Formulation of doxycycline loaded chitosan microspheres in glyceryl monooleate-based drug delivery systems for periodontitis

Abstract

The purposes of this study were to develop chitosan microspheres containing doxycycline hyclate and incorporate into glyceryl monooleate-based drug delivery system for the treatment of periodontal disease. The chitosan microspheres were prepared by using emulsification and ionotropic gelation method. The Box-Behnken experimental design was used as a tool for optimize the formulation. From the result obtained the fomulations comprising of doxycycline hyclate load (%), chitosan (%) and sodium tripolyphosphate (STPP) (%) as 75:3:15, 75:4:10 and 30:3:10 were selected. The microspheres could sustain release of doxycycline hyclate over a period of 24 hrs and followed square root of time kinetic which indicated that the rate of release was diffusion controlled. The accelerated stability study at 40, 50, 60 and 70 ℃ and the Arrhenius plot indicated that the predicted shelf-lives of microsphere formulations comprising of doxycycline hyclate load (%), chitosan (%) and STPP (%) of 75:3:15, 75:4:10 and 30:3:10 were 47.04, 245.65 and 22208.38 days, respectively. The ternary phase diagram consisted of triglyceride: glyceryl monooleate: water was constructed and the structure of liquid crystalline phases was investigated by using polarized light microscopy. Regarding the ability to form the reverse hexagonal liquid crystalline phase, the formulation containing triglyceride: glyceryl monooleate: water of 6:15:79 was selected as the drug delivery system. The release study indicated that the chitosan microspheres incorporated in glyceryl monooleate-based drug delivery system could prolong the release of doxycycline hyclate over a period of 48 hr and also followed square root of time kinetic. Additionally, the doxycycline hyclate loaded chitosan microspheres in glyceryl monooleate-based drug delivery system exhibited in vitro antimicrobial activity against Staphylococcus aureus ATCC 6538P, which was found in the periodontal pockets of patients with periodontitis