Solid formulations of liquid biologically active agents such as propofol

摘要

Disclosed is a solid product suitable for reconstitution to an essentially clear, stable aqueous solution, comprising an intimate mixture of at least one amphiphilic copolymer which includes a hydrophilic part that comprises at least one member selected from the group consisting of poly(N-vinylpyrrolidone), poly(N-2-hydroxypropylmethacrylamide), poly(2-ethyl-2oxazoline), poly(glycidol), poly(2-hydroxyethylmethacrylate), poly(vinylalcohol), polymethacrylic acid derivatives, poly(vinylpyridinium), poly((ammoniumalkyl)methacrylate), poly((aminoalkyl)methacrylate) and combinations and derivatives thereof, and at least one liquid biologically active agent such as propofol loaded within said amphiphilic copolymer, in such a manner that said liquid biologically active agent is intimately associated with said amphiphilic copolymer in a substantially solid product; The aqueous solution which is produced by reconstituting the solid contains the biologically active agent as stable nanodispersions or micelles and is substantially free of organic solvent. Also disclosed is an apparatus and a process for preparing the solid product comprising forming an aqueous solution of at least one linear, branched or star-shaped amphiphilic copolymer, under conditions to achieve micelle or nanodispersion formation; adding the liquid biologically active agent to the solution to form a second mixture; and treating said second mixture under conditions effective to remove water, while forming a substantially solid product.