Solid crystal suspensions containing griseofulvin - Preparation and bioavailability testing

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• 作者：Elena Reitz^a ; Chris Vervaet^b ; Reinhard H.H. Neubert^c ; Markus Thommes^a ; ^{Markus.Thommes@uni-duesseldorf.de}
• 关键词：Extrusion ; Granulation ; Suspension ; Crystallization ; Dispersion
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：83
• 期：2
• 页码：193-202
• 全文大小：950 K

文摘

The improvement of the bioavailability of poorly soluble drugs has been an important issue in pharmaceutical research for many years. Despite the suggestion of several other technologies in the past, drug particle size reduction is still an appropriate strategy to guarantee high bioavailability of various drugs. A few years ago, the Solid Crystal Suspension (SCS) technology was suggested, in which crystalline drug particles are ground and dispersed in a highly soluble crystalline carrier by a hot melt extrusion process.

The current study demonstrates the scale-up of the SCS technology to standard, lab-scale extrusion equipment¡ªa change from previous investigations, which used small batch sizes. A twin-screw extruder was modified to account for the rapid crystallization of the carrier. The screw speed and the barrel temperature were identified as critical process parameters and were varied systematically in several experimental designs. Finally, parameters were identified that produced extrudates with rapid dissolution rates.

After extrusion, the extrudates were milled to granules and then tableted. These tablets were investigated with respect to their bioavailability in beagle dogs. It was found that drug particle size reduction in the hot melt extrusion led to 3.5-fold higher bioavailability in these dogs than occurred with the physical mixture of the used substances. The solid crystal suspension formulation had a slightly higher bioavailability than the marked product.

In conclusion, the SCS technology was successfully scaled up to lab-scale equipment, and the concept was confirmed by a bioavailability study.