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Hydroxypropyl-β-Cyclodextrin and β-Cyclodextrin as Tablet Fillers for Direct Compression

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Abstract

Cyclodextrins are cyclic carbohydrates widely used as complexing and non-complexing excipients in drug delivery systems. The purpose of this work was to study the ability of hydroxypropyl-β-cyclodextrin and β-cyclodextrin to act as tablet fillers for direct compression. In this way, several parameters of the cyclodextrins were evaluated, namely: (i) the flow properties such as angle of repose, flow time, Carr index, and Hausner ratio; (ii) the compaction behavior, specifically the energies and forces exerted during tableting, the plasticity index, the lubrication efficiency, and compression profiles (force/time and work/displacement of the upper punch); and (iii) the influence on carbamazepine release characteristics from uncoated tablets, i.e., dissolution rate and disintegration time. In addition, these properties of the cyclodextrins were compared with those from other commonly used direct compression fillers (lactose monohydrate, mannitol, calcium hydrogen phosphate dihydrate, and microcrystalline cellulose) and co-processed excipients (microcrystalline cellulose/mannitol and lactose monohydrate/cellulose). Three main conclusions can be drawn: (i) the studied cyclodextrins can be used as tablet fillers for direct compression; (ii) hydroxypropyl-β-cyclodextrin showed better properties than β-cyclodextrin mainly at the level of the physics of compression (higher values of plasticity index and lubrication efficiency) and of the drug release characteristics (faster and greater dissolution rate and a shorter disintegration time); and (iii) lactose monohydrate and hydroxypropyl-β-cyclodextrin displayed the best results. As there are people intolerant to lactose, hydroxypropyl-β-cyclodextrin, although its cost is higher, can be considered a good substitute for lactose.

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Acknowledgements

Jaime Conceição is grateful to Fundação para a Ciência e a Tecnologia (FCT) and PhD Programme in Medicines and Pharmaceutical Innovation (i3DU) for funding this work through the scholarship with the reference PD/BD/127813/2016. To Roquette®, Meggle Excipients & Technology, JRS Pharma, and FMC Health and Nutrition for supplying free samples of the excipients.

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Authors and Affiliations

  1. UCIBIO—ReQuimTe, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, n.° 228, 4050-313 Oporto, Porto, Portugal

    Jaime Conceição & José Manuel Sousa Lobo

  2. Research Institute for Medicines (iMed.ULisboa), Department of Galenic Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

    Oluwatomide Adeoye & Helena Maria Cabral-Marques

  3. Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria

    Oluwatomide Adeoye

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

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Conceição, J., Adeoye, O., Cabral-Marques, H.M. et al. Hydroxypropyl-β-Cyclodextrin and β-Cyclodextrin as Tablet Fillers for Direct Compression. AAPS PharmSciTech 19, 2710–2718 (2018). https://doi.org/10.1208/s12249-018-1115-z

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