CONTROLLED RELEASE OF NALTREXONE PAMOATE FROM LINEAR POLY(ORTHO ESTERS)

Linear poly(ortho esters) prepared by the reaction between 3,9-bis(ethylidene 2,4,8,10 tetraoxaspiro [5,5] undecane) and various ratios of trans-cyclohexanedimethanol (t-itCDM) and 1,6-hexanediol (1,6-HD), were investigated as bioerodible matrices for the controlled release of naltrexone, a narcotic antagonist. Because naltrexone is a basic compound and poly (ortho esters) are stable in base, the neutral naltrexone pamoate was used in these studies. Since a therapeutically effective device requires a daily release of at least 4 mg/day, devices with a drug loading of at least 50 wt. % had to be used. In order to achieve such a high loading, a very soft polymer based on 100 wt. % 1,6-hexanediol was found to be optimal. As found in previous studies, polymer erosion and drug release was found to depend on the nature and concentration of the incorporated acidic excipient used to catalyze polymer erosion. With naltrexone pamoate, excellent control could be achieved by the use of 1 wt.% suberic acid and 25×4×1.25 mm polymer slabs that released naltrexone pamoate for 21 days at a constant 3 mg/day were prepared. © 1990.