Evaluation of solid state properties of solid dispersions prepared by hot-melt extrusion and solvent co-precipitation.
The solid state properties of solid dispersions of Compound A in hypromellose acetate succinate (HPMC-AS) prepared by hot-melt extrusion (HME) and solvent co-precipitation (CP) processes were evaluated using powder X-ray diffractometry (PXRD), thermal analysis, optical microscopy, scanning electron microscopy (SEM), FT-IR and Raman spectroscopy, water vapor sorption analyzer, and surface area by BET. PXRD indicated that both processes converted the crystalline drug into amorphous solid dispersions with a glass transition temperature around 104-107 degrees C and both products have similar spectroscopic and hygroscopic properties. The two products have similar true densities; however, the CP product is more porous and has a larger specific surface area than the HME product, as indicated by the BET results and SEM micrographs. Dissolution study using USP apparatus 2 showed that the CP product had a faster dissolution profile, but slower intrinsic dissolution rate than the HME product. The two products have acceptable physical stability after storage in 40 degrees C/75% RH chamber for 3 months. However, the HME product is more stable than the CP product in aqueous suspension formulation.
Dong
Zedong
Z
Pharmaceutical and Analytical Research & Development, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, United States. zedong.dong@roche.com
Chatterji
Ashish
A
Sandhu
Harpreet
H
Choi
Duk Soon
DS
Chokshi
Hitesh
H
Shah
Navnit
N
D018938:Caco-2 Cells; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004055:Differential Thermal Analysis; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients; D006801:Humans; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives; D008855:Microscopy, Electron, Scanning; D008859:Microscopy, Polarization; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013696:Temperature; D014961:X-Ray Diffraction
D005079:Excipients; D012997:Solvents; D065347:Hypromellose Derivatives; D008747:Methylcellulose