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Using thermal analysis as quality control for famotidine polymorph contamination

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Abstract

It is well known that undesirable polymorphs in active pharmaceutical ingredients, in any proportion, can cause harm, both financially and to the health of patients. Famotidine (FTD) exhibits three known polymorphs, A, B, and C, which differ in their physicochemical properties. Form B is pharmaceutically preferred because it shows better biopharmaceutical properties. This study used thermal analysis as the main tool in the quality control of polymorphs in FTD batches. The impact on solubility, polymorphic stability, and dissolution profile of tablets was also studied. One batch (called F01), of five characterized, showed contamination with polymorph A. F01 was ~ 2.6 times less soluble than the pure form B batch (called F05) in pH 4.5 phosphate buffer, the recommended US Pharmacopoeia dissolution medium for FTD tablets. Moreover, it was observed that after storage for 3 months (40 ± 2 °C and RH of 75 ± 5%), F05 also showed contamination with form A, representing a risk that should be monitored during the quality control of FTD raw materials and drug formulations. Nevertheless, tablets manufactured with these batches did not show differences in their dissolution profiles, indicating that the amount of form A found in F01 was not sufficient to alter release of the drug from the formulated tablet. Therefore, thermal analysis is efficient in detecting polymorphic contaminations of FTD raw materials, suggesting adequate and fast methods for quality control of drug products and thus, avoiding compromised therapeutic efficacy.

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Acknowledgements

This study was partially financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001. The authors acknowledge the Brazilian funding FAPEMIG (APQ-01819-14 and APQ-01931-16), FINEP (Refs. 134/08 and 179/12) for financial support. We also thank CAPES (J.T.J.F.) for the research fellowships.

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Authors and Affiliations

  1. Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas, Brazil

    Jennifer T. Jacon Freitas, Olimpia M. M. Santos Viana, Rudy Bonfilio & Magali Benjamim Araújo

  2. Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Jennifer T. Jacon Freitas

  3. Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Prêto, Brazil

    André L. Morais Ruela

  4. Instituto de Química, Universidade Federal de Alfenas, Alfenas, Brazil

    Marcello G. Trevisan

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  1. Jennifer T. Jacon Freitas
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Freitas, J.T.J., Viana, O.M.M.S., Bonfilio, R. et al. Using thermal analysis as quality control for famotidine polymorph contamination. J Therm Anal Calorim 147, 13405–13412 (2022). https://doi.org/10.1007/s10973-022-11667-z

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  • DOI: https://doi.org/10.1007/s10973-022-11667-z

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