Stability of Lyophilized Sodium Prasterone Sulfate

Abstract

The stability, stabilization and degradation process of lyophilized sodium prasterone sulfate (DHA • S) were studied. A lyophilized product of DHA • S alone was rapidly decomposed at 50 °C. Polyvinylpyrrolidone (PVP) and glycine increased the stability, but the addition of dextran 40 or mannitol was not effective. The pH of a reconstituted solution of aged lyophilized product of DHA • S changed to a lower pH value, that is, the pH of the reconstituted solution at zero time and after the lyophilized product was kept for 28 days at 50 °C were 5.6 and 2.2, respectively. The pH of a reconstituted solution of the product, which was stabilized by the addition of PVP or glycine, changed very little after extended storage. From these results, it was assumed that one of the degradation products was a strongly acidic compound, perhaps sodium bisulfate, which was formed by the hydrolysis of DHA • S.

If a compound which neutralizes the acidic compound, formed by the decomposition of DHA • S, is added to the lyophilized product, it is assumed that the product may be stable. To confirm this assumption, a buffering agent such as amino acid and phosphate-citrate was added to the product. These samples showed good stability after storage at 50 °C for 3 weeks. From these results, the degradation process was examined.