Effects of absorption enhancers in chloroquine suppository formulations: IIn vitro release characteristics

The need to develop chloroquine suppository formulations that yield optimal bioavailability of the drug has been emphasized. This study demonstrates t he effects of incorporation of known absorption-enhancing agents (nonionic surfactants and sodium salicylate) on the in vitro release characteristics of chloroquine from polyethylene glycol (1000:4000, 75:25%, w/w) suppositor ies. The release rates were determined using a modification of the continuo us flow bead-bed dissolution apparatus for suppositories. Results showed th at the extent of drug release from suppositories containing any of three su rfactants (Tween 20, Tween 80 and Brij 35) was 100%, whereas 88% release wa s obtained with control formulation (without enhancer) (P<0.05). However, T ween 20 was more effective than Brij 35 and Tween 80 in improving the drug release rate. There was a concentration-dependent effect with Tween 20, and 4% (w/w) of this surfactant was associated with the highest increase in th e rate of drug release from the suppositories. Sodium salicylate at a conce ntration of 25% (w/w) also significantly enhanced the drug release rate, bu t a higher concentration of the adjuvant markedly reduced both the rate and extent of drug release. Combined incorporation of Tween 20 and sodium sali cylate did not significantly modify (P>0.05) the rate of drug release when compared to the effect of the mon effective single agent. Due to their effe cts in improving the drug release profiles coupled with their intrinsic abs orption-promoting properties, it is suggested that incorporation of 4% (w/w ) Tween 20 and/or 25% (w/w) sodium salicylate in the composite polyethylene glycol chloroquine suppository formulations, may result in enhancement of rectal absorption of the drug. This necessitates an In vivo validation. (C) 1999 Elsevier Science B.V. All rights reserved.