Varenicline and Maltodextrin Combination: A Promising Approach for Reducing Nitrosamine Impurities in Solid Dosage Forms

Abstract

This research article investigates the use of varenicline and maltodextrin combination to reduce the nitrosamine impurities in varenicline tablets, a medication used to treat nicotine addiction. Nitrosamines are carcinogenic compounds that have been found in varenicline, raising concerns about its safety. Drug excipient compatibility was initially performed with all possible excipients, including maltodextrin, to identify potential approaches for reducing nitrosamine impurities. The results showed that maltodextrin was more effective than other excipients in reducing nitrosamines in the drug product. This finding provided an indication for the use of maltodextrin as a potential solution to the nitrosamine problem in varenicline tablets. The study involved preparing varenicline-maltodextrin formulations and analyzing the formulations for nitrosamine impurities. The finished formulation was prepared by simple mixing of varenicline, maltodextrin, disintegrant, filler, lubricant, and compression using suitable tooling, followed by aqueous film coating. The formulated tablets were tested for assay, content uniformity, dissolution in release media, and multimedia, and the results were found to be satisfactory. The results showed that the varenicline-maltodextrin combination significantly reduced nitrosamine content, and all other parameters were satisfactory. In addition, the nitrosamine impurity levels were significantly reduced to less than 3 ppm after 30 days of storage at 50±2°C/75±5 % RH. Moreover, more than 85% of drug release was observed in all tested release media, meeting the predefined specifications for BCS-based biowaiver. These findings suggest that the use of varenicline and maltodextrin combination is a promising approach to improve the safety of varenicline.