Acetylsalicylic acid is a well-known and frequently used active pharmaceutical ingredient due to its long history of use, multiple effects, and relatively simple synthesis. Active pharmaceutical ingredients are incorporated into medicines, which must be safe, of high-quality, and effective. Stability is a critical quality attribute, which is why it is important to thoroughly evaluate the stability of the active ingredient itself and its compatibility with excipients that may be used in the drug formulation.
In this master thesis, we have developed and validated two methods for evaluating the assay of acetylsalicylic acid and its three selected impurities C, D and E – based on pharmacopeial methods. Using both developed methods, we evaluated the intrinsic stability of acetylsalicylic acid, its stability in binary mixtures with selected excipients, and stability in finished products already on the market. The finished products were different dosage forms: uncoated, film-coated, chewable, and effervescent tablets, all with the same declared content of the active ingredient but different compositions and primary packaging.
The results of testing the intrinsic stability of the active ingredient were consistent with the literature data. In the solid state, moisture is the most important factor for instability, sunlight has a negligible effect, while oxygen has no impact on stability. In solution, temperature has a strong influence, acidic conditions less than basic ones, and the influence of sunlight is no longer negligible. The selected oxidants have no effect on stability.
Among the selected excipients, the stability of the active ingredient was lowest in mixtures with sodium carbonate and bicarbonate, sodium carboxymethylcellulose, monosodium citrate, hypromellose, and silicon dioxide, and to a lesser extent, with the dye sunset yellow FCF and orange flavour. Here, relative humidity also had a considerable influence on stability. Most of the mentioned excipients can be found in film-coated tablets, in which acetylsalicylic acid is also most unstable, and effervescent tablets. Its higher stability in chewable tablets is probably due to their bilayer composition, while the simplest composition of uncoated tablets is the reason for the highest stability of acetylsalicylic acid. The results of stability testing also explain why the primary packaging of plain compressed tablets can be semi-permeable to moisture, while impermeable packaging is required for the other tablets.
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