Roller compaction of pharmaceutical excipients and excipient-drug blends
Abstract
An instrumented Fitzpatrick Model L-83 Chilsonator was used to evaluate the granulation of pharmaceutical materials using roller compaction. The instrumentation measured the compaction forces produced during roller compaction. The effects of the compactor parameter settings on the characteristics of the granulations produced were evaluated. The granulations were also evaluated for physical characteristics which would influence the tableting behavior of these materials. The excipients studied were several grades of microcrystalline cellulose and hydrous lactose roller compacted as single materials. The two drug blends were an aspirin blend and an acetaminophen blend. The effects of compactor parameter settings on the characteristics of the granulations produced were evaluated using a quadratic regression model. The response variables monitored were the particle size distribution and the compressibility of the granulations produced by roller compaction. The reduced models obtained differed for each of the materials evaluated. The effect of the compactor parameters on the material being compacted depended not only on the system variables but also on the material deformation properties. Response surface plots were generated to enable prediction of the compactor parameter settings which would produce granulations with the desired particle size distributions and compressibility. The flow, friability, bulk density, particle size distribution and compressibility of the granulations produced by roller compaction were evaluated. Particle size distribution size changes depended on the compactor parameter levels. The compressibility or deformation tendencies were reduced for all granulations that showed an increase in the geometric mean particle size. The magnitude of the compressibility changes depended on the compactor parameter levels used and the deformation properties of the material. The material did not show any improvement in flow. This flow testing was performed without the addition of a lubricant to the final granules. The bulk densities of the granulations of the excipients all showed an increase over the uncompacted powder. The drug blends had a mixture of increasing and decreasing bulk densities depending on the compactor parameter levels used for production. With optimal compactor settings granulations with good tableting properties can be produced.
Degree
Ph.D.
Advisors
Peck, Purdue University.
Subject Area
Pharmacology
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