DEVELOPMENT OF A BIODEGRADABLE INJECTIBLE INSITU FORMING IMPLANT

ABSTRACT

BACKGROUND: In situ forming implants are pharmaceutical liquid formulations that generate solid or semi-solid matrix depots following administration into the body. Solidification upon administration occurs via phase inversion/transformation as a result of pH, solvent or temperature changes. AIM: The aim of this study is to develop an injectable biodegradable insulin-loaded in situ forming implant for the sustained release of insulin intended for a more efficient management of insulin-dependent (Type 1) diabetes mellitus. METHOD: Chitosan (200mg) was dissolved in 8ml of 0.1M hydrochloric acid and left to stand for 24 hours to create a transparent solution. The chitosan solution was then sterilized by autoclaving at 120˚C for 15 minutes. The sterilized chitosan solution was then placed on an icepack held at 4˚C for 10 minutes and insulin dissolved in phosphate buffer solution (pH 7.4) was added to the solution with continuous stirring. Different concentrations of β-glycerophosphate solutions previously prepared and filtered through a 0.22 µm filter was added drop wise to the chitosan-insulin solution under stirring for 10 minutes. The final 10 ml solution containing 2% (w/v) chitosan and 5-14% (w/v) β-GP and maintained in a refrigerated condition of 4˚C was then used for further studies such as tests for pH measurement, turbidity, gelation time, gelation duration and in vitro insulin release kinetics. RESULTS: The results obtained from the study showed that pH values of the various implant formulations ranged from 5.0-5.5, turbidity values ranged from 375-630 NTU, the gelation time was found to be from 20-35 minutes, while the gelation duration ranged from 24 to 41.8 hours. The in vitro release studies shows that the implant exhibited an initial burst release ranging from 2.33% to 20.16%, due partly to the erosion of drug held at the surface of the matrix core. Maximum drug release after 72 hours ranged from 58.16%, to 74.69%. Release of the active drug from the matrix core was found to be diffusion-driven and follows a near- zero order kinetics (Higuchi). CONCLUSION: Insulin-loaded in situ forming implants were successfully developed locally which may provide a more efficient long term management of insulin dependent (Type 1) diabetes mellitus with improved patient compliance and a better therapeutic index than currently available injectable forms of the drug.