Evaluation of CZ-resin vials for packaging protein-based parenteral formulations.

Due to the fact that some proteins have a tendency to bind to glass surfaces, plastic CZ-resin vials were evaluated as an alternative material to glass vials for packaging protein-based parenteral formulations. Physico-chemical tests including protein binding, extractable evaluation, oxygen permeation, light transmission and moisture loss were performed. Data show that two proteins (A and B) were found to bind to USP type I glass but not to CZ-resin. The CZ-resin vials passed all USP test specifications for extractables (organic extractable, non-volatile residue and residue on ignition). The oxygen permeation rate (79.06 cm(3)mm/m(2)24 h atm) was consistent with that reported by the vendor (67 cm(3)mm/m(2)24 h atm). The value obtained for light transmission, which was also found to be consistent with that reported by the vendor, shows that these vials offer no protection from light. The average moisture loss from 2 cm(3) vials filled with water was gravimetrically determined to be 0.04 mg/day/vial when the vials were stored at 40 degrees C/75% relative humidity (RH). Assuming a 1cm(3) product fill, this corresponds to approximately a 3% loss over a 2-year period. However, moisture loss was found to be negligible at the typical storage condition of 5 degrees C for protein formulations. The physico-chemical tests indicate that CZ-resin vial is a suitable candidate for packaging parenteral formulations since it shows low moisture loss at typical storage condition of 5 degrees C, and does not leach out extractables. However, it should not be used for light-sensitive and oxygen-sensitive parenteral formulations. For proteins A and B, the CZ-resin vial is a viable alternate to the use of glass vials since it offered significantly less protein binding. Protein binding in general, should be evaluated on a case by case basis, since it may vary for different proteins and under different formulation conditions.

Model development for O(2) and N(2) permeation rates through CZ-resin vials.

The headspace of vials containing oxygen-sensitive formulations is filled with a nitrogen blanket. This paper presents the development of a mathematical model to predict the oxygen and nitrogen permeation rates through the walls of plastic CZ-resin vials. The model estimates the time required for a nitrogen-filled vial to reach ambient nitrogen and oxygen levels. The permeation of oxygen and nitrogen through the vial is governed by Fick's law and may be described by an exponential equation. Using the values for oxygen and nitrogen permeation through CZ-resin vial, the half-lives for the decrease in nitrogen level and increase in oxygen level was found to be 150 days and 15 days, respectively. This result can be attributed to the greater permeability of CZ-resin vial to oxygen (79.06 cm(3)-mm/m(2)-24 h-atm) when compared with nitrogen (12 cm(3)-mm/m(2)-24 h-atm). The ingress of oxygen into CZ-resin vials was determined experimentally and it was found to verify the model. These results indicate that CZ-resin vials may be inappropriate for packaging oxygen-sensitive formulations even in the presence of a nitrogen-filled headspace.