Cinira Fandaruff1, Thiago Caon2, Andrea Mariela Araya-Sibaja3, Gabriela Schneider Rauber4, Marcos Antônio Segatto Silva4, Cláudia Maria Oliveira Simões5, Carlos Eduardo Maduro de Campos6, Adailton João Bortoluzzi7, Jackson Antônio Lamounier Camargos Resende8, Silvia Lucia Cuffini9. 1. Laboratório de Controle de Qualidade, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, UFSC Campus Reitor João David Ferreira Lima, s/n Trindade, Florianópolis, Santa Catarina, CEP: 88040-900, Brazil. cinira_fandaruff@hotmail.com. 2. Laboratório de Farmacotécnica e Cosmetologia, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis, Brazil. 3. Laboratorio Nacional de Nanotecnología LANOTEC-CeNAT-CONARE, San José, 1174-1200, Costa Rica. 4. Laboratório de Controle de Qualidade, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, UFSC Campus Reitor João David Ferreira Lima, s/n Trindade, Florianópolis, Santa Catarina, CEP: 88040-900, Brazil. 5. Laboratório de Virologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil. 6. Laboratório de Difração de Raios-X, Departamento de Física, Universidade Federal de Santa Catarina, Florianópolis, Brazil. 7. Laboratório de Bioinorgânica e Cristalografia, Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Brazil. 8. Pós-Graduação em Ciências dos Materiais, Universidade Federal de Mato Grosso, Instituto de Ciências Exatas e da Terra - CUA, Barra do Garças, Brazil. 9. Pós-Graduação em Engenharia e Ciências dos Materiais, Universidade Federal de São Paulo, São José dos Campos, Brazil.
Abstract
PURPOSE: To understand the anomalous behavior of Saquinavir Mesylate (SQVM) in sodium decyl sulfate (SDS) medium during a dissolution test through a crystallographic analysis of the crystal obtained. As a result, it will be possible to elucidate its crystal structure and carry out a complete solid-state characterization of the API. METHODS: The solid form obtained was characterized by a structural analysis through X-ray single crystal and powder diffraction. The crystallographic structures of the new salt and the SQVM were compared. In addition, a complete solid-state characterization of SQVM raw material was carried out by techniques such as diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), Raman spectroscopy, scanning electron microscopy and a dissolution method. RESULTS: A new salt consisting of SQVM and SDS was crystallized and its crystal structure was elucidated and reported herein for the first time. The anionic part of SDS interacts with the cationic segment of SQVM to obtain a new salt designated as SQV-DS, which precipitates. The main difference between the two structures occurs in the c-axis expansion, which increases from 15.966 (5) to 21.1924 (14), respectively. CONCLUSIONS: Some of the strategies to enhance the dissolution rate of poorly aqueous soluble APIs include the use of surfactants such as SDS in the dissolution medium, as well as in the formulated products. However, there have been constant reports of a dissolution rate slowdown by some surfactants. The interaction mechanisms between the APIs and the dissolution medium containing surfactants need to be carefully investigated in current pharmaceutical formulations. Graphical Abstract.
PURPOSE: To understand the anomalous behavior of Saquinavir Mesylate (SQVM) in sodium decyl sulfate (SDS) medium during a dissolution test through a crystallographic analysis of the crystal obtained. As a result, it will be possible to elucidate its crystal structure and carry out a complete solid-state characterization of the API. METHODS: The solid form obtained was characterized by a structural analysis through X-ray single crystal and powder diffraction. The crystallographic structures of the new salt and the SQVM were compared. In addition, a complete solid-state characterization of SQVM raw material was carried out by techniques such as diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), Raman spectroscopy, scanning electron microscopy and a dissolution method. RESULTS: A new salt consisting of SQVM and SDS was crystallized and its crystal structure was elucidated and reported herein for the first time. The anionic part of SDS interacts with the cationic segment of SQVM to obtain a new salt designated as SQV-DS, which precipitates. The main difference between the two structures occurs in the c-axis expansion, which increases from 15.966 (5) to 21.1924 (14), respectively. CONCLUSIONS: Some of the strategies to enhance the dissolution rate of poorly aqueous soluble APIs include the use of surfactants such as SDS in the dissolution medium, as well as in the formulated products. However, there have been constant reports of a dissolution rate slowdown by some surfactants. The interaction mechanisms between the APIs and the dissolution medium containing surfactants need to be carefully investigated in current pharmaceutical formulations. Graphical Abstract.
Authors: Cristiane R D Hoffmeister; Cinira Fandaruff; Maíra A da Costa; Lucio M Cabral; Luciana R Pitta; Stanley E R Bilatto; Livia D Prado; Daniel S Corrêa; Leandro Tasso; Marcos Antônio S Silva; Helvécio V A Rocha Journal: Eur J Pharm Sci Date: 2016-12-29 Impact factor: 4.384
Authors: Ana Beloqui; María Ángeles Solinís; Alicia R Gascón; Ana del Pozo-Rodríguez; Anne des Rieux; Véronique Préat Journal: J Control Release Date: 2012-12-22 Impact factor: 9.776