Study On Quality And Stability Of Tylosin Tartrate Granules

Tylosin is a kind of Macrolide antibiotics for animal.The United States obtained it from the Streptomyces fradiae in1959.We use its tartrate or phosphate in the main clinical.It have a relatively strong inhibitory and killing effect on Gram-positive, mycoplasma and spirochetes.It have the same inhibiting role in killing of the most Gram-negative bacteria.Our company obtained The Invention patents of Tylosin tartrate granules(Publication Number CN1562066A) in2004.We bought a dry granulation machine in2009. We produce tylosin tartrate granules, tylosin phosphate granules. On the basis of information from literature, the modern research conditions and the molecular structure of itself, this thesis studies quality research methods of tylosin tartrate granules. Determine the appropriate testing conditions by high performance liquid chromatography and other modern analytical techniques,and the drafting of a scientific and rational development of quality standards, and its stability were investigated for the control of product quality and the development of quality standards to provide the test data.1Study on the quality of tylosin tartrate granulesIn this thesis, the characteristics of tylosin tartrate granules were investigated through apearance, solubility illumination test and moisture test and this produet was proved to have no significant moisture. Tylosin tartrate granules are identified mainly by chemical identification method, UV spectrophotometry, retention time of HPLC, infrared spectrum and differential response of tartrate.This product is a kind of preparation. According to the chemical properties of the materials and preparation process, it is determined the related substances, acidity, clarity of solution, tyramine, granularity, dry weight loss, heavy metals, residue on ignition and residual solvents used in the extraction of inspection, content of tartaric acid such as the product of the inspection items.Because of the molecular structure of the product and the characteristics of extract, the material became the focus of the study product quality. The variety of related substances were determined by high performance liquid chromatography.The appropriate chromatographic conditions to detect were determined by method validation.Because we add L-tartaric acid in the refining process, We can find the quantity of L-tartaric acid by content of product’s tartaric acid and pH in the refining process of this product, select the phenlomen column (5μm,250mm×4.6mm).The results of methodology show that the method specificity, reproducibility and sensitivity are in line with determined requirements.According to "Chinese Veterinary Pharmacopoeia"2010edition, Appendix81, the determination of residual organic solvents and ICH requirements for drug introduced in the production process of harmful organic solvent residue to be checked.According to the extraction route of the product, the third solvent butyl acetate. Reference to the guiding principles of limited standards, regulations of butyl acetate least were0.5%.Residual solvent in the basic raw material was not detected,raw materials have been solvent residues can be effectively controlled with internal standard method, the performance indicators of methodology was verified and the result method is feasible.According to the nature of the product, cylinder-plate method for the determination of tylosin tartrate contents methods and method validation carried out, including linear and scope, recovery, precision, solution stability, and through the turbidimetry confirmed the accuracy of high performance liquid chromatography. The study of quality above provides the test data for the control of product quality and the development of quality standards.2Quality standard and drafting instruction of tylosin tartrate granulesIn a comprehensive study on quality, combined with the actual situation, formulate a scientific and reasonable quality standard, including the character, pH, granularity, related substances determination and so on. Determination of physical constants are mainly using chemical methods, UV spectroscopy, HPLC, identification of the differential response of tartrate, tartric content and related substances was determined by high performance liquid chromatography,assay was determined by cylinder-plate method and gas chromatography solvent residues. Others include residue on pH, granularity, dry weight loss and so did the experiment carefully.Development of drafting instructions for the project quality standards and indicators of reasonable and necessary to do further instructions.3Stability examine of tylosin tartrate granulesOn the basis of quality standards above, in accordance with the requirements of Pharmacopoeia Appendix,conducted stability study of tylosin tartrate granules, including the influence factor tests, the middle test, accelerated testing and long-term stability test. The results showed that tylosin tartrate granules more stable to light, high temperature (100℃) somewhat less stability, instability of acid, alkali and oxidant.The results for tylosin tartrate granules storage conditions and provides the basis for the development period, as well as the quality of preparation process and the preparation provided reliable information.