TH-302 Hepatic Arterial Embolization Microspheres

Objective: This topic combines the advantages of hepatic arterial embolization microspheres and the treatment characteristics of TH-302.TH-302 is used as a model drug to prepare TH-302 hepatic artery embolization microspheres.Method:(1)Through single-factor experiments,several factors that have a great influence on the particle size and entrapment efficiency of the microspheres were investigated.The evaluation indicators were the particle size,entrapment efficiency,drug loading,and in vitro release of the microspheres.The optimized formulation and preparation process of the microspheres were screened.Because of the higher particle size requirements of the embolization microspheres,the purpose of this study was to prepare embolic microspheres of three particle size ranges of 75-100μm,100-200μm,and 200-300μm.(2)The experiment also examined the external conditions such as light irradiation,high temperature,high humidity,60 Co irradiation,sterilization,and the long-term conditions at a temperature of 4°C±2°C,a humidity of(60±10)%,and a temperature of 25°C± 2 °C,humidity is(60 ± 10)% of the microsphere stability under accelerated conditions.Results:(1)Through the determination of the solubility of TH-302,it was determined thatthe preparation method of the microspheres was a single emulsion-solvent evaporation method.The established content and release determination methods were simple,specific,and the recovery rate and precision were all high.Higher.In addition,the drug is prone to degradation under in vitro release conditions.This experiment establishes a linear relationship between the actual degradation peak area of the drug and the theoretical degrading drug.The linear equation is Aactual=0.0523mdegredation-1.4166(R2 = 0.9919 n=6).It has been verified that this formula can accurately calculate the actual amount of released microspheres.(2)Determine the basic prescription of the microspheres through single-factor experiments:The microsphere carrier material is a PLGA with a molecular weight of 9800,ester capped,and75:25,the aqueous phase concentration is 5%,and the oil-water phase volume ratio is 1:15.The desired particle size of the microspheres was prepared by varying the rotational speed and emulsification time of the impeller.The appearance of the microspheres was characterized by Malvern laser particle size analyzer,camera-ready optical microscope and scanning electron microscope.It was found that the microspheres of the three particle size segments prepared in this experiment had a uniform particle size distribution.The microspheres with three particle size segments were 90.84μm±1.17μm,193.51μm±1.47μm,221.60μm±1.45μm,respectively.The surface of the microspheres was smooth and round,and the encapsulation rates were45.70%±0.55% and 42.01%±0.14,respectively.%,48.36% ± 0.98%,burst release were: 9.91% ±0.38%,18.55% ± 0.64%,6.67% ± 0.60%,and the three prescriptions had good reproducibility.(3)Influencing factors Experimental studies prove that microspheres should be preserved under low temperature and dark conditions;under accelerated conditions for 3 months,the content of microspheres does not change significantly,but the flowability of microspheres deteriorates;accelerated experiments for three months There was no significant change in the content and fluidity of the microspheres under the conditions.After 60 Co irradiation,it was found that theγ-ray had less influence on the drug substance than the drug-loaded microspheres,and 60 Co irradiation was not suitable for the microsphere preparation.Sterilization.The burst release of the sterilized microspheres was smaller than before sterilization,but the overall drug release trend was consistent with that before sterilization.Conclusion: The single-factor experiment was used to determine the optimal formulation of microspheres of different particle size.The preparation method is simple,the microspheresobtained are smooth and round,the entrapment efficiency is high,and the microspheres have a low burst release rate.Sexual studies have shown that the drug should be stored under conditions of low temperature and light protection.After sterilization,it was found that 60 Co irradiation sterilization is not suitable for the sterilization of the microspheres.