Development Of Doxycycline Hyclate In Situ Gel

Periodontal disease is one of the world's most prevalent chronic diseases, which has been considered as a possible risk factor in some systemic diseases, periodontal disease seriously threaten to people's quality of life. Traditional delivery methods-systemic administration can lead to side effects and low bioavailability. The local delivery can make drug stay in periodontal pockets, but the use of some agents can cause to patients' pain, resulting in poor compliance and poor treatment effect. In situ gel, a novel sustained-release delivery system, can resolve above problems. Based on polymer materials happens in response to the external stimulus, in situ gel (ISG) occur polymer dispersion or a reversible conformational change under physiological conditions , and the solution transform to gel completely. Correspondingly, in situ gel can be divided into the temperature -sensitive, pH-sensitive, ion-sensitive and removal solvent precipitation. Remove solvent precipitation-ISG can be used in the treatment of periodontal diseases. In situ gel can be injected into periodontal pockets by small needles. Upon contact with the gingival crevicular fluid (GCF), the liquid product solidifies and adheres to the periodontal pockets, then allows for sustained release of drugs, thus ensuring a high effective drug concentration in the periodontal pockets, improving the bioavailability, increasing drug efficacy, and reducing side effects. The agents can occur self-elimination, avoiding the need to remove the polymer system from the site of implantation after its use, thereby increasing patient compliance. Additionally the preparation method is simple, so that in situ gel has a very good value and wide development prospects.In this study, doxycycline hyclate, the first choice of drug treatment of periodontal disease, was selected as model drug. Biodegradable, biocompatible PLGA and non-toxic NMP was used to formulate the in situ gel. Syringeability and solidification of doxycycline hyclate in situ gel prepeared by different composition was preformed. This study determined the main factors of in vitro release by single factor test, and discussed the results. In vitro release rate as the index, orthogonal test was used to optimize formulation. Finally the bast formulation was determined as PLGA (Mn = 10000):NMP: doxycycline hyclate = 25% :65%:10%.In this study, the quality doxycycline hyclate in situ gel was assessed. The in situ gel was the yellow transparent and uniform liquid which had good flowability. Rheological study showed that the in situ gel was Newtonian fluid, and its flowability was good. Doxycycline hyclate in situ gel, prepared by the optimal formulation, had 20% of the burst at 2 hours, then released slowly over 10 days, and the cumulative release rate reached above 90% at 37℃. The preliminary study of the release mechanism showed that the in situ gel fit the first realese and Fick diffusion mechanism. Doxycycline hyclate contents of in situ gel were detected by HPLC method, and the results showed that content meets the requirements.Preliminary stability and irritating studies of doxycycline hyclate in situ gel show that the in situ gel was sensitive to light, should be stored in dark place, and it was stability, security and no stimulation.