Vitamin C Injection Stability Test
1. Stability of pharmaceutical preparations The basic requirements for pharmaceutical preparations should be safety, efficacy and stability. Stability refers to the stability of the drug in vitro. Drug preparation stability generally includes chemical, physical, biological three aspects: (1) chemical stability refers to the drug due to hydrolysis, oxidation and other chemical degradation reactions, so that the drug content (and potency), color changes; (2) physical stability refers to such as suspension drug particles clumping, crystalline growth, emulsions, delamination, rupture, colloidal preparations, aging, tablets, disintegration, dissolution rate changes, etc.; (3) biological Stability generally refers to the drug preparation due to microbial contamination, and the product deterioration, corruption. 2. chemical kinetic method chemical kinetic method that is to establish a mathematical model between the concentration of the reactants and the reaction rate in order to study the degradation of the drug method. 3. stability study method in the study of the stability of the preparation in order to determine the validity of the preparation (or storage period), the general use of room temperature sampling and accelerated test method. Room temperature sample inspection method is reliable but requires a longer period of time (generally 2-3 years), and accelerated test method (such as constant temperature accelerated test method) can be in a shorter period of time to make a preliminary estimate of the expiration date or storage period.
Operation method
Vitamin C injection stability test
Principle
The basic requirements of drug preparations should be safety, effectiveness and stability. If the drug deteriorates, it will not only reduce the therapeutic effect, but also some drugs will even produce toxic side effects, therefore, the stability of the drug preparation is very important for the safety and effectiveness of the preparation. The chemical stability of drugs is mainly manifested in the degradation reaction of oxidation and hydrolysis of drug preparations due to the influence of temperature, humidity, light, pH value and so on. The chemical structure of the drug is different, its degradation reaction is also different. The molecular structure of vitamin C is extremely unstable due to the presence of an enediol group that is highly susceptible to oxidation, and its degradation reaction is a primary reaction. Factors affecting the stability of vitamin C injection are mainly oxygen in the air, metal ions, pH, temperature and light, etc. Its degradation is slower at room temperature, so it is often used to study its stability by accelerated test method. Move 1. Accelerated test methods For more product details, please visit Aladdin Scientific website.
(1) Test temperature selection: 70℃, 80℃, 90℃, 100℃.
(2) Sampling interval time selection: 70 ℃ interval 24h, 80 ℃ interval 12h, 90 ℃ interval 6h, 100 ℃ interval 3h.
(3) Test method: the same batch of vitamin C injection wrapped in gauze were placed in four selected temperature thermostatic water bath, when the temperature of the injection and the water bath temperature is the same, immediately take a sample of 5 (for the zero time samples) and timing, and then according to the set interval time to take samples, the number of samples at each temperature interval are 4 times, the samples are removed, it should be immediately cooled or placed in the refrigerator for preservation, and then measured separately. The content of remaining vitamin C in the samples was then determined respectively.
2. Determination of content
Mix the 5 vitamin C injections of each sample, precisely absorb 1 ml in a 100 ml iodine measuring flask, add 15 ml of distilled water and 2 ml of acetone, shake well, let it stand for 5 min, add 4 ml of dilute acetic acid and 1 ml of amylose indicator solution, titrate with 0.1 mol/L iodine solution until the solution shows blue color and lasts for 30 s. The content of the remaining vitamin C in the sample should be determined separately. Every 1 ml of iodine solution (0.1 mol/L) is equivalent to 8.806 mg of vitamin C. The solution was titrated with 0.1 mol/L iodine solution.
3. Processing of results
(1) Data recording: The vitamin C content of the samples taken out at each temperature during each heating time and the original samples without heating test were determined separately, and the number of ml of iodine solution consumed was recorded. The ml of iodine solution consumed at time zero (i.e., the initial concentration) was taken as the 100% relative concentration, and the ml of iodine solution consumed by the other samples at each heating time was compared with it to obtain the percentage of the respective relative concentration (Cr, %). The experimental data were recorded in the table below.
(2) Calculate the reaction rate constants of vitamin C for four test temperatures (K70°C, K80°C, K90°C, K100°C) and calculate the drug expiration date. (1) Make a lgCr-t diagram. ② According to the first-order reaction equation, linear regression of t with lgCr leads to a linear equation, and from the slope of the equation, K at each experimental temperature can be found and recorded. ③Use Arrhenius' law, K = Ae-E/RT or lgK = -ERT/2.303 + lgA to lgK to 1/T linear regression, a straight line, from the slope of the straight line to find out the activation energy of the oxidative degradation of vitamin C, and from the straight line interception to find out the frequency factor. ④ Find the K25°C at room temperature (25°C). Then, according to t 0.9 = 0.1054/K25℃, the expiration date of vitamin C injection at room temperature (25℃) can be calculated.