Continuous low-dose feeding of highly active pharmaceutical ingredients in hot-melt extrusion

Abstract

Context: Manufacturing solid low-dose pharmaceutical products has always the homogeneity challenge. In continuous manufacturing, there is the additional challenge of feeding active pharmaceutical ingredient (API) dry powder at low rates. This paper presents a method for feeding API particles into a continuous extrusion process using a suspension. The challenges for feeding and the product homogeneity are both addressed.

Objective: The objective of this study is to demonstrate the feasibility of manufacturing low-dose extrudates by feeding the API particles in a diluted anti-solvent suspension.

Materials and methods: Extrudates with an Ibuprofen content of 0.021% and 0.043% (w/w) were prepared by feeding a 0.9% w/w suspension of Ibuprofen particles into a Coperion extruder.

Results and discussion: The homogeneity (RSD) of extrudates was tested during a time span of 30 min and had values between 2% and 7%.

Conclusion: Feeding particles in an anti-solvent suspension offers a simple feeding option for API and minor components which yield products of desired homogeneity. The liquid feeding approach offers a simplified process with enhanced process control possibilities.

Keywords:

• API homogeneity
• continuous manufacturing
• hot-melt extrusion
• liquid feeding
• low-dose solid products

Disclosure statement

The author reports that they have no conflicts of interest.

Funding information

Research Center Pharmaceutical Engineering is funded by the Austrian COMET Program under the auspices of the Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT), the Austrian Federal Ministry of Economy, Family and Youth (BMWFJ) and by the Province of Styria (Styrian Business Promotion Agency, SFG). COMET is managed by the Austrian Research Promotion Agency, FFG.