International Journal of Nanomedicine 2015-01-01

Optimization, ex vivo permeation, and stability study of lipid nanocarrier loaded gelatin capsules for treatment of intermittent claudication.

Marwa Ahmed Sallam, María Teresa Marín Boscá

Index: Int. J. Nanomedicine 10 , 4459-78, (2015)

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Abstract

In this study, an optimized nanodispersible oral dosage form (containing a lactate ester) was developed for cilostazol (CZL). CZL is a phosphodiesterase inhibitor used for intermittent claudication. We aimed to improve the dissolution rate and absorption of CZL giving it a better chance of oral bioavailability, and to evaluate its stability on storage. Suitable compositions of nanoemulsion preconcentrate formulations were screened via solubility and compatibility tests. Response surface methodology and a desirability approach were applied to optimize preconcentrates containing minimum amount of surfactant mixture, maximum amount of lipid, and possessing the smallest globule size, with the highest emulsification and dissolution rates and minimum risk of drug precipitation. As part of the optimization process, the main effect, interaction effects and quadratic effects of amounts of lipid, and surfactant/co-surfactant ratio on % transmittance, globule size, emulsification time, drug precipitation, and drug release were investigated. The optimized formulation consisting of 28.9% butyl lactate, 28.9% Capryol, 27.82% Solubilisant Gamma 2429, and 14.18% Transcutol possessing a globule size of 60 nm was mixed with Aerosil 200. This gave uniform free flowing granules, which were characterized for surface and powder properties. The self-nanoemulsifying granules (SNEGs) filled into hard gelatin capsules showed two- and threefold increase in CZL released compared with conventional tablet and pure drug, respectively. The amount of drug permeated using non-everted sac technique from the SNEGs was twofold higher than that permeated from the tablet suspension. The shelf life was 526 days at 25°C. Our study illustrated that the developed SNEGs, with bioenhancing ingredients, held great potential as a superior alternative to traditional oral formulations of CZL.