Formulation Optimization and Evaluation of Microemulsion Based Transdermal Therapeutic System for Nitrendipine

Abstract

Microemulsion based transdermal therapeutic system (TTS) for nitrendipine was developed and evaluated with the aim to improve bioavailability and further therapeutic efficacy. Pseudoternary phase diagrams were constructed for the microemulsions composed of isopropyl myristate (IPM), cremophor and propylene glycol (S_Mix) as oil, surfactant, and cosurfactant, respectively. Box-Behnken statistical design was employed to optimize the formulations. IPM, S_Mix and water; cumulative amount permeated across skin, flux, and lag time were selected as independent and dependent variables, respectively. The formulations were evaluated for permeation parameters across rat abdominal skin using Franz diffusion cells. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The flux of optimized formulation could meet target flux. The optimized formulation was further formulated as reservoir system (ME-TTS) and evaluated for in vivo bioavailability in rabbits. The bioavailability study reveal that about 3.7 times of improvement (p < 0.05) after transdermal administration of ME-TTS compared oral suspension. A new microemulsion system for transdermal delivery of nitrendipine was developed and optimized using Box-Behnken statistical design.

Keywords:

• Bioavailability
• Box-Behnken
• microemulgel
• microemulsion
• nitrendipine
• optimization
• pharmacokinetics

Acknowledgments

Dr. Ramesh Gannu thank AICTE, New Delhi, India for providing financial assistance in the form of National Doctoral Fellowship (NDF) during research work. The authors also acknowledge the liberal help of US Vitamins, Mumbai, India and Dr. Reddy's Laboratories, Hyderabad, India providing nitrendipine and Cremophor EL in the form of gift samples, respectively.