Hydrochlorothiazide is a diuretic drug and belongs to Biopharmaceutical Classification System class IV, having poor water solubility and low permeability, thus proportionally affecting its oral bioavailability and clinical efficacy. The final dosage forms play a significant role in influencing the rate and extent of absorption of class IV drugs from the gastrointestinal tract. In this work, nanoparticles of hydrochlorothiazide were produced and isolated using a supercritical CO2-assited top-spray coating process, with microcrystalline cellulose as carrier particles with hydrochlorothiazide yield between 60% and 80%. Solid state characterisation and morphological evaluation confirmed the presence of stable hydrochlorothiazide Form I nanoparticles within a size range of 300-500 nm. All the isolated nanoparticles presented a 3-fold increase in the dissolution rate of hydrochlorothiazide at gastric and intestinal pH. The increase in the dissolution rate was accompanied by significantly higher flux (similar to 2-4-fold) across a dialysis membrane compared to the as-received hydrochlorothiazide.