Application of HPMC HME polymer as hot melt extrusion carrier in carbamazepine solid dispersion

Abstract

Aim

This work is to investigate the application characteristics of a new hot melt extrusion (HME) polymer (HME-grade hydroxypropyl methylcellulose, namely HPMC HME 15LV) in solid dispersion by HME.

Methods

Carbamazepine (CBZ) was chosen as the model drug. And two types of solid dispersion system was prepared by HME, that is, single carrier system which was composed of PVP VA64(VA64) or Soluplus (SOL), and binary carrier which was composed of HPMC HME 15LV and SOL. Phase analysis of the extrudates were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The dissolution, moisture absorption and thermal stability CBZ solid dispersion (CBZ-SD) were also investigated. In addition, the mechanism that affects the capsule dissolution was evaluated by the viscosity test and infiltration capability test.

Results

CBZ-SD was prepared by HME. DSC and PXRD results indicated that CBZ was amorphous in all solid dispersions. Unlike CBZ-SD powder with high dissolution, CBZ-SD capsules showed the variable gelatinization phenomenon during dissolution and different dissolution behaviors, which can be interpreted by the viscosity test and infiltration capacity test. Furthermore, compared with single carrier system, CBZ-SD made by binary carrier exhibited lower moisture absorption and better thermal stability, which is benefit to the long-term stability of CBZ-SD.

Conclusion

HPMC HME 15LV, as a new HME carrier, has certain advantages in producing well CBZ-SD preparation. Its low viscosity can prevent the gelatinization phenomenon during capsule dissolution, as well as suitable T_g and low hygroscopicity were also benefit to the stability of CBZ-SD.

Keywords:

• HPMC HME 15LV
• Hot melt extrusion
• Dissolution
• Gelatinization
• Thermal stability
• Hygroscopicity

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was financial supported by National Natural Science Foundation of China (Grant No. 81603048 and 81773908), Natural Science Foundation of Jiangsu Province (Grant No. BK20160752), Fundamental Research Funds for the Central Universities (Grant No. 2016ZPY014) and program of the “333 high-level personnel training project (No. BRA2015392)” Young Leaders in Science and Technology of Jiangsu Province and Public Technology Service Center of Nano drug Preparation and Evaluation of Jiangsu Province.