From Liquid to Solid: Formulation and Characterization of Testosterone-Loaded S-SMEDDS Pellets Using a 24 Factorial Design

Abstract The solidification of self-microemulsifying drug delivery systems (SMEDDS) represents a significant advance in the transition from self-microemulsifying technology to industrial-scale production. A solid self-microemulsifying drug delivery system of testosterone (TST/S-SMEDDS) was developed using the extrusion-spheronization technique, with the aim of converting the liquid SMEDDS into a solid dosage form. Testosterone-loaded S-SMEDDS pellets were formulated based on a 2 4 full factorial design, including triplicates at the central point, to optimize the formulation parameters. The resulting pellets were characterized in terms of particle size distribution, sphericity, flow properties, disintegration time and redispersibility behavior. Thermogravimetric Analysis and Differential Scanning Calorimetry (TG/DSC) and Fourier Transform Infrared Spectroscopy (FT-IR) were employed as preliminary screening tools to evaluate the compatibility between the testosterone-containing SMEDDS and pellet excipients. No events indicating incompatibility between the compounds in the evaluated temperature ranges were observed. The addition of solid excipients did not demonstrate significant changes in droplet size and polydispersity index (PDI) after SMEDDS reconstitution, which remained in the range of 170–190 nm and 0.2–0.3 for particle size and the PDI value, respectively. The TST concentration per gram of pellet was 30.8 μg, 20.2 μg and 21.1 μg for the formulations F1, F16 and F19 respectively. Graphical Abstract