Insulin administration buccal

Deformable vesicles of phospholipids, known as transfersomes, have recently been investigated for buccal delivery of insulin [83]. Transfersomes are morphologically identical to liposomes, but these vesicles can respond to external stresses by rapid shape transformations requiring low energy. This high deformability allows them to deliver therapeutics across buccal barriers. Sodium cholate or sodium deoxycholate is incorporated into the vascular membrane to prepare transfersomes. Pharmacological bio availability of insulin after administration of deformable vesicles is higher relative to subcutaneous insulin and buccal conventional insulin vesicles. 

Developments in the administration of insulin through the skin, the mouth, the nose, and the lung have been reviewed (183). Methods of absorption other than subcutaneous, such as nasal insulin, buccal insulin, rectal insulin, and insulin in enteric-coated capsules, are still experimental. A problem in nasal administration is still how to get a daily reproducible dose (184). The frequency of hypoglycemia is comparable to the frequency with subcutaneous insulin (185). Nasal irritation, sometimes with congestion, and dyspnea (186) can occur. Pulmonary insulin, delivered by aerosol inhalation, is another experimental method. No lung obstruction was reported, but the uptake varied considerably (187). 

In an effort to develop an effective bioadhesive system for buccal administration, insulin was encapsulated into polyacrylamide nanoparticles by the emulsion solvent evaporation method [98]. Though nanoparticle formation ensures even distribution of the drug, pelleting of the nanoparticles was performed to obtain three-dimensional structural conformity. In addition, it was hypothetized that the pelletized particles will remain adhered to the mucosa, leading to good absorption. While studying bioadhesion and drug release profiles, it was found that the... 

Al-Achi, A., and R. Greenwood. 1993. Buccal administration of human insulin in streptozocin-diabetic rats. Res Commun Chem Pathol Pharmacol 82 297. 

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). 

In addition, the buccal delivery of insulin in rabbits has been shown to be increased from approximately 3-5% by co-administration of edetate (least effective), sodium dextransulfate, sodium methoxysalicylate, sodium deoxycholate, sodium lauryl sulfate, sodium taurocholate and Brij 35 (most effective) with Brij 35 increasing the bioavailability of insulin to 12% by this route. 

With the exception of a few approved products for nasal administration of peptides and the very recent regulatory approvals of delivery systems for both pulmonary and buccal delivery of insulin, there is relatively little precedence with the worldwide regulatory approval process for non-invasive delivery systems incorporating protein or peptide pharmaceuticals. Consequently, there is limited specific information... 

In the treatment of diabetes mellitus, insulin is generally administered by injection. However, the injections may cause local side effects and allergic reactions, and may also result in the patients physical and mental pain. Thus, alternative routes of administration such as nasal [2], buccal [3], pulmonary [4], rectal [5], and ocular [7] have... 

Insulin is generally administered parenterally (subcutaneous injection), although many researchers and companies are developing alternative administration methods, i.e., oral, buccal, (Oral-lyn) or pulmonary (Exubera) [10], These methods require greatly increased dosage in the case of buccal or pulmonary administration or additives to improve the bioavailability of orally administered insulin (including encapsulation, permeabilization, or chemical stabilization additives). No intesti-nally absorbed (oral) version of insulin has yet been proven effective and received FDA approval. 

The ocular, buccal, rectal, and vaginal routes of administration all have inherent limitations and serious drawbacks for delivery of insulin and therefore are highly unlikely to be of any use for chronic insulin therapy. 

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