Development of sustained-release lipophilic calcium stearate pellets via hot melt extrusion.

Eva Roblegg, Evelyn Jäger, Aden Hodzic, Gerold Koscher, Stefan Mohr, Andreas Zimmer, Johannes Khinast

文献索引：Eur. J. Pharm. Biopharm. 79(3) , 635-45, (2011)

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摘要

The objective of this study was the development of retarded release pellets using vegetable calcium stearate (CaSt) as a thermoplastic excipient. The matrix carrier was hot melt extruded and pelletized with a hot-strand cutter in a one step continuous process. Vegetable CaSt was extruded at temperatures between 100 and 130°C, since at these temperatures cutable extrudates with a suitable melt viscosity may be obtained. Pellets with a drug loading of 20% paracetamol released 11.54% of the drug after 8h due to the great densification of the pellets. As expected, the drug release was influenced by the pellet size and the drug loading. To increase the release rate, functional additives were necessary. Therefore, two plasticizers including glyceryl monostearate (GMS) and tributyl citrate (TBC) were investigated for plasticization efficiency and impact on the in vitro drug release. GMS increased the release rate due to the formation of pores at the surface (after dissolution) and showed no influence on the process parameters. The addition of TBC increased the drug release to a higher extent. After dissolving, the pellets exhibited pores at the surface and in the inner layer. Small- and Wide-Angle X-ray Scattering (SWAXS) revealed no major change in crystalline peaks. The results demonstrated that (nearly) spherical CaSt pellets could be successfully prepared by hot melt extrusion using a hot-strand cutter as downstreaming system. Paracetamol did not melt during the process indicating a solid suspension. Due to the addition of plasticizers, the in vitro release rate could be tailored as desired.Copyright © 2011 Elsevier B.V. All rights reserved.