High Drug-loading Simvastatin Formulation: Hot Melt Extrusion and Self-microemulsifying Drug Delivery System

Simvastatin (SIM) is a widely prescribed lipid-lowering agent; however, its clinical efficacy is hindered by poor aqueous solubility and low oral bioavailability. This study aimed to comparatively evaluate two formulation strategies—hot-melt extrusion (HME) and self-microemulsifying drug delivery system (SMEDDS)—for improving the solubility and delivery of high drug-loading SIM formulations.

Formulations were prepared using HME and SMEDDS, respectively. The HME formulation, employing Eudragit^® EPO as the optimal polymeric carrier, was comprehensively characterized via thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and fourier-transform infrared spectroscopy (FTIR) to investigate its thermal behavior, crystallinity, and molecular interactions. The SMEDDS formulation, composed of Capryol^® 90, Kolliphor^® EL, and ethyl carbitol, was evaluated based on particle size distribution and visual grading to assess its self-emulsification performance.

dissolution studies demonstrated a superior release profile for SIM-SMEDDS (~ 83% at 120 min) compared to SIM-HME (~ 65% at 180 min for HF-4 powder). Controlled-release evaluations revealed that the HF-4 HME tablet exhibited a stable release (~ 61% at 600 min), while the S-SMEDDS SF-5 tablet showed a progressive release reaching ~ 85% at 360 min. Despite the dissolution advantage of SMEDDS, SIM-HME showed a significantly higher drug-loading capacity (20% w/w) compared to SMEDDS (5% w/w for immediate release and 1.6% w/w for sustained release in the S-SMEDDS tablet).

Overall, the in vitro findings indicate that while SMEDDS is more effective in enhancing the dissolution rate of SIM at low drug loading, HME enables a moderate solubility enhancement together with sustained release at significantly higher drug-loading capacity. These two delivery systems present complementary benefits, and their application should be tailored based on specific formulation objectives and therapeutic requirements. Further in vivo studies will be required to confirm clinical translation.