title: Nanonization of itraconazole by high pressure homogenization: stabilizer optimization and effect of particle size on oral absorption.
abstract: This study was performed to optimize stabilizer systems used in itraconazole (ITZ) nanosuspensions to achieve the greatest extent of size reduction and investigate the effect of particle size on the in vitro dissolution and oral absorption of ITZ. The nanosuspensions were prepared by high pressure homogenization and characterized for particle size, zeta potential, and surface morphology. A central composite method was applied to identify a multiple stabilizer system of Lutrol F127 and sodium lauryl sulfate for optimal particle size reduction. By using the optimized system, an ITZ nanosuspension was prepared that showed the particle size results in good agreement with the values predicted by the model. The nanosuspension was physically stable at 25°C for 1 week. The crystalline form of ITZ was not altered. The ITZ dissolution rate is directly correlated to its particle size, and a smaller particle size yields a faster dissolution rate. Pharmacokinetics study was performed using four ITZ suspensions with various particle sizes in rats (n = 3). A significant increase in both maximal plasma concentration of drug and area under the drug concentration-time curve (AUC) was shown when the particle size was reduced from micrometer to nanometer. However, the AUC was not significantly affected by further reduction of the particle size within the nano-size range.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: shiruimao156@hotmail.com.
authors.forename: Shirui
authors.initials: S
authors.lastname: Mao
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois 60064.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois 60064.
authors.forename: Luk Chiu
authors.initials: LC
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
mesh_terms: D000042:Absorption; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D009061:Mouth Mucosa / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013817:Thermography; D014961:X-Ray Diffraction
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D017964:Itraconazole