Selection of Optimal Hydrate/Solvate Forms of a Fibrinogen Receptor Antagonist for Solid Dosage Development
| Autor: | Michelle L. Bray, Michael J. Kaufman, Hossain Jahansouz |
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| Rok vydání: | 1999 |
| Předmět: |
Stereochemistry
Fibrinogen receptor Administration Oral Pharmaceutical Science Platelet Glycoprotein GPIIb-IIIa Complex Crystal structure Dosage form law.invention Drug Stability Fibrinolytic Agents X-Ray Diffraction law Crystallization Chromatography High Pressure Liquid Sulfonamides Aqueous solution Calorimetry Differential Scanning Chemistry Humidity Azepines General Medicine Solubility Polymorphism (materials science) Thermogravimetry Hydrate Fibrinolytic agent Nuclear chemistry |
| Zdroj: | Pharmaceutical Development and Technology. 4:81-87 |
| ISSN: | 1097-9867 1083-7450 |
| Popis: | The objective of this work was to compare the physicochemical properties of four crystalline forms of the fibrinogen receptor antagonist L-738,167 [2(S)-[p-toluenesulfonyl amino]-3-[[[5,6,7,8-tetrahydro-4-oxo-5-[2-(piperidin-4-yl)ethyl] -4-H-pyrazolo[1,5-a][1,4] diazepin-2-yl] carbonyl]amino]-propionic acid] to determine the best form for use in the development of oral dosage formulations. Four crystalline forms [form A (trihydrate), form B (pentahydrate), form C, and form D] were compared using x-ray powder diffractometry, thermal analysis, and moisture sorption studies. The trihydrate, form A, was demonstrated to hydrate upon exposure to relative humidity (RH) above 50% at room temperature (25 degrees C) with conversion to the pentahydrate. The pentahydrate, form B, converted to the trihydrate at room temperature when exposed to humidity levels below 25% RH. The crystalline pentahydrate was shown to be stable to dehydration upon storage at 30 degrees C/60% RH and 40 degrees C/75% RH for 3 months. The suspension of form A or form D in water resulted in conversion to form B, the stable hydrated form in an aqueous environment. Form C has a unique crystalline structure that is stable in an aqueous environment and not subject to hydration/dehydration with changes in relative humidity and thus may offer some advantages in pharmaceutical development. |
| Databáze: | OpenAIRE |
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