Use of thermodynamic parameters for design of double-walled microsphere fabrication methods.

Double-walled microspheres (DWMS), with drug localized to the particle core, present a promising route for control of drug release rates, for example, by varying the degradation rate or erosion mechanism of the polymer used to form the shell or the thickness of the shell. DWMS are often difficult to fabricate, however. Thermodynamic descriptions for polymer-polymer immiscibility, drug distribution between phases and polymer-solution spreading coefficient provide predictions of appropriate solvents and polymer concentrations for efficiently producing well-formed DWMS. As an example, thermodynamic parameters for a polyphosphoester/poly(D,L-lactide-co-glycolide) (PLG) DWMS system, encapsulating piroxicam, have been calculated and the predictions tested experimentally. Appropriate choices of solvents and initial polymer concentrations resulted in DWMS with the desired polyphosphoester shells and piroxicam located selectively in PLG cores.