Provisional Biopharmaceutical Classification of Some Common Herbs Used in Western Medicine

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 (D₀) 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 D₀. 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.

Biotransformed product, genistein 7-O-phosphate, enhances the oral bioavailability of genistein

“…For genistein, a high clogP value leads to low aqueous solubility and poor dissolution profile, which may reduce the proportion of genistein contacting enterocytes (Lennernäs, 2007). Previous reports revealed an aqueous solubility of genistein of only about 10 µM (Waldmann et al, 2012), and in this study, we found a low dissolution rate in simulated aqueous gastrointestinal fluids (Fig. 3B).…”

“…Waldmann et al reported that genistein has water solubility of 11.65 µg/mL at neutral pH (Waldmann et al, 2012), so the aqueous solubility of genistein is much less than the "highest dose strength" of 30 mg fully dissolved in 250 mL water. We evaluated solubility with excess G7P dissolved in a small amount of deionized water at 37°C.…”

“…According to the Merck Index, genistein is practically water-insoluble; and Waldmann et al concluded that genistein is a Biopharmaceutical Classification System (BCS) IV substance because of its low aqueous solubility within the physiologically relevant pH ranges and has low intestinal permeability (Waldmann et al, 2012). These disadvantages lead to the depletion of genistein absorption from dietary intake and contribute to its poor oral bioavailability.…”

Mechanism-Based Inhibitory and Peroxisome Proliferator-Activated Receptor α–Dependent Modulating Effects of Silybin on Principal Hepatic Drug-Metabolizing Enzymes

“…Silymarin, a flavonoid complex extracted from milk thistle plant Silybum marianum, has been widely used for centuries in the therapy of liver diseases and a host of other diseases (Pade and Stavchansky, 2008;Waldmann et al, 2012). Silybin is one of the major and pharmacologically active compounds in silymarin and has been developed and marketed as a drug in China for the therapy of liver diseases (Fong et al, 2013).…”

Dissolution Testing of Herbal Medicines: Challenges and Regulatory Standards in Europe, the United States, Canada, and Asia

“…Additionally, to quantify herbal markers dissolved in buffer media, herbal residues have to be tested for the presence of analytical markers to ensure saturation solubility is reached. Another approach to determine provisionally the pH dependent solubility of analytical herbal markers was reported by Lang et.al (12). The software program ADMET Predictor was used to estimate biopharmaceutically relevant descriptors such as solubility.…”