Evaluation of Manufacturer-to-Manufacturer Variability of Croscarmellose Sodium: Influence on the Dissolution of Sitagliptin Tablets (Water-Soluble Drug) and Escitalopram Tablets (Sparingly Soluble Drug)

Abstract

The present study aimed to investigate if the manufacturer variability of croscarmellose sodium, a superdisintegrant, could have an impact on the dissolution of sitagliptin phosphate (a highly water-soluble drug) and escitalopram oxalate (a sparingly soluble drug) from their tablets. Some of the physicochemical properties of croscarmellose sodium (CCS) powders obtained from four different manufacturers were studied. Tablets containing 25mg sitagliptin phosphate and 10mg escitalopram oxalate were prepared, and the effects of the source and varying concentration of CCS (0, 1, 3, and 5%w/w) on the disintegration time and dissolution rate of the mentioned drugs were investigated. The results of the following tests: degree of substitution, residue on ignition, loss on drying, content of water-soluble material, and pH, carried out according to the USP/NF CCS monograph, were within the acceptance criteria for all four products. However, considerable differences were found in the swelling behavior of CCS samples, differentiating them into two groups of highly swelling and low-swelling products. The disintegration times of the tablets containing different quantities of the various CCS samples were similar, which confirms the indiscriminatory nature of this test. However, the highly swelling CCSs resulted in tablets with superior dissolution profiles. While with the highly water-soluble drug, increasing the concentration of low-swelling CCSs to 3 or 5% could improve the dissolution profiles; in the case of sparingly soluble drug, this was not possible. Therefore, functional differences between CCSs produced by various manufacturers are affected by the drug solubility and the ratio of the disintegrant used in the formulations.