Folic acid–PVP nanostructured composite microparticles by supercritical antisolvent precipitation

• Coprecipitation of spherical PVP + folic acid microparticles was obtained using SAS.
• Nanoparticles (down to 50 nm), sub-microparticles (0.29–0.65 μm) and microparticles (0.8–3.8 μm) were obtained.
• Crystallinity, drug effective loading, drug release profiles and FA degradation were measured.
• Folic acid dissolution rate was significantly increased in the coprecipitated powders.

In this work, supercritical antisolvent (SAS) precipitation was proposed for the production of polyvinylpyrrolidone (PVP)–folic acid (FA) microspheres, to test the applicability of this technique to the production of coprecipitates of biomedical interest with improved bioavailability. The effect of SAS operating parameters, such as polymer/drug ratio, pressure, temperature and concentration was investigated to identify successful process conditions. We obtained different kind of precipitates: nanoparticles with a mean diameter down to 50 nm, sub-microparticles with a mean diameter in the range 0.29–0.65 μm and microparticles in the range 0.8–3.8 μm. These powders were characterized to determine drug effective loading and drug release profiles and to measure FA degradation. These analyses revealed that SAS process allowed the production of PVP–FA coprecipitates only in specific ranges of SAS process parameters and in the case of microparticles production. The drug dissolution rate of the PVP + FA coprecipitates in a phosphate buffered saline solution (PBS) was about 20 times faster than the one of unprocessed FA. Moreover, SAS process had no significant detrimental effect on the stability of the vitamin. We tried to explain the precipitation mechanisms producing the observed morphologies and the large improvement of the FA dissolution rate, when it was encapsulated in PVP microparticles.