Generex Biotechnology Receives Australian Patent for Buccal Delivery System for Insulin

Generex Biotechnology Corporation (Toronto, Canada, www.generex.com) has received an Australian patent for its micellar system for delivering macromolecules through the buccal lining. The company believes this system can improve patient compliance, particularly for insulin.

The key to the patented delivery system is the protection provided by the excipients, which form a spherical micelle of surfactant molecules in which the hydrophilic “heads” remain in contact with the solution while the hydrophobic “tails” remain in the center, surrounding the protein and shielding it from digestion by buccal enzymes. The micelles are formed by proteinic pharmaceutical agents, all “generally recognized as safe” (GRAS). Examples include an alkali metal C8 to C22, alkyl suflate, or alkali metal salicylate. The formulation also includes at least one absorption-enhancing compound, such as lecithin.

The total size of the micelle particles ranges from 1 to 10 nm, a size that ensures penetration through the buccal membranes. The insulin is administered using a metered-dose inhaler, and about 10–12% of the drug is absorbed.

The primary motivation for developing this formulation was to improve patient compliance, says Anna Gluskin, president and CEO of Generex. “About 12–17% of diabetic patients must take insulin to survive,” she explains. “The other 83% are saying, ‘I’m okay. I’m not really sick.’” With a formulation that does not require injections, she believes, more of those patients will be willing to take insulin.

The buccal administration also can help patients maintain more even insulin levels, because it is easy for patients to titrate their doses according to what they eat, and to space out administration before and after a meal. Each puff of the inhaler administers 10 insulin units, one of which will be absorbed. So if a patient needs 10 units, Generex advises splitting the dose, to five puffs before the meal and five after.

“It is much better to surround the meal with insulin,” says Gluskin. “That’s what happens in a healthy individual.” Patients using injectables are unlikely to do this, she adds, thus risking postprandial hyperglycemia, which can damage heart muscle. Also, in Generex’s formulation, the insulin is absorbed quickly, reaching Tmax in 30 minutes, and eliminated in about 1.5–2 hours. “There is no danger of hypoglycemia, because we don’t dose again until all the insulin is gone,” says Gluskin.

The company already has a buccally delivered insulin product, “Oral-lyn,” on the market in Ecuador, and undergoing trails in other countries. Generex expects to gain market approval in Mexico in less than eight months, in Europe and Canada in 12–18 months, and in the US in two to three years. The delivery system received US patent approval in July of this year.

The delivery system can be used for larger molecules as well. “We have shown successful absorption for molecules from 36,000 daltons, which is the size of insulin, to 180,000 daltons, in monoclonal antibodies,” Gluskin says.

Earlier this year, Pfizer launched the first non-injectable insulin, “Exubera,” in a form inhaled to the lungs.