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    Home > Medical News > Medical Research Articles > Talking about: The influence of BCS classification on the solubility, permeability and dissolution of API

    Talking about: The influence of BCS classification on the solubility, permeability and dissolution of API

    • Last Update: 2021-06-30
    • Source: Internet
    • Author: User
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           BCS classification introduction

           The human bioequivalence study (Bioequivalence, BE) is a means to prove the therapeutic equivalence between preparations

           In 1995, Amidon et al.
    [1] proposed the Biopharmaceutics Classification System (BCS) to classify drugs according to solubility and permeability, and use this to predict drug absorption in the body


           Prior to this, it is difficult to have a scientific theory that can be used as a basis to propose a bioequivalence exemption to regulatory agencies
    As the concept of BCS is put forward and continues to be demonstrated, more and more regulatory agencies have begun and accepted bioequivalence exemptions based on BCS


           In August 2000, the FDA issued guidelines for the application of BCS to the bioequivalence exemption for immediate-release solid oral dosage forms
    WHO released Technical Report Series No.
    937 in 2006, in which Annex 7 and Annex 8 introduced BCS-based bioequivalence exemptions, and EMA released bioequivalence research guidelines in 2010

    China also issued the "Guiding Principles for the Exemption of Human Bioequivalence Tests" (Announcement No.
    87 of 2016) in May 2016 [2]


           The BCS system is a scientific framework that classifies drugs according to their water solubility and intestinal permeability
    When it comes to the absorption rate and extent of the active pharmaceutical ingredient (Active Pharmaceutical Ingredient, hereinafter referred to as API) in oral solid common-release preparations, the BCS system mainly considers the following three key factors, namely: drug solubility (Solubility), intestinal tract Intestinal permeability and Dissolution


           Drug solubility (Solubility)

           The solubility of pharmaceutical preparations is measured by the highest dose of the drug.
    In the pH range of 1~7.
    5, the highest dose of the drug can be dissolved in no more than 250ml of water, which is defined as a high-solubility drug, otherwise it is defined as a low-solubility drug


           Intestinal permeability

           Membrane permeability of a drug is a comparison between oral drug preparations and the results of an intravenous reference dose or intestinal perfusion balance dose study.
    If the absorption of the drug in the intestine is not less than 90%, the drug is defined as high membrane permeability


           Dissolution of preparations (Dissolution)

           The dissolution of the preparation is a key factor that affects the absorption of the drug in the body.
    Generally, the solubility of BCSⅡ and BCSⅣ drugs is poor.
    Therefore, in the preparation process, some special preparation methods are usually considered to improve the dissolution of the drug in the body.


           According to the BCS classification system, drugs are divided into the following four categories:

           Category I: High Solubility- High Permeability

           Category II: Low Solubility-High Permeability (Low Solubility-High Permeability)

           Category III: High Solubility-Low Permeability (High Solubility-Low Permeability)

           Category IV: Low Solubility-Low Permeability

           BCS-based bioequivalence exemption

           The therapeutic equivalence between preparations generally requires in vivo bioequivalence studies to demonstrate, but if in vitro studies can fully prove that there is no difference in in vivo performance, then this study can be exempted
    For a specific dosage form, when a certain standard is met, BCS can be used as a tool for applicants and regulatory agencies to judge whether the bioequivalence study can be exempted


           Other factors affecting the application for bioequivalence exemption.
    When an oral solid common-release preparation applies for a bioequivalence exemption based on the BCS classification, it should be noted that the following factors may affect the bioequivalence exemption:

           01 Accessories

           BCS1 drugs: Excipients may sometimes affect the absorption rate and degree of absorption of the drug
    Generally speaking, the use of approved common excipients for normal-release preparations will not affect the absorption rate and degree of absorption of the BCS1 type of fast-dissolving normal-release preparations


           BCS3 drugs: This class of drugs is different from BCS1 drugs.
    If you want to apply for a bioequivalence exemption, you must have a more adequate scientific basis


           02 Prodrug

           The permeability of the prodrug usually depends on the mechanism and (anatomically) site of the transformation drug
    If the prodrug-drug conversion is mainly manifested after the intestinal membrane permeates, the permeability of the prodrug should be measured

    If the conversion occurs before the intestinal membrane permeates, the permeability of the drug should be determined


           03 Compound preparation

           When the active components in the oral solid regular-release compound preparations are all BCS1 drugs, the biologic exemption can be applied for according to the requirements of BCS1 drugs, but it should be proved that there is no drug metabolism between each component and between each component and all excipients.
    Otherwise, you cannot apply for an exemption


           04 The biological exemption based on BCS does not apply to the following situations

           (1) Medicines with narrow treatment range

           The bioequivalence exemption is not applicable to the preparations designed according to the narrow treatment range that are restricted by the concentration of the therapeutic drug or the monitoring of the efficacy
    Such as: digoxin, lithium preparations, phenytoin, theophylline and warfarin anticoagulant


           (2) Oral absorption preparations

           Since the BCS classification is based on the penetration and absorption of the gastrointestinal mucosa, it is not suitable for oral absorption preparations, such as preparations similar to sublingual tablets or subbuccal tablets
    For buccal tablets, orally disintegrating tablets, etc.
    , it is not suitable if the preparation is absorbed from the oral cavity



           [1] Amidon GL, Lennern?s H, Shah VP, et al.
    A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability [J].
    Pharm Res.
    1995, 12 (3 ): 413-420.

           [2] State Food and Drug Administration.
    Notice of the General Administration on Issuing the Guiding Principles for Exemption of Human Bioequivalence Tests (No.
    87 of 2016)

           [3] FDA guidelines

           [4] WHO guidelines

           [5] EMA guidelines

           [6] NMPA guidelines

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