Micronization and microencapsulation of felodipine by supercritical carbon dioxide.
Felodipine (FLD) is a poorly water-soluble drug. To improve its dissolution rate, the rapid expansion of supercritical solutions (RESS) technique was used to prepare micronized FLD drug particles, which were encapsulated in poly-(ethylene glycol) 4000 (PEG 4000). The physical properties of the encapsulated drug particles were characterized by a variety of analytical methods, including optical light microscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (powder-XRD) and the dissolution behaviour of FLD was studied in the microparticles. The supercritical condition of micronized FLD occurred at a relatively high pressure and moderate temperature. FLD-PEG 4000 microparticles compared well with micronized FLD. RESS was effective in reducing the particle size of FLD; spot-shaped micronized FLD and popcorn-shaped FLD-PEG 4000 microparticles were observed. The particulate properties of the microparticles included a narrow distribution and uniform size. Thermodynamic analysis showed an implantation interaction between FLD and PEG 4000 molecules, but no polymorphism in the micronized FLD or FLD-PEG 4000 microparticles. FLD-PEG 4000 microparticles had a significantly faster drug dissolution rate than micronized FLD. These data show that RESS can be used to prepare FLD-PEG 4000 microparticles with small particle size (2-6 microm) and enhanced dissolution rate.
Chiou
Andy Hong-Jey
AH
Graduate Institute of Medical Science, Taipei, Taiwan, ROC. chiouhj@yahoo.com.tw
Cheng
Hsiu-Cheng
HC
Wang
Da-Peng
DP
D002245:Carbon Dioxide / Q000737:chemistry*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D002627:Chemistry, Physical; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D005240:Feasibility Studies; D015736:Felodipine / Q000737:chemistry*; D008863:Microspheres; D015394:Molecular Structure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013816:Thermodynamics
D002245:Carbon Dioxide; D011092:Polyethylene Glycols; D015736:Felodipine