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<p>This study aimed to enhance oral bioavailability of Fimasartan Potassium Trihydrate (FPT), an angiotensin Ⅱ receptor blocker by developing Solid lipid nanoparticles (FPT-SLNs) to overcome p-glycoprotein (p-gp) efflux and significantly enhance membrane permeability, thereby improving FPT absorption and oral bioavailability. FPT-loaded solid lipid nanoparticles were developed utilizing high-speed homogenization/ultrasonication. The Box Behnken Design (BBD) is utilized for optimization, by analysing the effect of independent factors (lipid concentration, surfactant concentration &amp; high-speed homogenizer speed), dependent factors (particle size and drug entrapment efficiency). The results revealed that lipid concentration had a significant effect on entrapment efficiency, whereas surfactant concentration and homogenization speed were the primary determinants of particle size, Both demonstrated statistical significance as determined by F-value &amp; p-value. Optimized FPT-SLNs had a particle size of 173 ± 4&#xa0;nm, PDI 0.276 ± 0.02, zeta potential of -22.7±(-2.84) and entrapment efficiency of 78.29 ± 2.74%. The optimized FPT-SLNs showed a sustained release pattern for 24&#xa0;h, with 87.99 ± 3.14% cumulative release. Compared to the standard FPT, improved FPT-SLNs showed a greater drug permeability. A pharmacokinetics study on rats showed that FPT-SLNs exhibited significantly higher C<sub>max</sub> and AUC<sub>0−24</sub> than pure FPT. With a nearly 2-fold increase in relative bioavailability (F). These experimental data support that SLN made of glyceryl monostearate (GMS) and Tween-20 could improve oral FPT absorption. Differential scanning calorimetry, X-ray diffraction, and Attenuated Total Reflectance-Infrared studies revealed no chemical reactivity between FPT and GMS, while TEM analysis verified the improved SLNs’ spherical form and ideal particle size. The mean particle size, %EE, PDI, did not significantly change after 3 months at 25˚C ± 2˚C/ 60 ± 5% RH storage, according to accelerated stability studies. Due to their increased bioavailability, FPT-SLNs are believed to be a suitable oral delivery system.</p> Graphical Abstract <p></p>

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“Development, Statistical Optimization and Evaluation of Fimasartan-Loaded Solid Lipid Nanoparticles Using Box Behnken Design for Oral Bioavailability Enhancement in Hypertension Management”

  • 期刊论文

  • 发表日期：

    2026年5月21日

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  • Ravikiran. M. Suryawanshi,
  • Pavan S. Bhumbare,
  • Shailesh S. Chalikwar,
  • Pankaj G. Jain

摘要

This study aimed to enhance oral bioavailability of Fimasartan Potassium Trihydrate (FPT), an angiotensin Ⅱ receptor blocker by developing Solid lipid nanoparticles (FPT-SLNs) to overcome p-glycoprotein (p-gp) efflux and significantly enhance membrane permeability, thereby improving FPT absorption and oral bioavailability. FPT-loaded solid lipid nanoparticles were developed utilizing high-speed homogenization/ultrasonication. The Box Behnken Design (BBD) is utilized for optimization, by analysing the effect of independent factors (lipid concentration, surfactant concentration & high-speed homogenizer speed), dependent factors (particle size and drug entrapment efficiency). The results revealed that lipid concentration had a significant effect on entrapment efficiency, whereas surfactant concentration and homogenization speed were the primary determinants of particle size, Both demonstrated statistical significance as determined by F-value & p-value. Optimized FPT-SLNs had a particle size of 173 ± 4 nm, PDI 0.276 ± 0.02, zeta potential of -22.7±(-2.84) and entrapment efficiency of 78.29 ± 2.74%. The optimized FPT-SLNs showed a sustained release pattern for 24 h, with 87.99 ± 3.14% cumulative release. Compared to the standard FPT, improved FPT-SLNs showed a greater drug permeability. A pharmacokinetics study on rats showed that FPT-SLNs exhibited significantly higher Cmax and AUC0−24 than pure FPT. With a nearly 2-fold increase in relative bioavailability (F). These experimental data support that SLN made of glyceryl monostearate (GMS) and Tween-20 could improve oral FPT absorption. Differential scanning calorimetry, X-ray diffraction, and Attenuated Total Reflectance-Infrared studies revealed no chemical reactivity between FPT and GMS, while TEM analysis verified the improved SLNs’ spherical form and ideal particle size. The mean particle size, %EE, PDI, did not significantly change after 3 months at 25˚C ± 2˚C/ 60 ± 5% RH storage, according to accelerated stability studies. Due to their increased bioavailability, FPT-SLNs are believed to be a suitable oral delivery system.

Graphical Abstract