An Investigation into the Influence of Drug-Polymer Interactions on the Miscibility, Processability and Structure of Polyvinylpyrrolidone-Based Hot Melt Extrusion Formulations

Chan, Siok-Yee, Qi, Sheng and Craig, Duncan Q.M. (2015) An Investigation into the Influence of Drug-Polymer Interactions on the Miscibility, Processability and Structure of Polyvinylpyrrolidone-Based Hot Melt Extrusion Formulations. International Journal of Pharmaceutics, 496 (1). pp. 95-106. ISSN 0378-5173

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Abstract

While hot melt extrusion is now established within the pharmaceutical industry, the prediction of miscibility, processability and structural stability remains a pertinent issue, including the issue of whether molecular interaction is necessary for suitable performance. Here we integrate the use of theoretical and experimental drug–polymer interaction assessment with determination of processability and structure of dispersions in two polyvinylpyrrolidone-based polymers (PVP and PVP vinyl acetate, PVPVA). Caffeine and paracetamol were chosen as model drugs on the basis of their differing hydrogen bonding potential with PVP. Solubility parameter and interaction parameter calculations predicted a greater miscibility for paracetamol, while ATR-FTIR confirmed the hydrogen bonding propensity of the paracetamol with both polymers, with little interaction detected for caffeine. PVP was found to exhibit greater interaction and miscibility with paracetamol than did PVPVA. It was noted that lower processing temperatures (circa 40 °C below the Tg of the polymer alone and Tm of the crystalline drug) and higher drug loadings with associated molecular dispersion up to 50% w/w were possible for the paracetamol dispersions, although molecular dispersion with the non-interactive caffeine was noted at loadings up to 20% w./w. A lower processing temperature was also noted for caffeine-loaded systems despite the absence of detectable interactions. The study has therefore indicated that theoretical and experimental detection of miscibility and drug–polymer interactions may lead to insights into product processing and extrudate structure, with direct molecular interaction representing a helpful but not essential aspect of drug–polymer combination prediction.

Item Type: Article
Uncontrolled Keywords: hme,solid dispersion,hot melt extrusion,solubility parameter,melting point depression,polyvinylpyrrolidone
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 19 Dec 2015 07:14
Last Modified: 31 Oct 2019 14:38
URI: https://ueaeprints.uea.ac.uk/id/eprint/55778
DOI: 10.1016/j.ijpharm.2015.09.063

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