The robustness and flexibility of an emulsion solvent evaporation method to prepare pH-responsive microparticles

Abstract

A microparticle preparation method based on an emulsion of ethanol in liquid paraffin stabilised using sorbitan sesquioleate which produces enteric microparticles of excellent morphology, size and pH-sensitive drug release was assessed for its robustness to changes in formulation and processing parameters. Prednisolone and methacrylic acid and methyl methacrylate copolymer (Eudragit S) were the drug and polymer of choice. Emulsion solvent evaporation procedures are notoriously sensitive to changes in methodology and so emulsion stirring speed, drug loading, polymer concentration and surfactant (emulsifier) concentration were varied; microparticle size, encapsulation efficiency, yield and in vitro dissolution behaviour were assessed. The yield and encapsulation efficiency remained high under all stirring speeds, drug loadings and polymer concentrations. This suggests that the process is flexible and efficiency can be maintained. Surfactant concentration was an important parameter; above an optimum concentration resulted in poorly formed particles. All processing parameters affected particle size but this did not alter the acid resistance of the microparticles. At high pH values the smaller microparticles had the most rapid drug release. In conclusion, the microparticle preparation method was resistant to many changes in processing, although surfactant concentration was critical. Manipulation of particle size can be used to modify the drug release profiles without adversely affecting the gastro-resistant properties of these pH-responsive microparticles.