The adsorption of recombinant-derived proteins to glass and polymeric materials used in their packaging and delivery remains a problem. Loss of these very expensive proteins to surface adsorption not only results in reduced yields during purification and scale-up, but also to decreased therapeutic efficacy. The purpose of the present investigation was to inhibit/minimize adsorption of a model protein, namely, recombinant human granulocyte colony stimulating factor (rhG-CSF) to glass, polyvinyl chloride (PVC), and polypropylene by inclusion of select solvent additives. Solvent additives used to inhibit/minimize surface adsorption included glycerin, U.S.P. (0.5%, 1%, 5%, and 25% v/v), Pluronic® F-127 (0.005%, 0.05%, and 0.5% w/w), Pluronic® F-68 (0.005%, 0.05%, and 0.5% w/w), Tween® 80 (0.005% and 0.05% w/w) and Tween® 20 (0.005%, 0.05%, and 0.5% w/w). Over the rhG-CSF concentration range of 0.0 ng/ml to 300 ng/ml, the amount of rhG-CSF bound per cm2 of PVC increased with an increase in the rhG-CSF concentration tested. At rhG-CSF equilibrium concentrations of 262 ±3.7 ng/ml and 136 ± 1.9 ng/ml, the rhG-CSF bound/cm2 of PVC at 22°C and 45°C reached a maximum of 37.6 ±9.8 ng/cm2 and 165.2 ±11.7 ng/cm2, respectively. The adsorption isotherms determined at each temperature were described by the classic Freundlich equation. Moreover, the rate of adsorption of rhG-CSF to PVC was extremely rapid. The mean values of the percent of rhG-CSF bound to PVC after only 10 minutes of equilibration at 22°C and 45°C were 92.8 ± 9.2 percent and 97.3 ± 17.9 percent, respectively. The mean values of the percent of rhG-CSF bound to PVC at 22°C and 45°C after 24 hours were 52.4 ± 10.9% and 70.0 ± 9.7%, respectively, indicating that some desorption of rhG-CSF does occur during 24 hr. However, surface adsorption of rhG-CSF to PVC was shown to be irreversible over a 1 hr time period. Using viscometry, an estimate of the thickness of the adsorbed layer of rhG-CSF to glass was determined to be approximately 1 µm. The overall rank order of the solvent additives for minimizing adsorption of rhG-CSF to PVC was Tween 20 > Tween 80 > Pluronic F-127 > Pluronic F-68. Tween 20 was the most effective solvent additive for inhibiting surface adsorption of rhG-CSF to parenteral vials made of either glass or polypropylene.
- Received July 19, 1995.
- Accepted November 15, 1995.
- Copyright © Parenteral Drug Association. All rights reserved.
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