Provisional Biopharmaceutical Classification of Some Common Herbs Used in Western Medicine Sarah Waldmann, † May Almukainzi, † Nadia Araci Bou-Chacra, ‡ Gordon L. Amidon, § Beom-Jin Lee, ∥,+ Jianfang Feng, ⊥ Isadore Kanfer, # Joan Zhong Zuo, ∇ Hai Wei, ○ Michael B. Bolger, ◆ and Raimar Lö benberg* ,† † Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada ‡ Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo Brazil § College of Pharmacy, The University of Michigan, Ann Arbor, Michigan, United States ∥ College of Pharmacy, Kangwon National University, Chuncheon, Korea + College of Pharmacy, Ajou University, Suwon, Korea ⊥ Shanghai University of Traditional Chinese Medicine, Shanghai, China # Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa ∇ School of Pharmacy, Chinese University of Hong Kong, Hong Kong, China ○ Center for Chinese Medical Therapy and System Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China ◆ Simulations Plus, Inc., Lancaster, California, United States ABSTRACT: The aim of this study was to classify some markers of common herbs used in Western medicine according to the Biopharmaceutical Classification System (BCS). The BCS is a scientific approach to classify drug substances based upon their intestinal permeability and their solubility, at the highest single dose used, within the physiologically relevant pH ranges. Known marker components of twelve herbs were chosen from the USP Dietary Supplement Compendium Monographs. Different BCS parameters such as intestinal permeability (P eff ) and solubility (C s ) were predicted using the ADMET Predictor, which is a software program to estimate biopharmaceutical relevant molecular descriptors. The dose number (D 0 ) was calculated when information from the literature was available to identify an upper dose for individual markers. In these cases the herbs were classified according to the traditional BCS parameters using P eff and D 0 . When no upper dose could be determined, then the amount of a marker that is just soluble in 250 mL of water was calculated. This value, M x , defines when a marker is changing from highly soluble to poorly soluble according to BCS criteria. This biopharmaceutically relevant value can be a useful tool for marker selection. The present study showed that a provisional BCS classification of herbs is possible but some special considerations need to be included into the classification strategy. The BCS classification can be used to choose appropriate quality control tests for products containing these markers. A provisional BCS classification of twelve common herbs and their 35 marker compounds is presented. KEYWORDS: Biopharmaceutical Classification System, markers, herbs, herbal extracts, permeability, solubility, dose number ■ INTRODUCTION For any orally administered drug product, the main parameters controlling rate and extent of drug absorption are aqueous solubility and gastrointestinal permeability. 1 The Biopharma- ceutical Classification System (BCS) introduced by Amidon et al. 1 classifies drugs into four classes according to these two parameters using the highest therapeutic dose within the physiologically relevant pH range of pH 1.2−7.4: • class Ihigh solubility, high permeability • class IIlow solubility, high permeability • class IIIhigh solubility, low permeability • class IVlow solubility, low permeability The FDA has adapted the BCS for regulatory and scientific purpose. The BCS classification of a drug can make postapproval changes of a finished product or generic drug approval possible without the need to undertake in vivo studies. 2 Based on the BCS classification, waivers for in vivo bioequivalence testing of immediate-release oral solid dosage forms of class I drugs can be granted if dissolution testing can demonstrate that two products are similar in vitro. The term biowaiver is defined by the World Health Organization (WHO) as approving a generic medicine based on strictly defined dissolution criteria relating to the active pharmaceutical ingredient (API) as a surrogate measure for in vivo bioequivalence testing. 3 The concept of biowaivers can be Received: March 31, 2011 Revised: November 14, 2011 Accepted: February 17, 2012 Published: February 18, 2012 Article pubs.acs.org/molecularpharmaceutics © 2012 American Chemical Society 815 dx.doi.org/10.1021/mp200162b | Mol. Pharmaceutics 2012, 9, 815−822