Plumb Pharmaceuticals LLC — Department of Health and Human Services SBIR Phase I: NIDA

Description

Opioid misuse is a world wide problemand it is increasingThe epidemic has shifted from a problem largely confined to urban areas to one that is both urban and ruralMaintenance therapy helps alleviate situational cravings and makes addiction therapy more effectivebut methadone clinics are largely confined to larger citiesbuprenorphine must be prescribed by physicians with a specific waiverand it may be difficult to findwaiveredphysicians in rural areasNaltrexone is an opioid antagonist that has broad usage in the treatment of opioid addictionNaltrexone may be prescribed by any physicianno special authorization is necessaryNaltrexone is only an opioid antagonistand is not subject to diversionunlike methadone and buprenorphinemaking naltrexone therapy more acceptable to more conservative populationsNaltrexone is the only approved maintenance therapy available to certain sensitive professionsand the only maintenance therapy available in certain parts of the worldlike RussiaThe original naltrexone formulation is a daily oral pillDaily oral naltrexone is effectivebut is subject to significant medication compliance issuesA monthly formulation of extended release naltrexoneVivitrolis availableand improves medication compliance compared to daily oral pillsbut it suffers from variations in release rates over its duration as well as significant side effects that reduce patient willingness to continue treatmentMedication complianceand efficacywould be improved if the interval between injections could be increased to greater thanmonth and if the release rates were more stable over timeOur companyPlumb Pharmaceuticalsis developing an extended release formulation of naltrexone and has assembled the technical expertise and the business team necessary to developtest and eventually commercialize this formulation for addiction maintenanceOur proprietary Advanced Quantload technology can potentially extend the release period of naltrexone from the currentmonth toweeksmonthsin opioid maintenance patients with a very stable release rateAnweek release period would be of special benefit to patients in rural areasWe will develop this ultra extended release naltrexone formulation by completing of the following AimsDetermine optimal encapsulation procedureand characterize the productMilestoneEstablish efficientandgtloading of naltrexonea ratio of at leastmg naltrexone per mg phospholipidand characterize liposomes for size and type using light scattering analysis and or single particle optical sizingand cryoelectron microscopyDetermine the in vitro release characteristics of the AQL Nal formulation from AimMilestonethe lead formulation will releaseof its naltrexone in vitro at a uniform rate commensurate with anweek in vivo release periodConduct preliminary pharmacokinetics on the lead formulation in ratsnMilestoneThe lead formulation will demonstrateng mL blood serum concentrations forweeks with minimal systemic side effects localized tissue reactionsIn Phase IIwe will further refine the productperform GLP experiments in animals and first in human trials Project Narrative! The purpose of this project is to develop a formulation of naltrexone encased in liposomes that will providemonths of medication from a single injectionThis medication will be used for the treatment of addiction in humansThe product that results from these studies would potentially improve opioid addiction treatmentespecially in rural areasand would only be administered in a controlled environment !