abstract
- Protein drugs such as insulin are almost universally delivered via glass syringes lubricated with silicone oil. It is not uncommon for prefilled syringes (PFS) to become cloudy, which may affect bioavailability or total drug dose. To examine the role, if any, of the silicone oil lubricant in this process, a systematic evaluation of the degree of insulin denaturation and aggregation as a function of silicone oils of different molecular weights was undertaken. The former was measured using fluorescence changes of aqueous insulin/silicone dispersions, while the latter examined changes in turbidity as a function of mixing and silicone oil type; the results were confirmed at two different insulin concentrations and agitation speeds. Lower molecular weight silicones led to the most rapid denaturation and aggregation, and when examined in blends of silicones at a fixed viscosity of 1000 cSt, commonly used for syringe lubrication, more rapid denaturation/aggregation was noted in blends of silicones containing the largest fractions of low molecular weight materials. As a consequence, the molecular weight profile of silicone lubricants should be established prior to the preparation of prefilled syringes.