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Fluidized Bed Hot Melt Granulation with Hydrophilic Materials Improves Enalapril Maleate Stability

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Abstract

This work aimed at developing enalapril maleate granules in order to improve its stability in solid dosage form. Granules were prepared by hot melt granulation using a fluidized bed apparatus. Gelucire 50/13®, polyethylene glycol 6000 e Poloxamer 407® were studied and compared as binders in 2 × 2 factorial designs where the proportions of enalapril maleate, binders and spray dried lactose were varied. The granulation process resulted in high yields and granule sizes that indicated the prevalence of particles coating. Furthermore, the granules obtained showed adequate flowability and a fast dissolution rate of enalapril maleate with almost 100% of the drug released in 10 min. The stability of enalapril maleate in hard gelatin capsules showed that the drug stability was greatly increased in granules, since for raw drug, the remaining content of enalapril maleate after 91 days was 68.4% and, for granules, the content was always above 93%. This result was confirmed by the quantification of the degradation products, enalaprilat and diketopiperazine, which were found in very low content in granules samples. The results demonstrate that fluidized bed hot melt granulation with hydrophilic binders is a suitable alternative for improving the chemical stability of enalapril maleate.

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ACKNOWLEDGMENTS

The financial support from FAPESP (2005/05191-2 and 2011/20872-7), CNPq (PQ-2), CAPES (PhD scholarship to T.F. Guimarães) and FAPEG is gratefully acknowledged. Authors would like to thank Rudolf Barth Electron Microscopy Platform of the Oswaldo Cruz Institute/FIOCRUZ for the SEM operation and micrographs.

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Authors and Affiliations

  1. Fundação Oswaldo Cruz (FIOCRUZ), Farmanguinhos - Manguinhos, Avenida Sizenando Nabuco 100, Rio de Janeiro, RJ, 21045-900, Brazil

    Thiago F. Guimarães

  2. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, 14040-903, Ribeirão Preto, SP, Brazil

    Thiago F. Guimarães, Amanda C. C. Comelli & Luís A. P. Freitas

  3. Labmaq do Brasil Ltda, Ribeirão Preto, Via Anhanguera km 304, CEP 140140125, SP, Brazil

    Luciana A. Tacón

  4. Faculdade de Farmácia, Universidade Federal de Goiás, Setor Universitário, Goiânia, GO, 74605-220, Brazil

    Talita A. Cunha & Ricardo N. Marreto

Authors
  1. Thiago F. Guimarães
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  2. Amanda C. C. Comelli
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  3. Luciana A. Tacón
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  4. Talita A. Cunha
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  5. Ricardo N. Marreto
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  6. Luís A. P. Freitas
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Corresponding author

Correspondence to Luís A. P. Freitas.

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Guimarães, T.F., Comelli, A.C.C., Tacón, L.A. et al. Fluidized Bed Hot Melt Granulation with Hydrophilic Materials Improves Enalapril Maleate Stability. AAPS PharmSciTech 18, 1302–1310 (2017). https://doi.org/10.1208/s12249-016-0593-0

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