Quantitative analysis of a granulation milling process, evaluation of granule strength using an instrumented mill, and investigation of granule compression behavior
Abstract
An instrumented Quadro Comil$\sp{\circler}$ was used to evaluate the milling of a pharmaceutical granulation. The effects of changing mill speed, screen hole size, impeller type, and impeller-screen clearance on milling time and work, as well as particle size reduction were investigated. Screen hole size had the largest effects on milling time and work as well as particle size reduction, while impeller type had the largest effects on overall milling performance. A new impeller design was tested and found to enhance milling efficiency by improving both particle size reduction and mill output rate. Data from the instrumented mill were also used to develop a new test for granule strength. The milling test was compared to the granule crushing strength test and the granule friability test. The time and work required to mill a specific amount of granules proved to be a more sensitive, reproducible, and simple method to measure granule strength than the other tests evaluated. Good correlation between milling tests and the standard tests was also seen, indicating that the milling tests did give an accurate measurement of granule strength. The effect of granule strength on granule compression behavior was investigated. Granule behavior during compression was studied using Heckel plot analysis. The tensile strength of tablets prepared from granules having different strengths was also determined. None of the tests performed were able to clearly reveal the influence of granule strength on either granule compression behavior or tablet tensile strength. Lack of correlation between granule strength and fragmentation propensity was attributed to test conditions and the relative similarity of the granules. In the cases of the slope and the tablet tensile strength tests, the compression pressures at which these criteria became important were beyond the pressures where granule strength effects were predominant.
Degree
Ph.D.
Advisors
Peck, Purdue University.
Subject Area
Pharmacology
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