Sustained-release hot melt extrudates of the weak acid TMP-001: A case study using PBB modelling
Fabian Jung1, Manuela Thurn2, Katharina Krollik3
1Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Theodor-Stern-Kai 7, D-60596 Frankfurt, Germany; Institute of Pharmaceutical Technology, Goethe University, Max-von-Laue-Straße 9, D-60438 Frankfurt/Main, Germany.
Summary
L-arginine enhances amorphous drug delivery systems made via hot melt extrusion. This pore-forming agent stabilizes the drug
Area of Science:
- Pharmaceutical Technology
- Drug Delivery Systems
- Materials Science
Background:
- Hot melt extrusion (HME) is a key technology for amorphous drug delivery systems.
- Sustained-release formulations using HME are gaining pharmaceutical industry interest.
- TMP-001, a drug candidate for Multiple Sclerosis, requires advanced formulation strategies.
Purpose of the Study:
- To develop and evaluate sustained-release formulations of TMP-001 using L-arginine as a pore-forming agent via HME.
- To assess the impact of L-arginine concentration on drug release and physical stability.
- To characterize promising formulations for further development.
Main Methods:
- Development of four HME prototypes with varying L-arginine concentrations (0-20%).
- Biorelevant release testing in FaSSIF-v2 to evaluate dissolution profiles.
- Characterization of amorphous state stability, crystal structure, and milling properties.
- Application of a physiologically-based biopharmaceutics model for bioavailability assessment.
Main Results:
- Drug release in FaSSIF-v2 ranged from 44.7% to 90.5% after 24 hours across prototypes.
- L-arginine significantly stabilized the amorphous state of TMP-001.
- Favorable impact of L-arginine on milling and drug release characteristics was observed.
- Two formulations were selected for advanced characterization based on release and stability.
Conclusions:
- L-arginine is a valuable excipient for HME-based sustained-release formulations.
- L-arginine improves physical stability and processing of amorphous drug systems.
- The developed formulations show potential for effective delivery of TMP-001.
