Chlorhexidine delivery system

Controlled and sustained drug delivery has recently begun to make an impression in the area of treatment of dental diseases. Many researchers have demonstrated that controlled delivery of antimicrobial agents, such as chlorhexidine [128-130], ofloxacin [131-133], and metronidazole [134], can effectively treat and prevent periodontitis. The incidence of dental caries and formation of plaque can also be reduced by controlled delivery of fluoride [135,136]. Delivery systems used are film-forming solutions [129,130], polymeric inserts [132], implants, and patches. Since dental disease is usually chronic, sustained release of therapeutic agents in the oral cavity would obviously be desirable. 

A newer development in controlled local delivery, one that utilizes the antiseptic chlorhexidine as the antimicrobial agent, has been introduced in a number of countries and was recently cleared by the FDA for use in the United States. This delivery system, PerioChip (manufactured by Perio Products Ltd., Jerusalem, Israel distributed by Dexell Pharmaceuticals, Edison, NJ), was developed in Israel and has been tested in the United States as well as in Europe. 

Drug delivery from LLC phases of oligo(ethylene oxide)-alkyl ether (i.e., (E0) -0-alkyl) surfactants have also been explored but to a much lesser extent than GMO. For example, the L, Qn, and Hu phases of commercial Brij-96 surfactant (i.e., (EO)io-O-oleyl) (Fig. 18) formed with water and other additives, have been explored for release of ephedrine hydrochloride, tenoxi-cam [145], and topical dermal delivery of benzocaine [146]. Work in this area has found that the amount of water swelling the hydrophilic domains of the LLC phase increases drug diffusion and release [145]. In addition to this work, the L phase of the (EO)2i-0-stearyl/oil/water system has been explored for dermal delivery of itraconazole [147] and the L and Hi phases of the (E0)7-0-Ci3 i5 (i.e., Symperonic A7)/water system have been explored for the release of the model drug chlorhexidine diacetate [148]. 

Nanocapsules appear a promising approach as a drug system for topical application. The transport of chlorhexidine-loaded poly(e-caprolactone) nanocapsules through full-thickness and stripped hairless rat skin was investigated [48]. The flexibility of nanocapsules assured a satisfying bioadhesion to the skin, whereas the rigidity of the carrier limited the molecular spill into the skin and controlled the drug delivery to the skin. 

---