Abstract. Solid lipid nanoparticles (SLNs) of duloxetine hydrochloride (DLX) were prepared to circumvent the problems of DLX, which include acid labile nature, high first-pass metabolism, and highdosing frequency. The DLX-SLNs were prepared by using two different techniques, viz. solvent diffusion method and ultrasound dispersion method, and evaluated for particle size, zeta potential, entrapment efficiency, physical characteristics, and chemical stability. Best results were obtained when SLNs were prepared by ultrasound dispersion method using glyceryl mono stearate as solid lipid and DLX in ratio of 1:20 and mixture of polysorbate 80 and poloxamer 188 as surfactant in concentration of 3%. The mean particle size of formulation and entrapment efficiency was 91.7 nm and 87%, respectively, and had excellent stability in acidic medium. Differential scanning calorimetry and X-ray diffraction data showed complete amorphization of DLX in lipid. In vitro drug release from SLNs was observed for 48 h and was in accordance with Higuchi kinetics. In vivo antidepressant activity was evaluated in mice by forced swim test. DLX-SLNs showed significant enhancement in antidepressant activity at 24 h when administered orally in comparison to drug solution. These results confirm the potential of SLNs in enhancing chemical stability and improving the efficacy of DLX via oral route. The SLN dispersion was converted into solid granules by adsorbing on colloidal silicon dioxide and characterized for particle size after redispersion, morphology, and flow properties. Results indicated that nanoparticles were successfully adsorbed on the carrier and released SLNs when dispersed in water.
A simple, specific and sensitive reverse phase high performance liquid chromatographic method was developed and validated for simultaneous determination of ezetimibe and simvastatin from pharmaceutical dosage forms. The method uses C18 ODS Hypersil column and isocratic elution. The mobile phase composed of acetonitrile:phosphate buffer (pH 4.5, 0.01M) in the ratio of 65:35 v/v was used at a flow rate of 1.0 ml /min. UV detector was programmed at 232 nm for first 10 min and at 238 nm for 10 to 20 min. All the validation parameters were in acceptable range. The developed method was effectively applied to quantitate amount of ezetimibe and simvastatin from tablets. The method was also applied suitably for determining the degradation products of ezetimibe and simvastatin.
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