Study On The Release Rate In Vitro And Quality Of Tilmicosin Microcapsules Granules

Tilmicosin possesses a excellent antibacterial activity and a remarkable therapeutic effect.As a result,it is widely used in the treatment of diseases such as respiratory diseases and mastitis of livestock and poultry.In this study,the tilmicosin microencapsulated granules prepared by research group were selected to screen the optimal process batches.The quality control and stability of the optimal process batch preparations were studied further.The optimal prescription of tilmicosin microcapsules granules was screened out by performing a study on dissolution in vitro,and a comparative study on the dissolution in vitro of pulmotil tilmicosin premix was performed.A study on the quality control of the screened optimal prescription was performed and its stability was investigated to provide a theoretical scientific basis for the production and clinical use of tilmicosin microcapsules granules.Dissolution in vitro test took the first method of the Chinese Veterinary Pharmacopoeia dissolution measurement as a reference(basket method),rotation speed:100 r/min,p H1.2 solution,p H4.3 acetate buffer solution(containing 0.5%Tween-80),p H6.8 phosphate buffer solution(containing 0.5%Tween-80)were chosen and used as an in vitro release medium.The samples were taken at different time points and measured by the high performance liquid chromatography.The release amount of tilmicosin microcapsules granules and pulmotil tilmicosin premix at different time points were calculated and the cumulative release curve was drawn to observe its release situation.The results showed that pulmotil tilmicosin premix was completely released in three release media at 0.5 hour and didn’t have an effect of sustained release;the optimal prescription of tilmicosin microcapsules granules was screened out from 18 different prescriptions according to their release situation.In this optimal prescription,the tilmicosin microcapsules granules were released by 10.99%at a condition of p H1.2 solution at 0.5hour,ensuring that tilmicosin could smoothly pass the stomach and reduce the damage to acidic environment;under a condition of p H4.3 acetate buffer(containing 0.5%Tween-80)and p H6.8 phosphate buffer(containing 0.5%Tween-80),the drug was released slowly and only released completely in 5～6 hours,it can avoid burst release and achieve a good sustained release effect,which ensures that it be released throughout the pig’s intestines before the pig defecates.The results of study on the method for the quality control of tilmicosin microcapsules granules are as follows,its specificity is good.The blank excipients have zero interference to the extraction method established in this test.The concentration has a good linear relation with the peak area when the concentration falls in the range of 20～2000μg/m L,R~2>0.999;the recovery rate ranges from 98.62%to 100.03%when the concentration is low,moderate and high,RSD(%)is between 0.4184 and 0.4354,the accuracy is good;both the intra-batch RSD(%)and inter-batch RSD(%)of different liquid chromatographs are less than 1,and the repeatability is good.All the other test items are in line with the"Guidelines for the Validation of Analytical Methods for Veterinary Drugs in the 2015 Edition of the Veterinary Pharmacopoeia of the People’s Republic of China and Verification requirements for quality control analysis methods for chemical substances in the veterinary in the Technical Guidance and Principles for Veterinary Drug Research".The labeled amounts of content determination results are all between 95%and 105%,which also met the requirement of quality standards.The results of the stability test study were as follows:In this study,the three conditions,light,temperature and humidity,were tested.When the tilmicosin microcapsules granules were completely exposed to strong light for 10 days,the drug content of tilmicosin dropped by 14.6%,while the content of samples in pure aluminum packaging and aluminum-plated packaging did not obviously change.Therefore,tilmicosin microcapsules granules are sensitive to strong light and should be kept out of light;while under a condition of high temperature and high humidity,no significant change in the content of sustained-release granules was noted,indicating that the tilmicosin microcapsules granules are not sensitive to temperature and humidity;the results of long-term test and accelerated test were all in line with the Technical guidelines for the study of veterinary chemical stability in the Technical Guidance and Principles for Veterinary Drug Research.It is recommended to store it at room temperature in the dark and ventilated place.This experiment has established a method of determination of tilmicosin microcapsules granules,and this method has been verified by quality control research methodology.The results showed that all the indicators met the requirements,the method is able to accurately determine the content of tilmicosin microcapsules granules.At the same time,the preparation has a good effect of sustained release,and can effectively mask the bitter taste of tilmicosin,providing a broader research prospect for respiratory diseases and mastitis diseases in livestock and poultry.