Naltrexone, poly

Several narcotic antagonists, including naloxone, naltrexone, L-methadone, and cyclazocine, have been incorporated in lactide homopolymers and lactide/glycolide copolymers. Cyclozocine was incorporated in poly(L-lactide) in the form of films (81,82). Lamination of drug-polymer films with a drug-free film created a reservoir device and eliminated the burst observed with the monolithic films originally tested. 

FIGURE 16A Daily rate of release of naltrexone from a poly-e-caprolactone-co-lactic acid capsule (reservoir device) under in vitro conditions. (From Ref. 89.)... 

Table IV. Calculated and Experimental Solubilities (mg/ml) of Progesterone and Naltrexone in Water, Poly(e-capro-lactone) and Poly(ethylene-co-vinyl acetate)...

Although the Alza poly(ortho ester) system has never been structurally identified other than by its tradename Chronomer, and later Alzamer, several publications provide a general description of the use of the polymer for the release of naltrexone (46) and contraceptive steroids (47. 48, 49). 

Because poly (ortho esters) are stable in base and because naltrexone is a base with a pKa of 8.13 which produces a saturated aqueous solution having a pH of about 10, it can not be used as such and a neutral or slightly acidic salt must be used. Therefore, the salt naltrexone pamoate was used. Use of pamoates to decrease water solubility of various drugs has been described. 

Release of naltrexone. The release of naltrexone using poly (ortho ester) II has already been discussed in Sect. 4.2.5. Since it was not possible to form highly loaded devices that had useful mechanical properties due to an interaction between naltrexone and the polymer at the device fabrication temperatures, it was decided to use the ductile polymer since naltrexone could be mixed into the polymer at room temperature and with appropriate mechanical mixing, high drug loadings could be achieved. 

Dinarvand R, Moghadam SH, Sheikhi A, Atyabi F. Effect of surfactant HLB and different formnlation variables on the properties of poly-D,L-lactide microspheres of naltrexone prepared by double emulsion technique. Journal of Microencapsulation. March 2005 22(2) 139-151. PubMed PMID 16019900. 

Maa, YF. and Heller, J. (1990) Controlled release of naltrexone pamoate from linear poly(ortho esters) J. Controlled Release, 14, 21. 

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