Nanostructured lipid carriers containing ondansetron hydrochloride by cold high-pressure homogenization method: Preparation, characterization, and pharmacokinetic evaluation

Abstract

Nanostructured lipid carriers (NLCs) loaded with ondansetron hydrochloride, a water-soluble drug, were developed for sustained-release delivery. A modified cold high-pressure homogenization method was used, and the pH-dependent solubility of the drug was exploited to obtain NLCs with an enhanced entrapment efficiency. The conditions for cold high-pressure homogenization were optimized at 500 bars for 6 cycles. The pH of the aqueous phase was 7.4, which led to an improvement of the entrapment efficiency to approximately 90%. Certain variables of the formulation composition were evaluated for their influences on ondansetron hydrochloride-loaded NLCs. The transformation of the drug to an amorphous state in NLCs was indicated by differential scanning calorimetry and X-ray powder diffraction. The optimized formulation consisted of tristearin: Phosal (R) 53MCT: drug (60:40:15, w/w) with 0.5% Tween (R) 80 (w/v). This formulation exhibited a sustained-release characteristic of the drug in vitro. After single subcutaneous injections in rats, the optimized ondansetron hydrochloride-loaded NLCs prolonged the drug release for up to 96 h with an extended mean resident time and enhanced systemic exposure compared to the drug solution. The developed NLCs might be an efficient approach to prolong the therapeutic effect of ondansetron hydrochloride for the management of chemotherapy- and radiotherapy-induced emesis.