Preparation and characterization of nanocrystals for solubility and dissolution rate enhancement of nifedipine.
Poorly water-soluble drugs such as nifedipine (NIF) (approximately 20 microg/ml) offer challenging problems in drug formulation as poor solubility is generally associated to poor dissolution characteristics and thus to poor oral bioavailability. In order to enhance these characteristics, preparation of nifedipine nanoparticles has been achieved using high pressure homogenization. The homogenization procedure has first been optimized in regard to particle size and size distribution. Nanoparticles were characterized in terms of size, morphology and redispersion characteristics following water-removal. Saturation solubility and dissolution characteristics were investigated and compared to the un-milled commercial NIF to verify the theoretical hypothesis on the benefit of increased surface area. Crystalline state evaluation before and following particle size reduction was also conducted through differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) to denote eventual transformation to amorphous state during the homogenization process. Through this study, it has been shown that initial crystalline state is maintained following particle size reduction and that the dissolution characteristics of nifedipine nanoparticles were significantly increased in regards to the commercial product. The method being simple and easily scaled up, this approach should have a general applicability to many poorly water-soluble drug entities.
Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles, Campus Plaine, CP 207, Boulevard du Triomphe, Brussels 1050, Belgium.
J
J
Hecq
M
M
Deleers
D
D
Fanara
H
H
Vranckx
K
K
Amighi
D002121:Calcium Channel Blockers / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003890:Desiccation; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures; D009543:Nifedipine / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D013997:Time Factors; D014961:X-Ray Diffraction
D002121:Calcium Channel Blockers; D009543:Nifedipine