Optimization of a Self-MicroemulsifyingDrug Delivery System (SMEDDS) of Ziprasidone using a Quality by Design (QbD) Approach

Abstract

Ziprasidone hydrochloride is a poorly water-soluble atypical antipsychotic exhibiting dissolution-limited oral absorption. The present study aimed to develop and optimize a Self-Microemulsifying Drug Delivery System (SMEDDS) of Ziprasidone using a Quality by Design (QbD) approach to enhance its solubility and dissolution performance. Preformulation studies identified Labrafac WL1349, Cremophor RH40, and PEG 400 as suitable oil, surfactant, and co-surfactant, respectively. A Box–Behnken Design was employed to optimize the effects of oil concentration, surfactant concentration, and Smix ratio on droplet size, self-emulsification time, cumulative drug release, polydispersity index, and percent transmittance. The optimized formulation consisted of 20% oil, 50% surfactant, and a 3:1 Smix ratio. It exhibited a droplet size of 129 nm, self-emulsification time of 25 sec, drug release of 95.7%, and transmittance of 98.6%. The optimized SMEDDS demonstrated rapid emulsification, excellent clarity, nanosized droplets, and improved dissolution, indicating its potential for enhancing the oral bioavailability of Ziprasidone.