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Abstract

Azelnidipine is a calcium channel blocker with low water solubility and high lipophilicity and is intended for treating angina pectoris and hypertension. This study aimed to increase and enhances the solubility of azelnidipine through its incorporation in D - - tocopheryl polyethylene glycol/polyxamer188 (TPGS/P188) micelles for oral administration and substantially increasing the extent of drug absorption.

Nine formulations (A1-A9) were prepared by direct dissolution method using a combination of D- - TPGS 1000 succinate and Poloxamer 188. The size of the particle, polydispersity index (PDI), surface charge, and entrapment capacity were measured. The optimum formula was subjected to further characterization including in-vitro release study, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction study (XRD), Differential scanning calorimetry (DSC), and atomic force microscopy (AFM). The study showed that A9 was the optimum formula depending on the particle size (24.22±7.61), polydispersity index (0.24±0.09), zeta potential (-4.35±3.7), and entrapment efficiency percentage (84.35±0.65). The small particle size, narrow size distribution, high entrapment efficiency, and negative near-neutral Zeta potential of formula A9 significantly improve the drug transport and absorption via intestinal epithelium. they are of prime importance for both in vitro and in vivo stability of Azelindipine-loaded micelles.

The profile of release showed controlled release characteristics of azelnidipine from formula (A9) compared to plain drug release. The controlled release of Azelindipine could avoid precipitation of the drug in the gut and improve its absorption. whereas rapid release of Class 2 drugs might lead to precipitation of the drug in GIT environment before absorption. Solubility study showed enhancement of the drug solubility in micellar solution, this can improve significantly the bioavailability. FTIR showed azelnidipine compatibility with TPGS/P188 copolymers and absence of chemical interaction.

DSC and XRD showed the transformation of azelnidipine into an amorphous form and confirmed its localization inside the micelles. AFM study showed smooth spherical morphology of formula (A9). Depending on these results, formula (A9) is regarded as a promising nanocarrier for azelnidipine delivery.

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