Improving the chemical stability of amorphous solid dispersion with cocrystal technique by hot melt extrusion.
OBJECTIVE
To explore in-situ forming cocrystal as a single-step, efficient method to significantly depress the processing temperature and thus minimize the thermal degradation of heat-sensitive drug in preparation of solid dispersions by melting method (MM) and hot melt extrusion (HME).


METHODS
Carbamazepine (CBZ)-nicotinamide (NIC) cocrystal solid dispersions were prepared with polymer carriers PVP/VA, SOLUPLUS and HPMC by MM and/or HME. The formation of cocrystal was investigated by differential scanning calorimetry and hot stage polarized optical microscopy. State of CBZ in solid dispersion was characterized by X-ray powder diffraction and optical microscopy. Interactions between CBZ, NIC and polymers were investigated by FTIR. Dissolution behaviors of solid dispersions were compared with that of pure CBZ.


RESULTS
CBZ-NIC cocrystal with melting point of 160°C was formed in polymer carriers during heating process, and the preparation temperature of amorphous CBZ solid dispersion was therefore depressed to 160°C. The dissolution rate of CBZ-NIC cocrystal solid dispersion was significantly increased.


CONCLUSIONS
By in-situ forming cocrystal, chemically stable amorphous solid dispersions were prepared by MM and HME at a depressed processing temperature. This method provides an attractive opportunity for HME of heat-sensitive drugs.
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, Guangdong, People's Republic of China.
Xu
X
Liu
Ming
M
Lu
Zhefei
Z
Guo
Lin
L
Huang
Xin
X
Feng
Chuanbin
C
Wu
D018712:Analgesics, Non-Narcotic / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000737:chemistry*; D003460:Crystallization / Q000379:methods*; D004355:Drug Stability; D005615:Freezing; D009536:Niacinamide / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D033362:Powder Diffraction; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014803:Vitamin B Complex / Q000737:chemistry*; D014961:X-Ray Diffraction
D018712:Analgesics, Non-Narcotic; D011108:Polymers; D014803:Vitamin B Complex; D009536:Niacinamide; D002220:Carbamazepine