Suitability of a flat die press for the manufacture of pharmaceutical pellets by extrusion/spheronization

Abstract

Background: Flat die presses are commonly used for the compaction of food, wood, waste, feedstuff, and chemicals. Because of their large capacity, low price, and high production speed, flat die presses represent a promising alternative for conventional extruders used in the pharmaceutical industry. In this work the feasibility of using the flat die press 14-175 for the manufacture of pharmaceutical pellets by extrusion/spheronization was investigated. Method: Pellet formulations containing different model drugs (theophylline, paracetamol, hydrochlorothiazide, or furosemide) and excipients (lactose, mannitol, dicalcium phosphate dihydrate, or starch) with different solubility properties were produced using κ-carrageenan as pelletization aid. Pellets with high and low drug strength were tested. The prepared pellet formulations were assessed in terms of size, size distribution, shape, and release properties. Results: All pellet formulations showed a high yield of the pelletization process and a narrow size distribution. The median aspect ratio was approximately 1.1 indicating acceptable roundness with exception of the pellets produced with high dose of furosemide because of the small-sized needle-shaped active ingredient. The dissolution profiles of the produced formulations showed fast drug release with low standard deviation thus suggesting good batch uniformity. Conclusion: The flat die press is a promising choice for the production of pellets by wet extrusion/spheronization with high formulation robustness.