Study On The Clarithromycin Lipid Composition For Injection

In order to reduce the pain on intravenous infusion of clarithromycin, using Cholesterol sulfate sodium as the drug carrier, we prepared clarithromycin lipid composition which was visually clear before infusion. A formulation composed of clarithromycin/ Cholesterol sulfate sodium(1:1molar ratio) was identified as a formulation which is chemically and physically stable. Studied the hemolysis of this formulation and foud the hemolysis of this formulation can be reduced by phospholipids. At last a formulation composed of clarithromycin /cholesterol sulfate sodium/ phospholipids (1:1:2) was identified as the best formulation which can be infused at a drug concentration of 20mg/ml. The average particle size was 75．4nanometer, ranging from 52 nanometer to 135 nanometer.To investigate the every freeze-drying process and the cryoprotectant formulation which can preserve the vesicles stable in freeze-drying. A good technique and formulation were confirmed which maintain the lipid composition structure and improve stability. The particle diameter distribution and the efficiency of lipid composition before and after freeze-drying were researched. Stability experiments demonstrated the formulation had adequate physical and chemical stability.Clarithromycin has the dimethylamino moiety as the only ionizable group and hence it has limited solubility in aqueous media which complicates it’s dissolution testings under sink conditions. Hence, we studied the solubility of clarithromycin affected by PH, surfactant concentration and alcohol concentration. Ingeneral, the solubility increased with the decrease in buffer PH. However, the additional of tween80 in the buffer offered marginal enhancement in drug solubility, and the enhancement in drug solubility was observed only at methanol concentrations>75%. Based on these results, the dissolution studies were conducted in Tris buffer solution and 5%Dextrose, and the sink conditions were simulated by using large volume of media.The pharmacological experiment results indicated that clarithromycin lipid composition had less irritation than clarithromycin lactobionate solution, toxicity in rats which was less than that of clarithromycin lactobionate.