Objectives: Design, development and characterization of controlled release transdermal drug delivery system of carvedilol using Design Expert® software for managing hypertension. Materials and Methods: CV undergoes extensive first-pass metabolism due to low oral bioavailability approx ~24% and biological half-life ~6 hr. Available CV preparations have drawback of poor patient compliance due to increase in dosing frequency and making the therapy less effective. Phospholipid E80, glycerol and cholesterol were used for preparing CVGs via film hydration technique. Optimization was done using Central Composite Design under Design Expert software. While PVP and EC in a ratio of 4:1 in chloroform (5 mL) with plasticizer dibutyl phthalate (30%) were used for preparing Matrix type transdermal patch containing CVGs. Results: Optimized CVGs showed 115.7 nm particle size, and -16.4 mV zeta potential. TEM analysis also showed similar vesicle size and reveals globular structure of CVGs. Nearly 0.31 mm thickness, 0.14 % g weight variation, 99.13% flatness and 98.72% drug content was found in Matrix type transdermal patch having CVGs Transdermal patch with Franz diffusion cell showed approx. 90% release upto 48 hr during in-vitro permeation studies. In-vivo pharmacological assessment was done for efficacy estimation of GVs transdermal patch by N-nitro-L-arginine methyl ester which produced significant hypertension in rats. The application of CVGs transdermal patch resulted in a gradual decrease in BP, with the maximum effect from the patch observed at 10 hr (p < 0.001), the effect continued for 48 hr clearly indicating the gradual release of drug by transdermal patch for a long period. Conclusion: Developed novel transdermal patch having CV loaded glycerosomes may be considered as a promising approach for controlled release of drug with effective hypertension management.
Keywords: Transdermal, Carvedilol, Design Expert, Glycerosomes, Hypertension, CCD.