title: The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions.
abstract: 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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhefei
authors.initials: Z
authors.lastname: Guo
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Li
authors.forename: Huishi
authors.initials: H
authors.lastname: Pang
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
mesh_terms: D002626:Chemistry, Pharmaceutical; D004061:Diflunisal / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry* / Q000592:standards; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005615:Freezing; D006358:Hot Temperature; D006801:Humans; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D012996:Solutions
chemical_list: D004337:Drug Carriers; D011108:Polymers; D012996:Solutions; D004061:Diflunisal
keywords: amorphous solid dispersion; chemical stability; hot-melt extrusion; hydrogen bond; interaction