Solid lipid nanoparticles of irbesartan: preparation, characterization, optimization and pharmacokinetic studies

ABSTRACT Irbesartan is an antihypertensive with limited bioavailability and solid lipid nanoparticles (SLN) is one of the approaches to improve bioavailability. Solid lipid nanoparticles were prepared using glyceryl monostearate by solvent emulsification method followed by probe sonication. Irbesartan loaded SLNs were characterized and optimized by parameters like particle size, zeta potential, surface morphology entrapment efficiency and in vitro release. The optimized formulation was then further evaluated for the pharmacokinetic studies in Wistar rats. Irbesartan-loaded SLN of particle size 523.7 nm and 73.8% entrapment efficiency showed good bioavailability in Wistar rats and also showed optimum stability in the studies. The SLN prepared using glyceryl monostearate by solvent emulsification method leads to improve bioavailability of the drug.

Formulation Development and Evaluation of Paclitaxel Loaded Solid Lipid Nanoparticles Using Glyceryl Monostearate.

Solid Lipid Nanoparticles (SLNs) are important because of their size and stability. SLNs have been reported as an alternative drug delivery device to traditional polymeric nanoparticles. SLNs are in submicron range (50- 1000nm) and are composed of physiologically tolerated lipid components. At room temperature the particles are in solid state. They are made up of bio-compatible and bio-degradable materials capable of incorporating lipophilic and hydrophilic drugs. Paclitaxel is a Di-terpenoid Pseudo-alkaloid having anti-neoplastic activity particularly against primary epithelial, ovarian carcinoma, Breast cancer, Colon Cancer, Brain Cancer, Lungs cancer and AIDs Related Kaposi’s Sarcoma. Paclitaxel is an effective drug against Aggressive Cancer’s because it adversely affect the process of cell division by preventing restructuring. The present study is to investigate the probability of incorporating paclitaxel in SLNs using Glyceryl Mono-stearate (GMS) as a lipid matrix, poly-oxy ethylene (Brij 97) as a surfactant, soya-lecithin as a co-emulsifier. Paclitaxel loaded SLNs are prepared by Solvent emulsification and evaporation method using ultra sonication and optimization of critical process variables were carried out to develop stable SLNs. The average particle size of SLNs was found to be 63nm ± 5.77 with Poly dispersity index (PDI) 0.272 ± 0.02 and entrapment efficiency was found 94.58%. The stability studies and zeta potential were performed at refrigerated temperature (2-8 OC) indicating no significant increase in particle size after one month storage. In-vitro release studies showed initial burst release followed by controlled release for 48hrs (about 73%). The release profile was fitted into Higuchi’s model (r2=0.9774). The drug diffuses from SLNs at a comparatively slower rate as the distance for diffusion increases.

Design and Characterization of Glyceryl Monostearate Solid Lipid Nanoparticles Prepared by High Shear Homogenization.

Aims: The aim of this study was to explore the practicability of preparation of solid lipid nanoparticles of Glyceryl monostearate containing Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide as model drugs. The physicochemical properties of the prepared formulae like particle size, drug entrapment efficiency, drug loading capacity, yield content and in-vitro drug release behavior were also measured. Methodology: Solid lipid nanoparticles loaded with three model lipophilic drugs were prepared by high shear hot homogenization method. The model drugs used are Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide. Glyceryl monostearate was used as lipid core; Tween 20 and Tween 80 were employed as surfactants and lecithin as co-surfactant. Many formulation parameters were controlled to obtain high quality nanoparticles. The prepared solid lipid nanoparticles were evaluated by different standard physical and imaging methods. The efficiency of drug release form prepared formulae was studied using in vitro technique with utilize of dialysis bag technique. The stability of prepared formulae was studied by thermal procedures and infrared spectroscopy. Results: The mean particle diameter measured by laser diffraction technique was (194.6±5.03 to 406.6±15.2 nm) for Dibenzoyl peroxide loaded solid lipid nanoparticles, (220±6.2 to 328.34±2.5) nm for Erythromycin loaded solid lipid nanoparticles and (227.3±2.5 to 480.6±24) nm for Triamcinolone acetonide loaded solid lipid nanoparticles. The entrapment efficiency and drug loading capacity, determined with ultraviolet spectroscopy, were 80.5±9.45% and 0.805±0.093%, for Dibenzoyl peroxide, 96±11.5 and 0.96±0.012 for Triamcinolone acetonide and 94.6±14.9 and 0.946±0.012 for Erythromycin base respectively. It was found that model drugs showed significant faster release patterns when compared with commercially available formulations and pure drugs (p˂0.05). Thermal analysis of prepared solid lipid nanoparticles gave indication of solubilization of drugs within lipid matrix. Fourier Transformation Infrared Spectroscopy (FTIR) showed the absence of new bands for loaded solid lipid nanoparticles indicating no interaction between drugs and lipid matrix and being only dissolved in it. Electron microscope of scanning and transmission techniques indicated sphere form of prepared solid lipid nanoparticles with smooth surface with size below 100 nm. Conclusions: Solid lipid nanoparticles with small particle size have high encapsulation efficiency, and relatively high loading capacity for Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide as model drugs can be obtained by this method.