Microemulsion based Transdermal Gels of Isradipine to Enhance Bioavailability: In vitro and In vivo Evaluation

Abstract

Aim: The main objective of the current investigation was to develop and evaluate the microemulsion based transdermal gel for isradipine, poorly water soluble and low bioavailable drug. Materials and Methods: Saturation solubility studies of the drug were conducted in various solvents and oils. Oleic acid, Tween 80 and Transcutol P were selected as oil phase, surfactant and cosurfactants, respectively, as the drug was having highest solubility in these solvents. The pseudo-ternary phase diagrams were constructed using water titration method by varying surfactant to the co-surfactant (Smix) ratio as 1:1, 1:2, 1:3, 2:1, and 3:1. Microemulsion formulations ratios were selected from the constructed pseudo-ternary phase diagrams. Results and Discussion: Microemulsion prepared with oil to Smix ratio of 1:9 (F9) was found to be stable with the globule size of 50.4 ± 3.54, and has more % of drug diffusion of 88.4 ± 1.9% within 6 h and has been selected for the preparation of microemulsion based gel (MEBG) using carbopol 934 as gelling agent. The prepared gel has shown 96.74 ± 2.8% drug releases in 8 h which was higher than control gel. In vivo pharmacokinetic studies conducted in rabbits revealed that the bioavailability of MEBG was increased 5.4 times compared to oral suspension. Conclusion: This demonstrates avoidance of first pass metabolism and oral degradation and indicates the effective management of plasma profile of isradipine when it is administered as MEBG through transdermal route.