Preformulation studies for the development of a parenteral liquid formulation of the immunomodulator, peldesine

Peldesine (BCX-34) is a potent inhibitor of the enzyme purine nucleoside phosphorylase (PNP). The object of this study was to determine the preformulation parameters of BCX-34 and subsequently prepare a sterile liquid formulation for intravenous infusion. Ionization and solubility parameters were assessed prior to formulation development. Three pKa values of approximately 4.0, 5.2 and 10.3 were assigned for BCX-34. The pH-solubility profile showed an increase in solubility when the pH of the solution was less than the pKa1 value of 4.0 and when the pH was more than the pKa3 value of 10.3. BCX-34 has an octanol-water partition coefficient of approximately 7:1 (Log P = 0.8). The Van't Hoff temperature dependent solubility when measured over a range of 4-40 degrees C produced a heat of solution (delta Hc) of 7.68 kcal/mole. Based on these preformulation observations, two parenteral formulations containing 1 and 5 mg/mL of BCX-34 were prepared in an acidified saline solution and filled into 30 cc and 100 cc glass vials. Both formulation batches were sterile filtered, while only one 1 mg/mL batch was terminally autoclaved. The long-term stability of both solutions was performed and compared. Results of this study show that the drug product was stable. Following a screening study, Lactated Ringer's injection USP was selected as a suitable infusion medium for the dilution of the drug concentrate solutions.