INVESTIGATING PHARMACEUTICAL CO-CRYSTALS AS A MEANS TO IMPROVE THE SOLUBILITY OF A DRUG
Issue Date
2012-05-31Author
Brown, Rebecca Anderson
Publisher
University of Kansas
Format
126 pages
Type
Thesis
Degree Level
M.S.
Discipline
Pharmaceutical Chemistry
Rights
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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Show full item recordAbstract
Recently co-crystals have emerged as a potential approach to improve the solubility, dissolution, and bioavailability of active pharmaceutical ingredients (API). Often co-crystal formation is studied in the development stage in order to solve an issue (with solid form or formulation) or to expand intellectual property. However, co-crystals may have the potential of enhancing the developability of a poorly soluble lead candidate in the discovery stage. In this study, piroxicam, a BCS (Biopharmaceutical Classification System) Class II compound with low solubility, was chosen as a model drug to explore this possibility. The solution phase reaction crystallization method was chosen over slow evaporation as a way to make co-crystals because it can produce pure co-crystals that can be scaled by simply using the solubility data of the parent and coformer. A screen of carboxylic acid coformers yielded six piroxicam co-crystals which were characterized. Co-crystal aqueous solubility was measured and models were used to calculate co-crystal pH dependent solubility. Intrinsic dissolution rates of the co-crystals were measured in biorelevant media. Co-crystals were found to be more soluble and the dissolution rates were lower than the parent. Piroxicam oral exposure in rat from the co-crystals was determined and was similar to free piroxicam.
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- Pharmaceutical Chemistry Dissertations and Theses [141]
- Theses [3772]
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