eprintid: 1423805 rev_number: 39 eprint_status: archive userid: 608 dir: disk0/01/42/38/05 datestamp: 2014-03-22 07:30:02 lastmod: 2021-10-05 00:31:33 status_changed: 2014-08-21 14:03:09 type: article metadata_visibility: show item_issues_count: 0 creators_name: Pina, MF creators_name: Zhao, M creators_name: Pinto, JF creators_name: Sousa, JJ creators_name: Craig, DQM title: The Influence of Drug Physical State on the Dissolution Enhancement of Solid Dispersions Prepared Via Hot-Melt Extrusion: A Case Study Using Olanzapine ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D10 divisions: G08 keywords: olanzapine, dissolution, solid dispersion, polymer, amorphous, crystallinity, particle size note: © 2014 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. abstract: In this study, we examine the relationship between the physical structure and dissolution behavior of olanzapine (OLZ) prepared via hot-melt extrusion in three polymers [polyvinylpyrrolidone (PVP) K30, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) 6:4, and Soluplus® (SLP)]. In particular, we examine whether full amorphicity is necessary to achieve a favorable dissolution profile. Drug–polymer miscibility was estimated using melting point depression and Hansen solubility parameters. Solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. All the polymers were found to be miscible with OLZ in a decreasing order of PVP>PVPVA>SLP. At a lower extrusion temperature (160°C), PVP generated fully amorphous dispersions with OLZ, whereas the formulations with PVPVA and SLP contained 14%–16% crystalline OLZ. Increasing the extrusion temperature to 180°C allowed the preparation of fully amorphous systems with PVPVA and SLP. Despite these differences, the dissolution rates of these preparations were comparable, with PVP showing a lower release rate despite being fully amorphous. These findings suggested that, at least in the particular case of OLZ, the absence of crystalline material may not be critical to the dissolution performance. We suggest alternative key factors determining dissolution, particularly the dissolution behavior of the polymers themselves. date: 2014-04 official_url: http://dx.doi.org/10.1002/jps.23894 vfaculties: VFLS oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_source: WoS-Lite elements_id: 931719 doi: 10.1002/jps.23894 lyricists_name: Craig, Duncan lyricists_name: Gomes Pina, Maria lyricists_name: Zhao, Min lyricists_id: DQMCR05 lyricists_id: MDEFA82 lyricists_id: MZHAO40 full_text_status: public publication: Journal of Pharmaceutical Sciences volume: 103 number: 4 pagerange: 1214 - 1223 issn: 0022-3549 citation: Pina, MF; Zhao, M; Pinto, JF; Sousa, JJ; Craig, DQM; (2014) The Influence of Drug Physical State on the Dissolution Enhancement of Solid Dispersions Prepared Via Hot-Melt Extrusion: A Case Study Using Olanzapine. Journal of Pharmaceutical Sciences , 103 (4) 1214 - 1223. 10.1002/jps.23894 <https://doi.org/10.1002/jps.23894>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1423805/1/jps23894.pdf