Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Kalabhavan Campus, Vadodara 390001, Gujarat, India.
Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Kalabhavan Campus, Vadodara 390001, Gujarat, India.
Colloids Surf B Biointerfaces. 2018 May 1;165:37-44. doi: 10.1016/j.colsurfb.2018.02.011. Epub 2018 Feb 9.
The aim of the current investigation was to develop solid lipid nanoparticles of olmesartan medoxomil using hot homogenization method to improve its oral bioavailability. Central composite design was applied to optimize the formulation variables; lipid X1 (Glyceryl monostearate) and surfactant X2 (Poloxamer: Tween 80). The particle sizes were in the nanometer range and spherical shaped for all prepared solid lipid nanoparticles formulations and the zeta potential absolute values were high, predicting good long-term stability. In vitro study of olmesartan loaded solid lipid nanoparticle exhibited controlled release profile for at least 24 h. The rate and extent of drug diffusion was studied using dialysis sac, rat's stomach and intestine tissues; study demonstrated that drug release from the solid lipid nanoparticles was significantly higher than drug suspension. In vivo pharmacokinetic study of olmesartan loaded solid lipid nanoparticles revealed higher Cmax of 1610 ng/mL, higher AUC of 15492.50 ng/mL and increased relative bioavailability by almost 2.3 folds compared to marketed formulation. These results clearly indicate that olmesartan loaded solid lipid nanoparticles are shown to have enhanced bioavailability and effective therapeutic result and thus would be an excellent way to treat hypertension. Hence, these solid lipid nanoparticles could represent as a great potential for a possible alternative to conventional oral formulation in the treatment of hypertension.
本研究旨在通过热熔匀化法制备奥美沙坦酯固体脂质纳米粒，以提高其口服生物利用度。采用中心复合设计对处方变量进行优化，即脂质 X1（单硬脂酸甘油酯）和表面活性剂 X2（泊洛沙姆：吐温 80）。所有制备的固体脂质纳米粒制剂的粒径均在纳米范围内，呈球形，且 Zeta 电位绝对值较高，表明具有良好的长期稳定性。体外研究表明，载奥米沙坦的固体脂质纳米粒具有至少 24 小时的控释特性。通过透析袋、大鼠胃和肠组织研究了药物的扩散速度和程度；研究表明，固体脂质纳米粒中药物的释放明显高于药物混悬剂。载奥米沙坦固体脂质纳米粒的体内药代动力学研究表明，与市售制剂相比，Cmax 提高了 1610ng/mL，AUC 提高了 15492.50ng/mL，相对生物利用度提高了近 2.3 倍。这些结果清楚地表明，载奥米沙坦固体脂质纳米粒具有增强的生物利用度和有效的治疗效果，因此将成为治疗高血压的一种理想方法。因此，这些固体脂质纳米粒可能成为治疗高血压的传统口服制剂的一种潜在替代方法。
