Determination of Salicylic Weight in Aspirin

Determination of Salicylic Weight in Aspirin

Introduction

Aspirin is a common analgesic drug used to reduce pain. The drug works by inhibiting substances in the body that mediate pain. Fever and inflammatory processes. Sometimes aspirin can be used in the prevention of heart attack, stroke, and chest pains. Previous studies have reported successful treatment of heart failure and sinus rhythm. Comparison between aspirin and warfarin singled out aspirin as more superior than warfarin (Homma et al., 1861). The IUPAC name of salicylic acid is ortho-hydroxybenzoic acid or 2-hydroxybenzoic acid. This compound has been used historically to reduce pain in 400 B.C. Salicylic acids are naturally found in the willow leaves. Pharmaceutical companies use none-polar solvents to extract the compound from the willow leaves and purify it before incorporating it into aspirin tablets. The extraction methods influence the amount of salicylic acid found in different brands, aspirin tablets (Nordström and Rasmuson, 1669).

The crystal structure of salicylic acid is monoclinic. This structure was previously elucidated by (Bacon & Jude, 1973). According to the structure generated by Bacon & Jude, intramolecular hydrogen bonding holds the hydroxyl groups to the carbonyl oxygen. The rigid bonding characteristics of the molecule makes the structure to be less flexible and a diminished intramolecular hydrogen bonding capability of the molecule. This structure of the molecule explains the reduced ability of the compound to dissolve in polar solvents (Bacon & Jude, 1973). However, despite the elucidation of the structure, there is only limited information about the solubility of this molecule and the effect of temperature on its solubility. The structure of salicylic acid is shown in figure 1.

Active Ingredients: The active ingredient in aspirin tablet is the salicylic acid.

Inactive Ingredients: The inactive ingredients are Carnauba Wax, Corn Starch, and Powdered Cellulose.

The function of inactive ingredients: The corn starch inactive ingredient is added as a binding agent and a filler. The carnauba wax is added to coat the tables for easier swallowing.

Figure 1: The structure of salicylic acid (Nordström and Rasmuson, 1669)

Purpose of the experiment

The current experiment adopted the acetone dissolution method to extract and estimate the amount of salicylic acid in different aspirin tablets acquired from different manufacturers. The main objective was to determine the difference in salicylic acid concentration in different aspirins from different companies. The experiment hypothesized that aspirin from different companies contains a different level of salicylic acid.

Research question

Is there a significant difference in the amount of salicylic acid in aspirin tablets obtained from different companies?

Methodology

Materials: The materials used in this experiment included aspirin tablets samples, acetone, mortar and pestle, and Buchner funnel. The aspirin samples were divided into two groups as follows: Sample- 1: CARVA from Square pharmaceuticals, Sample-2: Ecosprin from Acme pharmaceuticals:

Sample-2: Carva from Square pharmaceuticals:

Sample-2: Ecosprin from Acme pharmaceuticals:

Sample preparation

Tablets used in the experiment were acquired from the Ecospirin and Square pharmaceuticals. A total of 40 tablets were used in the analysis and were prepared by crushing the 40 tablets in mortar and pestle. After crushing, the powdered tablets were dissolved in 20 ml of acetone solvent and used for extraction of salicylic acid.

Experimental procedures

The solution prepared above was heated while stirring to ensure proper mixing.  Heating increases the rate at which the aspirin components dissolve in the solvent. The solution was allowed to cool in the open for 1 hour. The cooled solution was vacuum filtered using the Buchner funnel. To recover the acetylsalicylic acid, the filtered solution was evaporated to remove acetone. The acetone method for the extraction of salicylic acid from aspirin tablets is useful in the determination of the amount of salicylate in aspirin. The setup of equipment is shown in the diagram below.

Figure 2: The arrangement of experimental equipment

The chemical reaction for the synthesis of active ingredient from aspirin

The reaction between aspirin and sodium hydroxide is an acid-base reaction in which acetylsalicylic acid reacts with the base sodium hydroxide to produce the salt sodium acetylsalicylate and water. In this chemical reaction sodium hydroxide reacts with the salicylic acid active component of aspirin but not with the starch binders, as shown in the following equation:

The structural equation is shown below:

The chemical reaction for the separation of salicylic acid

Acetylsalicylic acid is a weak acid that undergoes slow hydrolysis. In this reaction, each acetylsalicylic acid reacts with two hydroxyl ions. To increase the rate of reaction, a known amount of base was added, and HCL titration performed to determine the amount of unreacted base. To estimate the amount of acetylsalicylic acid, the amount of unreacted base is subtracted from the initial amount of base. This gives the amount of base that reacted with the acety-salicylic acid. The titration reactions are shown below.

The presence of starch confirmed by iodine

The iodine test is used to test for the presence of starch. Since starch is used in the manufacture of aspirin when the aspirin tablet is crushed and iodine added to the powdered aspirin, the color changes to purple. This confirms the presence of starch as part of the non-active ingredients in aspirin. The purity of extracted salicylic acid depends on the presence of starch in aspirin tablets. The presence of starch may hinder the extraction process, hence the presence of the impurities in the salicylic acid extracted. The limitation of the method used in this experiment is the possibility of obtaining a salicylate extract with incomplete evaporation. Incomplete evaporation would mean that some acetone remains unevaporated, eventually increasing the weight of the resultant salicylic acid. To reduce the error rate caused by incomplete evaporation, the time for drying should be increased. Increasing the evaporation period ensures that no acetone remains in the beaker, increasing the accuracy of the measurements obtained. Besides, cooling the solution for 1 hour before vacuum filtration helps to ensure that most of the unwanted impurities sediments at the bottom of the flask. This way, it is easier to filter the solution and reduce the number of impurities that would have increased the weight of the extracted salicylic acid.

Raw data

The weight of salicylic acid was determined by subtracting the importance of the conical flask from the total weight and recorded in grams.

Table 1: The raw data from the experiment

Weight of Salicylic acid in aspirins from two different companies

The analysis of the concentration of salicylic acid in tablets obtained from the two separate companies revealed significant variations in the concentration of this compound. The highest weight was 4.79, while the lowest was 1.97. See table 2 below.

 Table 2: The amount of salicylic acid

Trials for each aspirin brand

The comparison of trial values from the two brands revealed that Square carva tablets recorded higher values than Ecospirin, as shown below.

1. Ecospirin

Figure 1: Graphical representation of values derived from the different trials of Ecospirin tablets.

1. Square Carva

Graphical representation of the Square carva values.

The mean weight of Salicylic acid in two aspirin Companies

The mean amount of salicylic acid in the Square Carva brand was higher than that in Ecospirin. These findings confirmed the study hypothesis. The hypothesis that the amount of salicylic acid in different aspirin obtained from various companies are not the same was proved right by the results of this experiment.

The average weight of salicylic acid in the two aspirin brands

Discussion

The findings of the study showed that the amount of salicylic acid in the two brands was not similar. In light of the results obtained from the experiment, the hypothesis that the weight of salicylic acid in aspirin is not identical in aspirin from different companies is accepted. The mean weight of salicylic acid in Square Carva was slightly higher than that in Ecospirin (2.35 grams versus 1.95 grams). The difference in weight of salicylic acid was, however, small (0.4 grams). From table one, it is evident that five trials were performed for Ecospirin versus seven trials for Square Carva. The results obtained per trial also supported the hypothesis.

Our experiment results imply that pharmacists may potentially prescribe an overdose or underdose of medication it the manufacturer declared values are not accurate, as demonstrated in this experiment. Moreover, our findings reaffirmed that there is always a variation in the content of drugs manufactured by different companies. In this regard, the prescription of salicylic acid-containing medicines from different companies should be prescribed separately based on the amount of the salicylic acid present.

The experimental design adopted in this experiment included a random selection of 40 tablets from the two companies and determinations of the amount of salicylic acid at a one-time point. This experimental design is effective in providing information about the variables tested (weigh of salicylic acid) in the tablets manufactured by the two companies. The experiment replication was done in 10 trials. Replication of the experiment is essential as it helps to ensure that the values obtained are realistic by calculating the average amount of salicylic acid (Lamal, 31). The experimental precision was determined by performing the experiment in replicated and comparing within replicate results. The closer the replicate results were to each other indicated that the precision of the study was high.

Furthermore, the study was shown to be precise by comparing the results obtained to those previously reported in the literature. For instance, our findings were consistent with the results of the previous experiment that explored the difference between salicylic acid in aspirin from different companies (Dacić et al., 564). However, despite the substantial agreement of results between the current experiment and other studies, observations about variation in chemistry methods adopted have been made.

The fact that some variations were recorded between the manufacturer values and the experimental values supported the findings we reported in our experiment. The study by Dacic and colleagues showed a significant deviation of the weight salicylic acid from the manufacturer’s declaration from 100mg to 104.407mg per tablet. The variation was 4.407mg, which was significantly lower than the value of 0.4 g that our experiment reported.

The errors in the measurement of the current method resulted from the low accuracy of the method used. For example, the manual determination of the weight of different components by weighing balance could be a potential source of errors. Therefore, the accuracy of our findings was affected by confounding factors, including the calibration of the weighing balance (Ewers and Didham, 120). Another primary source of errors in our experiment was random errors in sample weight. For instance, some tables were heavier than others, yet they were the same brand. Such errors were further enhanced by the random tablet selection method, which resulted in the selection of tablets with varying wrights. Such random errors are uncontrollable. These random errors in the samples affected the accuracy of the experiment results.

A number of confounding factors were not considered in the experiment—for instance, the effects of inactive components of aspirin on the solubility of salicylic acid in acetone. The binders, fillers may reduce the solubility of salicylic acid, and lubricants added as the inactive components. Most binders and fillers are starch in nature, and considering starch as an organic compound, some of the starch could as well dissolve in acetone. Upon evaporation of acetone, the slid remaining as salicylic acid could be composed of both salicylic acid and a small quantity of starch from the inactive portion of the tablet. The effect of starch solubility in acetone could result in obtaining a higher weight of the salicylic acid more than the actual weight.

The variations in the amount of salicylic acid present in the drug may have been caused by various factors, including poor equipment maintenance and calibration. The calibration of equipment used to perform sensitive measurements, including minimal weight, is very important. In our experiment, the weighting balance used was not calibrated hence affecting the measurements obtained. To correct this error, it is advisable to ensure that all equipment used in the experiment are calibrated. The lack of calibration of the weighing balance resulted in the variation in the weight of the tablets and affecting the overall accuracy of the method used (Iwunze, 2945). Standardization of methods for estimation of active compounds in aspirin should also be implemented to ensure that all the equipment is calibrated and their accuracy evaluated. Proper calibration of the material will help to ensure that results from different laboratories are in agreement.

A modification in the sample selection approach can be implemented to increase the accuracy of the experiment. For example, adopting a purposive sampling technique where all samples included are purposely picked to ensure they have the same would increase efficiency. The weight of the tablets primarily determines the accuracy of the experiment; hence by choosing tablets of the same weight reduced the probability of variations in the final results. Additionally, the experimental accuracy results can be improved by modification of some procedures such as the substitution of the manual evaporation of the solution with electric evaporation. The change will help to ensure that the process of evaporation is the same for all the trials. In our experiment, the amount of time taken completed the evaporation process varied from trial to trial. Furthermore, the amount of time taken to complete the process also differed. All these variations in the experimental procedures were potential sources of errors that would eventually impact the accuracy of the results obtained.

The accuracy of the experiment can be enhanced by factoring in the effects of uncontrollable factors such as the solubility of the starch used as binders in the tablets. This can be performed by determining the solubility rate of starch in acetone in terms of grams. Then, the weight determined as starch solubility factor can be deducted from the final weight of salicylic acid obtained. This approach is referred to as a correction for errors. If all the modifications proposed are appropriately implemented, the final weight gained for salicylic acid will be more accurate, and the precision errors reduced.

Finally, subjecting the results obtained to quality control would significantly help to improve the reliability of the experiment results. This can be actualized by including both positive and negative control in the experiment. Our experiment did not include this vital component. The positive and negative control provides the limits of measurement within which the test results should fall. Any test results out of the positive and negative ranges should be considered an outlier and removed from the study results. By removing outlier results from the experiment, the accuracy of experimental results is increased.

Conclusion

The hypothesis tested in this experiment was that the weight of salicylic acid in aspirin manufacture by different companies varies significantly. Indeed, the finding of our experiment showed that the hypothesis was correct and hence accepted. Our study reported that the aspirin manufactured by Square carva had considerably high levels of salicylic acid compared to that produced by Ecospirin. The experiment results obtained in this experiment were affected by various factors, including calibration of the weight balance, the evaporation method used in the acetone evaporation step, and the lack of positive and negative control tests. To improve the test results of the experiment, it is advisable to consider calibration of the equipment before it is used, adopting a proper sample selection method, inclusion of the positive and negative control tests, and considering all the possible confounding factors that may affect the experiment results.

References

Dacić, M., et al. “UV-VIS Determination of Acetylsalicylic Acid in Aspirin Tablets Using Different Solvents and Conditions.” International Conference on Medical and Biological Engineering, Springer, 2019, pp. 563–67.

Ewers, Robert M., and Raphael K. Didham. “Confounding Factors in the Detection of Species Responses to Habitat Fragmentation.” Biological Reviews, vol. 81, no. 1, Cambridge University Press, 2006, pp. 117–42.

Homma, Shunichi, et al. “Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm.” New England Journal of Medicine, vol. 366, no. 20, Mass Medical Soc, 2012, pp. 1859–69.

Iwunze, M. O. “Absorptiometric Determination of Acetylsalicylic Acid in Aqueous Ethanolic Solution.” Analytical Letters, vol. 41, no. 16, Taylor & Francis, Nov. 2008, pp. 2944–53, doi:10.1080/00032710802440574.

Lamal, Peter A. “On the Importance of Replication.” Journal of Social Behavior and Personality, vol. 5, no. 4, Select Press, 1990, p. 31.

Nordström, Fredrik L., and Åke C. Rasmuson. “Solubility and Melting Properties of Salicylic Acid.” Journal of Chemical & Engineering Data, vol. 51, no. 5, ACS Publications, 2006, pp. 1668–71.