Pharmaceutical heterogeneous systems III. Inhibition of stearate lubricant induced degradation of aspirin by the use of certain organic acids
✍ Scribed by M. A. Zoglio; H. V. Maulding; R. M. Haller; S. Briggen
- Publisher
- John Wiley and Sons
- Year
- 1968
- Tongue
- English
- Weight
- 345 KB
- Volume
- 57
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
The acceleration of aspirin degradation in capsule formulations where an alkali stearate is employed as a lubricant can be inhibited by the inclusion of malic, hexamic, or maleic acid. The acids when included at a level of 2 0 percent by weight of the complete mixture achieve a level of inhibition at which it could be said that the preparations are stable with respect to salicylic acid content. The mechanisms operative in these systems and the factors contributing to successful inhibition are described. Moisture content of the capsule mix and in the gelatin capsule shell is studied in regard to effects on the stability of aspirin and the dissolution rate of aspirin from the capsule formulations considered.
HE ASPIRIN MOLECULE is subject to insta-T bility whenever moisture is present in appreciable amounts in an aspirin formulation (1).
Excipients as well as physiologically active substances which influence the pH of the moisture in the solid dosage form can influence the rate of degradation. Aspirin hydrolysis is accelerated a t both low and moderately high pH values (2). Substances, such as antacids, have been cited as being detrimental to aspirin stability (3). In a recent study the acceleration of aspirin hydrolysis by alkali stearate lubricants was demonstrated (4). The physicochemical mechanism leading to this effect was explained on the basis of a reaction between the lubricant and aspirin. The reaction leads to formation of a soluble alkali salt of aspirin which maintains the moisture in the formulations at a hydroxyl ion concentration and greatly accelerates the breakdown of aspirin.
The object of the present study was to investigate the feasibility of including organic acids of comparable or lower pKa values and greater solubility than aspirin to compete for the magnesium cation creating an environment buffered close to the