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Abstract. The aim of this study was to investigate the combined influence of three independent variables on the permeation kinetics of lisinopril from hydrogels for transdermal delivery. A three-factor, threelevel Box-Behnken design was used to optimize the independent variables, Carbopol 971 P (X 1 ), menthol (X 2 ), and propylene glycol (X 3 ). Fifteen batches were prepared and evaluated for responses as dependent variables. The dependent variables selected were cumulative amount permeated across rat abdominal skin in 24 h (Q 24 ; Y 1 ), flux (Y 2 ), and lag time (Y 3 ). Aloe juice has been first time investigated as vehicle for hydrogel preparation. The ex vivo permeation study was conducted using Franz diffusion cells. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the cumulative permeation of LSP in 24 h (Q 24 ) was Y 1 =1,443.3-602.59X 1 +93.24X 2 +91.75X 3 − 18.95X 1 X 2 -140.93X 1 X 3 -4.43X 2 X 3 -152.63X 1 2 -150.03X 2 2 −213.9X 3 2 . The statistical validity of the polynomials was established, and optimized formulation factors were selected by feasibility and grid search. Validation of the optimization study with 15 confirmatory runs indicated high degree of prognostic ability of response surface methodology. The use of Box-Behnken design approach helped in identifying the critical formulation parameters in the transdermal delivery of lisinopril from hydrogels.

Silibinin, a major constituent of silymarin, is widely used for its hepatoprotective effects. This study investigated the effect of silibinin on the pharmacokinetics of oral nitrendipine in rabbits. In first set of experiment, male New Zealand rabbits were pretreated with silibinin (50 mg/kg, PO) for 7 days and on last day nitrendipine (10 mg/kg, PO) was administered. In second set, both silibinin and nitrendipine were coadministered to examine acute effect of silibinin on nitrendipine pharmacokinetics. The plasma concentration of nitrendipine was estimated by high performance liquid chromatography and different pharmacokinetic parameters were calculated using WinNonlin(®) software. Coadministration of silibinin had no significant effect on pharmacokinetics of nitrendipine when compared to control group. However, a 1.89-1.57-fold increase in area under the concentration-time curve and peak plasma concentration (C max), respectively, of nitrendipine was observed in silibinin pretreated group. The mean C max was 0.034 ± 0.005 μg/mL (nitrendipine alone) and 0.054 ± 0.006 μg/mL (nitrendipine after pretreatment with silibinin). The time to reach C max, elimination rate constant and elimination half-life of nitrendipine were not significantly different among control and silibinin treated groups. This study demonstrates that silibinin increase plasma concentration of nitrendipine. Henceforth, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing nitrendipine to the patients already taking silymarin.

A simple and sensitive high performance liquid chromatographic (HPLC) method for quantification of buspirone (BUSP) in rabbit serum was developed and validated. BUSP and internal standard (IS), diltiazem hydrochloride were extracted into dichloromethane and separated using an isocratic mobile phase, on a Kromasil C(8) column. The eluent was monitored by UV detector at 235 nm and at a flow rate of 1.0 mL min(-1). The linearity range of proposed method was 1-3000 ng mL(-1). The intra-day and inter-day coefficient of variation and percent error values of the assay method were less than 15% and mean recovery was more than 97 and 96% for BUSP and IS, respectively. The method was found to be precise, accurate, and specific during the study. The method was successfully applied for pharmacokinetic study of buspirone after application of reservoir based transdermal therapeutic system of BUSP to rabbits.

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