| Purinostat hydrochloride was a kind of first synthetic hydroxamic acid histone deacetylase inhibitor with good antitumor activity.Because of the poor solubility of Purinostat hydrochloride,prescription was designed and optimized to improve its solubility.taking into account the characteristic of the structure,clinical treatment and stability about Purinostat hydrochloride,this experiment will prepare it be powder injection.A preliminary study on the quality of the product after the preparation of Purinostat hydrochloride powder.The specific work were as follows:1.The preparation of purinostat hydrochloride powder for injectionAccording to purinostat hydrochloride compound structure features,this experiment consulted similar target sites or compound patents and identified the main prescription,on the basis of which we optimizated the formulation.Finally we got the prescription of purinostat hydrochloride powder for injection that was purinostat hydrochloride : 9g,arginine: 27 g,meglumine 63 g,hydroxypropyl betacyclodextrin:180g,mannitol:72g,ultra pure water volume to 900 ml,according to our general made bottle containing 30 mg purinostat hydrochloride powder for injection of 300 bottles.According to the features of dosage form of purinostat hydrochloride powder injection and preparation process related reference freeze-dried powder injection preparation process,we determined the preparation process,speed,temperature,time,filtration sterilization and freeze drying process and parameters.Finally we got the following preparation process of purinostat hydrochloride powder for injection:(1)swelled hydroxypropyl betacyclodextrin Weighed the prescribed amount of hydroxypropyl betacyclodextrin,placed in a 1L beaker,added 400 ml water for injection,magnetic stirred 3h in 50℃ water bath(speed 500rpm),swelled,standby.(2)preparation of inclusion compound Weighed the prescribed amount of meglumine and arginine,placed in a 2L beaker,added well swelled hydroxypropyl betacyclodextrin solution,stirred until dissolved after 800 rpm 10min,then joined the prescriptions amount purinostat hydrochloride,continue stirred until dissolved about30 min.(3)regulation p H Added the prescription of mannitol,continued to stir until dissolved.The p H value of the solution was adjusted to 10.1 by 1mol/L hydrochloric acid,used the water for injection to constant the solution volume to 900 ml.(4)depyrogen Added 900 mg activated carbon and 500 rpm magnetic stirred to adsorb 30 min,0.22μm microporous membrane filtrated.(5)packaging and freeze-drying The content was measured by HPLC,according to the bottle contained 30 mg purinostat hydrochloride,we calculated the filling volume,filled,lyophilized and capped.2.The quality Study on purinostat hydrochloride powder for injection(1)The Characteristics of purinostat hydrochloride powder for injectionThe characteristics of the three batches of samples was studied,and the character of purinostat hydrochloride powder for injection was obtained.(2)The identification of purinostat hydrochloride powder for injectionThe identification of the three batches of samples was studied,and the identification methods of purinostat hydrochloride powder for injection was obtained.(3)The examination of purinostat hydrochloride powder for injectionThe three batches of samples were examined according to the requirements of the Chinese pharmacopoeia in the 2015 edition,such as acidity,insoluble particles,the clarity and color of the solution,the difference in the volume of the solution,the visible foreign matter,the pyrogen,the residual solvent,the moisture and the osmotic pressure.The method of determinating the content of related substances and validated were by high performance liquid chromatography method.The results indicated that the method had good specificity,strong durability,good linear relationship with its principal component method.The content of related substances was determined by principal component self calibration method without correction factor and the related substances can be accurately measured by this method of purinostat hydrochloride powder for injection.(4)The content determination of purinostat hydrochloride powder for injectionThe methods of determinating the content of purinostat hydrochloride powder for injection were established by high performance liquid development and validated.The method validation results indicated that the method had good specificity,durability,accuracy and high precision,good linear relationship.The content of purinostat hydrochloride powder for injection was determined by one point external standard method and the experiment results showed that the method could be used to accurately measure the content of the purinostat hydrochloride in the powder injection. |
PDF Full Text Request