Tags

Type your tag names separated by a space and hit enter

The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions.
J Pharm Pharmacol. 2014 Feb; 66(2):285-96.JP

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).

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.

Authors+Show Affiliations

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24433427

Citation

Guo, Zhefei, et al. "The Utilization of Drug-polymer Interactions for Improving the Chemical Stability of Hot-melt Extruded Solid Dispersions." The Journal of Pharmacy and Pharmacology, vol. 66, no. 2, 2014, pp. 285-96.
Guo Z, Lu M, Li Y, et al. The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions. J Pharm Pharmacol. 2014;66(2):285-96.
Guo, Z., Lu, M., Li, Y., Pang, H., Lin, L., Liu, X., & Wu, C. (2014). The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions. The Journal of Pharmacy and Pharmacology, 66(2), 285-96. https://doi.org/10.1111/jphp.12145
Guo Z, et al. The Utilization of Drug-polymer Interactions for Improving the Chemical Stability of Hot-melt Extruded Solid Dispersions. J Pharm Pharmacol. 2014;66(2):285-96. PubMed PMID: 24433427.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions. AU - Guo,Zhefei, AU - Lu,Ming, AU - Li,Yongcheng, AU - Pang,Huishi, AU - Lin,Ling, AU - Liu,Xu, AU - Wu,Chuanbin, Y1 - 2013/10/25/ PY - 2013/05/11/received PY - 2013/08/25/accepted PY - 2014/1/18/entrez PY - 2014/1/18/pubmed PY - 2014/9/11/medline KW - amorphous solid dispersion KW - chemical stability KW - hot-melt extrusion KW - hydrogen bond KW - interaction SP - 285 EP - 96 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 66 IS - 2 N2 - 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. SN - 2042-7158 UR - https://www.unboundmedicine.com/medline/citation/24433427/The_utilization_of_drug_polymer_interactions_for_improving_the_chemical_stability_of_hot_melt_extruded_solid_dispersions_ L2 - https://doi.org/10.1111/jphp.12145 DB - PRIME DP - Unbound Medicine ER -