The aim of this research was to study the effect of marketed tablet (Crestor®) powder suspension (MTPS) and nanoparticle formulation of rosuvastatin calcium (RC) on the pharmacokinetic (PK) and pharmacodynamic (PD) parameters in hyperlipidemia rats. The hyperlipidemia is induced by intraperitoneal injection of Triton-X-100 in 0.9 %w/v saline solution. The marketed tablet was dispersed into suspension. The RC loaded nanoparticles (RC-NPs) are prepared by homogenization method. The prepared RC-NP formulation was characterized for size, drug excipient compatibility and crystallization by differential scanning calorimeter (DSC), morphology by SEM, stability at room temperature, in-vitro dissolution and in-situ absorption in rats. Further, the pharmacokinetic and pharmacodynamic studies were conducted in hyperlipidemia rats. The size of the RC-NP formulation was found to be 183.4 ± 4.5 nm and to be nearly spherical by SEM. DSC studies revealed that no interaction and RC converted to amorphous form in RC-NP formulation. RC-NP formulation was physically and chemically stable over two months at room temperature. The drug release was found to be 25.8 ± 2.5 and 89.96 ± 2.8 % in five mins, respectively from MTPS and RC-NP formulations. The P_eff of MTPS and NP of RC was 1.8 ± 0.2 × 10⁻⁵ and 2.7 ± 0.3 × 10^-5 cm/s, respectively. From the PK studies, the enhancement in the oral bioavailability was found to be 2.4-folds when compared to MTPS formulation and statistically significant (p < 0.05). PD study of RC-NP formulation in hyperlipidemic rats exhibited decrease in lipid profile for 24 h, while MTPS exhibited a decrease in lipid profile for 12 h. Therefore, the results conclusively demonstrate the nanoparticles of RC showed significant enhancement in the PK and PD parameters.

本研究的目的是研究市售片剂 (Crestor®) 粉末悬浮液 (MTPS) 和瑞舒伐他汀钙 (RC) 纳米颗粒制剂对高脂血症大鼠药代动力学 (PK) 和药效学 (PD) 参数的影响。高脂血症是通过腹膜内注射 0.9%w/v 盐水溶液中的 Triton-X-100 引起的。将市售片剂分散成悬浮液。RC 负载纳米粒子 (RC-NPs) 是通过均质化方法制备的。通过差示扫描量热仪 (DSC) 对制备的 RC-NP 制剂的尺寸、药物赋形剂相容性和结晶进行表征，通过 SEM 表征其形态，室温稳定性、体外溶出度和原位大鼠吸收。此外，在高脂血症大鼠中进行了药代动力学和药效学研究。发现 RC-NP 配方的尺寸为 183.4 ± 4.5 nm，并且通过 SEM 几乎是球形的。DSC 研究表明，在 RC-NP 配方中没有相互作用并且 RC 转化为无定形形式。RC-NP 配方在室温下物理和化学稳定超过两个月。发现 MTPS 和 RC-NP 制剂的药物释放在五分钟内分别为 25.8 ± 2.5 和 89.96 ± 2.8 %。MTPS的 P _eff和 RC 的 NP 分别为 1.8 ± 0.2 × 10 ^-5和 2.7 ± 0.3 × 10 ^-5厘米/秒，分别。从 PK 研究中发现，与 MTPS 制剂相比，口服生物利用度的提高是 2.4 倍，并且具有统计学意义（p < 0.05）。RC-NP 制剂在高脂血症大鼠中的 PD 研究显示脂质分布降低 24 小时，而 MTPS 显示脂质分布降低 12 小时。因此，结果最终证明了 RC 纳米颗粒在 PK 和 PD 参数方面表现出显着增强。