Matrix effects of the hydroethanolic extract and the butanol fraction of calyces from Physalis peruviana L. on the biopharmaceutics classification of rutin.

OBJECTIVES: The Biopharmaceutics Classification System (BCS) categorizes active pharmaceutical ingredients according to their solubility and permeability properties, which are susceptible to matrix or formulation effects. The aim of this research was to evaluate the matrix effects of a hydroethanolic extract of calyces from Physalis peruviana L. (HEE) and its butanol fraction (BF), on the biopharmaceutics classification of their major compound, quercetin-3-O-rutinoside (rutin, RU). METHODS: Rutin was quantified by HPLC-UV, and Caco-2 cell monolayer transport studies were performed to obtain the apparent permeability values (Papp ). Aqueous solubility was determined at pH 6.8 and 7.4. KEY FINDINGS: The Papp values followed this order: BF > HEE > RU (1.77 ± 0.02 > 1.53 ± 0.07 > 0.90 ± 0.03 × 10-5  cm/s). The lowest solubility values followed this order: HEE > RU > BF (2.988 ± 0.07 > 0.205 ± 0.002 > 0.189 ± 0.005 mg/ml). CONCLUSIONS: According to these results, rutin could be classified as BCS classes III (high solubility/low permeability) and IV (low solubility/low permeability), depending on the plant matrix. Further work needs to be done in order to establish how apply the BCS for research and development of new botanical drugs or for bioequivalence purposes.

Establishment of modified biopharmaceutics classification system absorption model for oral Traditional Chinese Medicine (Sanye Tablet).

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the new drugs of traditional Chinese medicine, Sanye Tablet is employed as a hypolipidemic in the traditional medicine, but the biopharmaceutical properties of the drug is still unclear. AIM OF THE STUDY: Through the study of biopharmaceutical properties, the classical biopharmaceutics classification system (BCS) can be used to classify and predict the in vivo absorption properties. On this basis, the biopharmaceutical properties closely related to traditional Chinese medicine preparations are added and a modified BCS model is established to predict and judge the absorption degree of traditional Chinese medicine compound. MATERIALS AND METHODS: Representative components of Sanye Tablet were selected and subjected to different in vitro tests. The experimental results were compared with the results of the BCS to evaluate the accuracy and applicability to Sanye Tablet. We take parameters of dissolution and stability based on product characteristics into account. A "modified-BCS" was developed and the results of the improved method and the classic method were compared. Also the ability of each classification system to predict and determine the extent of absorption of the Chinese herbal compound was investigated based on the absolute bioavailability of representative components. RESULTS: For classic BCS, the five representative components (except for nuciferine) are all class III, nuciferine is class I/II obtained by Caco-2 cell assay and class III/IV obtained by everted gut sac assay. For modified BCS, paeoniflorin is class III, rutin, hyperoside and salvianolic acid B are class III/IV, and nuciferine is class I/II based on Caco-2 cell assay, class III/IV based on everted gut sac assay. Nuciferine is the best of the five components, with absolute bioavailability reaching 61.91% based on in vivo bioavailability test. CONCLUSIONS: The five representative components (except for nuciferine) are all class III/IV, which correlates well with the absolute bioavailability results and demonstrates that they are poorly absorbed substances. The correlation between the classification results obtained using the "modified-BCS" and absorption in the body is better than the correlation obtained using the classic method, suggesting that the improved BCS is more suitable for the characterization of Sanye Tablet. These results indicate that the oral formulation of Sanye Tablet is a BCS III/IV drug.