Aspirin degradation

It is easily forgotten that aspirin degrades to acetic as well as salicylic acid. And, indeed, any smell aspirin might have is due to acetic acid. However, the volatility of acetic acid does not make the determination of acetic acid a reliable tool to measure stability or degradation. 

Talc is chemically unreactive in general. For aspirin formulations, it was found that talc impurities, such as calcium carbonate and calcium silicate, were responsible for the aspirin degradation observed [42], Impurities such as iron oxide and aluminum silicate did not affect the stability of the aspirin. 

The majority of medicines today are formulated as tablets [1], Tablets are formulated rapidly and economically, and they have high patience compliance. Also, many compounds, such as aspirin, degrade rapidly in solution and are formulated in solid dosages to increase stability [2]. Drug substances that are oils, liquids, and solids may be formulated into capsules, tablets, lyophiles, creams, or microsuspensions. Administration may be through ingestion, injection, topical application, inhalation, and other routes. The reader may consult other texts for discussion of formulation options [1,3]. Formulations are selected for stability and the ability to best deliver the active agent to the affected area of the patient or consumer. 

Chang H-K, V itworth CW. Aspirin degradation in mixed polar solvents. Drug Dev Ind Pharm 1984 10 515-526. 

Figure 28. Aspirin degradation curve (62.5°C,water content 10%). Observed , predicted from Eq. (2.67). (Reproduced from Ref. 277 with permission.)...

Carlsson, D. O., Hua, K., Forsgren, J., and Mihranyan, A. (2014). Aspirin degradation in surface-charged TEMPO-oxidized mesoporous ciystalline nanocellulose, Int J. Pharm., 461,74-81. 

As the following pages of this section will show, there is hardly a new method of analysis which is not immediately tried for the determination of aspirin as such, or in formulations and biological fluids. The analysis of aspirin is intricately interwoven with that of salicylic acid, its precursor and degradation product. From the very first, residual salicylic acid was determined by the convenient reaction with ferric salts — typical for phenols — which give a violet complex with salicylic acid. 

Stability and decomposition kinetics of aspirin both as a solid and in solution continue to be studied. The topochemical decomposition pattern of aspirin tablets has been explored.175 The degradation of aspirin in the presence of sodium carbonate and high humidity was studied by x-ray diffraction.176 The activation energy of decomposition by water vapor in the solid state was found to be 30 kcal/mol.177 The effect of common tablet excipients on aspirin in aqueous suspension was also studied.178... 

Fung et al. (44) studied the interaction of bilirubin, a product of heme degradation, with HSA by frontal analysis. They examined especially the displacement of bilirubin by aspirin. It was found that the free-bilirubin concentration increased to a clinically signihcant level when increasing amounts of aspirin were added. 

In a high-pressure liquid chromatography assay of aspirin tablets, 10 extracts are made and the extracts are diluted with mobile phase solution, which consists of acetonitrile/0.1 M sodium acetate buffer pH 4.5 (10 90) and analysed sequentially. If the rate constant for the degradation of aspirin in the mobile phase is O.OfOl h " at room temperature how long can the andyst store the solutions at room temperature before the degradation of the analyte is greater than 0.5% ... 

The application of a ruggedness test to the assay of Aspirin and its major degradation product, salicylic acid... 

The first case study we will consider is the assay of aspirin together with its major degradation product salicylic acid [19], This application study was selected as the HPLC assay of aspirin is well covered in the literature and we could select factors to test from the variety of HPLC conditions used in these published methods. This test was performed using a reflected saturated factorial design requiring a total of 15 experiments. 

One of the potential problems with this assay is that the samples and standards could further degrade during their assay, thus altering the original ratio of aspirin to salicylic acid. The above solvent mix has been shown to reduce the rate of degradation to an insignificant level [28]. 

Certain functional groups in drug molecules are prone to chemical degradation. Drugs with an ester functional group are easily hydrolysed e.g., aspirin is easily hydrolysed to salicylic acid. Similarly, many drug molecules are susceptible to oxidation because of certain oxidizable functional groups, e.g. alcohol. 

The synthesis of kinins can be inhibited with the kallikrein inhibitor aprotinin. Actions of kinins mediated by prostaglandin generation can be blocked nonspecifically with inhibitors of prostaglandin synthesis such as aspirin. Conversely, the actions of kinins can be enhanced with ACE inhibitors, which block the degradation of the peptides. Indeed, as noted above, inhibition of bradykinin metabolism by ACE inhibitors contributes significantly to their antihypertensive action. 

Drugs in solution formulations may be more susceptible to chemical reactions leading to degradation. The most common reactions are hydrolysis, oxidation, and reduction. Usually, the reaction rate or type is inLuenced by pH. For example, the hydrolysis of acetylsalicylic acid (aspirin) is pH dependent, and its pH-rate proLle shows a large and complex variation dfrls to four distinct mechanistic patterns (Alibrandi et al., 2001). Therefore, it is essential to monitor and understand the chemical stability of the drug in pH-adjusted formulations. 

Duddu and Weller (27) measured the stability of a freeze-dried aspirin formulation in the region of T% and pointed out the significant error introduced by measuring the degradation rate above Ts and extrapolating to temperatures below Tg. For a system with a Ts of about 36°C, extrapolation of 40°, 45°, and 50°C data yielded a predicted rate constant of 0.009 day-1 at 22°C, whereas the observed value was 0.003 day-1. 

The degradation of aspirin by hydrolysis in an aqueous suspension was carried out and is represented in Figure 5.4. What is the apparent rate constant for the hydrolysis of the aqueous aspirin suspension What is the hydrolysis rate constant in an aqueous phase Assume the initial concentration is 0.21 mole/L. The solubility of aspirin is... 

The plot of the reciprocal of k - kf against 1/[L] is linear, with a slope of 1 / [K(kc - kf)] and an intercept of 1 / (kc - kf). Figure 5.36 shows the stabilization of prostacyclin by the derivatives of P-cyclodextrin. However, not all inclusion complexes provide the stabilization of drugs. In many cases, drug degradation is enhanced via inclusion complex formation [e.g., prostaglandin E and E2/p-cyclo-dextrin (P-CD), aspirin/p-CD],... 

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