Role of Solvent Selection on Crystal Habit of 5-Aminosalicylic Acid—Combined Experimental and Computational Approach
| Autor: | Jukka Rantanen, Nawin Pudasaini, Christian R. Parker, Stefan U. Hagen, Andrew D. Bond |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Pharmaceutical Science
02 engineering and technology 010402 general chemistry 01 natural sciences law.invention Crystal chemistry.chemical_compound law Polymer chemistry Crystallization Crystal habit Mesalamine Tetrahydrofuran Acicular Aqueous solution Tetramethylurea Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology 0104 chemical sciences Oxygen Solvent chemistry Solvents Adsorption 0210 nano-technology |
| Zdroj: | Journal of Pharmaceutical Sciences. 107:1112-1121 |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2017.12.005 |
| Popis: | Many active pharmaceutical ingredients exhibit a needle-like (acicular) crystal habit, which can significantly complicate their downstream processing. In this study, the acicular crystal habit of a model active pharmaceutical ingredient, 5-aminosalicylic acid (5-ASA), was modified by addition of selected organic solvents to the typical aqueous crystallization process. 5-ASA was crystallized by a pH shift from 7.5-8 to 4 in the presence of methanol, acetonitrile, acetone, tetramethylurea, tetrahydrofuran or dimethyl sulfoxide at 25% v/v, or butanol at 9% v/v. Changes to the experimentally observed crystal habit are rationalized by considering adsorption energy calculations for the solvent molecules onto the morphologically important crystal faces. The crystal habit was influenced most significantly by organic solvents containing a good H-bond acceptor atom, particularly oxygen in acetone, tetramethylurea, tetrahydrofuran, and dimethyl sulfoxide. Such solvents have strongly stabilizing adsorption energies onto the fast-growing crystal faces, and their presence in solution thereby serves to modify the acicular habit of 5-ASA. The developed knowledge base on crystal interface-solvent interactions can form a basis for further engineering of an optimal crystal habit for 5-ASA. |
| Databáze: | OpenAIRE |
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