Eudragit®-based injectable implants as bone-fracture barrier membranes and depot for controlled release of drugs

INTRODUCTION

Bone-fractures` healing can be influenced by secluding the fracture area to block access of inflammatory cells and surrounding tissue ingrowth. Eurdagit® RL-based barrier membranes can support adhesion, proliferation and osteoblastic differentiation of human mesenchymal stem cells¹ (hMSC), and we have recently demonstrated that these membranes significantly increase the extent of critical bone defect repair. The purpose of the present study was to develop an injectable dosage form seconding the previously demonstrated properties, for minor fractures where surgery is not indicated.

METHODS

Eudragit® polymers were dissolved with other additives in organic injectable solvents. The solidification was evaluated by injecting the solution in either an aqueous gel or liquid medium (PBS). Drug release was determined from in-situ solidified implants by medium-replacement technique to maintain sink conditions and remove the residues of the organic solvents.

RESULTS

Eudragit® polymers form relatively low viscosity solution in N-methylpyrrolidone (NMP) and some other injectable solvents. The phase separation character of the solutions upon contact with non-solvent can be influenced by addition of salts, notably calcium chloride. With additives, the polymeric solutions solidify immediately and retain shape under vortexing after

REFERENCES

1. Ada Grin, et al, In vitro study of a novel polymeric mesenchymal stem-cell coated membrane, J. DRUG DEL. SCI. TECH., 19 (4) 241-246 (2009)