PAIN THERAPEUTICS, INC. — Department of Health and Human Services SBIR Phase I: NIDA

Description

Project Summary Abstract Under this Fast Track proposal we will develop FenrockTM an abuse deterrent transdermal fentanyl patch based on our proprietary co crystal of naltrexone NTX and its carefully selected conformer methyl furfural MFF This NTX MFF co crystal NTX Co has the desired properties to stay in a crystalline solid form in the patch when applied to skin as intended but to dissociate to deliver NTX when abused by chewing swallowing solvent extraction smoking or heating and inhaling We will first develop analytical methods needed to measure the three patch components fentanyl NTX and MFF We will perform preformulation studies to assess solid state interaction of NTX Co with fentanyl and various excipients as well as compatibility with various pressure sensitive adhesives The stability of NTX Co in the presence of fentanyl and the list of acceptable excipients and adhesives will determine potential compartmental designs We will then begin formulation development by testing several potential fentanyl and NTX Co patch components compartments and characterizing them individually in in vitro in dissolution and flux across an artificial membrane under use and abuse simulations These results and adhesion testing will determine the Phase I milestone selection of up to three patch prototype concepts with integrated fentanyl and NTX Co compartments Phase II of this proposal will begin with production of these three patch prototype designs and their in vitro testing under use and abuse paradigms These include D tissue models of transdermal and buccal absorption and in vitro tests to mimic chewing swallowing solvent extraction and volatilization by heating or smoking A final ex vitro test will assess transdermal absorption in excised human skin Up to two patch prototypes will be selected for a PK study in rats to compare fentanyl absorption rate to that of the Duragesic fentanyl patch Based on these data one or two prototypes will be selected for a dermal irritation study in rats and a PK study in minipig that will guide the IND enabling studies in minipig the required species for transdermal products We will use the rat conditioned place preference paradigm to determine the optimal relative doses of NTX Co and fentanyl such that enough NTX is released under scenarios of abuse to reduce the rewarding effects of fentanyl and provide a measure of safety With the PK dermal irritation and relative dose determination completed one formulation will be selected and a GLP tox lot manufactured We will then conduct a dose range finding study and the pivotal day GLP tox in minipig At the completion of the proposed work Fenrock will be ready for GMP scale up and clinical trials Project Narrative Abuse and accidental misuse of transdermal fentanyl patches is a serious health issue when exposed to liquids or put in the mouth a day supply of this fast acting and highly potent opiate is delivered quickly We proposed to develop FenrockTM an abuse deterrent transdermal fentanyl patch based on our proprietary co crystal of naltrexone The co crystal will remain in the patch undelivered when applied as intended but will release naltrexone to counteract the fentanyl if the patch is abused by chewing swallowing solvent extraction smoking or heating and inhaling