Mesoporous silica: a solution for amorphous stabilization of poor glass formers
Introduction: Amorphous formulation technologies to improve oral absorption of poorly soluble active pharmaceutical ingredients (APIs) have become increasingly prevalent. Currently, polymer based amorphous formulations manufactured by spray drying, hot melt extrusion (HME), or coprecipitation are most common. However, these technologies have challenges in terms of the successful stabilization of poor glass former compounds in the amorphous form. An alternative approach is mesoporous silica, which stabilizes APIs in non-crystalline form via molecular adsorption inside nano-scale pores.
Aims and Hypothesis: The aim of this work was to first develop amorphous formulations for two poorly soluble poor glass formers using mesoporous silica and hot melt extrusion as model technologies. After successful formulation development, the formulations were assessed from a stabilization perspective, considering both solid state and dissolution performance. It was hypothesized that mesoporous silica would show enhanced amorphous stability for poorly soluble poor glass formers compared to hot melt extrusion.
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Conclusions: Although polymeric-based amorphous solid dispersions are most prevalent, they may not be suitable for poorly soluble compounds that are also poor glass formers. These compounds, which demonstrate both poor solubility and poor amorphous stability, are challenging for formulation with typical polymer-based technologies due to possible phase separation and recrystallization. Ultimately, these compounds may have an increased risk of failure during pharmaceutical development, as they constitute a risk from both a bioavailability and amorphous stability perspective. In this study, we demonstrated that poor glass forming APIs have increased risk of recrystallization in polymer-based amorphous solid dispersions. By contrast, mesoporous silica was shown to provide optimal stabilization for such APIs. Therefore, mesoporous silica could be an attractive formulation technology to expand the formulation toolbox for APIs that are poor glass formers.
Article information: Daniel Joseph Price, Felix Ditzinger, Anita Nair, Jennifer Dressman, Christoph Saal, Martin Kuentz