Project Summary
The addition of antioxidants to pharmaceutical products is a potential approach to inhibit nitrosamine formation, particularly in solid oral dosage forms like tablets and capsules. The objective was to assess the effect of ten antioxidants on the permeability of four Biopharmaceutics Classification System (BCS) Class III drugs. Bidirectional drug permeability studies in the absence and presence of antioxidants were performed in vitro across MDCK-II monolayers. The effect of ten antioxidants on four BCS Class III drug permeability was investigated using in vitro epithelial cell model. SLS was used as a positive control. Assuming the use of 2 % (w/w) of antioxidants in 500 mg pharmaceutical tablets, the antioxidants did not alter the permeability of ranitidine hydrochloride, cimetidine, acyclovir or pirenzepine. Also, permeability studies with equivalent of 5 % (w/w) of ascorbic acid and cysteine in ranitidine and cimetidine were conducted, and no excipient effect was observed. Results indicate that at least 10 mg of tested antioxidant can be incorporated in drug formulations to potentially prevent NDSRIs while not affecting the passive intestinal permeability of low permeable drugs.