Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: Pharmacokinetic and pharmacodynamic evaluation.

The intent of this investigation was to improve pharmacokinetic (PK) and pharmacodynamic (PD) effects of Rosuvastatin calcium (RC) by solid lipid nanoparticles (SLNs). RC is anti-hyperlipidemic drug with low oral bioavailability (20%) due to first-pass metabolism. Hot homogenization followed by ultrasonication method was used to prepare RC-SLNs with stearic acid, glyceryl behenate and glyceryl trilaurate as lipid matrices, egg lecithin and poloxamer 188 as surfactants. The prepared SLNs were tested for particle size, PDI, zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro release. Further, PK and PD studies were conducted on selected SLNs. No changes in physical stability of the optimized SLN were observed at refrigerated and room temperature for 90days. SLNs prepared with glyceryl trilaurate having average size of 67.21±1.71nm, PDI of 0.25±0.01, ZP of -28.93±0.84mV with 93.51±0.34% EE was considered as optimized. DSC and XRD studies revealed that no interaction occurred between the drug and lipid. SEM and TEM studies revealed that SLNs were nearly spherical in shape. PK studies showed improvement in the oral bioavailability (extent of absorption) of SLNs by 4.6-fold when compared to that of suspension. PD study of SLNs in hyperlipidemic rats exhibited a decrease in lipid profile for 36h, while a suspension exhibited for 24h.

Dudhipala N ，Veerabrahma K 《-》

Role of Isradipine Loaded Solid Lipid Nanoparticles on the Pharmacodynamic Effect in Rats.

Isradipine (ID), is an antihypertensive drug, having low oral bioavailability (15-24%) due to poor aqueous solubility (0.01 mg/mL) and also hepatic first-pass metabolism. Among various approaches, Solid lipid nanoparticles (SLNs) were developed using stearic acid, glyceryl monostearate as lipid matrices for improving the oral bioavailability of ID. ID-SLNs were prepared by using hot homogenization followed by ultrasonication. The prepared SLNs were characterized for size, PDI, zeta potential (ZP), entrapment efficiency (EE) and drug content. In vitro release studies were performed in 0.1NHCl and pH 6.8 phosphate buffer of by open tube method. Physical stability of the SLNs was observed at refrigerated temperature and room temperature for 90 days. Further, pharmacodynamic study was conducted in wistar rats. SLNs prepared with GMS having size of 188.6±3.6 nm, PDI of 0.273±0.052, ZP of - 21.8±2.7 mV with 86.86±0.75% EE were optimized. Differential scanning calorimetric (DSC) study revealed that no interaction between drug and lipid. In vitro release studies showed that more cumulative release of ID in pH 6.8 phosphate buffer than in 0.1NHCl during 24 h. The lyophilized SLN formulation was used in knowing morphology of SLNs, and was found to have spherical shape with increased polydispersity by Scanning electron microscopy. Pharmacodynamic study of SLNs in fructose induced hypertensive rats showed a decrease in systolic blood pressure for 36 h, when compared to suspension, which showed a decrease in systolic blood pressure for only 2 h. Thus, the results conclusively demonstrated the role of SLNs for a significant enhancement in pharmacodynamic effect of ID.

Thirupathi G ，Swetha E ，Narendar D 《-》

Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation.

Dudhipala N ，Veerabrahma K 《-》

Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design.

Dudhipala N ，Veerabrahma K 《-》

Attenuation of lipid levels in triton induced hyperlipidemia rats through rosuvastatin calcium nanoparticles: Pharmacokinetic and pharmacodynamic studies.

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 Peff 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.

Dudhipala NR ，Ettireddy SR ，Puchakayala GR 《-》