Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose.
The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.
College of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China.
Tao
T
Yi
Jiangling
J
Wan
Huibi
H
Xu
Xiangliang
X
Yang
D000284:Administration, Oral; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D005989:Glycerides; D065347:Hypromellose Derivatives; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009553:Nimodipine / Q000008:administration & dosage / Q000737:chemistry*; D009829:Oleic Acids / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D033362:Powder Diffraction; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014783:Viscosity
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D005989:Glycerides; D008055:Lipids; D009829:Oleic Acids; D009930:Organic Chemicals; C440220:Labrasol; C022131:cremophor; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D009553:Nimodipine; D008747:Methylcellulose; C033180:ethyl oleate