Controlled-release micropump

The controlled-release micropump (Figure 2) is a recently invented device that uses the principles of membrane transport and controlled release of drugs to deliver insulin at variable rates (20,26). With a suitable supply of insulin connected to the pump, the concentration and/or pressure difference across the membrane results in diffusion or bulk transport through the membrane ). This process is the basal delivery and requires no external power source. Augmented delivery is achieved by repeated compression of the foam membrane by the coated mild-steel piston. The piston is the core of the solenoid, and compression is effected when current is applied to the solenoid coil. Interruption of the current causes the membrane to relax, drawing more drug into the membrane in preparation for the next compression cycle. 

Figure 2. Schematic of the controlled-release micropump. Rate-controlling membrane is not present in early prototypes (26,).

Care had to be taken to fill the micropump with liquid since the presence of air bubbles in any of the lines would reduce the delivery rate. The portion of the pump below the membrane was filled with insulin-free phosphate buffered saline containing 0.5% (w/v) m-cresol (a preservative) via a tube connected to the pump outlet. When this portion was full, the membrane was laid onto the membrane support portion of the chamber, and the upper half of the chamber was reconnected to the controlled-release micropump. The upper half of the chamber constituted the 1-cm3 upstream reservoir for these experiments and was filled with radioactive feed solution through a needle inserted horizontally into the side of the membrane chamber. The top of the chamber was connected to a plastic three-way valve using the appropriate Luer-lok connections to permit filling. The valve was turned to seal the chamber and eliminate the pressure difference before the experiment. One of the ports of the valve was used... 

Pressure-Difference Driving Force. The effect of a l- xm polycarbonate microporous filter on basal and augmented delivery in the controlled-release micropump due to a pressure difference is shown in Figure 3. As the pressure difference was lowered (i.e., as the liquid level dropped in the falling head permeameter) the basal flow rate was reduced to less than 0.2 mL/day (pressure difference, approximately 0.8 cm H20). At this basal rate, operation with a 100-U/mL reservoir becomes practical. More importantly, the degree of augmentation was increased to more than 10 X from the... 

Insulin deposition in the controlled-release micropump is not expected to be important. While it was significant in one of the prototypes (Figure 4), changing the rate-controlling membrane from a hydrophobic polycarbonate filter to a hydrophilic Cuprophane or cellulose acetate membrane has apparently eliminated the problem. Although the situation may be different as longer-term experiments are performed, presumably the problems that may arise may relate more to the biological stability of the insulin reservoir than to insulin deposition. 

The mechanism of action of the controlled-release micropump is unclear. With a pressure difference, the rapid oscillatory movement of the piston during augmented delivery may be responsible for the increased delivery rate by lowering the overall resistance of the micropump to bulk flow (35). When only a concentration difference exists, on the other hand, augmentation can be attributed to a pressure difference superimposed during piston movement on the basal concentration difference, or to a mixing effect associated with piston movement. The physical relationship between piston movement and augmentation remains to be defined. 

A number of concerns regarding open-loop delivery of insulin in general, and delivery of insulin by the controlled-release micropump, in particular, remain to be resolved. The optimum site of insulin delivery (intravenous... 

A number of patented technologies for multiparticulate dosage forms have been described recently, such as the Micropump system, which is an osmotically driven coated microparticle system designed to increase the absorption time for rapidly absorbed drugs.59 Combination of water-soluble and water-insoluble polymers could provide enhanced controlled release rates and profiles. A patented technology (COSRx) has been reported to be capable of delivering various sophisticated release profiles. The formulation involves a guar-gum-based tablet and a combination of water-soluble and water-insoluble polymeric tablet coat.60... 

In polymeric membrane and matrix-based micropumps, the membrane or the matrix makes the essential component of the delivery device that controls the rate of release. In matrix controlled delivery, the rate of the hydrolytic breakdown of the matrix is the governing process. In polymeric membrane-controlled release, the rate of hydration of the membrane and the subsequent diffusion of drug are the rate-controlling steps. 

---