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Accelerated stability study of aspirin

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- 1. Biopharmacy lab Accelerated stability study of aspirin Page 1 Dr.Hussein AL Qadisyiah College of Pharmacy Accelerated Stability and Stress Testing As part of the current good manufacturing practice regulations, the FDA requires that drug products bear an expiration date determined by appropriate stability testing . The stability of drug products needs to be evaluated over time in the same container-closure system in which the drug product is marketed. When a manufacturer changes the packaging of a drug product (e.g., from a bottle to unit dose), stability testing must be performed on the product in its new packaging, and expiration dating must reflect the results of the new stability testing. Accelerated stability studies are designed to increase the rate of chemical degradation or physical change of a drug substance or drug product by using exaggerated storage conditions as part of the formal stability studies. Data from these studies, in addition to long-term stability studies, can be used to assess longer-term chemical effects at non- accelerated conditions and to evaluate the effect of short-term excursions outside the label storage conditions such as might occur during shipping. Results from accelerated testing studies are not always predictive of physical changes. Stress testing of the drug substance or drug product can help identify the likely degradation products, which in turn can help establish the degradation pathways and the intrinsic stability of the molecule. The nature of the stress testing will depend on the individual drug substance and the type of drug product involved. Principle The method of accelerated testing of pharmaceutical products based on the principles of chemical kinetics . According to this technique, the k values for the decomposition of a drug in solution at various elevated temperatures are obtained by plotting some function of concentration against time . The logarithms of the specific rates of decomposition are then plotted against the reciprocals of the absolute temperatures and the resulting line is extrapolated to room temperature. The k25 is used to obtain a measure of the stability of the drug under ordinary shelf conditions.
- 2. Biopharmacy lab Accelerated stability study of aspirin Page 2 Dr.Hussein AL Qadisyiah College of Pharmacy Arrhenius equation It is desirable to determine the stability of the active ingredient in the drug so that a shelf life or expiration date may be assigned to the product. The shelf life is the length of time required for the product potency to be reduced to some percentage of its original value. For most products, this is the t90 or time at which the product retains 90% of its original potency. Although the drug's stability at room temperature is of interest, a stability study at room temperature would take too long. Therefore, studies are conducted at elevated temperatures in accordance with the Arrhenius equation: where,
- 3. Biopharmacy lab Accelerated stability study of aspirin Page 3 Dr.Hussein AL Qadisyiah College of Pharmacy Kapp = apparent rate constant (min-1 ) α = frequency constant (min-1 ) Ea = activation energy (cal/mol) R = gas constant (1.987 cal./K mol) T = absolute temperature (K) Again, an equation of the form y = mx + b is generated, indicating that a semi-log plot of Kapp vs. the reciprocal of the absolute temperature (1/T) should yield a straight line with a negative slope equal to -Ea/R. This line can be extrapolated to the value of 1/T that corresponds to room temperature and the predicted rate constant for the reaction at room temperature can be taken from the y- axis. Finally, the shelf life of the drug at room temperature can be determined. We will consider the shelf life to be the time for which at least 90% of the drug remains active, and this will be denoted t90: Accelerated stability study of aspirin Aspirin undergoes hydrolysis with the resultant degradation products being salicylic acid and acetic acid. Aspirin → Salysilic Acid + Acetic Acid the degradation of aspirin in a solution buffered at pH = 7.5 will follow first order kinetics; that is, the reaction will appear to be a first order reaction, dependent only on the concentration of one reactant; i.e. aspirin (ASA or simply A). The integrated form of a first order rate expression above is: It is easier to measure the increasing concentration of the product, salicylic acid (SA) than it is to measure the decreasing aspirin concentration, A. Therefore the experiment follows the appearance of SA, and relates the SA concentration to the concentration of A.
- 4. Biopharmacy lab Accelerated stability study of aspirin Page 4 Dr.Hussein AL Qadisyiah College of Pharmacy One mole of salicylic acid is produced when one mole of aspirin degrades; so, using the ratio of the molecular weights of aspirin to salicylic acid, we can determine the weight of aspirin degraded for each mg of salicylic acid produced. Therefore, each milligram of salicylic acid present represents the degradation of 1.3 milligrams of aspirin. Since the amount of aspirin initially present is known and since the amount of aspirin, which has degraded, can be determined, the amount of aspirin remaining can be calculated. Procedure In this experiment, three group will work in a team; each group member will conduct the experiment at a different temperature (50°C, 70°C, and 80°C) and then collaborate the data to hand in one lab report per student Standard Curve. Construct a standard curve for SA using the same procedure mention for aspirin in this case we will use the same standard curve of aspirin. Aspirin hydrolysis procedure 1. Each group in the team will perform the experiment at one temperature, and data for different temperature runs will be shared among team. A constant temperature hot plate is sets on 50,70 and 80 Co 2. Add approximately 195 mL of the water+5mL ethanol in 200 ml beaker and place it into the constant temperature bath. Allow the contents to come to the specified temperature. 3. Weigh 100 mg of aspirin and add the powder to beaker Note: As soon as aspirin is added to water, it begins to degrade. It is therefore important to take your initial sample quickly after water is added to the aspirin .
- 5. Biopharmacy lab Accelerated stability study of aspirin Page 5 Dr.Hussein AL Qadisyiah College of Pharmacy 4. Immediately take a 5 mL sample and replace it with 5ml water place in a sample container. This sample will correspond to time zero. Complete the volume to 20 ml with water 5. Read the absorbance at 310 nm 6. Continue to pipet and analyze 5ml samples from the aspirin beaker every 15 minutes for 60 minutes. Do not remove the beaker when sampling so the temperature can remain stable. Record the results Data Analysis 1. Using the equation you obtained in the Beer’s Law plot ( from . Standard Curve), determine the concentration of salicylic acid (SA) for each absorbance reading. 2. Determine the amount of acetylsalicylic acid degraded Adrgd for each sample time and record results in Table each milligram of salicylic acid present represents the degradation of 1.3 milligrams of aspirin 3. Determine the amount of acetylsalicylic acid remaining for each sample time and record results in Table 4. Obtain the results for three different temperatures from other teams and record the results in Table 5. Plot ln (Arem) vs. time for each temperature and determine the slope of the line at each temperature. A sample plot is shown below for a single temperature. You may plot the data for the other temperatures on the same graph, or on separate graphs, as you wish.
- 6. Biopharmacy lab Accelerated stability study of aspirin Page 6 Dr.Hussein AL Qadisyiah College of Pharmacy 6. Calculate Kapp for each temperature: -Kapp = slope of the above plot. Record the results in Table 7. For each temperature, calculate the value of 1/T, where T is the temperature in Kelvin. Record the values in Table . Also calculate and record the values of ln(Kapp) for each Temperature. 8. Construct an Arrhenius Plot by plotting ln Kapp vs. 1/T. Find the slope and intercept. The slope will be equal to –E/R and the intercept will be equal to ln(α). A sample plot is provided below. Please note that there will be only one line on this plot. Each data point represents the K value from a different temperature, so you will have three data points. 9. Use Arrhenius Equation to Determine the Kapp at room temperature (25 °C = 298K). Remember, (–E/R) is the slope of the plot above, and ln(α) is the intercept. 10.Determine the shelf life of aspirin in a buffered solution at t90 using Equation Note: each student has to write his own result and report

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