31 A Modified-Release Drug Delivery Technology Containing Amphetamine-Ion Exchange Complexes

Abstract The proprietary, immediate and extended drug delivery technologyLiquiXR® utilizes an ion-exchange resin that complexes with amphetamine or any active moiety that can be protonated and is water-soluble. The active ingredient of the drug product forms a complex with an ion exchange polymer of the resin resulting in micron-sized particles. A portion of these particles is then coated with an aqueous, pH-independent polymer designed to provide sustained release of drug product. The polymer coating applied to the ion-exchange resin particles is of varying thickness, allowing for extended release of active drug while uncoated particles provide for immediate release of drug. The micron-sized particles lend themselves to being formulated into an appropriate dosage form: solid/chewable tablet, liquid suspension, orally disintegrating tablet, film, or capsules. Active ingredient of drug product is subsequently released from the dosage form in millions of particles, with release driven by a combination of ion exchange and diffusion. After drug release, the ion-exchange resin particles are excreted in the feces. The release characteristics of LiquiXR allow for customized, sustained release of active drug ∼24hours post dose. Mechanistically, drug particles enter the gastrointestinal (GI) tract. As positively-charged ions from GI fluids diffuse across the coating, it displaces drug ions from product and they diffuse through the coating and into the GI fluids for absorption. As the coating is of variable thickness, some drug product takes longer to diffuse and absorb, providing for the delayed drug release characteristics. The LiquiXR drug delivery technology has already been successfully utilized in the development of treatment options (liquid suspension and chewable tablet) that offer rapid absorption and sustained plasma levels after once-daily dosing. LiquiXR is utilized in Dyanavel® XR (amphetamine extended-release oral suspension; AMPH EROS), which is indicated for treatment of ADHD. It comprises 2.5mg/mL amphetamine base and uses LiquiXR technology to provide an immediate release component followed by an extended-release profile. Efficacy of AMPH EROS was established in children 6 to 12 yr in a Phase 3, placebo-controlled laboratory classroom study. In that study, ADHD symptoms in children on an individually optimized dose of amphetamine (range 10–20mg/day) were statistically significantly improved compared with symptoms in children treated with placebo. For children treated with AMPH EROS, onset of effect was demonstrated at 1hour after dosing, and efficacy was observed through 13hr post-dose. The effect size (ES) was comparable to ES demonstrated for other psychostimulants tested in studies using a similar design. The efficacy data reported for AMPH EROS provides an excellent example of the potential utility and clinical application for other active drug products requiring an immediate and extended release profile. Funding Acknowledgements: Support provided by Tris Pharma, Inc.