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

Research output: Contribution to journalArticlepeer-review

Authors

  • Deen Huang
  • Ziyuan Xie
  • Qiuhong Rao
  • Evangelos Liamas
  • Piaopiao Pan
  • Shixia Guan
  • Ming Lu
  • Qingguo Li

Colleges, School and Institutes

External organisations

  • Guangzhou University of Chinese Medicine
  • The First Affiliated Hospital of Sun Yat-Sen University

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.

Bibliographic note

Funding Information: The present work was financially supported by the National Natural Science Foundation of China (No. 51103184 ), the National Natural Science Foundation of Guangdong Province (No. 2018A030313335 ), the Fundamental Research Founds for the Central Universities (No. 12ykpy08 ), the Science Program for Overseas Scholars of Guangzhou University of Chinese Medicine (Torch program), and the Guangdong Science and Technology Program ( 2017ZC0140 ; 2017ZC0157 ). Funding Information: The present work was financially supported by the National Natural Science Foundation of China (No. 51103184), the National Natural Science Foundation of Guangdong Province (No. 2018A030313335), the Fundamental Research Founds for the Central Universities (No. 12ykpy08), the Science Program for Overseas Scholars of Guangzhou University of Chinese Medicine (Torch program), and the Guangdong Science and Technology Program (2017ZC0140; 2017ZC0157). The authors declare that there was no conflict of interest in the preparation of this manuscript. Publisher Copyright: © 2019 Elsevier B.V. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

Details

Original languageEnglish
Pages (from-to)316-324
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume565
Publication statusPublished - 30 Jun 2019

Keywords

  • Amorphous solid dispersion, Bioavailability, Heat-sensitive, High melting point, Hot melt extrusion, Recrystallization, Tadalafil

ASJC Scopus subject areas