title: Development and optimization of solid dispersion containing pellets of itraconazole prepared by high shear pelletization.
abstract: This study investigated the solid dispersion containing pellets of itraconazole for enhanced drug dissolution rate. The influence of process parameters used during high shear pelletization on the pellet properties including pellet size and dissolution rate was also studied. Solid dispersions of itraconazole were prepared with Eudragit E100, a hydrophilic polymer, by a simple fusion method followed by powdered and characterized by differential scanning calorimetry and X-ray powder diffraction. Solid dispersions containing pellets were consequently prepared using a lab-scale high shear mixer. In order to improve the product quality, a central composite design was applied to optimize the critical process variables, such as impeller speed and kneading time, and the results were modeled statistically. Itraconazole was presented as an amorphous state in the solid dispersion prepared at a drug to polymer ratio of 1:2. Both studied parameters had great effect on the responses. Powdered solid dispersion and pellets prepared using the optimal parameter settings showed approximately 30- and 70-fold increases in dissolution rate over the pure drug, respectively. Solid dispersion prepared by simple fusion method could be an option for itraconazole solubility enhancement. Pelletization process in high shear mixer can be optimized effectively by central composite design.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Guanhao
authors.initials: G
authors.lastname: Ye
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
authors.forename: Paul Wan Sia
authors.initials: PW
authors.lastname: Heng
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D017964:Itraconazole / Q000737:chemistry*; D008956:Models, Chemical; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D033362:Powder Diffraction; D011208:Powders / Q000592:standards; D011786:Quality Control; D015203:Reproducibility of Results; D033081:Shear Strength; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D013997:Time Factors
chemical_list: D000179:Acrylates; D000935:Antifungal Agents; C477020:Eudragit E100; D005079:Excipients; D011108:Polymers; D011208:Powders; D017964:Itraconazole