Study Of Extended Release Minocycline Hydrochloride In Situ Gel For Treatment Of Periodontitis

Periodontal diseases are bacterial infections caused by biofilms matures. Minocycline（MINO） is a tetracycline antibiotics with broad-spectrum antimicrobial activity against pathogenic bacterium of periodontitis. A new drug delivery system using minocycline hydrochloride as the model drug, in situ gel, was designed in this study for the treatment of periodontitis.HPLC method was established to determine the drug content and in vitro drug release in/from the preparations. It was indicated from the results that the HPLC method was reliable and simple. The partition coefficient of MINO·HCl in n-octanol/water system and its stability in water with or without adding stabilizing agent were studied, providing basics for the preparation formulation design.The effect of formulation factors and preparation parameters on the quality of in situ gel was studied using size and size distribution, flowability and centrifugation stability as the criteria, based on which the basic formulations and preparation conditions were determined. Franz diffusion cell was applied to study the in vitro drug release from MINO·HCl in situ gel. The effect of release area, amount of gel, and formulation factors and preparative parameters on in vitro drug release was investigated to further optimize the formulation and preparation conditions.Rheology study of in situ gel solution showed that G’、G"、ηof the solution increased sharply andδbegin to decrease when contacted with water. These results indicated that the part of in situ gel solution contacted with water turned into gel.The inner structure of in situ gel was studied by fluorescence microscope, transmission electron microscope and the infinite amplified surface testing designed by the author. The result showed that the inner structure of in situ gel solution was filled with particles coated with a film which was presumed to be hydrophobic polymer.Drug analysis method was established using filter paper strip to collect the gingival crevicular fluid （GCF） for preliminary in vivo drug release study in the periodontal pocket of rabit. On the 7th day after drug adminstration, the concentration of MINO in the GCF was 34.3331μg·mL^-1 which was much higher than the MIC (1μtg·mL^-1) of MINO, indicating that the MINO·HCl in situ gel can prolong drug release significantly. Experimental periodontitis model of rats that imitated the clinical pathological characteristics was established using rats. The result of pharmacodynamics study showed that the MINO·HCl in situ gel could reduce the clinical indexes of periodontal disease （BOP, GI, DPP） significantly. Histopathological analysis of the rat’s gingival tissue showed that MINO·HCl in situ gel could lessen the inflammatory reaction of periodontitis effectively. The irritation testing of lagophthalmus showed that MINO·HCl in situ gel was safe to apply on mucosa. It is indicated that the MINO·HCl in situ gel is an ideal drug delivery system for periodontitis therapy.