Original Research ARTICLE
Solubility, miscibility and amorphization of paracetamol in solid-state mixtures with hypromellose
- 1Gdańsk Medical University, Poland
Hydroxypropyl methylcellulose (hypromellose) is a widely known excipient commonly used in the preparation of drug formulations. It can interact with some active pharmaceutical ingredients (APIs), thereby contributing to a reduction in crystallinity, serve as a solvent for API or form stable dispersion with no tendency to aggregation. The aim of the present study was to investigate the effect of hypromellose on the solubility, miscibility and amorphization of paracetamol in mixture with this polymer. Homogenized mixtures of paracetamol with hypromellose were studied using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier transform infrared (FTIR) and Raman methods to obtain a deeper insight into the interactions between ingredients in solid state including phase diagram construction for crystalline API and amorphous polymer. A DSC study revealed potential interaction between ingredients resulting in reduced paracetamol crystallinity. This was proved using heating-cooling-heating test to confirm paracetamol amorphization. FTIR and Raman investigations excluded chemical reaction and hydrogen bonding between ingredients. The phase diagram developed facilitates predictions on the solubility of API in polymer, on the mutual miscibility of ingredients and on the temperature of mixture glass transition.
Keywords: paracetamol, Hypromellose, phase diagram, solubility with polymer, miscibility with polymer, glass transition in mixture, interactions
Received: 08 Oct 2018;
Accepted: 07 Jan 2019.
Edited by:José Das Neves, i3S, Instituto de Investigação e Inovação em Saúde, Portugal
Reviewed by:Marcello Locatelli, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy
Ashok K. Sundramoorthy, SRM Institute of Science and Technology, India
Copyright: © 2019 Leyk and Wesolowski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Marek Wesolowski, Gdańsk Medical University, Gdańsk, Poland, firstname.lastname@example.org