Huang, D, Xie, Z, Rao, Q et al. (6 more authors) (2019) Hot melt extrusion of heat-sensitive and high melting point drug: Inhibit the recrystallization of the prepared amorphous drug during extrusion to improve the bioavailability. International Journal of Pharmaceutics, 565. pp. 316-324. ISSN 0378-5173
Abstract
Using tadalafil (TD) as a representative of heat-sensitive drug with high melting point and strong crystallization tendency, we observed that recrystallization of the prepared amorphous materials during extrusion can result in failure of amorphous solid dispersion (ASD) extrusion. Such recrystallization process of amorphous TD during reheating process was investigated systematically. Our results show that spray-dried amorphous TD sample is more prone to recrystallize (occurs from 150 °C) in comparison to the melt-quenched amorphous TD sample (recrystallizes from 190 °C). Poor stability of the spray-dried TD sample is likely due to an excessive amount of available surface area. Co-extruding Soluplus with spray-dried amorphous TD at 160 °C could yield ASD at 10% drug loading and crystalline solid dispersion above 20% drug loading. The method that spray drying 20% TD with 80% Soluplus and then extruding the spray-dried sample can obtain ASD at 20% drug loading at 160 °C, 142 °C lower than the melting point of TD (302 °C). More importantly, the samples prepared by such strategy exhibited a substantially improved bioavailability compared to the samples that were prepared by either spray-dried or hot-melt extruded processes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Elsevier B.V. All rights reserved. This is an author produced version of an article published in International Journal of Pharmaceutics. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Hot melt extrusion; Amorphous solid dispersion; Heat-sensitive; High melting point; Recrystallization; Tadalafil; Bioavailability |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds) > FSN Colloids and Food Processing (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 02 Dec 2021 12:53 |
Last Modified: | 25 Jun 2023 22:50 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.ijpharm.2019.04.064 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:181014 |