Melt pelletisation of a hygroscopic drug in a high shear mixer. Part 1. Influence of process variables.
The applicability of a high shear mixer for melt pelletisation of binary mixtures of sodium valproate and glycerol monostearate was investigated. The effects of binder concentration, impeller speed, jacket temperature and massing time on mean pellet size and size distribution were examined in a 2(4)-factorial design. Binder concentration and impeller speed were found to be the most important variables influencing the mean granule size and size distribution. An increase in each of those accelerated the granule growth. Due to the solubility of the drug in the molten binder very low amounts of binder were necessary for the formation of pellets. The modified high shear mixer was found to be suitable for batch sizes of 1-4 kg; granule growth was delayed with increasing load. A common pellet growth pattern, which can be divided into three phases, was derived and confirmed from all trials. The process was monitored by means of a torque measuring system. The torque-time curve can be used to detect the beginning of the destruction phase.
Thies
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Department of Pharmaceutics and Biopharmaceutics, Christian-Albrecht-University, Gutenbergstrasse 76, 24118, Kiel, Germany.
Kleinebudde
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D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D015203:Reproducibility of Results; D013223:Statistics as Topic; D013696:Temperature; D013997:Time Factors; D014635:Valproic Acid / Q000737:chemistry
D005079:Excipients; D005989:Glycerides; D004364:Pharmaceutical Preparations; D014635:Valproic Acid