ABSTRACT
BACKGROUND:Novel drug delivery systems are new approaches that combine innovative development, formulations, new technologies and novel methodologies for delivering pharmaceutical products into the body to safely achieve its desired pharmacological effects. In situ forming implants (ISFU) are an attractive model of novel drug delivery. They are injected as solutions and upon reaching the body, transform into a gel or solid implant via techniques that trigger this transformation. These techniques include temperature variation, pH, cross-linking, ion exchange etc.
AIM: The aim of this study is to design and formulate an in situ forming implant system of insulin for the management of insulin dependent (Type 1) diabetes mellitus.
METHOD: The solvent exchange/solvent removal technique was employed in the formulation. Varying concentrations of polymeric solutions ranging from 8-14% (w/v) of polylactic glycolic acid (PLGA) were prepared by dissolving the copolymer in sufficient quantity of N-methyl-pyrollidine at 50˚C, and then cooled to 15˚C in an ice pack. The required amount of the drug (insulin) dissolved in phosphate buffer solution (pH 4)was added and gently dispersed within the polymeric solution with stirring at 200 rpm for 30 minutes using a magnetic stirrer. The resulting solution was then sterilized by passing through a bacterial filter and stored in an air-tight container at 4-8˚C in a refrigerator. It was then used for further studies such as tests for pH, turbidity, gelation time, gelation duration and in vitro drug release kinetics.
RESULTS: The results obtained from the study showed that pH values of the various implant formulations ranged from 6.0 to 6.5, turbidity values ranged from 380 to 860 NTU, the gelation time was found to be from 10 to 18 minutes, while the gelation duration ranged from 10 to 48 hours. The in vitro release studies shows that the implant exhibited an initial burst release ranging from 6.83% to 28.67%, due partly to the erosion of drug held at the surface of the matrix core. Maximum drug release after 72 hours ranged from 62.66% to 77.63%. 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 injectable in situ forming implants can provide long-term management of insulin dependent (Type 1) diabetes mellitus with an improved patient compliance. The possibility of obtaining a controlled release from this delivery system can result in a better therapeutic index compared to currently available injectable forms of the drug as it helps to eliminate peak and troughs characteristics usually obtainable from other forms. It therefore offers a steady state plasma concentration over a prolonged period of time.
