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Orodispersible Carbamazepine/Hydroxypropyl-β-Cyclodextrin Tablets Obtained by Direct Compression with Five-in-One Co-processed Excipients

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Abstract

The development of orodispersible tablets (ODTs) for poorly soluble and poorly flowable drugs via direct compression is still a challenge. This work aimed to develop ODTs of poorly soluble drugs by combining cyclodextrins that form inclusion complexes to improve wetting and release properties, and directly compressible co-processed excipients able to promote rapid disintegration and solve the poor flowability typical of inclusion complexes. Carbamazepine (CBZ) and hydroxypropyl-β-cyclodextrin (HPβCD) were used, respectively, as a model of a poorly soluble drug with poor flowability and as a solubilizing agent. Specifically, CBZ—an antiepileptic and anticonvulsant drug—may benefit from the studied formulation approach, since some patients have swallowing difficulties or fear of choking and are non-cooperative. Prosolv® ODT G2 and F-Melt® type C were the studied five-in-one co-processed excipients. The complex was prepared by kneading. Flow properties of all materials and main properties of the tablets were characterized. The obtained results showed that ODTs containing CBZ/HPβCD complex can be prepared by direct compression through the addition of co-processed excipients. The simultaneous use of co-processing and cyclodextrin technologies rendered ODTs with an in vitro disintegration time in accordance with the European Pharmacopoeia requirement and with a fast and complete drug dissolution. In conclusion, the combination of five-in-one co-processed excipients and hydrophilic cyclodextrins may help addressing the ODT formulation of poorly soluble drugs with poor flowability, by direct compression and with desired release properties.

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Acknowledgments

We would like to thank the JRS Pharma and Fuji Chemical Industries for supplying free samples of the excipients. We are also thankful to Materials Centre of the University of Porto (CEMUP) for the expert assistance with SEM analysis.

Funding

Jaime Conceição is grateful to Fundação para a Ciência e a Tecnologia (FCT, Portugal) and PhD Programme in Medicines and Pharmaceutical Innovation (i3DU) for funding this work through the grant [PD/BD/127813/2016]. This work was also supported by the Applied Molecular Biosciences Unit-UCIBIO which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019).

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Authors and Affiliations

  1. UCIBIO/REQUIMTE, MedTech-Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, no. 228, 4050-313, Porto, Portugal

    Jaime Conceição & José Manuel Sousa Lobo

  2. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

    Oluwatomide Adeoye & Helena Cabral-Marques

  3. Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma Group (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain

    Angel Concheiro & Carmen Alvarez-Lorenzo

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  1. Jaime Conceição
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  2. Oluwatomide Adeoye
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  3. Helena Cabral-Marques
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  6. José Manuel Sousa Lobo
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Correspondence to Jaime Conceição.

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Conceição, J., Adeoye, O., Cabral-Marques, H. et al. Orodispersible Carbamazepine/Hydroxypropyl-β-Cyclodextrin Tablets Obtained by Direct Compression with Five-in-One Co-processed Excipients. AAPS PharmSciTech 21, 39 (2020). https://doi.org/10.1208/s12249-019-1579-5

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