Accelerated ketoprofen release from polymeric matrices: Importance of the homogeneity/heterogeneity of excipient distribution

Autor: E Gue, Juergen Siepmann, E. Delcourt, Jean-François willart, S. Muschert, Marc Descamps, Florence Danede
Rok vydání: 2013
Předmět:
Zdroj: International Journal of Pharmaceutics. 457:298-307
ISSN: 0378-5173
DOI: 10.1016/j.ijpharm.2013.09.023
Popis: Polymeric matrices loaded with 10–50% ketoprofen were prepared by hot-melt extrusion or spray-drying. Eudragit® E, PVP, PVPVA and HPMC were studied as matrix formers. Binary “drug–Eudragit® E” as well as ternary “drug–Eudragit® E-PVP”, “drug–Eudragit® E-PVPVA” and “drug–Eudragit® E-HPMC” combinations were investigated and characterized by optical macro/microscopy, SEM, particle size measurements, mDSC, X-ray diffraction and in vitro drug release studies in 0.1 M HCl. In all cases ketoprofen release was much faster compared to a commercially available product and the dissolution of the drug powder (as received). Super-saturated solutions were obtained, which were stable during at least 2 h. Importantly, not only the composition of the systems, but also their inner structure potentially significantly affected the resulting ketoprofen release kinetics: For instance, spray-drying ternary ketoprofen:Eudragit® E:HPMC combinations led to a more homogenous HPMC distribution within the systems than hot-melt extrusion, as revealed by mDSC and X-ray diffraction. This more homogenous HPMC distribution resulted in more pronounced hindrance for water and drug diffusion and, thus, slower drug release from spray-dried powder compared to hot-melt extrudates of identical composition. This “homogeneity/heterogeneity effect” even overcompensated the “system size effect”: the surface exposed to the release medium was much larger in the case of the spray-dried powder. All formulations were stable during storage at ambient conditions in open vials.
Databáze: OpenAIRE
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