Glimepiride solid lipid nanoparticles: Formulation, Evaluation and In-Vivo study

Introduction: Solid lipid nanoparticles(SLNs) have been reported as an alternative drug delivery system to traditional polymeric nanoparticles. Many studies were carried out and aimed to determine the enhancement ability of... [ view full abstract ]

Introduction: Solid lipid nanoparticles(SLNs) have been reported as an alternative drug delivery system to traditional polymeric nanoparticles. Many studies were carried out and aimed to determine the enhancement ability of (SLNs) on the solubility of many poorly water soluble drugs and consequently, the improvement of their bioavailability.
Methodolgy: To enhance the bioavailability of glimepiride, SLNs were formulated using two different polymers (compritol and glycelymonostearate) in a fixed drug: lipid polymer ratio (1:20). Two different ratios of three different surfactants were used. GMP-SLNs were prepared adapting two different techniques namely, hot fusion method and solvent emulsification method. The prepared GMP-SLNs were evaluated with respect to encapsulation efficiency, yield value ,particle size, zeta potential, image analyzer, and TEM analyzer. The DSC analysis and PXRD analysis were carried out on selected formulae. The pharmacokinetic study of the selected GMP-SLNs formula (F2) was carried out on male Newzeland white rabbits and the results were compared with those of marketed product (Amaryl ® 4mg tablets).
Results: The resulted values revealed that most of the solid lipid nanoparticles were of circular shape, the particle size ranging from 104 nm to 334 nm with zeta potential ranged from -9.34 mV to -38.6 mV. The resulted EE% values ranged from 97.8±0.25% to 99.7± 0.23%. The yield values were from 97.88±2.37 % to 98.96±2.03%. TEM analysis of SLNs formulae F2 and F8 showed rounded and discrete shaped particles. The DSC analysis results of F2 and F8 showed that there were no interactions between the drug and the used excipients. PXRD diffractograms of F2 and F8 showed lamellar lattice in case of SLNs and crystalline lattice in case of the compritol, glyceryl monostearate and drug powders in bulk state. The pharmacokinetic study and statistical analysis of the selected formulae (F2) showed that (F2) significantly enhanced the rate of GMP absorption from GIT and at 0.5, 2 & 6 hrs compared to the marketed product. The resulted Cmax was 28.1mg/ml, Tmax was 5.94 hrs, t1/2 abs was 1.53 hrs, t1/2ele. was 18.1 hrs, (maximum amount of drug absorbed) was 2018 µg, F was 1 and the bioavailability (F relative) was 100%.