Preparation and characterization of azelnidipine-loaded D-α-tocopheryl polyethylene glycol succinate (TPGS) / solutol micelles

Abstract

Azelnidipine is a calcium-channel antagonist classified as a “class 2” drug with high permeability and low aqueous solubility. It is used in the treatment of angina pectoris and hypertension without reflex tachycardia. Improvement of the solubility of azelnidipine and increasing drug’s bioavailability can be achieved through the drug encapsulation in solutol / D-α-tocopheryl polyethylene glycol succinate (TPGS) micelles. Six formulas were prepared by direct disso¬lution after using different amounts of solutol and TPGS. TPGS and solutol act as solubilizers, permeation enhancers, and P-glycoprotein inhibitors. The particle size, particle size distribution, zeta potential, and entrapment efficiency were determined. Depending on particle size and entrapment efficiency, formula #6 was selected and subjected to in vitro dilution stability and in vitro release studies. The results obtained showed that formula #6 was the best formula, with a high entrapment efficiency percentage equal to 86.5%±0.58% and a small particle size equal to 21.9±7.75 nm that did not change significantly after dilution up to 100-fold; a fact that reveals the high thermodynamic and kinetic stability of the optimum formula. The formula #6 release profile showed a controlled release of the drug from micelles when compared to plain drug release. Based on these results, polymeric nanomicelles are regarded as a promising delivery system for azelnidipine.