Effect of Irradiation on Parathyroid Hormone PTH(1-34) Coated On a Novel Transdermal Microprojection Delivery System to Produce a Sterile Product-Adhesive Compatibility

Terminal sterilization via gamma-irradiation or e-beam and aseptic processing were evaluated as a means to manufacture the sterile product of parathyroid hormone 1-34 coated on a novel transdermal microprojection delivery system. The main difference of the two methods is the inclusion and exclusion of the coated formulation for irradiation during terminal sterilization and aseptic processing, respectively. Both gamma-irradiation and e-beam of the final product resulted in increased PTH(1-34) oxidation, which could be reduced by lowering the irradiation dose or the irradiation temperature. Minimizing moisture and oxygen levels inside the primary packaging could effectively limit PTH oxidation to <2% initially, but the stability continued deteriorating to fall below the purity specification over 3-month storage. Aseptic processing has its own challenge as one of the device components, acrylic-based adhesive, was found to be incompatible with the peptide due to volatile compound(s) released from the irradiated adhesive. Although the nature of the volatile compounds was not fully understood, we developed a screening method capable of rapidly and effectively identifying an alternate adhesive. This study proved that aseptic processing is the choice of the sterile manufacturing approach and wouldn't compromise the target of achieving >= 2-year, ambient-temperature storage stability. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2123-2134, 2010