Department of Pharmaceutical Engineering, Inje University, Gimhae, Gyeongnam 621-749, Republic of Korea.
Int J Pharm. 2013 Mar 10;445(1-2):108-16. doi: 10.1016/j.ijpharm.2013.01.067. Epub 2013 Feb 8.
The purpose of this study was to develop supersaturatable formulations for the enhanced solubility and oral absorption of sirolimus. Supersaturatable formulations of hydrophilic polymers and/or surfactants were screened by formulation screening, which is based on solvent casting. The solid dispersion particles in the optimized formulations were prepared by spray drying. The particles were characterized in vitro and in vivo. The most effective supersaturatable formulation found in the formulation screening process was hydroxypropylmethyl cellulose (HPMC)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), followed by HPMC-Sucroester. In addition, the supersaturated state generated from HPMC-TPGS and HPMC-Sucroester 15 particles prepared by spray drying significantly improved the oral absorption of sirolimus in rats. Based on the pharmacokinetic parameters and supporting in vitro supersaturated dissolution data, the enhanced supersaturation properties of sirolimus led to enhanced in vivo oral absorption. In addition, the experimental results from the formulation screening used in our study could be useful for enhancing the bioavailability of sirolimus in preformulation and formulation studies.
本研究旨在开发可提高西罗莫司溶解度和口服吸收的超饱和制剂。通过基于溶剂浇铸的制剂筛选，筛选出亲水性聚合物和/或表面活性剂的超饱和制剂。通过喷雾干燥制备优化配方中的固体分散颗粒。对颗粒进行了体外和体内的表征。在制剂筛选过程中发现的最有效的超饱和制剂是羟丙甲纤维素（HPMC）-D-α-生育酚聚乙二醇 1000 琥珀酸酯（TPGS），其次是 HPMC-蔗糖酯。此外，喷雾干燥制备的 HPMC-TPGS 和 HPMC-Sucroester 15 颗粒形成的超饱和状态显著提高了西罗莫司在大鼠体内的口服吸收。基于药代动力学参数和支持的体外超饱和溶解数据，西罗莫司增强的超饱和特性导致体内口服吸收增强。此外，我们研究中使用的制剂筛选实验结果可用于增强西罗莫司在预配方和制剂研究中的生物利用度。
