Improved physicochemical characteristics of felodipine solid dispersion particles by supercritical anti-solvent precipitation process.
Solid dispersions of felodipine were formulated with HPMC and surfactants by the conventional solvent evaporation (CSE) and supercritical anti-solvent precipitation (SAS) methods. The solid dispersion particles were characterized by particle size, zeta potential, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), solubility and dissolution studies. The effects of the drug/polymer ratio and surfactants on the solubility of felodipine were also studied. The mean particle size of the solid dispersions was 200-250 nm; these had a relatively regular spherical shape with a narrow size distribution. The particle size of the solid dispersions from the CSE method increased at 1 h after dispersed in distilled water. However, the particle sizes of solid dispersions from the SAS process were maintained for 6 h due to the increased solubility of felodipine. The physical state of felodipine changed from crystalline to amorphous during the CSE and SAS processes, confirmed by DSC/XRD data. The equilibrium solubility of the felodipine solid dispersion prepared by the SAS process was 1.5-20 microg/ml, while the maximum solubility was 35-110 microg/ml. Moreover, the solubility of felodipine increased with decreasing drug/polymer ratio or increasing HCO-60 content. The solid dispersions from the SAS process showed a high dissolution rate of over 90% within 2 h. The SAS process system may be used to enhance solubility or to produce oral dosage forms with high dissolution rate.
Won
Dong-Han
DH
National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Republic of Korea.
Kim
Min-Soo
MS
Lee
Sibeum
S
Park
Jeong-Sook
JS
Hwang
Sung-Joo
SJ
D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004563:Electrochemistry; D015736:Felodipine / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D012995:Solubility; D012997:Solvents; D013607:Tablets; D014867:Water; D014961:X-Ray Diffraction
D012997:Solvents; D013607:Tablets; D014867:Water; D015736:Felodipine