Abstract
A root canal is one of the major components of a tooth. It is a long passage full of soft tissues, deep within thg, dentin of the tooth, adjoining the pulp chamber. The major cause of root canal infection is endodontic disease. Endodontic disease is a term used for three clinical conditions, which are: pulpititis, pulpal necrosis, and periradicular periodontitis. For the treatment of these clinical conditions, disinfection of root canal and root canal filling are required. A root canal filling is a deep filling to seal the space inside the roots of tooth to avoid infection of the tooth nerve. The aim of this project was to formulate and evaluate a sustained release, biodegradable local drug delivery system (DDS) for root canal filling. Two different salts of chlorhexidine were used as model drugs. The DDS consisted of chitosan, glyceryl monooleate (GMO), and hydroxyapatite. Tripolyphosphate sodium (TPP) was used as the crosslinker. Effect of drug load (1.1, 2.5, and 4.1 % (w/w)), salt forms used (diacetate vs. digluconate), chitosan concentration (1, 2, and 4 % (w/v)), and cross-linker concentration in the formulation on the in vitro release of chlorhexidine from the delivery system was investigated. The in vitro release was carried out at 37°C in artificial saliva. Chlorhexidine was analyzed by a HPLC method. Increase in the drug load also increased the release rate of the drug from both formulations containing different salts of chlorhexidine. At three different concentrations of chitosan ranging from 1% (w/v) to 4% (w/v), the percentage release of chlorhexidine containing digluconate salt from the DDS within 24 hrs was evaluated. The drug load was kept at 1.1% (w/w). Under these conditions, in vitro release of chlorhexidine was 56.6±12.0, 46.2±7.73, 36.5±13.8 respectively. Under similar experimental conditions, at higher drug load, increase in the chitosan concentration in the formulation retarded the release by 1.3-2 fold. The free flowing property of the implant was lost beyond 4% (w/v) chitosan concentration. To further sustain the drug release, a more hydrophobic salt (diacetete) was investigated. At any particular drug load, the rate of release of chlorhexidine from the digluconate salt was found to be 2 to 3 fold higher than the diacetate salt. At a constant drug load (2.5 % w/w), the release of chlorhexidine (% w/w) from a DDS containing diacetate salt and 4% (w/w) chitosan without a cross-linker was 36.41 ±9.42. With the incorporation of different concentrations of cross-linker at 0.2% (w/w) and 0.4% (w/w) the percentage release of chlorhexidine was found to be 28.76±6.91 and 20.54±5.85 respectively. The percentage of chlorhexidine released from the implants decreased 1.7 fold when TPP concentration increased from 0.0% (w/w) to 0.4 % (w/w). A sustained-release local delivery system containing two different salts of chlorhexidine was developed and evaluated. In vitro release of chlorhexidine from such DDS was dependent upon the different salt forms of chlorhexidine, chitosan concentrations, drug load, and cross-linker concentrations in the formulation. The effects of commercially available formulation (CALG®) with and without GMO on the release of chlorhexidine for a period of 7 days were also investigated. The percentage release of chlorhexidine from the commercially available formulation was found to be 2.04±1.02. Since the percentage release of chlorhexidine was found to be inadequate, attempt was made to modify the release. Polar additives such as GMO were directly incorporated in the formulation. The percentage release of chlorhexidine increased by 2.3 folds due to the incorporation of GMO in the formulation. Even though, incorporation of GMO enhanced the release, the overall release from the commercially product was very slow. Surface topography revealed that addition of GMO to the commercially available formulation substantially changed the crystalline structure of the matrix material. Change in the microstructure and decrease in crystallinity of the matrix might contribute to a higher diffusion of drug from such a matrix.