Degradation Of Aspirin Research Articles

Effect of aspirin on conformation and dynamics of membrane proteins in platelets and erythrocytes

The effect of the chemical modifications induced by aspirin (acetylsalicylic acid), acetyl chloride or salicylate on platelet membranes and erythrocyte ghosts has been investigated by means of fluorescence quenching and ESR spectroscopy in relation to our earlier findings of acetylation-induced reduction of platelet and erythrocyte membrane lipid fluidity. Only aspirin was found to induce disorders in the lipid-protein matrix and membrane protein conformation. The apparent distance separating the membrane tryptophan and bound 1-anilino-8-naphthalenesulphonate (ANS) molecules was decreased after aspirin action in both platelet and erythrocyte membranes. This resulted in a significant increase in the maximum energy transfer efficiency. The decrease in the ratio of the amplitudes of low-field peaks of weakly to strongly immobilized fractions of maleimide spin label (4-maleimido-2,2,6-6-tetramethylpiperidine-1-oxyl) and the rise in the relative rotational correlation time of iodoacetamide spin label [4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidine-l-oxyl] indicate that aspirin effectively immobilizes membrane proteins in the plane of the lipid bilayer, whereas neither acetyl chloride or salicylate gave rise to detectable effects. We conclude that aspirin-induced alterations in membrane protein structure induce a reorganization of lipid assembly as well as rearrangements in the membrane protein pattern, and consequently alterations in lipid-protein interactions. Thus, the interaction of aspirin with platelet and erythrocyte membranes may induce local confonnational changes in membranes, which are discussed in connection with impairment of platelet function. A new mode of protein chemical modification by aspirin is suggested which involves the generation of reactive salicylic residue during the fast degradation of aspirin under physiological conditions.

The use of thermal analysis and mass spectrometry to study the solid state behavior in pharmaceutical tablet mixtures

The behavior of aspirin in the presence of tablet excipients and in the presence and absence of moisture was investigated. The methods used for investigation were differential thermal analysis (DTA), thermogravimetry (TG), and direct ionization probe mass spectrometry (DIP-MS). In addition, the degradation of aspirin in the absence of moisture was investigated by TG, and the residue after the first decomposition on the TG curve was subjected to DIP-MS. A degradation mechanism for dry aspirin is postulated. Aspirin in tablet form was shown to be stabilized in the presence of increasing amounts of corn starch. These and related studies on the shelf-life of pharmaceutical products indicate possible interactions between the active ingredient and other ingredients of product formulations.

Stability of Aspirin in Solid Mixtures

It has been shown that the degradation of aspirin in mixtures may be monitored by thermal analytical techniques. The methodology employed differential scanning calorimetry and thermal gravimetric analysis by standard techniques providing simple and rapid analysis for screening the stability of aspirin in mixtures. The degradation was found to depend on the nature of the additive but, in particular, the presence of acidic or basic groups within its structure.

Degradation of Aspirin in Solutions

Degradation of Aspirin in Solutions

Aspirin Degradation in Mixed Polar Solvents

Degradation studies were conducted on 0.2% w/v aspirin liquid formulation in a wide range of water-propylene glycol mixtures and water-triethylene glycol diacetate mixtures at four temperatures. The effect of a surfactant, polyoxyethylene (20) sorbitan monolaurate, on aspirin stability was also investigated. There was a linear relationship between water content and degradation rate constants. The surfactant increased aspirin degradation in all formulations. Formulations containing the higher concentration of the surfactant showed the greater aspirin decomposition.

Determination of Related Compounds in Aspirin by Liquid Chromatography

A rapid liquid chromatographic procedure has been validated for the determination of salicylic acid, salsalate, acetylsalicylsali-cylic acid, and acetylsalicylic anhydride in aspirin. Samples are dissolved in methylene chloride and analyzed directly by adsorption chromatography in a 7-min separation using an isocratic mobile phase. Recoveries averaged 99% over a 200-10,000 ppm concentration range with standard deviations of <4% for the four compounds of interest. Detection limits ranged from 5 to 36 ppm. Compared to a recently published reversed-phase liquid chromatographic procedure for analyzing aspirin, this method is twice as fast, more sensitive, and avoids the use of hydroxylic solvents which lead to degradation of aspirin and acetylsalicylic anhydride.

Preliminary evaluation of dika fat, a new tablet lubricant.

Dika fat, a solid vegetable oil extracted from the kernels of Irvingia gabonensis var excelsia has been evaluated as a lubricant on the basis of its effect on the flow rate of granules, disintegration time and dissolution rate of tablets. The fat shows a maximal effect on flow at a concentration of 2.5% w/w. It produces better disintegration and dissolution profiles than magnesium stearte at all concentrations tested. The indication is that there is less degradation of aspirin in tablets containing this oil than there is in tablets containing magnesium stearate. The use of Dika fat (m.p. 39--40 degrees C) eliminates the hydrogenation step often necessary for vegetable oils.

Effect of other drugs and chemicals on the degradation of aspirin in vitro: possible extrapolation to in vivo metabolism of aspirin.

To assess the possible influence of other drugs and chemicals on the metabolic degradation of aspirin in man, their effect on the serum aspirin esterase activity was determined in vitro. The activation or inhibition of the enzyme as observed with these compounds suggest the possibility that simultaneous ingestion of these drugs with aspirin may influence the pharmacology and toxicity of the analgesic.

Stability of Aspirin in Liquid and Semisolid Bases V: Polyglycerol Esters

The stability of aspirin in decaglycerol tetraoleate, decaglycerol octaoleate, and decaglycerol decaoleate was studied at 4, 26, and 45°. Degradation of aspirin in these polyglycerol esters was temperature dependent. Aspirin demonstrated the greatest stability in decaglycerol octaoleate and the lowest stability in decaglycerol tetraoleate at all temperatures studied. The hydroxyl value and the viscosity of the polyglycerol ester appeared to influence the stability of aspirin.

Stability of Aspirin in Liquid and Semisolid Bases IV: Polyethylene Glycol 400 Diacetate and Triethylene Glycol Diacetate

The stability of aspirin in polyethylene glycol 400 diacetate and triethylene glycol diacetate was studied at 4, 26, and 45°. Degradation of aspirin in these vehicles was temperature dependent and appeared to follow a first-order rate. The results supported a previous conclusion of enhanced stability of aspirin in the substituted derivatives of polyethylene glycols.

Aspirin stability in substituted and nonsubstituted polyhydric alcohols in absence and presence of added water

The degradation of aspirin in methoxypolyethylene glycol 350, 550, and 5000 and unsubstituted polyethylene glycol 400 was studied at four temperatures. The rate of degradation was slower in methoxypolyethylene glycols than in unsubstituted polyethylene glycol. The data were then compared to those obtained in the presence of varying amounts of water added to the bases. The effect of water on the rate of degradation of aspirin was greater in methoxypolyethylene glycol than in polyethylene glycol. Slower degradation of aspirin in methoxypolyethylene glycol was due to the fact that the transesterification pathway is partly blocked in this base. A conclusion is made that the stability of aspirin in polyhydric alcohols may be achieved by blocking the free hydroxyl group in the molecules.

Ultrasonic Degradation of Aspirin in Mixed Solvent Systems

The effect of ultrasonic energy on the degradation of aspirin in ethanol-water, diethyl ether-water, and diethylene glycol-water solvent systems at various concentrations and temperatures was studied. It was found that the application of ultrasound to a system undergoing degradation would cause an increase in the rate, but would maintain the same kinetic order as in the control system. The heat of activation seems to be lowered by the mechanical vibrations of the ultrasonic energy. It is postulated that the ultrasonic vibration increases molecular collisions and the movement of the products away from each other, thereby producing a change in the overall rate of reaction. As the concentration ratio was increased in the diethylene glycol system, the subsequent increase in viscosity had a damping effect on the ultrasonic vibration.

Pharmaceutical Heterogeneous Systems III: Inhibition of Stearate Lubricant Induced Degradation of Aspirin by the Use of Certain Organic Acids

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 20 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.

Pharmaceutical Heterogeneous Systems II: Study of Hydrolysis of Aspirin in Combination with Fatty Acid Tablet Lubricants

Stearic acid USP, in combination with aspirin in tablets, capsules, and powder mixes increases the rate of salicylic acid formation over pure aspirin controls. The breakdown of aspirin in combination with stearic acid USP and reagent grade stearic and palmitic acids has been studied with regard to the relative suitability of the fatty acids in question as tablet lubricants. Commercial stearic acid was found to have a marked effect on acceleration of salicylic acid formation as compared to reagent palmitic and stearic acids which were 95% + pure (gas chromatography). In powders and tablets with a constant aspirin: fatty acid ratio (20:1) the degree of aspirin degradation reaches a maximum when the two reagent acids are mixed together at approximately the same molar ratio as found in stearic acid USP. This maximum closely parallels the minimum on the melting point curve for mixtures of stearic and palmitic acids.

Heterogeneous Catalysis of Aspirin Degradation in Chloroformic Solution and Its Relationship to the Determination of Salicylic Acid in Buffered Aspirin Products

Difficulties and spurious results were encountered when buffered aspirin tablets were subjected to the official test for salicylic acid. The present investigation was concerned with this problem and with a characterization of the behaviors of aspirin and salicylic acid in chloroformic solution in contact with chloroform-insoluble agents which are commonly used as buffering agents in buffered aspirin tablets. Two phenomena were studied which can have manifestations of analytical importance. Both aspirin and salicylic acid were found to be adsorbed by solids such as magnesium carbonate, aluminum glycinate, aluminum hydroxide, and magnesium trisilicate. Rate studies showed that chloroformic solutions of aspirin in contact with solid buffers were unstable and generated at a relatively rapid rate a compound with the chromatographic characteristics of salicylic acid. The rate of generation was shown to be due neither to the water or ethanol content of the chloroform nor to the presence of dissolved buffer. Rather, it was demonstrated that catalysis was due to solid surfaces. The addition of citric acid monohydrate to such systems resulted in an almost complete abolition of adsorption and catalysis.

Pharmaceutical heterogeneous systems I Hydrolysis of aspirin in combination with tablet lubricants in an aqueous suspension

The chemical mechanism that explains the accelerated hydrolysis demonstrated by aspirin when in combination with an alkali stearate, i.e., calcium stearate, in a solid dosage form has been elucidated by employing a suspension technique. The mechanism primarily involves a reaction of the alkali cation with aspirin in a solution to form a salt of aspirin which, in the presence of solvated aspirin, comprises a buffer system at a pH detrimental to the stability of aspirin. Using the kinetic data obtained from the suspension study, an attempt was made to predict aspirin stability in a solid dosage form. There is evidence presented to support the concept that stearic acid will serve as a medium for aspirin degradation at temperatures slightly above room temperature.

Acetylation of acetaminophen in tablet formulations containing aspirin

The degradation of aspirin in commercial products containing acetaminophen was found to be accompanied by the formation of diacetyl-p-aminophenol (DAPAP) or p-acetoxyacetanilid. This reaction product was not detectable using conventional acetaminophen analytical procedures, but was detected qualitatively by means of thin-layer chromatography. A procedure utilizing partition-column chromatography and gas-liquid chromatography was developed for the determination of DAPAP in products containing aspirin, acetaminophen, and caffeine. Commercial products were found to contain various levels of DAPAP up to 4 mg./tablet. Magnesium stearate was found to accelerate the reaction markedly.