Chemical stability of insulin in a delivery system environment.

Exposure of insulin solutions to elevated temperatures for prolonged periods of time will inevitably lead to chemical modifications of the hormone. Contact with different materials in dosing devices, other design-related factors and motion appear to be chemically more detrimental than storage in glass vials at the same temperature. An in vitro test, designed to mimic the in vivo situation, consisted of delivery of insulin at 37 degrees C while the device was constantly moved on a shaking apparatus. Insulin quality was assessed using high performance liquid chromatography. A polyethylenepolypropylene glycol-stabilized neutral human insulin solution (HOE 21 PH) was used. A single insulin derivative is the major modification product which, after passage of the complete infusion system, amounts to up to 10%. The biological potency of the derivative is indistinguishable from native insulin. Delivery of acidic insulin under implant conditions, leads to extensive and multiple insulin derivatization, even though the biological potency remains 95% after 4 weeks.