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• W3194468059 startingPage "121042" @default.
• W3194468059 abstract "Hot melt extrusion (HME) is a technique applied in the preparation of pharmaceutical amorphous solid dispersions (ASD). Notably it is important to prevent thermal degradation of heat-sensitive drugs during HME. In this study, we present a new strategy to improve chemical stability of pharmaceutical compounds during HME through the formation of eutectics with small molecules. Resveratrol (RES) was selected as the model compound because it is a heat-liable natural product with a very high melting point of 267 °C. When heated at its melting point for 3 min, it degrades by 40%. RES can co-crystallize with nicotinamide (NIC) in solution, however, it can only form a eutectic with NIC during heating. HPMCAS was selected as the polymer matrix and the drug loading of RES was fixed as 20% (weight ratio). The lowest extrusion temperature that can result to RES-HPMCAS ASD is 215 °C. At this temperature, RES shows 7.36% degradation during extrusion. Replacement of 21.4% HPMCAS with NIC decreased the melting temperature of NIC and thus lowered the minimal extrusion temperature to 155 °C. This effectively prevented thermal degradation of RES without negatively affecting non-sink dissolution. The only extra cost for this method is stricter storage conditions (low temperature and low humidity) due to the low glass transition temperature of NIC. Similar strategy may be applied to other heat-liable drugs in similar ways. This study demonstrates the use of eutectic formation for preventing thermal degradation of drug during extrusion of ASD." @default.
• W3194468059 created "2021-08-30" @default.
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• W3194468059 date "2021-09-01" @default.
• W3194468059 modified "2023-10-17" @default.
• W3194468059 title "Improving chemical stability of resveratrol in hot melt extrusion based on formation of eutectic with nicotinamide" @default.
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• W3194468059 doi "https://doi.org/10.1016/j.ijpharm.2021.121042" @default.
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• W3194468059 hasPublicationYear "2021" @default.
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