Systems for Insulin Delivery

An insulin delivery system, for example, might have the following hazards and associated classes ... 

Unlike the bedside or portable insulin delivery systems for which commercially available peristaltic or syringe pumps may be used, the key component of an implantable (open-loop) artificial pancreas is the specially developed miniature insulin pump. 

In a PEC used to deliver a protein, the latter is often used as one of the polyelectrolyte components of the complex. Examples of PECs in which one of the two polyelectrolyte components is an active substance itself, are complexes of chitosan and insulin. The PEC composed of trimethyl chitosan (TMC) and pegylated TMC (PEG-g-TMC) can be obtained simply by mixing the solutions of TMC and insulin at various mass and charge ratios. These PECs were stable in simulated intestinal fluid at pH 6.8. However, they disintegrated in simulated gastrointestinal fluid at pH 1.2. The PECs also protected insulin from temperature-induced denaturation up to 50 °C and from degradation by trypsin. Based on these results, the authors suggested that polyelectrolyte complexation can be a useful technique for fabrication of insulin delivery systems for oral administration. 

Pulmonary delivery currently represents the most promising alternative to parenteral delivery systems for biopharmaceuticals. Delivery via the pulmonary route moved from concept to reality in 2006 with the approval of Exubera, an inhalable insulin product (Chapter 11). Although the lung is not particularly permeable to solutes of low molecular mass (e.g. sucrose or urea), macromolecules can be absorbed into the blood via the lungs surprisingly well. In fact, pulmonary... 

J. Wang, Y. Tabata, and K. Morimoto. Aminated gelatin microspheres as a nasal delivery system for peptide drugs Evaluation of in vitro release and in vivo insulin absorption in rats. J Control Release 113 31-37 (2006). 

Makino K, Mack EJ, Okano T, Kim SW. A microcapsule self-regulating delivery system for insulin. J Controlled Release 1990 12 235-239. 

Jeandidier N, Boivin S. Current status and future prospects of parenteral insulin regimens, strategies and delivery systems for diabetes treatment. Adv Drug Dehv Rev 1999 35(2-3) 179-98. 

Morcol, T., et al. 2004. Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin. Int J Pharm 277 91. 

Al-Achi, A., and R. Greenwood. 1998. Erythrocytes as oral delivery systems for human insulin. Drug Dev Ind Pharm 24 67. 

The human intestine has evolved as a highly efficient organ to digest (i.e. hydrolyse) practically all the macromolecules in the human diet (albeit with the help of a few trillion bacteria ) with the exception of some plant fibres. To do this it possesses a formidable array of enzymes. This is particularly true for the digestion of proteins and peptides where peptidases are found in the stomach, are secreted by the pancreas in considerable quantities and are found on the surface of and inside intestinal epithelial cells. These enzymes work in a co-ordinated fashion to rapidly hydrolyse proteins. They present the major difficulty for designing oral delivery systems for therapeutic peptides, which may explain why 86 years after the first attempt to orally administer insulin (Bliss 1982), there is still not an oral insulin product available for diabetics. 

Hochman JH, Fix JA, LeCluyse EL (1994) In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoylcarnitine. J Pharmacol Exp Ther 269 813-822 Hoffman A, Qadri B (2008) Eligen insulin-a system for the oral delivery of insulin for diabetes. IDrugs 11 433 41... 

With the advent of new biotechnological techniques endogenous compounds like insulin, buserelin or octreotide have become available at affordable prices. All of these substances still have to undergo needle application. Until today the development of alternative delivery systems for the nasal, buccal, peroral, rectal and pulmonary routes for the administration of those class III drugs according to the biopharmaceutics classification system (BCS) (Amidon et al. 1995) could not keep pace with this development of endogenous compounds or is not economic enough for the health care payers (e.g. insulin application via the pulmonary route). 

A number of pharmaceutical companies are developing delivery systems for the delivery of macromolecules such as insulin. For example, The Inhale device system effectively disperses fine particles (which require a dispersion force far stronger than can be generated by a patient s inspiration) it also creates a stationary cloud to... 

Bjork, E., and Edman, P. (1988), Degradable starch microspheres as a nasal delivery system for insulin, Int. I. Pharm., 47,233-238. 

Pereswetoff-Morath,L.,and Edman, P. (1995),Dextran microspheres as a potential nasal drug delivery system for insulin—in vitro and in vivo properties, Int. J. Pharm., 124, 37 14. 

Ilium, L., Farraj, N. F., Fisher, A. N., Gill, I., Miglietta, M., and Benedetti, L. M. (1994), Hyaluronic acid ester microspheres as a nasal delivery system for insulin, J. Controlled Release, 29,133-141. 

Cationic thiomers are obtained from chitosan by reaction of thioglycolic acid with the primary amino groups in chitosan mediated by EDCCl. Thiomers are useful to formulate oral delivery systems for insulin, calcitonin and heparin. However, carbodiimide treated heparin may lose some of its anticoagulant properties. The potential of chitosan for the oral administration of peptides is also under consideration. ... 

FIGURE 40.2 Example Data Flow for Insulin Delivery System. 

The requirements for the insulin delivery system would include specific patient-safety needs such as ... 

A risk analysis is then required to confirm these safety requirements can be met, that the medical device will not malfunction, and that a safe state is maintained in relation to patient health. For the insulin delivery system a safe state is a shut-down state where no insulin is delivered. Over a short period this will not pose a threat to the diabetic s health. ... 

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