Naltrexone pamoate release

Fig. 25. Cumulative release of naltrexone pamoate from polymer slabs (25 x 4 x 1.25 mm) prepared from 3,9-bis (ethylidene-2,4,8,10-tetraoxaspiro [5,5] undecane) and 1,6-hexanediol at pH 7.4 and 37 °C. Numbers in parentheses indicate percent weight loss. Devices contain 50 wt% drug and varying amounts of suberic acid (SA). ( ) 3 wt% SA, ( ) J wt% SA, (O) no SA [46]. Reprinted with permission...

Preliminary results are shown in Figs. 36-38 [56]. As with 4-homosulfanilamide, the pH of the drug was found to have a significant effect on kinetics of release. Thus, naltrexone pamoate is acidic by virtue of its unreacted phenolic hydrogens and as shown in Fig. 36, release rate is relatively fast. On the other hand, naltrexone is basic and release rate as shown in Fig. 37 is slower. As shown in Fig.38, when a 50/50 mixture of the two forms is used, good linear release kinetics have been achieved. 

Fig. 36. Release of naltrexone pamoate from a polymer prepared from 1,2,6-hexanetriol and triethylorthoacetate at pH 7.4 and 37 °C. Polymer contains 50 wt% drug...

In the other application naltrexone pamoate was incorporated into a polymer prepared from 3,9-bis (ethylidene) 2,4,8,10-tetraoxaspiro [5,5] undecane and 1,6-hexanediol. In this particular application, it was necessary to use naltrexone pamoate since naltrexone free base wdth a pKa of 8.13 will produce a saturated aqueous solution having a pH of about 10. Because this would stabilize the polymer, the slightly acidic naltrexone pamoate was used. In this particular case, naltrexone pamoate without the incorporation of suberic acid w as able to catalyze polymer erosion and excellent, linear release was achieved over about 50 days. Incorporation of 1 and 3 wt% suberic acid decreased the time to total release to 30 and 10 days, respectively (Maa et al, 1990). 

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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