Injection devices, insulin

For persons with type 1 diabetes, insulin replacement therapy is necessary to sustain life. Pharmacologic insulin is administered by injection into the subcutaneous tissue using a manual injection device or an insulin pump that continuously infuses insulin under the skin. Interruption of the insulin replacement therapy can be life-threatening and can result in diabetic ketoacidosis or death. Diabetic ketoacidosis is caused by insufficient or absent insulin and results from excess release of fatty acids and subsequent formation of toxic levels of ketoacids. 

By the use of a breath-powered unit dose dry powder inhaler, which was adapted to the physical properties of TI, relative bioavailability was 50% for the first 3 hours and 30% over the entire 6-hour period in 12 healthy volunteers (Pfutzner et al. 2002). However, although the studies demonstrated pulmonary administration of TI has the advantages of fast onset of action, short duration of action, and lower variability over the SC injections of insulin no attempt has been made to compare pulmonary administration of insulin alone with the same inhaler device. This method of encapsulating biomacromolecules has some advantages and must be considered when electing to deliver a molecule. 

Robertson, K.E. Glazer, N.B. Campbell, R.K. The latest developments in insulin injection devices. Diabetes Educ. 2000,25, 135-152. 

The skin offers an even less naturally permeable boundary to macromolecules than the gastrointestinal tract. Thus, passive transdermal delivery of proteins and peptides using patch technology has not succeeded. Peptides and proteins can be shot through the skin into the body using high-pressure needle-less injection devices. The devices, which inject proteins like insulin, have been available for years, however they have failed to impress doctors or patients due to the associated discomfort and the potential for splash back to transmit blood-borne diseases such as AIDS or hepatitis. 

A silicone implant has been designed to provide a bolus dose when compressed externally over the skin with a finger. With an erodible palmitic acid implant to provide the basal insulin supply, as mentioned above, compression of a second implant of the silicone type has been used to deliver supplemental doses for better control of transient hyperglycemia episodes in diabetic rabbits. The dependable device is refillable percutaneously by injection ofan insulin suspension (Wang, 1989b, 1993). 

A number of external or internal pumps have been developed as insulin infusion pumps, or an artificial pancreas, which gives a more precise control over the body s insulin level. These devices normally inject the insulin solution directly into the patient s blood. Many of these "artificial pancreas devices are able to vary the rate of insulin administration, and much progress has been made to couple these pumps with a microprocessor controlled glucose sensor which would closely approximate normal pancreatic activity. Most of these infusion pumps utilize poly-(dimethylsiloxane). 0,41... 

Dosage form Lantus is a sterile solution of insulin glargine for use as an injection. Each milliliter of Lantus contains 100 lU insulin glargine. Lantus is available in 5 ml and 10 ml vials and cartridges for use only in a proprietary insulin delivery device (pen). 

Insulin pens are being increasingly used for intensive insulin therapy. For low doses, pens are more accurate than syringes (204). In 48 children and adolescents pen devices were more accurate than syringes when under 5 U of insulin had to be injected for higher doses pens and syringes were comparable (205). 

Hanas R, Ludvigsson J. Side effects and indwelling times of subcutaneous catheters for insulin injections a new device for injecting insulin with a minimum of pain in the treatment of insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1990 10(l) 73-83. 

The closed-loop type artificial pancreas (specifically 8-cell), which consists of an automatic continuous monitor of blood glucose level (BGL) and an automatic injector of insulin which are coupled with feed-back system, has great potential for prevention of diabetic complication such as micro-angiopathies(l). A large-scale closed-loop type artificial pancreas for bedside use has already been developed and is clinically used at some laboratories and hospitals (2-4). However, this device is limited to only bedside use. On the other hand, the open-loop type artificial pancreas which consists of only a insulin injecting pump without an automatic continuous monitor of BGL, has been developed and is going to be clinically used(5-7). This system, however, can not completely control BGL as well as the bare pancreas in a normal body and often causes lower BGL(8-9). 

Let us see how this works out for our diabetes problem. The only concept on the principle level in Figure 8-4 is to manage sugar in the blood. There are several groups on the method level those that use insulin and those that do not (Figure 8-6). Those with insulin can be divided again into three, with insulin provided by injection, via the mouth and via the lungs. The other ideas are on the device, part or detail level. 

We now start looking at devices and matter in our concept, starting with the new injector. The existing injectors are simple instruments as in Figure 8-8. The patient sucks up the required amount of insulin solution from a bottle (vial) and injects it at a suitable point and a suitable... 

There is a wide range of devices available to suit different applications. Some are ideally suited to chronic injections of varying doses of insulin several times a day, others are more suited to weekly dosing of the same dose of a therapeutic protein or even a monoclonal antibody. Still others will be capable of conveniently reconstituting lyophilized drug formulations... 

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