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Updated: May 3, 2026

Combinatorial Synthesis of and High-throughput Protein Release from Polymer Film and Nanoparticle Libraries
Published on: September 6, 2012
The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid
Zhefei Guo1, Ming Lu, Yongcheng Li
1School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Objective:
Interactions between drugs and polymers were utilized to lower the processing temperature of hot-melt extrusion (HME), and thus minimize the thermal degradation of heat-sensitive drugs during preparation of amorphous solid dispersions.
Methods:
Diflunisal (DIF), which would degrade upon melting, was selected as a model drug. Hydrogen bonds between DIF and polymeric carriers (PVP K30, PVP VA64, hydroxypropyl methylcellulose and Soluplus) were revealed by differential scanning calorimetry and Fourier transform infrared spectroscopy. The hot-melt extruded solid dispersion was characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and high-performance liquid chromatography (HPLC).
Key Findings:
The results of hot-stage polar microscopy indicated that DIF was dissolved in molten polymers at 160°C, much lower than the melting point of DIF (215°C). At this temperature, amorphous solid dispersions were successfully produced by HME, as confirmed by XRD and SEM. The related impurities in amorphous solid dispersions detected by HPLC were lower than 0.3%, indicating that thermal degradation was effectively minimized. The dissolution of DIF from amorphous solid dispersions was significantly enhanced as compared with the pure crystalline drug.
Conclusion:
This technique based on drug-polymer interactions to prepare chemically stable amorphous solid dispersions by HME provides an attractive opportunity for development of heat-sensitive drugs.
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