Verma et al – Production of Hydrochlorothiazide Nanoparticles with Increased Permeability Using Top-Spray Coating Process – Journal of Supercritical Fluids, Vol. 192, January 2023, 105788

Vivek Verma*, Pratikkumar Patel, Kevin M. Ryan, Sarah Hudson and Luis Padrela*

SSPC Research Centre, Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland
Corresponding Author: V. Verma (, L. Padrela (

Received 3 June 2022, Revised 26 October 2022, Accepted 27 October 2022, Available online 30 October 2022, Version of Record 15 November 2022.
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  • HTZ nanoparticles produced using supercritical CO2-assisted fluidised bed process.
  • High yield collection obtained for HTZ nanoparticles between 60% and 80%.
  • HTZ nanoparticles of 300–500 nm coated onto MCC carrier particles.
  • The dissolution rate of HTZ in the produced nanoformulation was improved by 3-fold.
  • The flux of dissolved drug was improved by 2–4-fold across a dialysis membrane.


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 (∼2–4-fold) across a dialysis membrane compared to the as-received hydrochlorothiazide.

Graphical Abstract
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