The control of Tween 80 in the pharmacopoeia of various countries is different. The Chinese Pharmacopoeia (CP) and the United States Pharmacopoeia (USP) are basically the same. Pharmacopoeia of various countries has no big difference in the provisions of hydroxyl value, saponification value, acid value, heavy metal, residue on ignition, moisture, viscosity, density and other indicators. But in general, the control standards of “European Pharmacopoeia” (EP) and “British Pharmacopoeia” (BP) are stricter than those of CP, USP, and “Japanese Pharmacopoeia” (JP), which are mainly reflected in the following aspects:
1) Impurity control BP strictly controls dioxane and ethylene oxide. Compared with BP, EP also increases the control of 2-chloroethanol, ethylene glycol and diethylene glycol. These five impurities are all Tween 80 The by-products of ethylene oxide used in the synthesis are likely to remain in the final product, and the above impurities have certain toxicity. EP uses headspace-gas chromatography to control these five impurities to better ensure product safety.
2) Control of peroxide value BP and EP control the peroxide value, which should not exceed 10.0. The peroxide value represents the degree of oxidation of fatty acid residues in Tween 80, and if the value is too high, the product is more severely oxidized. Excessive peroxide value may affect the stability of the formulation, so strict control of the peroxide value is required.
3) Control of fatty acid content CP, USP, and JP do not control the content of fatty acids (including oleic acid). EP stipulates the content of oleic acid, and BP is more specific. The main fatty acid oleic acid is specified at 58.0% to 85.0%. %, and other fatty acids that may be contained are also restricted, including myristic acid, palmitic acid, palmitoleic acid, stearic acid, linoleic acid, and linolenic acid, which may be mixed in the oleic acid used for synthesis. some impurities. The oleic acid used in the synthesis of foreign high-purity Tween 80 generally needs to control the content of other fatty acids to ensure the purity of Tween 80. BP’s control of fatty acids is the most stringent in the pharmacopoeia of various countries.
4) Production control of intravenous preparations In the pharmacopoeia of various countries, only EP clearly stipulates that if it is directly used in the production of intravenous preparations (there is no other depyrogenation step), the pyrogen should be checked. The method is as follows: the dose is 5mL per 1kg of rabbit body weight (with physiological sodium chloride solution to make 2mg·mL-1 concentration), which should meet the regulations.