Preparation and Release Mechanism of Tacrolimus Oral Self-microemulsion Matrix Sustained-release Pellets

OBJECTIVE To prepare tacrolimus self-microemulsion matrix sustained-release pellets and investigate its the release mechanism. METHODS Optimal formulation of tacrolimus self-microemulsion was screened by the central composite design-response surface methodology, and then the tacrolimus self-microemulsion matrix sustained-release pellets were prepared by extrusion spheronization technology with microcrystalline cellulose(MCC) as adsorbent and filler, ethyl cellulose(EC) and stearic acid(SA) as skeleton materials, 5% hypromellose(HPMC) solution as adhesive. Tacrolimus self-microemulsion matrix sustained-release pellets were prepared, also, their dissolution profiles were investigated in vitro. RESULTS The optimal formula of tacrolimus self-microemulsion was Crodamol EO︰Solutol HS15︰Transcutol P=15%︰52.5%︰32.5%. The optimal formulation of the matrix sustained-release pellets was 45% MCC, 3∶2 of EC∶SA and 12 mL 5% HPMC solution. Tacrolimus self-microemulsion matrix sustained-release pellets met the in vitro release standards of commercially available tacrolimus sustained-release capsules. The release mechanism was a combination of erosion and diffusion. CONCLUSION The optimized formulation of microemulsion matrix sustained-release pellets is stable and feasible, and its in-vitro release fits the intended purpose.