title: Hot melt extrusion (HME) for amorphous solid dispersions: predictive tools for processing and impact of drug-polymer interactions on supersaturation.
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.affiliation: Biomedical and Pharmaceutical Sciences, University of Rhode Island, 7 Greenhouse Road, Kingston, RI, USA. Electronic address: ashish14sarode@gmail.com.
authors.forename: Ashish L
authors.initials: AL
authors.lastname: Sarode
authors.affiliation: Pharmaceutical and Analytical Research and Development, Hoffmann-La-Roche Inc., 340 Kingsland St., Nutley, NJ, USA.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Sandhu
authors.affiliation: Pharmaceutical and Analytical Research and Development, Hoffmann-La-Roche Inc., 340 Kingsland St., Nutley, NJ, USA.
authors.forename: Navnit
authors.initials: N
authors.lastname: Shah
authors.affiliation: Pharmaceutical and Analytical Research and Development, Hoffmann-La-Roche Inc., 340 Kingsland St., Nutley, NJ, USA.
authors.forename: Waseem
authors.initials: W
authors.lastname: Malick
authors.affiliation: Biomedical and Pharmaceutical Sciences, University of Rhode Island, 7 Greenhouse Road, Kingston, RI, USA.
authors.forename: Hossein
authors.initials: H
authors.lastname: Zia
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D000935:Antifungal Agents / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D006118:Griseofulvin / Q000737:chemistry*; D006358:Hot Temperature; D007213:Indomethacin / Q000737:chemistry*; D017964:Itraconazole / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D009994:Osmolar Concentration; D044367:Phase Transition; D011109:Polymethacrylic Acids / Q000737:chemistry*; D033362:Powder Diffraction; D012212:Rheology / Q000379:methods; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D044366:Transition Temperature; D014783:Viscosity
chemical_list: D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000935:Antifungal Agents; C446821:Eudragit L100-55; D005079:Excipients; D011109:Polymethacrylic Acids; D017964:Itraconazole; D006118:Griseofulvin; D008747:Methylcellulose; C518398:Eudragit E PO; D007213:Indomethacin