Formulation and evaluation of in situ forming PLA implant containing tinidazole for the treatment of periodontitis

Abstract

Periodontitis is caused by periodontopathic bacteria and antibacterial agents are placed in a periodontal pocket with the intention of enhancing the local effect. To maximize the therapeutic effects while reducing the adverse effects, tinidazole was delivered by in situ forming system. One approach for reducing burst release rate was to testify in situ forming effect. The effect of 0%-10% (w/w) polyethylene glycol 400 and 3% (w/w) glycerol on the tinidazole release from a poly(DL-lactide) (PLA) injectable implant was evaluated. The results showed that the in vitro initial burst release rate was decreased in the presence of poly(ethyleneglycol) PEG 400 and glycerol. A formulation containing 30% (w/w) PLA (M(w) 7300) dissolved in 62% (w/w) N-methyl-2-pyrrolidone, 5% (w/w) PEG 400, and 3%(w/w) glycerol with 5% (w/w) tinidazole was shown to be optimum. Twelve adult beagle dogs were used in the periodontitis model. The treatment group I, II, and positive control group was administrated with gel containing 5%(w/w) tinidazole, 2.5%(w/w) tinidazole, and periocline, respectively. Dog studies revealed that periocline and the developed formulation could significantly decrease symptoms of periodontitis, and they were better than gel containing 2.5% (w/w) tinidazole. The developed formulation could sustain the release of tinidazole for local delivery over 7 days. These findings suggested that the developed formulation was a viable alternative to conventional drug to cure periodontitis.