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Title: “Small volume drug release testing using ultrasonic agitation: development, characterization, and applications”

Committee: Muhammad H Zaman, PhD – BU BME (Advisor) Mario Cabodi, PhD – BU BME (Chair) R. Glynn Holt, PhD – BU ME Catherine Grgicak – Rutgers CHEM Saif A Khan – National University of Singapore ChBE

Abstract: The first standardized methods for in vitro drug release testing of solid dosage forms were first introduced in the 1960s. Drug release testing has since become an important analytical measure along all stages of the drug development process. Despite the expanded role of dissolution testing and innovations in the types of dosage forms reaching the market, the fundamental methods and approaches to dissolution testing have not changed from their original introduction. This lack of innovation and one-size-fits-all approach to drug release testing has led to inefficiencies in testing and limited the scope of applications where this type of information could have an impact. In order to meet this gap, we have designed, characterized, and implemented a small volume drug release test using ultrasonic agitation to screen for differences in dosage form composition. Our approach aims to supplement official methods to address current pain points caused during multiple stages of the drug development process. The hydro-acoustic environment in the system was characterized as a function of input power and position of the acoustic source. Drug release behavior from tablets was also studied over these system parameters, and a preliminary mechanistic explanation is made linking the two. The interplay between fragmentation and diffusion on solid dissolution processes was then explored through a deterministic partial differential equation model. This model provides the first instance of time-evolving particle size distributions in a dissolution model. In the final sections of this dissertation, uses of the ultrasonic agitation mediated drug screening method are demonstrated at two different parts of the drug development process – during early formulation development for the study of composite microparticle matrix structure on drug release behavior and post market surveillance for the screening of substandard tablets.