News briefing： By discussing the preparation technology of long-acting oxytetracycline injection, the optimum production process and parameters were determined. The dosage of sodium sulfite, alpha-pyrrolidone, suspended white block and PVP were studied. The prescription
Abstract：By discussing the preparation technology of long-acting oxytetracycline injection, the optimum production process and parameters were determined. The dosage of sodium sulfite, alpha-pyrrolidone, suspended white block and PVP were studied. The prescription of oxytetracycline injection was determined by orthogonal test, and the content of oxytetracycline injection was determined by HPLC. The results showed that the sample was at room temperature. The process is stable and suitable for industrial production with controllable quality.
Sows with postpartum high fever, if not treated in time, will cause the decline of lactation function of sows, reduce the survival rate of piglets, and even cause the death of sows and sows. Long-acting oxytetracycline injection is the first choice drug for the treatment of postpartum high fever syndrome in sows. It has been rapidly popularized since the beginning of this century. In this paper, the key factors affecting the quality of oxytetracycline injection were studied. It is to optimize the optimum operating conditions of the process.
Experimental part
1.1 Instruments and reagents
Instrument LC-10AT High Performance Liquid Chromatography, CLASS-VP Chromatography Workstation, pHS-3B Type pH Meter
Oxytetracycline reference substance (purity 99.2%), oxytetracycline injection (specification 100ml:20g), injection grade oxytetracycline base (purity 99.2%), polyvinylpyrrolidone K17, alpha-pyrrolidone, formaldehyde sodium bisulfate, acetonitrile (chromatographic alcohol).
1.2 Determination Method
The content of oxytetracycline injection was determined by the chromatographic conditions in reference [1]. The chromatographic conditions were as follows.
Chromatographic column: DiamonsiLC18 column (250mm *4.6mm, 5um); mobile phase: 0.05mol/L potassium dihydrogen phosphate solution-acetonitrile, (adjusting pH value to 3.8 with phosphoric acid) (30:170); flow rate: 1.0mL/min; column temperature: 35 C; detection wavelength: 280nm; injection volume 10 mL.
2 Results and discussion
2.1 orthogonal test
Oxytetracycline solution is easy to be oxidized and its solubility is low, so antioxidants, organic solvents and stabilizers should be considered when screening prescriptions. In published literature [2,3], mixed solvents of alpha-pyrrolidone and N-methyl pyrrolidone are usually used as organic phase, but N-methyl pyrrolidone is more irritating and often causes animal pain in use. Sound therapy. In this study, a less irritating alpha-pyrrolidone was used as the organic phase and the dissolution requirement could also be met. Four factors and three levels of orthogonal test were conducted with polyvinyl pyrrolidone (PVPK17), alpha-pyrrolidone, sodium formaldehyde bisulfite (suspended white block) and sodium pyrosulfite as the investigating factors, arranged according to L9 (34) orthogonal table. Nine experiments were conducted. Samples were prepared according to the prescription in the table. Each sample was dissolved with 1.6g magnesium oxide and 23 g oxytetracycline and then filled in a brown cillin bottle. After sterilization at 115 C for 45 minutes, the color of the solution was observed and the content of the sample was determined. Factor level analysis was carried out with the change value of the content before and after sterilization as the index.
2.3 Selection of Sterilization Conditions
Orthogonal test table L9 (34)
1. Orthogonal test results
According to the principle that the greater the change value of injection before and after sterilization, the worse the stability of the sample, the best result is A1B3C3D3. Further analysis of the results shows that suspended white block has the greatest influence on the stability of injection, while alpha-pyrrolidone has the least influence. This is basically consistent with the results reported in some references [3].
2.2 Control of pH
According to the quality standard of oxytetracycline injection, the range of pH is 8.3-8.8. So monoethanolamine, diethanolamine and 5% carbonate are used respectively.
Sodium hydrogen and 1% sodium hydroxide were used as pH regulators. The results showed that the following tables were Li Jing, Changming and Changyongfang. According to the general requirements of the injection, in order to ensure the safety of the injection, sterilization of the solution after encapsulation was needed. 100, 30, 100, 45, 115, 45 minutes were selected. Oxytetracycline injection was sterilized under several sterilization conditions at 21 C for 15 minutes.
Test Table for Selection of Sterilization Conditions
2.4 Screening of Operating Temperature
In the preparation of injection, it is necessary to control the temperature. If the temperature is too high, the solution will be oxidized easily and the energy will be wasted. Operation temperature
If the temperature is too low, the dissolution time will be too long, the production cycle will be prolonged and the human and material resources will be consumed. Therefore, optimizing the optimum operating temperature is beneficial to solve the above problems. The optimum operating temperature for this product is optimized by testing several operating temperatures, such as 40, 45, 50, 55 ~C.
Operating Temperature Screening Test Table
The main factor affecting the stability of the product is the oxygen in the air. In addition to adding a certain amount of antioxidant in the prescription design, measures such as filling nitrogen and strictly using new boiling water for injection are also taken in the production process. Meanwhile, the time of exposure of the liquid to the air should be reduced as much as possible during the processing to improve the stability of the injection. In the selection of sterilization conditions, the product can not be sterilized at 100, 30 minutes, 100, 45 minutes. However, the product may be degraded at 121, 15 minutes due to excessive temperature. Therefore, the best sterilization conditions should be 115 ~45 min. In the optimization of operation temperature, there is no significant difference in solution color between 40 ~45 ~C, and too high operation temperature will lead to irreversible change of solution color. In normal production, it is more appropriate to control the operation temperature between 40 ~45 ~C.
3. conclusion
Experiments show that the best prescription for production is: PVPk177.50g, sodium sulfite 0.07g and alpha-pyrrolidine in 100 ml solution.
Ketone 50g, magnesium oxide 1.6g, suspended white cubes 0.5g, injection grade oxytetracycline 23g. In the prescription, suspended white cubes play a significant role in the stability of the product, which is the key factor affecting the stability of the product. At the same time, suspended white cubes in the prescription are not the more the better, the product has strong irritation, and it needs to be strictly limited to a certain concentration range. In the industrial production, the use of suspended white block in order to avoid excessive feeding by individual factories may lead to excessive irritation and dangerous application of the product. Under the experimental conditions, different pH regulators have no obvious effect on the stability, which is basically consistent with earlier reports [4]. In some reports [2, 3], amino acids are also used to regulate the pH of the product, because they are affected by our laboratory. The optimum sterilization conditions of this product are 115 C, 45 min, and the operating temperature is controlled between 40 and 45 C. It can ensure that the process control is simplified and the stable product is obtained at the same time.
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