A combination therapy to help smokers kick the habit has begun evaluation in Phase I pilot studies in the US. A sustained-release formulation of Cary Pharmaceutical's QuitPak has been developed with IntelGenx Technologies as an alternative smoking cessation therapy.
The new therapy, which combines bupropion and mecamylamine, is undergoing trials to determine the suitability of IntelGenx' extended release formulation for the once-daily treatment.
The two components in the novel treatment have both been approved by the US Food and Drug Association (FDA) independently, but Cary has obtained international patents for the combination and use of the medication.
Until 1997 Merck marketed mecamylamine as a hypertension treatment under the name Inversine, but never pursued the smoking cessation potential that was spotted as a side-effect of the drug treatment. Bupropion is the active ingredient in GlaxoSmithKline's smoking cessation product, Zyban, although was initially used in the company's antidepressant treatment, Wellbutrin.
Mecamylamine is a nicotine antagonist that works by blocking nicotine receptors in the brain. By blocking the receptors, the smoker is denied the pleasure from smoking a cigarette, and thus may be able to 'unlearn' the addictive behaviour. The precise mechanism of action of the second component, bupropion, is unknown, but it is believed to act on dopamine and norepinephrine levels in the 'addiction centre' of the brain.
"By blocking the nicotine receptors in the brain while minimizing withdrawal symptoms, QuitPak represents a new treatment approach for helping smokers to overcome their addiction to cigarettes." said Richard Olmstead, principal investigator for QuitPak at the University of California.
Representatives from the companies were unable to disclose detailed information regarding the specific formulation and tabletting of the product as patents have not yet been issued, but IntelGenx has proprietary controlled-release technologies including its two primary platforms - Tri-Layer Tablet Technology and Quick Release Wafer Technology.
The tri-layer technology uses a layering technique to control the release of active compounds. Tablets manufactured using the technology are produced with the active core layer covered by two erodible cover layers.
As the erodible layers begin to disintegrate, the active ingredient increasingly permeates through the cover layers. The company says tablets produced using this technique therefore produce 'quasi-linear' kinetics for releasing a chemical over a desired time period. The disintegration rate can be customised according to the properties of the active ingredient.
According to IntelGenx, the smoking cessation product they are working on is a 'monolayer' tablet, so therefore could incorporate only one erodible layer around the bupropion and mecamylamine active core.
According to IntelGenx, the tri-layer technique is a superior alternative to osmotic pump delivery systems, and offers significant manufacturing cost savings. The firm is applying the technology to develop products for a variety of indications, their lead product being a treatment for hypertension that has demonstrated in vitro equivalency with AstraZeneca's Toprol XL (metoprolol succinate) in the US and Beloc-ZOK (metoprolol tartrate) in Europe.
According to the company, the smoking cessation market is worth in excess of $1bn (€0.8bn) with around 1.3bn smokers worldwide to target. Commercialisation of the new QuitPak product is expected in 2009.