Formulation Development of Solid Self-Nanoemulsifying Drug Delivery Systems of Quetiapine Fumarate via Hot-Melt Extrusion Technology: Optimization Using Central Composite Design.

Abstract

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul® MCM, Gelucire® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes.