Solid Dispersion of Nateglinide in Polyoxy Ethylene-Polyoxy Propylene Block Copolymer: in vitro and in vivo Evaluation

Abstract:

Objective: The study was aimed to improve solubility and bioavailability of nateglinide preparing stable solid dispersions with polyoxy ethylene-polyoxy propylene block copolymer (poloxamer 188). Methods: The solid dispersions were prepared by the melting and solvent technique at 1:1, 1:2, 1:3 (w/w) of drug to carrier ratios. The formulations were characterized by fourier transform infrared spectroscopy, diffrential scanning calorimetry, X-ray diffraction, scanning electron microscopy, dissolution behaviour, stability and in vivo performance. Result and Discussion: The results showed an increase in solubility (52.57 fold) and an enhancement in dissolution of solid dispersions compared to pure nateglinide (P<0.05). FTIR showed retainment of individual peaks indicated few characteristics groups in the drug structure. The DSC thermograms and XRD pattern showed the significant change in crystallinity to amorphous of nateglinide. Pharmacokinetic study was performed in rabbits, showed improved bioavailability (1.71 fold, AUC) of nateglinide in solid dispersions (1:3 w/w). Similarly C_max and T_max of solid dispersions showed significant difference over the pure drug. Conclusion: The study indicated poloxamer 188 was suitable carrier and melting technique was suitable method for improvement of dissolution and bioavailability of nateglinide.

Key words: Nateglinide, Poloxamer 188, Bioavailability, Crystallinity, Solid dispersion.