| Local infusion in dairy cows refers to the dosage form applied in the breast or uterus,through the milk tube or with a catheter through the uterus.Compared with the systemic administration,the curative effect is better,and the tissue residue is lower.The development of rifaximin infusion provides an effective method for the treatment of cow mastitis and endometritis.The purpose of this study was to establish a HPLC method for the determination of rifaximin intrauterine infusion,and to develop a new rifaximin intramammary infusion which is stable,effective and also has good dispersion in milk,then the quality was evaluated.The determination method of content in the rifaximin intrauterine infusion which was established in this paper had strong specificity;The linear relationship within the concentration range of 10 μg/mL-320 μg/mL was good,by some calculations,the regression equation was Y=34600x-49100;The LOD was 0.25 μg/mL and the LOQ was 0.6 μg/mL;In accuracy test,recovery of QC samples(80%,100%,120%)ranged from 98.29%to 101.87%,RSD=1.24%,the results indicated that the method had high accuracy;In the investigation range of column temperature 35-45℃,flow rate 1.2-1.6mL/min,wavelength 274-278 nm,different mobile phase ratio,mobile phase pH 6.8-7.6,and different chromatographic column,the RSD of rifaximin content was 0.22%,0.29%,0.33%,0.48%,0.29%,0.52%respectively,the results showed that this method had high reliability.Six batches of samples were tested,and the content of rifaximin was 99.8%-102%.The determination method of content in the rifaximin intramammary infusion which was established in this paper also had strong specificity;The linear relationship within the concentration range of 20 μg/mL-100 μg/mL was good,by some calculations,the regression equation was Y=-6805X+25358;The LOD was 0.15 μg/mL and the LOQ was 0.4 μg/mL;The RSD of rifaximin content in the repeatability,method precision and intermediate precision tests were 0.48%,0.95%and 0.45%respectively,and the relative deviation of method precision and intermediate precision was 1.52%,so the precision was high;In accuracy test,recovery of QC samples(80%,100%,120%)ranged from 99.45%to 101.31%,RSD=0.61%,the results indicated that the method had high accuracy;In the investigation range of column temperature 25-45℃,flow rate 1.2-1.7 mL/min,wavelength 273-281 nm,mobile phase pH 6.8-7.6,different mobile phase ratio and different chromatographic column,the RSD of rifaximin content was 1.81%,0.65%,1.38%,1.54%,0.82%,1.28%respectively,the results showed that this method had good durability.Six batches of samples were tested,and the content of rifaximin was 99.08%-102.47%.In this article,through the single factor test and quadratic-regression rotatable orthogonal experiment,the best best formula and technological process of rifaximin intramammary infusion,as follows.The specification of the formulation was 5 mL:0.1 g,firstly a suitable amount of soybean oil was heated to 60-80℃,secondly 0.07 g glyceryl monostearate was added,and under continuous stirring using a thermostatic magnetic stirrer for 30 minutes,thirdly after cooling to 36-42℃,the 0.19 g lanolin was added and stirred until melted,fourthly 0.17 mL polysorbate 80,0.068 mL sorbitan oleate(span 80),0.1 g rifaximin(particle size 5-10μm)and the rest of soybean oil,finally after grinding until uniform,the formulation was potted and sterilized by 60 Co-y radiation.The samples were stable and had good dispersion in milk,of course it accord with the requirement of the Chinese Veterinary Pharmacopoeia(2015).In this paper,the accelerated stability,strong illumination and long-term stability were studied,later the local skin irritation of rifaximin intramammary infusion were determinated.(1)The character,moisture,asepsis,sedimentation volume ratio,particle size,content and related substances of rifaximin intramammary infusion were determined after being placed for 6 mouths under 30±2 ℃ and relative humidity 60±5%,being exposed for 10 days under 4500±500 Lx illumination and being stored for 18 months under 25±2℃ and relative humidity 60±5%,the results showed that all All test items were in accordance with the the requirement of the Chinese Veterinary Pharmacopoeia(2015),thus the preparation had good stability.(2)Rifaximin intramammary infusion(lactating cow)had no irritation to the skin and vaginal mucosa,and there was no abnormality in the histopathological examination of the mucosa,thus all were in accordance with safety test standard. |
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