Pluronic F‑68 Triblock Copolymer Architecture for a Next-Generation Self-Nanoemulsifying System: Overcoming Drug Trapping and Dosage Challenges of Candesartan Cilexetil.

Solidification of liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) is commonly used to avoid formulation leakage during storage. However, traditional solidification using the adsorption method has limitations, including the trapping of drugs within adsorbent pores and the high total dosage required. Pluronic F-68, a triblock copolymer, was utilized to prepare a polymeric SNEDDS with an in situ liquefying property (IL-SNEDDS) using candesartan cilexetil as a model drug. Drug solubility was examined to choose the optimum L-SNEDDS formulation. Afterward, S-SNEDDS and IL-SNEDDS were prepared and subjected to physicochemical characterization. In vitro dissolution was conducted to explore the influence of the formulation type on the dissolution profile of candesartan cilexetil (CC). The selected optimum L-SNEDDS formulation consisted of Tween-80:Imwitor-308:propylene glycol (2:1:1). The IL-SNEDDS formulation containing 7.5% w/w Pluronic-F-68 was selected as the optimum formulation with a liquefying temperature (34 °C) and liquefying time (75 s). Furthermore, physicochemical characterization revealed that candesartan cilexetil was present in the amorphous state within the prepared S-SNEDDS and IL-SNEDDS formulations, with no indication of a chemical interaction. In contrast to S-SNEDDS, IL-SNEDDS was able to enhance the dissolution of candesartan cilexetil with no sign of drug trapping. The present study presents a new approach that can overcome the limitations of traditional solid SNEDDS and enhance the application of SNEDDS as a pharmaceutical dosage form.