Preparation of ibuprofen/EC-PVP sustained-release composite particles by supercritical CO₂ anti-solvent technology

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO₂ anti-solvent technology.  With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles.  The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination.  The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 ℃, crystallization pressure 12 MPa, PVP concentration 4 mg·mL⁻¹, and CO₂ velocity 3.5 L·min⁻¹.  Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 μm.  IR and DSC analysis showed that PVP might complex with EC.  The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect.  Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO₂ anti-solvent technology.