Impact of Solvent Selection and Absorptivity on Dissolution Testing of Acetylsalicylic Acid Enteric-Coated Tablets

Abstract

The objective of this study was to investigate the effect of physiological conditions on the dissolution rate of acetylsalicylic acid (ASA) from two commercial brands compared against compendial tests. All parameters of the analysis were chosen according to ICH (Q2(R1)) guidelines and were validated statistically. The maximum wavelength (λ max ) and absorptivity (ε) for ASA were determined in different solvents at different pH values (6.8 and 4.9) by a validated UV-Vis spectrophotometric method. When ethanol (EtOH) was used as co-solvent, ε was found to be 3.15, and when 0.1 N NaOH was used, ε was 18.50. Dissolution tests were conducted according to pharmacopeia specifications; however, the lack of a direct specification in determining ε in the pharmacopeia has permitted enormous probabilities of employing different solvents. Herein, when NaOH was used to dissolve ASA, ε was calculated to be 18.50, and upon conducting compendial dissolution tests for enteric-coated tablets, only 20% of ASA was released after 4 h. When analyzing the same data using ε of 3.15 (calculated from dissolving ASA in EtOH), the amount of released ASA was found to be 95% after 2 h. Furthermore, the effect of a fed and fasted state pH was not significant on the dissolution rate, and both brands met the compendial requirements.

In Vitro Bioequivalence of Acetylsalicylic Acid and Implications in Public Health

“…These results are directly related to the Henderson-Hasselbach equation (pH = pKa + log [ I/NI], due to pKa of ASA = 3.5); i.e., in a dissolution medium at pH 6.8, the drug will be ionized in its carboxylate form (I) with greater solubility and dissolution (5,26). Thus, the in vitro dissolution medium that simulates gastric or intestinal fluid should be selected to predict an optimal dissolution profile (5). It is known that fasting gastric pH is acid (pH 1.2) and in the presence of food it can reach pH 4.9 (27).…”

“…It is known that fasting gastric pH is acid (pH 1.2) and in the presence of food it can reach pH 4.9 (27). In the duodenum, the pH is 6.5 (fasting and in the presence of food), in the ileum the pH is 7.4 (5). Previous studies have shown that the dissolution medium influences API release, and Krieg et al indicate that it is a determining factor of the biopharmaceutical phase (disintegration and dissolution) of oral solid pharmaceutical forms (28).…”

“…MDTs were between 5.5 (pH 1.2) and 15.9 minutes (pH 4.5), indicating that there is no correlation with mean gastric emptying (residence time), which under fasting conditions is between 15 and20 minutes. Based on the values of f 2 , DE%, and MDT, generics A and C dissolve more efficiently at pH 6.8, so the use of an enteric-coated ASA tablet would be justified, to prevent the pharmaceutical form from dissolving at the gastric level (i.e., avoiding gastrolesivity), and when it reaches the small intestine, it dissolves and is absorbed to a greater extent (5).…”

“…Twelve tablets were used for each generic formulation (A, B, and C) and reference (R) of ASA to evaluate the dissolution profile. The experimental conditions were: USP apparatus 2 (paddle), 900 mL of dissolution medium at pH 1.2, 4.5, and 6.8, 37 ± 0.5 °C, 75 rpm, and 8 pre-established sampling times (5,10,15,20,25,30,45, and 60 min), 5-mL sample volume, and no medium replacement.…”

“…Acetylsalicylic acid (ASA, 2-acetoxybenzoic acid, C 9 H 8 O 4 ), is a BCS class 1, non-steroidal antiinflammatory drug (NSAID). Due to the presence of a carboxylic group, ASA has a pKa of 3.5, so its solubility depends on the pH, and it is partially absorbed into the gastric mucosa and T mainly in the duodenal mucosa (5,6). In addition, 75% of the absorbed drug undergoes a presystemic effect or a first-pass effect on the intestinal wall (intestinal esterases) and in the liver (7).…”