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Pharmaceutics 2018, 10(3), 142; https://doi.org/10.3390/pharmaceutics10030142

Processing Impact on Performance of Solid Dispersions

1
Pharmaceutical Sciences, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ 07033, USA
2
Regulatory Affairs, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ 07033, USA
*
Authors to whom correspondence should be addressed.
Received: 23 June 2018 / Revised: 13 August 2018 / Accepted: 14 August 2018 / Published: 30 August 2018
(This article belongs to the Special Issue Dissolution Enhancement of Poorly Soluble Drugs)
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Abstract

The development of a weakly basic compound is often challenging due to changes in pH that the drug experiences throughout the gastrointestinal tract. As the drug transitions from the low pH of the stomach to the higher pH of the small intestine, drug solubility decreases. A stomach with a higher pH, caused by food or achlorhydric conditions brought about by certain medications, decreases even the initial solubility. This decreased drug solubility is reflected in lower in vivo exposures. In many cases, a solubility-enabling approach is needed to counteract the effect of gastrointestinal pH changes. Solid dispersions of amorphous drug in a polymer matrix have been demonstrated to be an effective tool to enhance bioavailability, with the potential to mitigate the food and achlorhydric effects frequently observed with conventional formulations. Because solid dispersions are in a metastable state, they are particularly sensitive to processing routes that may control particle attributes, stability, drug release profile, and bioperformance. A better understanding of the impacts of processing routes on the solid dispersion properties will not only enhance our ability to control the product properties, but also lower development risks. In this study, a weakly basic compound with greatly reduced solubility in higher pHs was incorporated into a solid dispersion via both spray drying and hot melt extrusion. The properties of the solid dispersion via these two processing routes were compared, and the impact on dissolution behavior and in vivo performance of the dispersions was investigated. View Full-Text
Keywords: solid dispersion; bioavailability; spray drying; hot melt extrusion; poorly water-soluble compound; in vitro and in vivo characterization solid dispersion; bioavailability; spray drying; hot melt extrusion; poorly water-soluble compound; in vitro and in vivo characterization
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Zhang, D.; Lee, Y.-C.; Shabani, Z.; Frankenfeld Lamm, C.; Zhu, W.; Li, Y.; Templeton, A. Processing Impact on Performance of Solid Dispersions. Pharmaceutics 2018, 10, 142.

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