Oral transmucosal drug delivery system for naltrexone for alcohol dependence trea

DESCRIPTION (provided by applicant): This proposed SBIR Phase I project will demonstrate the feasibility of developing a novel oral transmucosal drug delivery method and dosage form for alcohol dependence treatment. The proposed system is a small, thin, and flexible film, containing the treatment drug, naltrexone. It is applied intra-orally to affect a rapid onset of action, followed by moderate release of drug for extended pharmacological action. The Phase I project will consist of design, fabrication and in vitro evaluation of thin-film dosage forms. The dosage form is applied as needed when alcohol craving occurs. The method/dosage form is cost- effective, convenient (can be administered without water), and could fill the gaps of current patient and market needs. PROBLEM/OPPORTUNITY: There are two naltrexone products marketed for treatment of alcohol dependence: oral tablets and injectable depot formulation. The former suffers from low bioavailability, poor patient compliance, and significant side effects. The later overcomes bioavailability and patient compliance problems but is expensive, inconvenient and has injection site reaction. Proposed drug delivery system is expected to overcome the poor oral bioavailability of the oral naltrexone tablets, and high cost and inconvenience of the injectable naltrexone depot formulations. Results from this study are anticipated to lead to better efficacy, more convenient, and better patient compliance of alcohol-dependence medical treatment, and thus improve the health of alcoholism patients. This market sector is presently under-served and has substantial potential. The proposed technology could be extended and developed into improved dosage forms for other substance- addiction treatment medications. PLAN OUTLINE: Specific aims of the Phase I study are a) design and fabrication of film constructs with desired film properties (flexibility and integrity) and dose of naltrexone, b) development of in vitro drug release test method, and testing of the formulations, c) development of in vitro transmucosal permeation method using cultured mucosa tissues, and evaluation of candidate formulations to determine their bio-absorption efficiency, and d) stability study to determine shelf-storage stability of the prototype drug product. Plans for Phase II follow-on research include completing product development program, GMP manufacturing of PK (pharmaco-kinectic) and clinical batches, conducting in vivo PK study, and demonstration of efficacy in human clinical study. PUBLIC HEALTH RELEVANCE: The proposed drug delivery system is expected to result in improved efficacy and better compliance in the pharmacological therapies for alcohol dependence. This will reduce the public health burden of heavy drinking to our society and significantly reduce related healthcare costs. In addition, the proposed technology is a platform that could be extended and developed into improved dosage forms for other substance abuse medications.