Thermal stability of aripiprazole monohydrate investigated by Raman spectroscopy |
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| Affiliation: | 1. Department of Physics, Federal University of Ceará, PO Box 6030, 60455-970 Fortaleza (CE), Brazil;2. Grupo Materia Condensada, Gerencia de Investigación y Aplicaciones, Comisión Nacional de Energía Atómica, Av. Gral. Paz 149, 9 B1650KNA-San Martín, Argentina;3. Escuela de Ciencia y Tecnología, UNSAM, San Martín, Buenos Aires, Argentina;1. F. Hoffmann-La Roche Ltd., Wurmisweg, CH-4303 Kaiseraugst, Switzerland;2. University of Liege (ULg), CIRM, Department of Pharmacy, Laboratory of Analytical Chemistry, Quartier Hôpital, Avenue Hippocrate 15, B36, B-4000 Liege, Belgium;1. Clinical Pharmacology Unit and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea;2. Department of Psychiatry, College of Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea;1. Department of Chemistry, Iowa State University, 1605 Gilman Hall, Ames, IA 50011, United States of America;2. Small Molecules Analytical Chemistry and Quality Control, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States of America |
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| Abstract: | Aripiprazole (7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydrocarbostyril) is a well-known antipsychotic oral drug, whose molecular structure makes it suitable for polymorphism. Several crystalline structures were reported in the literature including anhydrate, hydrate and solvate modifications. It was observed that aripiprazole monohydrate exhibits a complex dehydration dynamics which was not completely elucidated. In this work the dehydration process of the aripiprazole hydrate was investigated by using Raman scattering, hot-stage microscopy and differential scanning calorimetry. The temperature evolution of the Raman spectra was analyzed through the multivariate statistical method of principal component analysis. Our results support that the dehydration process of aripiprazole is divided into two steps. First a diffusion-controlled loss of water followed by a fast nucleation and crystallization of the anhydrous form. |
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