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Yasuhiro TsumeYasuhiro Tsume, Ph.D., is a scientist at University of Michigan. He has worked in various research projects such as prodrug strategies, cancer therapeutics, in vivo predictive dissolution (IPD) methodologies, and translational studies.

In a recent article, in vivo predictive dissolution (IPD) methodology and subclassification for the Biopharmaceutics Classification System (BCS) class II and class IV are introduced and discussed. This report proposes a simple extension of BCS class II and class IV to include subclasses of acid (a), base (b), and neutral (c). Those drugs will be called BCS class IIa, IIb, IIc, IVa, IVb, and IVc. BCS class I and class III drugs are highly soluble regardless of pH condition. Therefore, the subclassification of BCS class I and class III is unnecessary. On the other hand, the physical property of class II and class IV drugs has a huge impact on drug dissolution in the aqueous solution. Hence, the selection of dissolution media and pH condition for in vitro dissolution studies of those drugs will be one of key factors to predict in vivo. The pH condition in the gastrointestinal (GI) tract is drastically changed from the stomach (pH 1-3) to the small intestine (pH 4.5-7.4). This pH change would directly affect the solubility of those BCS class II and IV drugs. Therefore, the subclassification of BCS class II and class IV drugs would make it easier to select the key condition of in vitro dissolution studies for in vivo prediction of drug dissolution. Eventually, the right selection of in vitro dissolution methods and conditions would allow biopharmaceutical scientists to predict accurate in vivo dissolution of test compounds and to speed up the design of those formulations.

The ordinal in vitro dissolution methodology is simple and practical and is a “it fits all” approach. It is well known that many factors of dissolution media can significantly affect drug dissolution-buffer capacity, buffer pH, ionic strength, and so on. For example, the main physiological buffer in the human intestine is bicarbonate, and a phosphate buffer has been used for in vitro dissolution because of its easy-to-handle characteristics. It will be okay if those in vitro dissolution studies lead to the right in vivo prediction. The problems are often the discrepancies reported between in vivo and in vitro dissolution. I believe that more science-based in vitro dissolution methodologies, which reflect the in vivo environment in the GI tract, can predict better in vivo dissolution. Therefore, such dissolution methodologies, we name it an in vivo predictive dissolution (IPD) methodology, will allow scientists to design drug formulation and dosage forms to optimize pharmacokinetics studies and, eventually, to obtain the better quality by design (QbD) and in vivo–in vitro correlation (IVIVC).

I believe that the selection of in vitro dissolution method and dissolution media based on physicochemical drug properties, BCS subclassification, will be the right first step to guide, focus, and create more in vivo–relevant in vitro dissolution methodology.