Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31605688
DOI
10.1016/j.xphs.2019.10.005
PII: S0022-3549(19)30639-2
Knihovny.cz E-resources
- Keywords
- amorphous solid dispersion(s) (ASD), bioavailability, extrusion, polymer chemical, degradation, formulation, glass transition(s), molecular weight, phase diagram(s), physical stability, solubility,
- MeSH
- Chemistry, Pharmaceutical * MeSH
- Drug Carriers * MeSH
- Polymers MeSH
- Excipients MeSH
- Drug Compounding MeSH
- Solubility MeSH
- Drug Stability MeSH
- Hot Temperature MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Drug Carriers * MeSH
- Polymers MeSH
- Excipients MeSH
For successful formulation of amorphous solid dispersions (ASDs) using hot-melt extrusion, it is imperative to understand the effect that heat and shear rate has on the physicochemical properties of the excipient. In this study, we investigated the influence of hot-melt extrusion parameters on solvent-free binary ASDs of ibuprofen (IBU), a model active pharmaceutical ingredient, in methacrylic acid-ethyl acrylate copolymer type A, 1:1, EUDRAGIT® L100-55 (EUD). To evaluate the impact of barrel temperature, screw speed, and residence time on EUD mass average molar mass and IBU release profile, size-exclusion chromatography and dissolution testing were used, respectively. The optimal conditions were established for IBU loadings less than 40 wt. %. For ASD formulations prepared using the ideal variables, spectral and thermal analyses confirmed that, under dry conditions at a temperature of 25°C, IBU remained amorphous during an 18-month storage period. After 28 months, formulations with active pharmaceutical ingredient content above 30 wt. % started to recrystallize. A temperature-composition phase diagram, constructed using melting point depression and glass-transition temperature measurements of IBU-EUD mixtures, correlated well with the long-term physical stability. The effect that minor-to-moderate polymer degradation within the extrudates has on their long-term physical stability and dissolution characteristics is analyzed and discussed.
References provided by Crossref.org
COSMOPharm: Drug-Polymer Compatibility of Pharmaceutical Amorphous Solid Dispersions from COSMO-SAC
