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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Self-microemulsifying drug delivery systems (SMEDDS) present challenges in industrial-scale production due to their liquid nature.
• Solid dosage forms are preferred for improved handling, stability, and patient compliance.

Purpose of the Study:

• To develop a solid self-microemulsifying drug delivery system (S-SMEDDS) of testosterone (TST).
• To convert liquid SMEDDS into a stable, solid dosage form using extrusion-spheronization.
• To optimize TST/S-SMEDDS pellet formulation parameters via a 2^4 full factorial design.

Main Methods:

• Extrusion-spheronization technique for pellet formation.
• Characterization of pellets: particle size distribution, sphericity, flow properties, disintegration, and redispersibility.
• Compatibility studies using Thermogravimetric Analysis (TG/DSC) and Fourier Transform Infrared Spectroscopy (FT-FTIR).

Main Results:

• No incompatibility observed between testosterone, SMEDDS components, and pellet excipients.
• Reconstituted SMEDDS maintained optimal droplet size (170-190 nm) and Polydispersity Index (PDI) (0.2-0.3).
• Achieved testosterone concentrations of 30.8 μg/g (F1), 20.2 μg/g (F16), and 21.1 μg/g (F19) per pellet.

Conclusions:

• Solidification of SMEDDS via extrusion-spheronization is a feasible method for industrial-scale testosterone delivery.
• The developed TST/S-SMEDDS pellets exhibit favorable physicochemical properties and formulation stability.
• This approach facilitates the transition of SMEDDS technology to robust solid dosage forms.