Tags

Type your tag names separated by a space and hit enter

Hot melt extrusion (HME) for amorphous solid dispersions: predictive tools for processing and impact of drug-polymer interactions on supersaturation.
Eur J Pharm Sci. 2013 Feb 14; 48(3):371-84.EJ

Abstract

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 (ITZ), 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 (η₀) was dependent on the melting point and consequently the state of the drug in the polymer at the softening temperature. The η₀ 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.

Authors+Show Affiliations

Biomedical and Pharmaceutical Sciences, University of Rhode Island, 7 Greenhouse Road, Kingston, RI, USA. Electronic address: ashish14sarode@gmail.com.Pharmaceutical and Analytical Research and Development, Hoffmann-La-Roche Inc., 340 Kingsland St., Nutley, NJ, USA.Pharmaceutical and Analytical Research and Development, Hoffmann-La-Roche Inc., 340 Kingsland St., Nutley, NJ, USA.Pharmaceutical and Analytical Research and Development, Hoffmann-La-Roche Inc., 340 Kingsland St., Nutley, NJ, USA.Biomedical and Pharmaceutical Sciences, University of Rhode Island, 7 Greenhouse Road, Kingston, RI, USA.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

23267847

Citation

Sarode, Ashish L., et al. "Hot Melt Extrusion (HME) for Amorphous Solid Dispersions: Predictive Tools for Processing and Impact of Drug-polymer Interactions On Supersaturation." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 48, no. 3, 2013, pp. 371-84.
Sarode AL, Sandhu H, Shah N, et al. Hot melt extrusion (HME) for amorphous solid dispersions: predictive tools for processing and impact of drug-polymer interactions on supersaturation. Eur J Pharm Sci. 2013;48(3):371-84.
Sarode, A. L., Sandhu, H., Shah, N., Malick, W., & Zia, H. (2013). Hot melt extrusion (HME) for amorphous solid dispersions: predictive tools for processing and impact of drug-polymer interactions on supersaturation. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 48(3), 371-84. https://doi.org/10.1016/j.ejps.2012.12.012
Sarode AL, et al. Hot Melt Extrusion (HME) for Amorphous Solid Dispersions: Predictive Tools for Processing and Impact of Drug-polymer Interactions On Supersaturation. Eur J Pharm Sci. 2013 Feb 14;48(3):371-84. PubMed PMID: 23267847.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hot melt extrusion (HME) for amorphous solid dispersions: predictive tools for processing and impact of drug-polymer interactions on supersaturation. AU - Sarode,Ashish L, AU - Sandhu,Harpreet, AU - Shah,Navnit, AU - Malick,Waseem, AU - Zia,Hossein, Y1 - 2012/12/23/ PY - 2012/11/05/received PY - 2012/12/12/revised PY - 2012/12/17/accepted PY - 2012/12/27/entrez PY - 2012/12/27/pubmed PY - 2015/6/30/medline SP - 371 EP - 84 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 48 IS - 3 N2 - 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 (ITZ), 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 (η₀) was dependent on the melting point and consequently the state of the drug in the polymer at the softening temperature. The η₀ 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. SN - 1879-0720 UR - https://www.unboundmedicine.com/medline/citation/23267847/Hot_melt_extrusion__HME__for_amorphous_solid_dispersions:_predictive_tools_for_processing_and_impact_of_drug_polymer_interactions_on_supersaturation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928-0987(12)00486-1 DB - PRIME DP - Unbound Medicine ER -