The development of roller compacted formulations using multivariate and dimensional analysis
Abstract
Roller compaction is the most commonly employed dry granulation process in the pharmaceutical industry. While previous research has demonstrated the operating parameters strongly influence the properties of the final product, a greater emphasis might be placed on the raw material attributes of the compacted formulation. To ascertain these relationships, partial least squares was employed to determine the extent to which the raw material attributes influence the post compacted ribbon, granule and tablet properties. This research looked to establish if models obtained with formulations of one API could predict the post compacted properties of similar formulations in terms of the excipients used, but the important difference of having a different API. Multivariate models showed that both the operating parameters and raw material attributes were essential in the prediction of ribbon porosity, post milled particle size and tablet tensile strength. In addition, near infrared spectroscopy and ribbon porosity (or solid fraction) were investigated as tools to extract the post compacted ribbon, granule and tablets properties from the roller compacted formulations. The research showed that the NIR slope and ribbon porosity can be used to extract the post roller compacted properties of the ribbons, subsequent granules and ultimate tablets. This makes near infrared spectroscopy an excellent tool for potential process feedback control. Finally, this project looked to establish if dimensionless variables could be used as criteria for scale up and transferability. This work was completed to establish the ground work for the development of a dimensionless relationship relating the operating parameters of the equipment to the porosity of the ribbon. The working hypothesis was three-fold, namely (i) that ribbons of the same porosity made with different equipment will have similar properties, (ii) that it is possible to establish an objective relationship between ribbon porosity and a combination of operating parameters and raw material attributes, and (iii) that by expressing such parameter combination as a dimensionless variable, it will be possible to use the same relationship for different pieces of roller compaction equipment. The dimensionless variable RP/RS*HFS*True Density*D2 was found to correlate well with the ribbon porosity for the formulations used in these experiments. Depending on the formulation, the average difference in ribbon porosity between the two units varied between 0.012 and 0.024.
Degree
Ph.D.
Advisors
Pinal, Purdue University.
Subject Area
Pharmacy sciences
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