UniORV，一种新型多单位剂型，改善了他克莫司在大鼠和人体内的生物药剂学性质。
UniORV, a New Multi-Unit Dosage Form, Improved Biopharmaceutical Properties of Tacrolimus in Rats and Humans.
机构信息
Sunsho Pharmaceutical Co., Ltd., 533-2, Ooiwa, Fujinomiya, Shizuoka, 418-0013, Japan.
Laboratory of Biopharmacy, School of Pharmaceutical Science, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
出版信息
Pharm Res. 2020 Mar 5;37(3):64. doi: 10.1007/s11095-020-02785-0.
PURPOSE
The aim of the present study was to develop a new multi-unit dosage formulation, Universal ORbicular Vehicle (UniORV), to improve the biopharmaceutical properties of tacrolimus (TAC).
METHODS
TAC-loaded UniORV (UO/TAC) was produced by the dripping and gelling of a solution comprising TAC, gelatin, starch syrup, and triethyl citrate at 0.5 w/w% drug loading. Its microstructure was elucidated by polarized light microscopy and the Raman mapping technique. The pharmacokinetic profiles of TAC after the oral administration of UO/TAC were evaluated in rats and healthy humans.
RESULTS
The dissolution behavior of UO/TAC was similar to that of commercial capsules, and the formation of nanoparticles was detected by TEM in dissolved media. In a stability study on UO/TAC, only 2.6 and 4.7% decreases in TAC concentrations were observed at 40± 2°C/75 ± 5% relative humidity for 4 months and at 50± 2°C for 2 months, respectively. A pharmacokinetic study on rats revealed a 30-fold higher AUC than that with crystalline TAC. A randomized double-blind crossover study on 8 healthy males showed that UniORV achieved a 1.4-fold increase in AUC and 34% decrease in inter-individual variation from the reference formulation.
CONCLUSION
The new dosage form UniORV is a promising approach to improve the dissolution, amorphous stability, and biopharmaceutical properties of TAC, which is a poorly water-soluble drug.
目的
本研究旨在开发一种新的多单位剂量制剂——通用球形载体（UniORV），以改善他克莫司（TAC）的生物制药特性。
方法
TAC 负载的 UniORV（UO/TAC）通过将包含 TAC、明胶、淀粉糖浆和柠檬酸三乙酯的溶液滴入凝胶中制得，药物载药量为 0.5 w/w%。通过偏光显微镜和拉曼映射技术阐明其微观结构。在大鼠和健康人中评估了 UO/TAC 口服后的 TAC 药代动力学特征。
结果
UO/TAC 的溶解行为与市售胶囊相似，在溶解介质中通过 TEM 检测到纳米颗粒的形成。在 UO/TAC 的稳定性研究中，在 40±2°C/75±5%相对湿度下放置 4 个月和在 50±2°C 下放置 2 个月时，TAC 浓度仅分别下降了 2.6%和 4.7%。在大鼠的药代动力学研究中，与晶型 TAC 相比，AUC 提高了 30 倍。在 8 名健康男性中进行的随机双盲交叉研究表明，UniORV 使 AUC 增加了 1.4 倍，个体间变异降低了 34%。
结论
新型制剂 UniORV 是改善 TAC（一种水溶性差的药物）的溶解、无定形稳定性和生物制药特性的有前途的方法。
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