Preparation of Phloroglucinol for Injection
|School||Central South University|
|Keywords||Injection with phloroglucinol Prescription process Quality Research Preparation stability Compatible Stability Vascular irritation Muscle irritation Hemolytic Systemic allergic|
1 The aim of the present study was designed to prepare for injection phloroglucinol, establish quality control methods, study the preparation stability and compatibility stability, and anaphylactic hemolytic and local irritation test in order to evaluate the safety of medication effectiveness, stability and quality control. 2 Method 2.1 prescription process selected by fillers, dope preparation, dosage of activated carbon investigated to determine the pH value range, eutectic melting point determination, freeze-drying process research optimize the injection phloroglucinol best prescription process, trial production batches of samples and quality testing, examine its formulation and process feasibility, stability, product quality is controlled, qualified. 2.2 quality research by Chinese Pharmacopoeia 2005 edition two Appendix injections, injection phloroglucinol traits, identification, inspection, content, and establish its quality control method. 2.3 Stability of trial by influencing factors, accelerated test and long-term trials investigated injection phloroglucinol preparation stability traits, pH, clarity, loss on drying, related substances, content, sterility and bacterial endotoxins check inspect the project focused on the effects of temperature, humidity, light on its nature. Before and after Compatibility solution Appearance, pH, osmolality, insoluble particles and content of the project focused study injectable phloroglucinol commonly used in clinical transfusion compatibility stability, provide the basis for the clinical use of drugs. 2.4 safety trials in the vascular irritation test, the observation of the rabbits were continuously 5d injection phloroglucinol and saline after the change, visual observation of the blood vessels of the injection site with or without congestive, whether the surrounding tissue edema and biopsy . Pyrogallol muscle irritation test between injections in rabbits about legs quadriceps within 48 h after injection animals were sacrificed and dissected remove the quadriceps, longitudinal cut, to observe the injection of local stimulus response to pathological school inspection. Hemolysis test, observe the injection with phloroglucinol whether in 4h hemolysis and agglutination. Systemic anaphylaxis test in guinea pigs after intraperitoneal the phloroglucinol injection of saline and 5% egg 0.5mL three times every other day after the first administration, 14d and 21d, respectively intravenous drug solution 1.0mL observe the attack animals 15min. 3 Results 3.1 prescription process study using mannitol injection phloroglucinol skeleton proppant formulated 10mg · mL-1 to be frozen solution added with 0.05% of the amount of fluid needle with activated carbon, 40 ℃ the insulation stand for 30min, pumping filtering off the charcoal. The solution pH value is controlled in the 4.0-6.0 range, the production is generally controlled at about 5.0. Eutectic melting point of about -2 ℃, the freeze-drying process is always time-consuming in about 40h. 3.2 Quality to study the characteristics of the product as a white or off-white loose lumps or powder. Identify (1) and (2) is formulated according to the the phloroglucinol chemical structure containing a phenolic hydroxyl, identification of (3) is based on the characteristics of liquid chromatography phloroglucinol enacted, the distinguishing specialization Operation is simple and fast. Formulation based on the measured results acidity range of 4.0-6.0. Related substances Department using content determination under the chromatographic conditions, with Octadecylsilanized silica gel as a filler, acetonitrile - water (9:91) as the mobile phase, detection wavelength 265nm, the number of theoretical plates isophthalic trihydroxybenzene peak should not be less than 3000. The system suitability test and acid, alkali, oxidation, light, the hot-destructive testing and the lowest detection limit examine the results show that: the basic impurities and degradation products in the sample main peak separation, the minimum detection limit to meet the testing requirements. Accumulation and stability test results according to the R \u0026 D of impurity detection data quality standards specified in the related substances limits lt; 1.0%. The other inspection reference to the relevant provisions in the Chinese Pharmacopoeia 2005 edition two Appendix injections under development. HPLC determination of phloroglucinol content, the results show that good linear relationship in the concentration range of 0.13-1.04mg · mL-1 specific, tested solution inspection 8h stable, high precision, good reproducibility, and the average recovery was 100.6%, RSD 0.46%; scientific, reasonable, effective quality control. The content of three batches of samples were 90.0% -110.0% within specified limits. 3.3 Stability of injection phloroglucinol influencing factors were investigated in 10d accelerated test to examine six months, long-term trials to examine the 24 months, the measurement results of the investigation index 0 months are basically no significant change The sample shown in the above-mentioned test conditions more stable. Stored valid tentatively scheduled for two years. Injection phloroglucinol with 0.9% sodium chloride, 5% dextrose and 10% dextrose injection compatibility test results show: 4h compatibility, liquid are still colorless liquid clarity, pH, osmolality, insoluble particulate and the content is basically no significant change in the compatibility of the physical and chemical stability, to be compatible. 3.4 security test rabbits intravenous phloroglucinol, no vascular abnormalities change biopsy revealed vascular tissue necrosis and degeneration, and control ears showed no significant pathological morphological differences used for intravenous infusion; intramuscular after administration no stimulation; hemolysis of red blood cells do not produce and unifying role; guinea pig allergy test negative. 4 Conclusion injection with phloroglucinol prescription process is reasonable and feasible, quality controlled, stable, safe drug use and effective.