Effect of cyclodextrins and polymers on triclosan availability and substantivity in toothpastes in vivo.
The aqueous solubility of triclosan is only about 10 microg/mL. This very low solubility can hamper its biological activity in the oral cavity, which could explain the mixed clinical results obtained from triclosan toothpaste trials. Triclosan availability in a silica-based toothpaste was improved through cyclodextrin solubilization. The triclosan in vivo availability was optimized through a series of phase-solubility studies and triclosan release studies. It was found that in toothpastes, natural beta-cyclodextrin (betaCD) was just as good a solubilizer as the more water-soluble betaCD derivatives. Furthermore, the amount of cyclodextrin could be reduced by as much as 60% through the addition of a small amount of carboxymethylcellulose (CMC), without affecting triclosan release from the toothpaste. Optimally, cyclodextrins resulted in an almost 3-fold enhancement of triclosan availability compared to an identical toothpaste containing no cyclodextrin. In vivo studies in humans showed that replacing triclosan with triclosan/betaCD in the toothpaste resulted in only moderate improvement in triclosan substantivity. However, replacing triclosan with triclosan/betaCD/CMC complex resulted in significant improvement in triclosan substantivity. Furthermore, the in vivo studies showed that replacing free triclosan with triclosan/betaCD/CMC complex resulted in an almost 3-fold increase in initial triclosan concentration in saliva after brushing and about 2-fold increase in duration of activity.
Loftsson
T
T
Department of Pharmacy, University of Iceland, P.O. Box 7210, IS-127 Reykjavik, Iceland. thorstlo@hi.is
Leeves
N
N
Bjornsdottir
B
B
Duffy
L
L
Masson
M
M
D000328:Adult; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D014100:Toothpastes / Q000032:analysis*; D014260:Triclosan / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*
D000891:Anti-Infective Agents, Local; D003505:Cyclodextrins; D005079:Excipients; D011108:Polymers; D014100:Toothpastes; D014260:Triclosan