A model of insulin delivery by a controlled release micropump.

A model has been developed to describe the delivery of insulin from a controlled release micropump (CRM). Basal delivery was provided by diffusion due to a concentration difference driving force across the CRM. This was modelled by considering the CRM to be a series of one-dimensional steady-state diffusion resistances. This delivery model was used to size prototypes and identify the piston, foam and the pump outlet as the controlling resistances to basal insulin transport. Augmented delivery by the CRM was achieved by repeated compression of a foam disk by a mild steel piston which was driven by a solenoid (tested voltage range 0-173 V DC; 5 msec "on" time; frequency 20-40 min-1). The increased delivery was attributed to the combination of mixing inside the pump barrel and displacement of barrel contents into the downstream reservoir. This action was approximated by a three-compartment model, which considered the CRM to consist of a well-mixed upstream reservoir and pump barrel (with a downstream reservoir) separated by two resistances: a constant upstream membrane resistance, (KmAm)-1, and a variable downstream mixing rate resistance, (Qd)-1. A least squares fit of the model to experimental data showed Qd to increase with the cube of the force on the piston and linearly with the compression frequency. In agreement with experimental results, the model predicted the upstream membrane to be rate controlling only at augmented pump resistances close to the value (KmAm)-1. These models were used to design an improved prototype (VIII) which is now being evaluated in vivo in pancreatectomized dogs for its efficacy in restoring and sustaining normoglycemia.