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Characterization of the indinavir raw materials stability in some pharmaceutical processes

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Abstract

This article characterizes the stability of indinavir sulfate using different analytical techniques of quality control to evaluate important steps in the manufacturing process of indinavir, specifically involving storage and compression. Indinavir A, B, and C were obtained from different suppliers and submitted to DSC, Karl Fisher, NIR, XRPD analyses and dissolution assay. DSC curves of indinavir presented endothermic peaks of fusion at 149–150 °C for indinavir A and B (form I) and 139–143 °C for indinavir C (form II). When indinavir A and B were submitted to high Relative Humidity (RH) pseudo-polymorphic form II was formed. Indinavir C converted into an amorphous substance when submitted to compression. Near infrared and Karl Fisher assays detected high values of water for indinavir C in relation to indinavir A and B. X-ray powder diffraction of indinavir B and C showed displacement of 0.05–0.10 θ in the peaks and higher angle of diffraction in relation to indinavir A. Amorphous indinavir C demonstrated a higher intrinsic dissolution rate than indinavir A and B. Indinavir form I should be monitored during the pharmaceutical process to avoid its conversion to indinavir form II or an amorphous substance which can alter the dissolution rate.

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Acknowledgements

The authors thanks to the CNPq for its financial support with grant number 402665/05-08 of the funding of research nº54/2005—Pharmaceutical Assistance/MS/CNPq. The authors also want to thank the Laboratório Industrial Farmacêutico do Estado de Alagoas (LIFAL) in the persons of Maria Rocha C. Acioli, manager of the department of quality assurance, Denise M. M. França and Solange S. Moura pharmacists and Maria Cícera C. Santos for the technical support in the selection of the raw materials, NIR and Karl Fisher analysis and Hallison M. Pires and Flaviano Gomes of for the intrinsic dissolution assay at the IDEF/UFPB. Also thanks are given to the Instituto de Macromoléculas Prof. Eloisa Mano at the Universidade Federal do Rio de Janeiro for its XRPD analysis.

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Authors and Affiliations

  1. Laboratório de Controle de Qualidade de Fármacos e Medicamentos, Grupo de Pesquisa em Tecnologia e Controle de Qualidade de Medicamentos, Escola de Enfermagem e Farmácia, Universidade Federal de Alagoas—UFAL, Campus A. C. Simões, Br 104 Norte, Km 97, Maceió, Estado de Alagoas, CEP 57072-970, Brazil

    Ticiano Gomes do Nascimento, Irinaldo D. Basílio Júnior, Camila B. Dornelas & Vanderson B. Bernardo

  2. Laboratórios Unificados de Desenvolvimento e Ensaios de Medicamentos, Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba—UFPB, Campus I, João Pessoa, Estado da Paraíba, CEP 58059-900, Brazil

    Rui O. Macêdo & Elisana A. Moura

  3. Laboratório Industrial Farmacêutico do Estado de Alagoas—LIFAL, Av. Salvador Lira s/n, Distrito Industrial Governador Luis Cavalcante, Tabuleiro dos Martins, Maceió, Estado de Alagoas, CEP 57082-000, Brazil

    Vânia N. Rocha

  4. Hungarian Academy of Sciences, Budapest University of Technology and Economics, Research Group of Technical Analytical Chemistry, Szt. Gellért tér 4, 1111, Budapest, Hungary

    Csaba Nóvak

Authors
  1. Ticiano Gomes do Nascimento
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  2. Irinaldo D. Basílio Júnior
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  3. Rui O. Macêdo
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  4. Elisana A. Moura
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  5. Camila B. Dornelas
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  6. Vanderson B. Bernardo
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  7. Vânia N. Rocha
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  8. Csaba Nóvak
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Correspondence to Ticiano Gomes do Nascimento.

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do Nascimento, T.G., Basílio Júnior, I.D., Macêdo, R.O. et al. Characterization of the indinavir raw materials stability in some pharmaceutical processes. J Therm Anal Calorim 102, 269–275 (2010). https://doi.org/10.1007/s10973-009-0446-0

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  • DOI: https://doi.org/10.1007/s10973-009-0446-0

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