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A New Saquinavir Mesylate-Sodium Decyl Sulfate Salt Discovered by Serendipity during an Anomalous Dissolution Test

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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.

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to thank Cristália Laboratory (Cristália Produtos Químicos e Farmacêuticos Ltda – São Paulo – Brazil) for donating saquinavir mesylate. The authors are also grateful to CNPq, CAPES, FAPESC, INCT-Catálise/FAPESC and FINEP for their financial support. We would also like to thank Laboratório Central de Microscopia Eletrônica (LCME) at UFSC for their valuable assistance. The authors declare that there are no conflicts of interests regarding this manuscript.

CRediT AUTHORSHIP CONTRIBUTION

Cinira Fandaruff: Investigation, Conceptualization, Formal analysis, Writing-Original Draft, Writing-Review & Editing. Thiago Caon: Validation. Andrea Mariela Araya-Sibaja:Writing-Review & Editing. Gabriela Schneider Rauber: Validation. Marcos Antônio Segatto Silva: Conceptualization, Supervision, Resources. Cláudia Maria Oliveira Simões: Resources. Carlos Eduardo Maduro de Campos: Investigation, Conceptualization, Formal analysis, Resources, Writing-Original Draft. Adailton João Bortoluzzi: Investigation, Conceptualization, Formal analysis, Resources, Writing-Original Draft. Jackson Antônio Lamounier Camargos Resende: Investigation, Conceptualization, Formal analysis, Resources, Writing-Original Draft. Silvia Lucia Cuffini: Investigation, Conceptualization, Supervision.

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Authors and Affiliations

  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, Gabriela Schneider Rauber & Marcos Antônio Segatto Silva

  2. Laboratório de Farmacotécnica e Cosmetologia, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis, Brazil

    Thiago Caon

  3. Laboratorio Nacional de Nanotecnología LANOTEC-CeNAT-CONARE, San José, 1174-1200, Costa Rica

    Andrea Mariela Araya-Sibaja

  4. Laboratório de Virologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil

    Cláudia Maria Oliveira Simões

  5. Laboratório de Difração de Raios-X, Departamento de Física, Universidade Federal de Santa Catarina, Florianópolis, Brazil

    Carlos Eduardo Maduro de Campos

  6. Laboratório de Bioinorgânica e Cristalografia, Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Brazil

    Adailton João Bortoluzzi

  7. Pós-Graduação em Ciências dos Materiais, Universidade Federal de Mato Grosso, Instituto de Ciências Exatas e da Terra – CUA, Barra do Garças, Brazil

    Jackson Antônio Lamounier Camargos Resende

  8. Pós-Graduação em Engenharia e Ciências dos Materiais, Universidade Federal de São Paulo, São José dos Campos, Brazil

    Silvia Lucia Cuffini

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  1. Cinira Fandaruff
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  2. Thiago Caon
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  6. Cláudia Maria Oliveira Simões
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Correspondence to Cinira Fandaruff.

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Fandaruff, C., Caon, T., Araya-Sibaja, A.M. et al. A New Saquinavir Mesylate-Sodium Decyl Sulfate Salt Discovered by Serendipity during an Anomalous Dissolution Test. Pharm Res 39, 189–200 (2022). https://doi.org/10.1007/s11095-022-03167-4

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  • DOI: https://doi.org/10.1007/s11095-022-03167-4

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