title: Predicting final product properties of melt extruded solid dispersions from process parameters using Raman spectrometry.
abstract: Raman spectrometry was utilized to estimate degraded drug percentage, residual drug crystallinity and glass-transition temperature in the case of melt-extruded pharmaceutical products. Tight correlation was shown between the results obtained by confocal Raman mapping and transmission Raman spectrometry, a PAT-compatible potential in-line analytical tool. Immediate-release spironolactone-Eudragit E solid dispersions were the model system, owing to the achievable amorphization and the heat-sensitivity of the drug compound. The deep investigation of the relationship between process parameters, residual drug crystallinity and degradation was performed using statistical tools and a factorial experimental design defining 54 different circumstances for the preparation of solid dispersions. From the examined factors, drug content (10, 20 and 30%), temperature (110, 130 and 150°C) and residence time (2.75, 11.00 and 24.75min) were found to have significant and considerable effect. By forming physically stable homogeneous dispersions, the originally very slow dissolution of the lipophilic and poorly water-soluble spironolactone was reasonably improved, making 3minute release possible in acidic medium.
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Budafoki út 8, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Vigh
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Budafoki út 8, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Drávavölgyi
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Budafoki út 8, Hungary.
authors.forename: Péter L
authors.initials: PL
authors.lastname: Sóti
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Budafoki út 8, Hungary.
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Pataki
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Budafoki út 8, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Igricz
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Budafoki út 8, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Wagner
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Budafoki út 8, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Vajna
authors.affiliation: Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, 1111 Budapest, Szt. Gellért tér 4, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Madarász
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Budafoki út 8, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Marosi
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Budafoki út 8, Hungary. Electronic address: nagyzsomborkristof@gmail.com.
authors.forename: Zsombor K
authors.initials: ZK
authors.lastname: Nagy
mesh_terms: D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D006358:Hot Temperature; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012995:Solubility; D013059:Spectrum Analysis, Raman / Q000379:methods; D013148:Spironolactone / Q000737:chemistry*; D044366:Transition Temperature; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D011109:Polymethacrylic Acids; D014867:Water; C038300:methylmethacrylate-methacrylic acid copolymer; D013148:Spironolactone
keywords: Amorphization; Degradation; Melt extrusion; Solid dispersion; Transmission Raman spectrometry