DEVELOPMENT AND CHARACTERIZATION OF TETRACYCLINE-POLY(LACTIDE GLYCOLIDE) FILMS FOR THE TREATMENT OF PERIODONTITIS

Local delivery of antibiotics has been shown to be effective in reducing periodontopathic microorganisms. The objective of this research was to develop a biodegradable, poly(D,L-lactide/glycolide), 85:15, (PLGA) film that was capable of delivering therapeutic concentrations of tetracycline HCI for a duration of two weeks into the intra-crevicular fluid within the inflamed periodontal pocket. Films (10 X 2 X 0.5 mm) containing varying amounts ( 10 to 25% w/w) of tetracycline HCl were prepared by film casting a dispersion of the drug in a solution of PLGA dissolved in methylene chloride. Differential dissolution studies were performed in buffer, pH 7.3, at 3 7-degrees-C. Both the rate and percent of drug released increased as drug loading and dissolution media pH increased. However, complete release of drug from the films was not obtained as 83.1 +/- 7.0 mug of tetracycline HCI per mg of PLGA was retained for all drug loadings. Linear relationships obtained for graphs of the percent released versus both the square root of time (r2 greater-than-or-equal-to 0.96) and drug loading (r2 greater-than-or-equal-to 0.99) indicated a matrix-controlled release from a porous, granular, monolithic system. Preliminary results from a clinical study with 8 periodontal, maintenance patients indicate that films containing 25% w/w tetracycline HCI were effective in decreasing the bacterial count in the intra-crevicular fluid and demonstrated a significant (p less-than-or-equal-to 0.01) microbial inhibition for two weeks over the control placebo film. The decrease in tetracycline HCI concentration in the gingival fluid was approximated by a first order relationship with the tetracycline HCI disappearance rate constant of 0. 19 days-1.