Investigating the density distribution of roller compacted ribbons
Abstract
The way in which pharmaceutical products are being developed and manufactured is changing as the focus is shifting to understand the link between material properties and manufacturing processes on critical quality attributes. However, with the increased cost of developing new products companies are looking for ways to expedite the development process while using less active pharmaceutical ingredient. In order to accomplish the desired state of development and manufacture, the use of material sparing techniques is on the rise. In addition, the use of process analytical technologies allow for real-time monitoring and control of critical material properties to ensure critical quality attributes of the product is met. Through the use of surrogate samples and near infrared spectroscopy it is possible to develop a robust and repeatable roller compaction process using the concepts of quality by design. This study investigates the use of surrogate compacts to develop robust and accurate near infrared spectroscopic chemometric models to predict roller compacted ribbon density. Also, the use of near infrared spectroscopy to identify and monitor the causes of the three dimensional density distribution of roller compacted ribbons in real-time using a multipoint fiber optic probe. Next, this study uses surrogate compacts to understand the impact of compact density on milled granule particle size distribution, granule bulk density, and final tablet tensile strength. The surrogate compact data is then used to predict the impact of the observed three dimensional roller compacted ribbon density distribution on these critical material attributes. Finally, this study discusses the future of pharmaceutical manufacturing in the desired state using the findings from the three studies to develop a robust and repeatable roller compaction process.
Degree
Ph.D.
Advisors
Pinal, Purdue University.
Subject Area
Pharmacy sciences
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