Non-invasive insight into the release mechanisms of a poorly soluble drug from amorphous solid dispersions by confocal Raman microscopy

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• 作者：Kateřina Punčochová ; ^a ; ^d ; ¹ ; Branko Vukosavljevic^b ; ^c ; ¹ ; Jaroslav Hanu&scaron ; ^a ; Josef Berá ; nek^d ; Maike Windbergs^b ; ^c ; ^{m.windbergs@mx.uni-saarland.de" class="auth_mail" title="E-mail the corresponding author} ; Franti&scaron ; ek &Scaron ; těpá ; nek^a ; ^{Frantisek.Stepanek@vscht.cz" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Confocal Raman spectroscopy ; Dissolution mechanisms ; Recrystallization ; Aprepitant ; Polymer ; Solid dispersion
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：101
• 期：Complete
• 页码：119-125
• 全文大小：1739 K

文摘

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.