Preliminary Evaluation of Polymer-Based Drug Composite Microparticle Production by Coacervate Desolvation with Supercritical Carbon Dioxide

Abstract

Drug/polymer particles incorporating phenytoin in polyvinylpyrrolidone (PVP) were prepared by desolvation of coacervates sprayed through an ultrasonic converging-diverging nozzle into supercritical (SC) carbon dioxide. The mean diameter of the particles produced and the crystallinity of phenytoin in the drug/polymer particles were evaluated with an Aerosizer DSP Particle Size Analyzer and powder X-ray diffraction, respectively. The drug release properties from the composite particles were evaluated using the USP 24 Method 2 rotational paddle method with UV detection. Spraying PVP in ethanol solution into SC carbon dioxide did not produce particles. However, a PVP coacervate in a mixture of ethanol and hexanes had lower viscosity than the solution, and spraying the coacervate into SC carbon dioxide through an ultrasonic converging-diverging nozzle produced micron sized particles. The use of a coacervate containing phenytoin and PVP likely led to increased interaction between drug and polymer and the composite particles contained amorphous phenytoin. The drug content in the composite particles approached theoretical values. The drug release rates from the composite particles produced from the coacervate were faster than those from particles produced by conventional SC methods and complete release was observed.