Hydroxycamptothecin Fat Emulsion Injection And Lyophilized

The method of high performance liquid chromatography (HPLC) was set up to determine the concentration of 10-hydroxycamptothecin (HCPT). The total solubility and lactone form's solubility of HCPT in different pH phosphate buffered saline (PBS) and mixtures of different ratio soybean oil and middle glyceride respectively. The apparent partition coefficients of HCPT in octanol/distilled water and octanol/pH5.0 PBS were determined, separately. The ratio of carboxylate form of HCPT into lactones form in different pH solutions was also investigated.HCPT lipid emulsion using a medium chain glyceride and soybean oil as the oil phase, the mixture of soybean phospholipids and Pluronic F68 as emulfier, glycerin solution as the water phase and oleic acid as stabilizer was obstained by high-pressure homogenization. The physical and chemical stability of emulsion were evaluated with incorporation ratio, the stability parameters of centrifugation, content of HPCT, appearance of emulsion and size of droplet. The optimized formulation was found by orthogonal based on the single factor test. Processing factors were optimized based on the optimized formulation: HPCT 0.01%, soybean oil and medium chain glyceride at ratio 1:3 10%, phospholipids 2.4%, oleic acid 0.2%, medium chain glyceride and soybean oil were dissolve in the absolute ethanol, solvent evaporation. Its solution was completed by wanning up the mixture(70℃)), the emulsifier-oil was added to 2.5% aqueous solution of glycerol and poloxamer 188 of the same temperature. This mixture was pre-emulsified using the Ultraturax at 8000 rpm for 15 min. Subsequently, the pH of the resulting emulsion was adjusted to about 6.0. Final emulsification was carried out by passing the coarse emulsion through a high pressure homogenizer nine times at a pressure of 90 MPa .The temperature of the emulsion was maintained at 40℃~50℃,filtration by 0.45μm membrane and sealed after nitrogen was added.The lyophilized emulsion was developed to improve the stability of the HCPT parental emulsion. Screening from the various cryoprotectant, maltose and mannitol were ensure to protect HCPT parental emulsion in freeze-drying. A good technique and formulation were confirmed to maintain the emulsion structure. Maltose and mannitol was optimized as protectant .Their concentrations were separately 8% and 2%. Mannito and maltose were added into the 1ml emulsion above, adding water to final volume 2 mL, lyophilized. A laboratory freeze drier was used. The emulsions were freezed at -40℃ for 8h, the first drying step was performed at -40℃ for 16h, Secondly, the temperature was increased to -15℃ for 6h and 10℃ for the following 6h.