Objective: Transmucosal buccal drug delivery could be an alternative for oral administration for systemic delivery of Verapamil Hydrochloride (VH), as it has low bioavailability 20 -35 % due to its extensive first pass metabolism and variable absorption at GIT. Method: Buccal patches of VH were prepared by solvent casting method using bioadhesive polymers HPMC K4M, Carbopol 934P, Chitosan acetate and Okra mucilage isolated from Hibiscus esculantus fruits, in various combinations as per 2 4 half factorial model. The prepared medicated patches were subjected for in vitro and ex vivo characterization. Results: The mass uniformity, thickness, drug content, surface pH and folding endurance for the medicated patches were found satisfactory. The formulation contains Chitosan acetate and Okra mucilage has moderate swelling 38.86 % w/w in 2h, ex vivo mucoadhesion strength 27.78 ± 0.12 g on porcine buccal membrane and sustained in vitro release rate as 73.14 % (F7) and Carbopol 934P. No significant changes were observed in the Physical and chemical characteristics during short term stability study. Chemical compatibility of VH with polymers was confirmed by FTIR spectroscopy. Conclusion: Overall, Chitosan acetate and Okra mucilage imparts good physical properties to the buccal patch, significantly controls release and diffusion of VH from the matrix film with satisfactory bucco-adhesion.

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Objective: A simple, selective and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) method to estimate repaglinide (REP) in rabbit plasma using rabeprazole (RAB) as an internal standard was developed and validated for various qualifications. Methods: The chromatographic separation was performed on C18 (2) analytical column (5 μ, 250×4.6 mm) using acetonitrile: 0.05% trifluoroacetic acid in water (55:45, v/v) as mobile phase at the flow rate of 1 ml/min. Validation of the analytical method was performed as per ICH guidelines. Results: The retention times of REP and RAB were found at ~4.3 and 5.1 min respectively, with adequate system suitability parameters (theoretical plates ≥3619, tailing factor ≤1.38, resolution factor 2.37). The method has linearity over a concentration range of 10 to 1000 ng/ml (r2=0.9987). The results of accuracy (≥98.17%), intra-, inter-day precision (≤2.9%), recovery (101.21±2.09%) and process efficiency (99.77±3.74%) found satisfactory with no matrix effect. The analyte in samples were found stable up to 6 h, 3 freeze-thaw cycles and not more than 2 mo corresponding to bench-top, short and long term stability studies respectively. Conclusion: The developed RP-HPLC method for estimation of REP in rabbit plasma was developed. The method was found to be rapid, cost-effective and accurate to estimate the REP from the sample matrix. The method can be a most useful tool for in vivo study of REP in the rabbit.

Background: Repaglinide (REP) is an antihyperglycemic drug having low bioavailability due to its extensive first-pass metabolism. The present study aimed to develop and pharmacokinetic investigte the thiolated chitosan (TC) based buccal tablets of REP for improved bioavailability. Methods: TC was prepared by conjugation of L-cysteine with chitosan. The amount of free thiol groups present in TC was determined by UV-spectrophotometry using Ellman’s reagent. TC based REP buccal tablets were prepared by two layers co-compression method and characterized for in vitro and ex vivo parameters. The in vivo performance of prepared REP buccal tablets was assessed by the pharmacokinetic study in New Zealand white rabbits. Results: The prepared TC resulted in 87%w/w yield with 52.3±3.2 μM free thiol functional groups per 10 mg of TC. The prepared formulations have good flow nature and compressibility, acceptable thickness (2.02 to 2.1 mm), weight (60.11 to 61.06 mg), surface pH (6.59 to 6.81) and drug content (98.92 to 101.08 %w/w). The presence of TC significantly improved the mucoadhesion strength, sustained the in vitro release and enhanced the ex vivo permeation of REP buccal tablets. The shelf life of REP buccal tablets was found to be 15.07 months in accelerated storage conditions. The prepared REP buccal tablets (V5) have area under the curve (712.22±15.91 ng/mL/h) and mean residence time (4.66±0.25 h) was 1.89 and 1.83 folds higher than oral bolus respectively. Conclusion: TC based REP buccal tablets are capable of controlled transbuccal release of REP for a prolonged time and have better bioavailability than oral bolus.

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