# Overcoming Solubility Challenges: Micronization of Berberine Using the GAS Antisolvent Technique

**Authors:** Guilherme S. B. Sakata, Patricia Viera de Oliveira, Gean Pablo S. Aguiar, J. Vladimir Oliveira, Marcelo Lanza

PMC · DOI: 10.1021/acsomega.5c01675 · ACS Omega · 2025-10-22

## TL;DR

This paper shows how to improve the solubility of berberine, a herbal compound, using a new technique to make it more effective for medical use.

## Contribution

The study introduces the GAS antisolvent technique for micronizing berberine, enhancing its solubility and dissolution rate.

## Key findings

- Berberine particles were reduced to 6.34 μm using the GAS technique.
- Dissolution rate increased by up to 18% after micronization.
- Functional groups remained intact, and melting temperature increased.

## Abstract

Berberine is a compound
widely used in Chinese herbal medicine.
It can potentially treat diabetes, cholesterol, and mental illnesses
and has antimicrobial effects. However, its application is limited
due to its low solubility in water, thus limiting its bioavailability.
Micronization techniques are used to increase the surface area and
improve the dissolution rate. The micronized particles were produced
using the antisolvent GAS technique at a temperature of 35 °C
and 80 bar. A solubility study with acetone, dichloromethane, ethanol,
methanol, 1-butanol, and 1-propanol was carried out. Fourier-transform
infrared spectroscopy analysis confirmed the preservation of functional
groups. Additionally, a reduction in particle size to 6.34 μm
was achieved, which contributed to an increase of up to 18% in cumulative
dissolution. Furthermore, an increase in melting temperature and dissolution
rate was observed. Thus, the antisolvent GAS technique proves to be
an efficient approach for particle micronization and the consequent
enhancement of dissolution properties.

## Linked entities

- **Chemicals:** Berberine (PubChem CID 2353), acetone (PubChem CID 180), dichloromethane (PubChem CID 6344), ethanol (PubChem CID 702), methanol (PubChem CID 887), 1-butanol (PubChem CID 263), 1-propanol (PubChem CID 1031)
- **Diseases:** diabetes (MONDO:0005015)

## Full-text entities

- **Diseases:** diabetes (MESH:D003920), mental illnesses (MESH:D001523)
- **Chemicals:** cholesterol (MESH:D002784), ethanol (MESH:D000431), GAS (MESH:D005708), acetone (MESH:D000096), methanol (MESH:D000432), water (MESH:D014867), dichloromethane (MESH:D008752), Berberine (MESH:D001599), 1-butanol (MESH:D020001), 1-propanol (MESH:D000433)

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12593154/full.md

## References

68 references — full list in the complete paper: https://tomesphere.com/paper/PMC12593154/full.md

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Source: https://tomesphere.com/paper/PMC12593154