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