POLYLACTIDE MICROPARTICLES PREPARED BY DOUBLE EMULSION EVAPORATION TECHNIQUE .1. EFFECT OF PRIMARY EMULSION STABILITY/

The process of microencapsulation of proteins by double emulsion/evapo ration in a matrix of polylactide (PLA) can be divided into three succ essive steps: first, an aqueous solution of the active compound is emu lsified into an organic solution of the hydrophobic coating polymer; s econd, this primary water-in-oil emulsion (w/o) is dispersed in water with formation of a double water-oil-water emulsion (w/o/w); third, th e organic solvent is removed with formation of solid microparticles. T his paper focuses on the effect of primary emulsion stability on the m orphology and properties of polylactide microparticles loaded with bov ine serum albumin (BSA) used as model drug. Depending on the stability of the primary emulsion, the internal structure of microparticles can be changed from a multivesicular to a matrix-like structure. Similarl y, the average porosity can be controlled in a range from a few tenths of a micron to ca. 20 to 30 microns. This morphology control could fi nd potential applications not only for the controlled drug delivery bu t also for the production of microporous particles intended for some s pecific applications, such as cell culture supports and chromatographi c matrices. Although, the interplay of several processing parameters ( polymer precipitation rate, polymer coprecipitation with interfacial c ompounds such as protein or surfactant, stirring rate,...) may not be disregarded, this study also indicated that a high loading of a hydrop hilic drug can only be expected from a stable primary emulsion. When t he stability of the primary emulsion is such as to prevent formation o f macropores (> 10 mu m), the total pore volume is close to that of th e originally dispersed aqueous drug solution.