Development of self-micellizing solid dispersion system employing amphipathic copolymer for the improvement of dissolution and oral bioavailability of cyclosporine A

The main objective of the present study is to develop a selfmicellizing solid dispersion(SMSD)system of cyclosporine A(CsA)using an amphiphilic copolymer,poly[MPC-co-BMA](pMB)to improve the biopharmaceutical properties of CsA(Fig.1A).Unlike conventional carrier compounds,pMB would perform the bifunctional ability as both polymeric carrier of solid dispersion system and solubilizer derived from a high micellizing property,which could be considered beneficial for the production of highly water soluble formulation of poorly water soluble compound[1].Improvement in the aqueous solubility has been believed to be a key consideration for acquiring potent pharmacological effects of BCS class II drug like CsA.

VISUALIZATION OF TURBULENT REACTIVE JET BY USING DIRECT NUMERICAL SIMULATION

Direct numerical simulation(DNS)of turbulent planar jet with a second-order chemical reaction(A+B→R)is performed to investigate the processes of mixing and chemical reactions in spatially developing turbulent free shear flows.Reactant A is premixed into the jet flow,and reactant B is premixed into the ambient flow.DNS is performed at three different Damk¨ohler numbers(Da=0.1,1,and 10).Damk¨ohler number is a ratio of a time scale of a flow to that of chemical reactions,and in this study,the large Da means a fast chemical reaction,and the small Da means a slow chemical reaction.The visualization of velocity field shows that the jet flow is developed by entraining the ambient fluid.The visualization of concentration of reactant A shows that concentration of reactant A for Da=1 and 10 becomes very small in the downstream region because the chemical reaction consumes the reactants and reactant A is diffused with the jet development.By comparison of the profiles of chemical reaction rate and concentration of product R,it is found that product R for Da=10 is produced by the chemical reaction at the interface between the jet and the ambient fluids and is diffused into the jet flow,whereas product R for Da=0.1 is produced in the jet flow after reactants A and B are well mixed.