Hot melt extrusion (HME) for amorphous solid dispersions: Predictive tools for processing and impact of drug-polymer interactions on supersaturation

被引:203
作者
Sarode, Ashish L. [1 ]
Sandhu, Harpreet [2 ]
Shah, Navnit [2 ]
Malick, Waseem [2 ]
Zia, Hossein [1 ]
机构
[1] Univ Rhode Isl, Kingston, RI 02881 USA
[2] Hoffmann La Roche Inc, Pharmaceut & Analyt Res & Dev, Nutley, NJ 07110 USA
关键词
Amorphous; Rheology; Hot melt extrusion; Solid dispersion; Interaction; Supersaturation; DIFFERENTIAL SCANNING CALORIMETRY; SOLUBILITY PARAMETERS; ORAL BIOAVAILABILITY; PHARMACEUTICAL APPLICATIONS; DOSAGE FORMS; II DRUGS; DISSOLUTION; DELIVERY; ITRACONAZOLE; EXCIPIENTS;
D O I
10.1016/j.ejps.2012.12.012
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The processing parameters for HME have been evaluated and the impact of solid state intermolecular drug-polymer interactions on supersaturation has been investigated. Poorly water soluble drugs Indomethacin (IND), Itraconazole (rrz), and Griseofulvin (GSF) and hydrophilic polymers - Eudragit EPO, Eudragit L-100-55, Eudragit L-100, HPMCAS-LF, HPMCAS-MF, Pharmacoat 603, and Kollidon VA-64 were selected for this study. Solubility parameters calculations (SPCs), differential scanning calorimetry (DSC), and rheological analysis of drug-polymer physical mixtures (PMs) was performed. The solid dispersions were manufactured using HME and characterized by powder X-ray diffraction (PXRD), polarized light microscopy (PLM), Fourier transform infra-red (FTIR) Spectroscopy, and dissolution study. Results obtained by DSC correlated well with SPC, showing single glass transition temperatures for all the PMs except ITZ in Eudragit EPO that depicted the highest difference in solubility parameters. The zero rate viscosity (eta(0)) was dependent on the melting point and consequently the state of the drug in the polymer at the softening temperature. The eta(0) of PMs was useful to estimate the processing conditions for HME and to produce transparent glassy HMEs from most of the PMs. The amorphous conversion due to HME was confirmed by PXRD and PLM. The solid state drug-polymer interactions occurred during HME could be confirmed by FTIR analysis. Highest supersaturation could be achieved for IND, ITZ, and GSF using Eudragit EPO, HPMCAS-LF, and Eudragit L-100-55, respectively where relatively higher stretching of the carbonyl peaks was observed by FTIR. Thus, the highest dissolution rate and supersaturation of poorly water soluble drugs could be attributed to drug-polymer interactions occurred during HME. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:371 / 384
页数:14
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