Date of Award

Summer 2008

Document Type

Thesis

Degree Name

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

Department

Chemical Engineering

First Advisor

Piero M. Armenante

Second Advisor

Robert Benedict Barat

Third Advisor

S. Mitra

Abstract

Almost 80% of drugs on the market are manufactured as solid dosage forms, such as tablets. Drug bioavailability increases as the particle size decreases and the surface area per unit volume of drug increases. Therefore, there is a keen interest by the pharmaceutical industry to develop techniques that can be used to manufacture particles of active pharmaceutical ingredients (API) in the nano/micro particle range. Impinging jets is one of the most promising techniques to do so.

In this work, a submerged impinging jet system coupled with an ultrasonic probe (sonicator) was used to precipitate Griseofulvin, a common, poorly water-soluble antifungal drug. The drug was initially dissolved in acetone and then precipitated using water as the antisolvent. Experiments were carried out for different values of the sonication power, impinging jet velocity, and reactor volume. Their effect on the size and morphology of the precipitated crystals was quantified. The crystals were analyzed using a laser diffraction method (for particle size distribution), electron microscopy (for crystal morphology), and X-ray diffraction (for crystallinity). The results obtained here indicate that increasing the sonication power, and, to a much more limited extent, the impinging jet velocity decreases the crystal size, but that eventually an asymptotic value of the mean particle size is achieved. The reactor volume does not appear to play a major role, at least in the system examined here. The results obtained in this work could have important implications for the manufacturing of drug particles for solid dosage form use.

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