Copolymers of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) were prepared and used to fabricate a membrane-controlled reservoir-type controlled-release delivery system for chlorhexidine that should be suitable for intra-oral use. The reservoir of the system was prepared by softening an 80:20 mixture of chlorhexidine diacetate and 50:50 HEMA:MMA copolymer with methyl ethyl ketone (MEK), and pressing standard amounts of the resulting dough-like mixture into silicone rubber molds. A membrane was applied to the reservoirs by rotating them through a solution of 30:70 HEMA:MMA copolymer in MEK. The finished oval-shaped controlled-release pellets were approximately 4.7 mm wide, 3.3 mm high, and 7.4 mm long, and contained 45.0 +/- 3.7 mg of chlorhexidine diacetate. The mean in vitro release rate of chlorhexidine diacetate from the pellets into 37 degrees C water was 608 +/- 55 micrograms/24 h for days 2 through 11, and 389 +/- 50 micrograms/24 h for days 15 to 30 of the test period. The chlorhexidine released on day 30 was biologically active, as determined by a serial dilution assay against Streptococcus mutans. The extended release of biologically active chlorhexidine at a controlled rate from this system suggests that it is worthy of further evaluation for the intra-oral therapy of chlorhexidine-treatable oral infections in non-compliant and physically or mentally compromised individuals.
This investigation comprised two studies evaluating the effects of an acidic calcium phosphate solution (CPS) on fluoride uptake in the enamel, glycolysis of dental plaque, the incidence of dental caries and urinary fluoride concentrations of rats wearing an intraoral fluoride-releasing device (IFRD). In the first study, CPS-fluoride treatment preceded the cariogenic challenge. In the second study, the cariogenic challenge preceded the treatments. In the first study, CPS treatments increased the ability of enamel to bind fluoride. However, the enamel-bound fluoride exerted a negligible effect on plaque glycolysis as measured by the pH decrease after sucrose challenge. In the second study CPS augmented the caries inhibition for both the sulcal-morsal and buccallingual surfaces. In both studies the IFRD significantly restricted the development of carious enamel on the sulcal-morsal surfaces and caused elevated concentrations of fluoride in the urine independent of CPS treatments.
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