ABSTRACT
Objective: Biopharmaceutics classification system (BCS) of five main pharmacological/toxic components (gallic acid, emodin, stilbene glycoside, physcion, and emodin-8-O-β-D-glucoside) of Polygoni Multiflori Radix Praeparata (PMRP) were carried out. Methods: The solubility and permeability of each representative component were studied by equilibrium solubility method and everted intestinal sac method, respectively. Using two softwares (Pipeline Pilot 7.5, ChemDraw 7.0) to predict the solubility and permeability parameters of each component. Classical BCS classification of measured and predicted values of representative components was conducted according to Food and Drug Administration (FDA) standards, and their correlation was evaluated. Results: The emodin, emodin-8-O-β-D-glucoside, and physcion in PMRP was preliminary determined as BCS IV drugs. THSG and gallic acid belong to BCS III drugs, and permeability was the main limiting factor in their absorption process. There was software which predicts false positives of anthraquinone in BCS classification studies. Conclusion: In this study, five main pharmacodynamic/toxic components of PMRP were classified by BCS method, which provided data support and technical reference for in vivo absorption prediction and in vitro safety evaluation of traditional Chinese medicine.
ABSTRACT
ABSTRACT BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) were proposed as tools for classifying drugs into four categories. Both systems consider the solubility as an important characteristic for the classification of compounds in drug development and in vivo disposition prediction. Although some results of drug solubility can be found in the literature, the aforementioned characteristic is not entirely clear when considering didanosine (ddI). Based on that, the solubility of ddI was evaluated using equilibrium and intrinsic dissolution methods. For the equilibrium method, excess amount of ddI was added to each media until obtaining a supersaturated solution and the mixture was submitted to agitation at 37 °C. For the intrinsic dissolution method, the drug was compressed into the Wood's apparatus matrix and subjected to dissolution in each media with agitation at 37 °C. The results obtained from the equilibrium method indicated that it was necessary 139.37 mL of pH 1.2 media, 87.72 mL of pH 4.5 media, 12.54 mL of pH 6.8 media, 5.03 mL of pH 7.5 media and 7.65 mL of purified water for drug solubilization. Furthermore, a very fast intrinsic dissolution rate (IDR) was obtained for each media: 0.1 mg/min/cm² (pH 1.2), 0.2 mg/min/cm² (pH 4.5), 0.2 mg/min/cm² (pH 6.8), 0.1 mg/min/cm² (pH 7.5) and 0.1 mg/min/cm² (purified water). Based on these results, ddI can be considered as a highly soluble drug for both equilibrium and intrinsic dissolution methods.
Subject(s)
Solubility , Biopharmaceutics , Didanosine/analysis , Systems Analysis , Pharmaceutical Preparations/classificationABSTRACT
The solubility and permeability on four kinds of flavonoids (kaempferol, hesperidin, apigenin, genistein) were test according to the theory of biopharmaceutics classification system (BCS), and their absorption mechanism. The solubility was investigated by the method in determination of solubility of "Chinese Pharmacopoeia 2010". To detect appearance permeability of compounds mentioned above, the appropriate concentrations were selected by the MTT method in cell transfer experiments in Caco-2 cell model, which established by in vitro cell culture method. Therefore, these compounds were classified with BCS according to solubility and permeability. In addition, to explore absorption mechanisms, the experiments in three different concentrations of compounds in high, medium and low in bidirectional transformation methods in Caco-2 cell model contacted. The study indicated that all of kaempferol, hesperidin, apigenin, genistein have the characteristics in low solubility and high permeability, which belong to BCSⅡ, and the absorption mechanism of kaempferol was active transportation. Whereas, hesperidin, apigenin, genistein were passive transportation. In this study, it carried out initial explorations on establishment of determination for solubility and permeability in flavonoids, and provided theoretical reference for further research on BCS in traditional Chinese medicine.