equivalency
Pharmaceutical Preparations
Cross-Over Studies
Volunteers
Fasting
Pharmacokinetics
Confidence Intervals
Population

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

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abstract = "The biopharmaceutics classification system (BCS) allows biowaiver for rapid dissolving immediate-release (IR) products of Class I drugs (high solubility and high permeability). The possibility of extending biowaivers to Class III high solubility and low permeability drugs is currently under scrutiny. In vivo bioequivalence data of different formulations of Class III drugs would support such an extension. The objective of this work was to demonstrate the bioequivalence of two marketed IR tablet products of a Class III drug, metformin hydrochloride, that are rapidly dissolving and have similar in vitro dissolution profiles. The effect of race on the systemic exposure of metformin was also explored. A randomized, open-label, two-period crossover study was conducted in 12 healthy Chinese male volunteers. Each subject received a single-dose of 500 mg of each product after an overnight fasting. The plasma concentrations of metformin were followed for 24 h. No significant formulation effect was found for the bioequivalence metrics: areas under concentration-time curve (AUC0-t, AUC0-∞) and maximal concentration (Cmax). The 90{\%} confidence intervals for the ratio of means were found within the acceptance range of 80-125{\%} for the log-transformed data. Based on these results, it was concluded that the two IR products are bioequivalent. The pharmacokinetic parameters of metformin in Chinese for both products were similar and were in good agreement with those reported for metformin IR tablets in other ethnic populations. This study serves as an example for supporting biowaiver for BCS Class III drugs.",
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Biowaiver extension potential to BCS Class III high solubility-low permeability drugs : Bridging evidence for metformin immediate-release tablet. / Cheng, Ching Ling; Yu, Lawrence X.; Lee, Hwei Ling; Yang, Chyun Yu; Lue, Chang Sha; Chou, Chen Hsi.

In: European Journal of Pharmaceutical Sciences, Vol. 22, No. 4, 01.07.2004, p. 297-304.

Research output: Contribution to journalArticle

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