In Vitro and In Vivo Performance of Different Sized Spray-Dried Crystalline Itraconazole

被引:32
作者
Kumar, Sumit [1 ]
Jog, Rajan [1 ]
Shen, Jie [1 ]
Zolnik, Banu [2 ]
Sadrieh, Nakissa [2 ]
Burgess, Diane J. [1 ]
机构
[1] Univ Connecticut, Sch Pharm, Dept Pharmaceut, 69 North Eagleville Rd,Unit 3092, Storrs, CT 06269 USA
[2] FDA CDER OPS, Silver Spring, MD 20993 USA
关键词
nano-crystalline powders; spray drying; DoE; itraconazole nano-crystals; bioavailability; nanoparticles; nanotechnology; milling; absorption; WATER-SOLUBLE COMPOUNDS; FORMULATION; NANOSUSPENSIONS; SOLUBILITY; BIOAVAILABILITY; PERMEABILITY; REDUCTION; PARTICLES; DRUGS;
D O I
10.1002/jps.24155
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The objectives of the present study were to formulate and optimize different sized liquid and solid nanocrystalline formulations and evaluate their in vitro and in vivo performance to determine the effect of particle size on the oral bioavailability of solid nanocrystalline formulations. Nanotechnology is a promising approach to solve the problem of poor oral bioavailability of Biopharmaceutical Classification System class II/IV compounds. However, the highly exposed surface area of nanocrystals and hence their high Gibb's free energy poses a great challenge to nanocrystalline suspension stabilization. In this study, stabilization was achieved by preparing spray-dried nanocrystalline powders. A design of experiment approach was utilized to optimize the nanocrystalline suspensions/powders. On the basis of drug solubility studies, polyvinylpyrrolidone 40 KDa and sodium lauryl sulfate were selected for wet milling processing. Mannitol was chosen as the auxiliary excipient for spray-drying processing. In vitro dissolution utilizing a United States Pharmacopeia (USP) apparatus II showed superior release profiles for both liquid and nanocrystalline powder formulations compared with coarse-sized and unmilled formulations. Significantly, the oral bioavailability of nanocrystalline formulations with particle size of 280 nm was more than 20 times that of the unmilled formulation, whereas the nanocrystalline formulation with particle size of 750 nm showed only a 2.8 times increase in bioavailability compared with the unmilled formulation. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3018-3028, 2015
引用
收藏
页码:3018 / 3028
页数:11
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