Case Study III: Formulation and Chemical Stabilization of a Peptide for Subcutaneous Administration
IriSys was presented with a hydrophilic peptide subject to degradation by hydrolysis for formulation development. The challenge was related to the requisite high dose and chemical stability. The formulation was to be suitable for subcutaneous administration at the highest possible drug concentration and would demonstrate two-years stability, with refrigeration if necessary. IriSys initiated a multivariate formulation screening process that included buffer species, buffer concentration, pH, and non-aqueous co-solvents. Data demonstrated the compound was more stable at pH 6 than at pH 7 and that there was no specific ion effect within the buffers that were studied. Drug concentrations as high as 200 mg/mL were achieved. Two primary degradant peaks were observed, one was a well known hydrolysis product, the other an unknown substance. The formation of these degradants was used to aid in determining which formulations were most stable. Surfactants and organic co-solvents provided a stability advantage at 40° C and 25° C however; at 5° C a precipitate was observed. IriSys was successful in achieving the high dose and chemical stability for two years without the need for refrigeration for a subcutaneous injectable product. The formulation represented a three fold increase in both drug concentration and stability over what had previously been achieved.
