Aspirin chemical stability

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. 

Attempts to modify aspirin chemically to either circumvent its potential gastrointestinal intolerance, its poor aqueous solubility (1 300), its poor stability toward hydrolysis (k = 0.002 h-1 which makes liquid dosage forms impossible) and, no doubt Bayer s original patent, has led to the synthesis and evaluation of hundreds of compounds over the years. The modifications involved derivatization of the carboxyl function (such as esters remov-... 

NMR and infrared (IR) spectroscopy are also used to investigate the chemical stability of drug substances. Determination of the hydrolysis rate of esters such as atropine by NMR,647 a nondestructive near-IR analysis of aspirin tablets,648 and determination of the hydrolysis rate of diltiazem by polarimetry649 have been reported. Unusual methods, such as measurement of the dielectric properties of dosage forms like gelatin and methylcellulose microcapsules (Fig. 160), have been used to detect physical changes.650-651 These changes... 

A new zeolite model, that features the a and c channels of clinoptilolite has been used to study the possible interactions of aspirin-water-zeolite, in order to know the behavior of the drug in a more complex system and the influence of water present in the zeolite channel. The calculations have been performed using the AMI semi-empirical method and acid and sodic clinoptilolite models. The results showed that the adsorption entalphy of aspirin in the acid structure is in the same order than that obtained for the sodic structure, although the nature of the interaction is different in each structure. The ester and aromatic groups were preferentially oriented to the model. In any case the chemical stability of aspirin is affected by the presence of water molecules in the system. 

Aspirin also interferes with the chemical mediators of the kallikrein system (see Chapter 17 Vasoactive Peptides), thus inhibiting granulocyte adherence to damaged vasculature, stabilizing lysosomes, and inhibiting the chemotaxis of polymorphonuclear leukocytes and macrophages. 

Many examples of the effects of tablet excipients on dmg decompositions are reported in the pharmaceutical literature. Chemical interaction between components in solid dosage forms may lead to increased decomposition. Replacement of the phenacetin in compound codeine and ARC tablets by paracetamol in NHS formulations in Australia in the 1960s (because of the undesirable side-effects of phenacetin), led to an unexpected decreased stability of the tablets. The cause was later attributed to a transacetylation reaction between aspirin and paracetamol and also a possible direct hydrolysis of the paracetamol (Scheme 4.15). 

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. 

Flow reactors of aU shapes, sizes, and uses are encountered in aU phases of fife. Examples of interest to bioengineers include the pharmaceutical industry, to produce aspirin, penicfifin, and other drugs the biomass processing industry, to produce alcohol, enzymes and other specialty proteins, and value added products and the biotechnologically important tissue and cell culture systems. The type of reactor used depends on the specific application and on the scale desired. The choice is based on a number of factors. The primary ones are the reaction rate (or other rate-limiting process), the product distribution specifications, and the catalyst or other material characteristics, such as chemical and physical stability. 

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