Compaction enhancement of pharmaceutical solids by engineered plasticization
Abstract
The objective of this research was two fold: to use near infrared (NIR) spectroscopy for real-time monitoring and control of key compact attributes: content uniformity, moisture content, relative density, tensile strength and Young's modulus, during roller compaction; and, to develop a model for predicting the improvement in compaction behavior, during roller compaction, due to the plasticization effect of ambient moisture. Initially, compact strength and the post-milling particle-size distribution were related to the slope of the best-fit line through the NIR spectra for samples prepared under different roller compactor settings. The relationship was, however, found to be dependent on the moisture content of the material. Moisture was also found to influence the key compact attributes. Hence, multivariate data analysis was used to relate the spectral data with the above key compact attributes. NIR calibration curves were generated using the spectral data collected on simulated compacts, i.e., tablets prepared under uni-axial compression, and tested on the simulated compacts and by monitoring the ribbons as they exited the roller compactor. For all compact attributes, the NIR predicted values agreed well with the values measured using a reference method. Effect of variation in ambient moisture levels on the compaction behavior of the model formulations was also studied by comparing the physical and mechanical properties of compacts prepared by roller compaction with those collected on the simulated compacts. For all materials, samples prepared at constant roller compactor settings showed constant density and a decrease in tensile strength with increasing moisture content. Surrogate tablets prepared at constant pressure showed the opposite effect, i.e., density increased while tensile strength remained almost constant with increasing moisture content. This suggests different influence of moisture on the material under roller compaction, in which the roll gap (i.e., thickness and therefore density) remains almost constant, vs. under uni-axial compression, in which the thickness is free to change in response to the applied pressure. Variation in the ambient moisture during roller compaction was also found to influence the characteristics of tablets produced from the granules obtained post-milling the compacts. A method to study this influence is also reported.
Degree
Ph.D.
Advisors
Morris, Purdue University.
Subject Area
Pharmaceutical sciences|Analytical chemistry|Organic chemistry
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