Date of Defense

9-4-1998

Department

Chemistry

First Advisor

T.C. Rob Ju, Pharmacia & Upjohn

Second Advisor

John Miller, Chemistry

Abstract

In this stufty several polymer series (HPMC F, E, K, and MC A) were evaluated for their effectiveness in precipitation inhibition of FA31A, a drug candidate for the treatment of Rheumatoid Arthritis. Effectiveness of precipitation inhibition increased with increasing hydrophobicity of polymer. The increased effectiveness with increased frydrophobicity was seen in bqth stages of precipitation: nucleation and crystal growth. Nucleation was the amount of time the drug/polymer remained in solution before precipitation began and was measured Ijy the induction period (Tind). The crystal growth stage began at the first sign of precipitation and ended at the time the concentration of the solution reached 85% of the original concentration (T85%). Both the T^d and T85o/o of the polymer increased as the hydrophobicity of the polymer increased. For a given hydrophobicity, the Ti„d and T85o/o increased with polymer molecular weight, indicating that increasing the molecular weight of the polymer also increased effectiveness of precipitation inhibition. Crystal growth was observed microscopically and the particle size of the precipitate was measured in two of the FA31 A/polymer solutions. The increase in crystal size and number over time facilitated aggregation and precipitation, resulting in decreased percent concentration ofthe solution.

Access Setting

Honors Thesis-Campus Only

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