Generex Biotechnology Corp. is developing innovative technologies for reliable, convenient, pain-free delivery of both small and large-molecule drugs. To date we have focused on creating a unique liquid formulation that can be administered directly into the mouth as an aerosol spray for absorption through the buccal mucosa, the mucous membranes that line the inner walls of the cheek.

The buccal mucosa offers a near ideal, non-invasive portal through which large-molecule drugs might enter the body. The large surface area of the buccal mucosa provides direct access to a rich network of blood vessels, offering the potential of rapid absorption of medications into the circulatory system. Using this route, drugs avoid the gastrointestinal system and other hostile environments.

Medications based on large molecules (also called macromolecules) are increasingly crucial to the treatment of many diseases and conditions. In fact, large-molecule biopharmaceutical products - including proteins, peptides, and nucleic acids-are sometimes referred to as "next generation" medicines. Unfortunately, large molecules have some challenging properties. They are:
Poorly absorbed through the epithelial membrane
Easily destroyed by gastrointestinal acids and enzymes
Relatively insoluble

Large-molecule drugs are therefore usually introduced into the body via injection and that is a problem. Injections are painful, inconvenient, and often must be delivered by trained medical staff. For these reasons, injection is not a user-friendly drug delivery system.

The discomfort of a daily regimen of injections increases patient anxiety, which clearly is an undesirable outcome in itself. Moreover, as anxiety increases, compliance decreases, and that has serious repercussions. For the individual patient, decreased compliance with a medication schedule often leads to a serious deterioration in health. For the health care system as a whole, decreased compliance is extremely costly - in the US alone, hospital and physician visits attributable to noncompliance have an estimated price tag of $8.5 billion.

Scientists in academic and commercial laboratories have attempted to find less invasive alternatives to injection of large-molecule drugs, but so far most of the results have not been useful. That is why the preliminary success of the Generex approach - buccal delivery of large-molecule drugs - is so exciting.

Generex Oral-lyn, is an insulin spray for the treatment of Type I and Type II diabetes. Generex Oral-lyn; is a safe, simple, fast, effective, and pain-free alternative to subcutaneous injections of prandial insulin and is conveniently delivered to the membranes of the oral cavity by a simple asthma-like device with no pulmonary (lung) deposition.

As a pain-free and convenient method of insulin delivery, Generex Oral-lyn will allow individual patients to "fine tune" and then maintain their metabolism resulting in an improved quality of life. Accordingly, Generex Oral-lyn provides the opportunity for the establishment of a new and more effective diabetes treatment paradigm.

RapidMist an advanced buccal drug delivery technology, is comprised of a proprietary formulation and a proprietary device design that is able to deliver drugs through the buccal mucosa safely, thereby eliminating the pain from and need for multiple injections. RapidMist has been shown to have a rapid onset of action with no lung deposition, precise dosage control, easy use and handling, and improved patient compliance.

The formulation involves the preparation of a proprietary process in which an active pharmaceutical agent is placed in a solution with a combination of absorption enhancers and other excipients classified generally recognized as safe ("GRAS") by the Food and Drug Administration ("FDA") when used in accordance with specified quantity and other limitations. The formulation is a liquid that contains a medication plus a number of enhancers. The enhancers are the key. They help the medication penetrate the epithelial membrane of the buccal mucosa, and they also promote rapid absorption of the drug into the circulatory system.

Enhancers are surface-active compounds, called surfactants. A surfactant is an organic chemical that contains both hydrophilic and hydrophobic ends. Because one end of a surfactant resists water and the other end embraces it, a surfactant has some unique characteristics. For example, under certain conditions, a surfactant assumes a micelle structure. In a micelle, the 'water-loving' ends of the surfactant form a protective shell around the 'water-hating' ends. Micelles are critical to drug delivery, because the protective shell of a micelle can be used to surround a large molecule. The micelle then carries the target molecule through cell membranes and even through cell walls.

A relatively small concentration of surfactant not only allows a drug to traverse mucous membranes rapidly, but it also increases both the solubility and the stability of the drug, which makes it possible to achieve therapeutic levels of the drug in blood plasma. After years of research and tests, our scientists have succeeded in identifying a unique combination of enhancers that makes it possible to deliver a large-molecule drug - insulin - as an oral spray that is absorbed through the buccal mucosa.