The objective of this study was to develop and validate the in vitro-in vivo correlations (IVIVCs) of three commercially available immediate-release solid dosage forms of indapamide using drug dissolution/absorption simulating system (DDASS). The in vitro dissolution profiles of three brands of immediate-release tablets were obtained using the USP I basket method and DDASS. A single-dose, three-way, crossover pharmacokinetic study for the tablets was carried out in six beagle dogs. Correlation models were developed for each immediate release formulation using cumulative percentage dissolved/eluted (Fd) versus cumulative percentage absorbed (Fa) and cumulative percentage permeated (Fp) versus cumulative percentage absorbed (Fa). Prediction errors were estimated for the Cmax and AUC to determine the validity of the correlation. Level A IVIVCs were established for the three brands between in vitro (dissolution and permeation) data from DDASS and in vivo data from dogs. Predicted plasma concentrations of each commercial brand were obtained from the dissolution and permeation profile data using the correlation models. A percent prediction error of <15% for the Cmax and AUC was found for all of the formulations, which validates the internal predictability of the IVIVC models obtained. However, the IVIVC models from the permeation data failed to predict the AUC. The results support the use of in vitro dissolution and permeation data as a surrogate for bioequivalent study and suggest that DDASS can be applied as an in vitro system for the validated-IVIVC development of BCS II solid drug formulations.

No abstract

No abstract

No abstract

Background: Terpene lactones are major components of ginkgo biloba extract which are used in cardiovascular and degenerative diseases. To study the involvement of transporters in the transport/disposition of ginkgolides A, B, C, and bilobalide, a bioanalytical assay was developed by LCMS/ MS system for the quantitation of intracellular levels of terpene lactones in cells expressing organic cation transporter 2 (OCT2). Methods: The assay involved an optimized simple sample handling with methyl tert-butyl ether for liquid-liquid extraction and reconstitution in modified dissolution solution. Pretreatment of samples with 50 μM ascorbic acid and the addition of ascorbic acid and formic acid in dissolution solution significantly reduced matrix effect and stabilized the postpreparative samples. Separations were performed by Zobrax RRHD column (extend-C18 1.8μm, 3.0 x 100mm) and acetonitrile gradient elution. The analysis was carried out in the negative ion scan mode using multiple reaction monitoring. Results: The method was validated for linearity (concentration range of 20-5000nM), accuracy (±13.1%), precision (<11.0%), recovery (94.31–105.9%), matrix effect (93.8-111.0%) and stability. Finally, the method was applied in the determination of intracellular concentrations of ginkgolides A, B, C, and bilobalide in Madin-Darby canine kidney (MDCK-mock) and MDCK-OCT2 cells in uptake study. Conclusion: The developed method was successfully validated. Results suggest that OCT2 is involved in the renal disposition of ginkgolide A, B, and bilobalide. This method would foster the study of transport mediated activity via the interaction of ginkgolides and bilobalide with cellular systems.