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Elucidating the Role of Dose in the Biopharmaceutics Classification of Drugs: The Concepts of Critical Dose, Effective In Vivo Solubility, and Dose-Dependent BCS

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Abstract

Purpose

To develop a dose dependent version of BCS and identify a critical dose after which the amount absorbed is independent from the dose.

Methods

We utilized a mathematical model of drug absorption in order to produce simulations of the fraction of dose absorbed (F) and the amount absorbed as function of the dose for the various classes of BCS and the marginal cases in between classes.

Results

Simulations based on the mathematical model of F versus dose produced patterns of a constant F throughout a wide range of doses for drugs of Classes I, II and III, justifying biowaiver claim. For Classes I and III the pattern of a constant F stops at a critical dose Dosecr after which the amount of drug absorbed, is independent from the dose. For doses higher than Dosecr, Class I drugs become Class II and Class III drugs become Class IV. Dosecr was used to define an in vivo effective solubility as Seff = Dosecr/250 ml. Literature data were used to support our simulation results.

Conclusions

A new biopharmaceutic classification of drugs is proposed, based on F, separating drugs into three regions, taking into account the dose, and Dosecr, while the regions for claiming biowaiver are clearly defined.

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Authors and Affiliations

  1. Laboratory of Biopharmaceutics & Pharmacokinetics Faculty of Pharmacy, National & Kapodistrian University of Athens, Athens, Greece

    Georgia Charkoftaki, Aristides Dokoumetzidis, Georgia Valsami & Panos Macheras

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  1. Georgia Charkoftaki
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  2. Aristides Dokoumetzidis
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  3. Georgia Valsami
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  4. Panos Macheras
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Correspondence to Panos Macheras.

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Charkoftaki, G., Dokoumetzidis, A., Valsami, G. et al. Elucidating the Role of Dose in the Biopharmaceutics Classification of Drugs: The Concepts of Critical Dose, Effective In Vivo Solubility, and Dose-Dependent BCS. Pharm Res 29, 3188–3198 (2012). https://doi.org/10.1007/s11095-012-0815-4

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