Intratablet S-nitrosation: A New Approach for the Oral Administration of S-nitrosothiols as Nitric Oxide Donors

Abstract

The primary S-nitrosothiol, S-nitroso-N-acetylcysteine (SNAC) is a nitric oxide donor with potential pharmaceutical applications for the oral treatment of hepatic steatosis and cirrhosis and for protection against gastric acid-peptic disorders. However, its low thermal stability precludes the preparation of stable dosage forms based on presynthesized SNAC. In this study, we describe an innovative strategy for the oral administration of SNAC based on its intratablet formation via the S-nitrosation reaction of its parent stable thiol, N-acetyl-L-cysteine by nitrous acid during the absorption of water by the tablet. The proposed strategy allows for the manufacturing of thermally stable oral dosage forms for the controlled release of SNAC in the enteric medium.

Keywords: N-acetyl-L-cysteine; S-nitroso-N-acetylcysteine; S-nitrosothiols; hydroxymethylpropylcellulose; nitric oxide; tablets.