title: Investigation of preparation methods on surface/bulk structural relaxation and glass fragility of amorphous solid dispersions.
abstract: The objective of this study was to investigate the effect of preparation methods on the surface/bulk molecular mobility and glass fragility of solid dispersions. Solid dispersions containing indomethacin and PVP K30 were chosen as the model system. An inverse gas chromatography method was used to determine the surface structural relaxation of the solid dispersions and these data were compared to those for bulk relaxation obtained by DSC. The values of τ(β) for the surface relaxation were 4.6, 7.1 and 1.8h for melt quenched, ball milled and spray dried solid dispersions respectively, compared to 15.6, 7.9 and 9.8h of the bulk. In all systems, the surface had higher molecular mobility than the bulk. The glass fragility of the solid dispersions was also influenced by the preparation methods with the most fragile system showing the best stability. The zero mobility temperature (T(0)) was used to correlate with the physical stability of the solid dispersions. Despite having similar T(g) (65°C), the T(0) of the melt quenched, ball milled and spray dried samples were 21.6, -4.2 and 16.7°C respectively which correlated well with their physical stability results. Therefore, T(0) appears to be a better indicator than T(g) for predicting stability of amorphous materials.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1 N 1AX, UK.
authors.forename: Peng
authors.initials: P
authors.lastname: Ke
authors.forename: Susumu
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Hisham
authors.initials: H
authors.lastname: Al-Obaidi
authors.forename: Graham
authors.initials: G
authors.lastname: Buckton
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D004339:Drug Compounding; D004355:Drug Stability; D007213:Indomethacin / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D011205:Povidone / Q000737:chemistry*; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011205:Povidone; D007213:Indomethacin