Insulin oral absorption

Equations (20) and (21) have been used to estimate the oral absorption of cefaclor, cefatrizine, and insulin. The simulated results compare favorably to the reported literature values in humans. The macroscopic mass balance approach provides a quick approximation to the fraction of dose absorbed and degraded for both passively and nonpassively absorbed drugs. 

It was discovered nearly 20 years ago that V(V) as vanadate and V(IV) as vanadyl can mimic some of the effects of insulin (stimulate glucose uptake and oxidation and glycogen synthesis) (512, 513). Vanadate is an effective insulin mimetic in the diabetic rat (514), but has proved to be too toxic for human use. Vanadyl, as VOS04, is also unsuitable because high doses are needed on account of its poor oral absorption. Vanadium complexes with organic ligands have proved to be less toxic and can have improved aqueous solubility and lipophil-icity. 

Drug interactions Sandostatin has been associated with changes in nutrient absorption, so it may effect the absorption of orally administered drugs. Concomitant administration of Sandostatin with cyclosporine may decrease blood levels of cyclosporine and result in transplant rejection. Patients receiving insulin, oral hypoglycemic agents, beta blockers. 

Chitosan capsules coated with HPMCP were also tested for insulin oral delivery (82). Using male Wistar rats, insulin-containing capsules were administered orally to the rats, each of which received, through polyethylene tubing, a total dose of 20 lU into their stomachs. The h5 oglycemic effect did not start until 6h after the administration. This was when the capsules had reached the colon. The bioavailability of the insulin from the CS formulation was 5.73% as compared to the intravenous injection. It was observed that certain absorption enhancers like sodium glycocholate increased the absorption of insulin in the large intestine (66). 

Insulin loaded nanocapsules dispersed in biocompatible microemulsion resulted in significantly greater reduction in blood glucose levels than aqueous insulin solution. This demonstrated that formulation of peptides within nanoc sules administered dispersed in microemulsion can facilitate oral absorption of encapsulated peptide. Such system can be prepared in situ by the interfacial polymerization of a w/o microemulsion. 

Mesiha, M.S., Ponnapula, S., Plakogiannis, F. Oral absorption of insulin encapsulated in artificial chyles of bile salts, palmitic acid and a-tocopherol dispersions. Int. J. Pharm., 249,1, 2002. 

Fonte, P., Nogueita, T., Gehm, C., Ferreira, D., Sarmento, B., 2011. Chitosan-coated solid lipid nanoparticles enhance the oral absorption of insulin. Drug Delivery and Translational... 

The incorporation of insulin into liposomes was done to deliver it specifically to the liver (a natural target organ for liposomes), prolong insulin action in the body, and enhance the oral absorption of insulin (early studies were reviewed in Ref. 322) Later, the liposomal insulin was used for intratracheal admninistration. It was shown that insulin incorporation into liposomes made of dipalmitoylphosphatidyl choline and cholesterol (7 2) resulted in an improved pulmonary uptake of insulin in rats and enhanced the h)q)oglycemic effect. 

Permeation enhancers are used to improve absorption through the gastric mucosa. Eor example, oral dehvery of insulin (mol wt = 6000) has been reported from a water-in-oH- emulsion containing lecithin, nonesterified fatty acids, cholesterol [57-88-5], and the protease inhibitor aprotinin [9087-70-1] (23). 

When diabetic rabbits (24) were treated with 50 IU of bovine insulin imbibed at 50 mg/g poly (acrylic acid) (Figure 14) no reduction in serum glucose over that achieved by the dry blend control could be detected. Pretreatment of the animals with oral doses of either a penetration enhancer, sodium taurocholate, or a protease inhibitor, aproteinin, failed to improve the insulin activity. One possible explanation for this unexpected lack of activity might be that the diseased animals exhibit impaired ileal absorption of fluids (25). 

The results obtained from A-II injected animals (Figure 15) confirmed that the peak arterial pressure response is a reliable indirect indicator of A-II absorption (27,25). On this basis it is very unlikely that oral administration of A- II-impregnated resin (Figure 16) resulted in any significant absorption, even at an A-II dose which was 25X higher than the maximally effective subcutaneous dose. As in the insulin studies, the detectable response was observed about two and one-half hours after dosing. 

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