Optimization of Glibenclamide Loaded Thermoresponsive SNEDDS Using Design of Experiment Approach: Paving the Way to Enhance Pharmaceutical Applicability.

Abstract

Thermoresponsive self-nanoemulsifying drug delivery systems (T-SNEDDS) offer a promising solution to the limitations of conventional SNEDDS formulations. Liquid SNEDDS are expected to enhance drug solubility; however, they are susceptible to leakage during storage. Even though solid SNEDDS offers a solution to this storage instability, they introduce new challenges, namely increased total dosage and potential for drug trapping within the formulation. The invented T-SNEDDS was used to overcome these limitations and improve the dissolution of glibenclamide (GBC). Solubility and transmittance studies were performed to select a suitable oil and surfactant. Design of Experiments (DoE) software was used to study the impact of propylene glycol and Poloxamer 188 concentrations on measured responses (liquefying temperature, liquefying time, and GBC solubility). The optimized formulation was subjected to an in vitro dissolution study. The optimized T-SNEDDS consisted of Kolliphor EL and Imwitor 308 as surfactants and oil. The optimized propylene glycol and Poloxamer 188 concentrations were 13.7 and 7.9% w/w, respectively. It exhibited a liquefying temperature of 35.0 °C, a liquefying time of 119 s, and a GBC solubility of 5.51 mg/g. In vitro dissolution study showed that optimized T-SNEDDS exhibited 98.8% dissolution efficiency compared with 2.5% for raw drugs. This study presents a promising approach to enhance pharmaceutical applicability by resolving the limitations of traditional SNEDDS.