Date of Award

Spring 2013

Document Type

Thesis

Degree Name

Master of Science in Chemical Engineering - (M.S.)

Department

Chemical, Biological and Pharmaceutical Engineering

First Advisor

Ecevit Atalay Bilgili

Second Advisor

Rajesh N. Dave

Third Advisor

Robert Benedict Barat

Abstract

One of the ways to improve the dissolution rate of poorly water-soluble drugs is to produce fine drug particles with increased surface area. This increase will lead to bioavailability enhancement. However, smaller drug particles are thermodynamically unstable and tend to aggregate or grow. Therefore, proper formulation and process parameters must be chosen to keep the particles small. In this study, fine drug particles of two model drugs, fenofibrate and ibuprofen, are prepared by the melt emulsification technique. The influence of suspension formulation (i.e., the inclusion of polymers and surface-active agents) on particle stability is investigated. Moreover, different agitation techniques during cooling are studied for their impact on the physical stability and recrystallization of molten drug particles. The use of both nonionic surfactant Pluronic F68 and high-intensity ultrasound during cooling produces fenofibrate and ibuprofen suspensions with enhanced short-term physical stability. The optimized fenofibrate suspension is blended with hydroxypropyl methylcellulose film solution and cast into a solid strip film by oven drying. The film is characterized by redispersion and by dissolution rate. Particles are recovered from the films in de-ionized water within 5 minutes with no size increase, and a marked increase in dissolution rate is observed in comparison to as-received particles. The feasibility of incorporating stable drug particles produced by melt emulsification into strip films and consequent enhancement of particle recovery and dissolution rate from these films are successfully demonstrated.

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