The different roles of surface and bulk effects on the functionality of pharmaceutical materials
Abstract
Understanding the variability in the functionality of pharmaceutical materials is one of the main concerns for assuring quality of a pharmaceutical product. Traditional methods to understand variability have yielded little success because they have been focused mainly on chemical purity. It is now widely recognized that physical attributes play a far greater role that previously anticipated. Despite this realization little to no real progress has been achieved in understanding variability of pharmaceutical material. This work shows that significant progress in understanding variability can be achieved using a material science based approach. The approach used here is to identify whether the variability in question can be associated to bulk effects or surface effects of the material and then follow-through with assessments made on the basis of appropriate functionality testing. Significant success based on this approach was achieved on specific topics, which include antiplasticization, excipient variability, nature of milling induced disorder and effect of dehydration conditions on the rehydration of anhydrous hydrates. The consistent theme of this work is on enhancing the understanding of the experimental trends of commonly used pharmaceutical materials and processes. These experimental trends would have been considered unexplained variability of the system and ignored. Using a prudent material science approach described above, which involves understanding the different roles of surface and bulk effects, a theoretical framework in each case, was developed. This framework not only helps us understand these experimental trends but also helps in predicting them. This aspect of the research has significant implications for the current and future manufacturing environment, where the overall goal is to continually increase the understanding of the process by explaining variability. The material science based approach used here also resulted in the development and/or exploration of novel characterization approaches. The surface characterization methods developed include detection of a solid-solid phase transition temperature from surface measurements and assessing flow properties of powders by linking surface energy measurements with topology measurements. The bulk characterization methods developed include a method to accurately measure isothermal structural relaxation.
Degree
Ph.D.
Advisors
Pinal, Purdue University.
Subject Area
Physical chemistry|Pharmaceutical sciences|Organic chemistry
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