Chemical Stability of Lyophilized Papaverine/Phentolamine/Alprostadil (Standro(R))

Kim, Sae Chul; Shim, Young Woo; Sung, Joo Young

Abstract

PURPOSE
To investigate the chemical stability of papaverine/phentolamine/alprostadil (Standro(R)) used for intracaver nous injection in patients with erectile dysfunction.
MATERIALS AND METHODS
Samples of lyophilized Standro(R) were stored at room temperature (25+/-2 degrees C) or in the refrigerator (4+/-2 degrees C). The pH and concentration of papaverine HCl, phentolamine mesylate, and alprostadil were measured at intervals by high-performance liquid chromatography.
RESULTS
At 24 months, the concentrations of papaverine, phentolamine, and alprostadil stored in the refrigerator and at room temperature were 99.7%, 98.9%, and 98.7% and 98.4%, 96.3%, and 93.3% of the original concentrations, respectively. When the product was stored in solution in the refrigerator for 19 weeks, the concentrations of the three drugs were 98.7%, 97.2%, and 88.0%, respectively. In 5 days at room temperature, the concentration of alprostadil dropped to 86.4%, which is below the minimum concentration for the product specified by the Korean Food and Drug Administration, although the concentrations of papaverine and phentolamine remained stable (99.6%, 98.4%). The pH of the three agents did not change significantly regardless of the storage conditions (temperature, duration, lyophilized or dissolved).
CONCLUSIONS
Lyophilized papaverine/phentolamine/alprostadil (Standro(R)) is chemically stable for at least 2 years at room temperature, although solutions need to be kept in the refrigerator and become less effective with prolongation of storage.