Transdermal Delivery of Buprenorphine Prodrugs
Small Business Information
ALLTRANZ, INC., 2277 Thunderstick Dr, LEXINGTON, KY, 40505
AbstractDESCRIPTION (provided by applicant): Currently buprenorphine (BUP) is used in the treatment of opioid abuse and for pain management. It can also be used improperly and abused as an opioid. In the United States, buprenorphine is marketed in sublingual and i njectable forms. While the drug provides effective treatment, these forms of drug delivery are not desirable because of their peak plasma level related side effects and short duration of action. Transdermal delivery of drugs decreases peak-related side eff ects, and is ideal for chronic therapies as one patch can deliver a constant rate of drug for up to one week. Initial positive preliminary data has encouraged AllTranz to seek funding to develop new buprenorphine prodrugs and optimize their use through a t ransdermal patch or gel drug delivery system. Prodrugs are chemically modified parent drugs that are more skin permeable than the parent, and once they cross the stratum corneum quickly separate back into the parent drug and prodrug moiety. We will also cr eate formulations for abuse deterrence for this opioid delivery system. Transdermal delivery systems, patches and gels, offer a number of improvements over other delivery systems. Patches and gels do not require swallowing, eliminating oral side effects an d bitter opioid taste concerns; nor do they require skin puncture by needles, eliminating pain and patient visits to a physician. Permeation through the skin allows the drug to directly enter the systemic circulation and avoid the first pass effect, decrea sing gastric side effects and liver damage effects in hepatocompromised drug abusers and critically ill patients. The transdermal BUP system that is available in Europe could benefit from a higher skin permeation rate, improvement in adhesion, an abuse det errent mechanism, a smaller patch size, less residual drug remaining in the patch after use, and the ultimate dosing flexibility of a transdermal gel. Less drug needed in the formulation means less drug for potential abuse when the patch is removed, as cur rently the European marketed patches still contain fifty percent of their drug load at the end of treatment. To make abuse more difficult still, we will create an abuse deterrent formulation with opioid antagonist non-permeating prodrug and/or coated parti cles. The altered antagonist will remain in the patch or gel and not enter the body at a therapeutic rate, but will block the euphoria effect of BUP if abuse is attempted via the injectable or buccal routes. Specifically we aim to synthesize prodrugs of BU P and create an abuse deterrent component with naltrexone. We then aim to assess their in vitro human skin permeation for optimum flux. The optimal drugs will be combined and reassessed to see that the formulation provides increased permeation of BUP from prodrug during transdermal transport while the delivery of altered naltrexone is prevented. In further studies we will develop the prototype product and apply for an IND and begin Phase I clinical trials. We will create a marketable transdermal drug that w ill significantly ai in the treatment of heroin abuse and chronic pain. Public Health Relevance: AllTranz is seeking funding to create a transdermal prodrug gel and improved patch of buprenorphine for treatment of opioid dependence and chronic pain. These transdermal systems would be abuse deterrent and more effective than currently marketed products of the controlled substance buprenorphine. The gel would be a non-invasive non-oral dosage form with ultimate dosing flexibility without the need for pa tch cutting. The patches will be designed to have less residual drug content after use making them more appealing from a regulatory perspective, they could have better adhesion properties if less of a more permeable drug could be used, and when higher deli very rates are desirable in terminal pain the patient would benefit from the increased drug loading possible with the faster prodrug permeation allowing a smaller patch size to be used.
* information listed above is at the time of submission.