title: Non-invasive insight into the release mechanisms of a poorly soluble drug from amorphous solid dispersions by confocal Raman microscopy.
abstract: In this study, we investigated the release mechanism of the poorly water soluble drug aprepitant from different amorphous solid dispersions using confocal Raman microscopy (CRM). Solid dispersions were fabricated based on either Soluplus®, as an amphiphilic copolymer and solubilizer, or on polyvinylpyrrolidone, as a hydrophilic polymer, in order to elucidate the influence of the polymer characteristics on the drug form and dissolution mechanisms. Aprepitant exhibited its amorphous form in both solid dispersions. However, the release differed depending on the polymer. The high complexation effect of Soluplus was shown to be a crucial factor for stabilization of the amorphous drug, resulting in continuous release without any recrystallization of aprepitant. In contrast, solid dispersions based on polyvinylpyrrolidone showed a different mechanism of dissolution; due to the good affinity of PVP and water, the polymer is dissolving fast, leading to phase separation and local recrystallization of the drug. The study highlights the complexity of release processes from solid dispersions and elucidates the influence of the polymer on drug release kinetics.
authors: Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague 6, Czech Republic; Zentiva, k.s., U Kabelovny 130, Prague 10, Czech Republic.
authors: Kateřina
authors: K
authors: Punčochová
authors: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany; Helmholtz Centre for Infection Research (HZI) and Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Delivery, Saarbruecken, Germany.
authors: Branko
authors: B
authors: Vukosavljevic
authors: Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague 6, Czech Republic.
authors: Jaroslav
authors: J
authors: Hanuš
authors: Zentiva, k.s., U Kabelovny 130, Prague 10, Czech Republic.
authors: Josef
authors: J
authors: Beránek
authors: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany; Helmholtz Centre for Infection Research (HZI) and Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Delivery, Saarbruecken, Germany. Electronic address: m.windbergs@mx.uni-saarland.de.
authors: Maike
authors: M
authors: Windbergs
authors: Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague 6, Czech Republic. Electronic address: Frantisek.Stepanek@vscht.cz.
authors: František
authors: F
authors: Štěpánek
mesh_terms: D000077608:Aprepitant; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D018613:Microscopy, Confocal / Q000379:methods; D009025:Morpholines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013059:Spectrum Analysis, Raman / Q000379:methods
chemical_list: D004337:Drug Carriers; D009025:Morpholines; D011108:Polymers; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D000077608:Aprepitant; D011092:Polyethylene Glycols; D011205:Povidone
keywords: Aprepitant; Confocal Raman spectroscopy; Dissolution mechanisms; Polymer; Recrystallization; Solid dispersion