Engineering Acyclovir-PVP coprecipitated microparticles obtained via different supercritical processes

Enhancing the release profile of poorly permeable drugs remains a major challenge in the pharmaceutical field. Coprecipitation with hydrophilic polymers offers a promising strategy to address this issue. The performance of drug delivery systems is largely influenced by particle size, shape, and distribution, critical factors for achieving controlled release and enhanced bioavailability. This study compares two micronization techniques, Supercritical Assisted Atomization (SAA) and Supercritical AntiSolvent (SAS) process, for the coprecipitation of the Acyclovir/Polyvinylpyrrolidone (PVP) system. The effects of polymer-to-drug ratio and total solute concentration were evaluated with respect to particle morphology and size distribution. The thermal behavior, drug loading efficiency, and release profile of the coprecipitates were also examined. Spherical microparticles with a D 50 ranging from 0.54 to 0.93 μm and a D 90 below 1.7 μm, were successfully produced via SAA, while SAS yielded smaller particles, with D 50 between 0.35 and 0.68 μm and D 90 lower than 1.06 μm, indicating high sample uniformity. UV-vis analysis revealed high acyclovir loading efficiencies for SAA microparticles (80-98%), with slightly lower values for SAS (74-82%). The in vitro release experiments showed that incorporating PVP markedly improved the drug’s release profile, supporting the effectiveness of supercritical processing methods in enhancing drug dissolution rate and potentially improving the bioavailability of compounds with permeability-limited absorption. • Acyclovir/PVP microparticles were produced via SAA and SAS techniques. • Particle size and morphology were tuned by varying solute concentration and ratio. • SAS produced smaller particles; SAA achieved higher drug loading efficiency. • Both methods significantly enhanced acyclovir’s dissolution rate in vitro. • Supercritical processes offer promising strategies for bioavailability improvement.