Effects of highly hygroscopic excipients on the hydrolysis of simvastatin in tablet at high relative humidity.

Effects of highly hygroscopic sorbitol, citric acid, sodium carboxymethyl cellulose or polyvinylpolypyrrolidone, on the hydrolysis of simvastatin in tablets at 25°/90% RH were studied. The simvastatin tablets were prepared by direct powder compression. Simvastatin and its hydrolyte, simvastatin acid, were quantitatively analysed by high performance liquid chromotography. The hygroscopicity, water swelling ratio, water solubility and pH of the four hygroscopic excipients were investigated. During the investigation period, the weight gain of sorbitol or citric acid increased faster than that of polyvinylpolypyrrolidone or sodium carboxymethyl cellulose at 25°/90% RH, accordingly, the moisture sorption of the tablets containing citric acid or sorbitol (T-3 or T-6) were more than that of the tablets containing sodium carboxymethyl cellulose or polyvinylpolypyrrolidone (T-4 or T-5). The increase of simvastatin acid content with time at 25°/90% RH for the tablets was in the following order: T-6 < T-4 < T-3 < T-5. The effects of the four excipients on the hydrolysis of simvastatin in tablet were related to not only their hygroscopicity but also their other properties, such as moisture retention capacity and pH. Sorbitol as hygroscopic excipient in tablet can most effectively prevent the hydrolysis of simvastatin in tablet.