Enhancement of dissolution and bioavailability of ezetimibe by amorphous solid dispersion nanoparticles fabricated using supercritical antisolvent process

Eun Sol Ha, Jeong Soo Kim, In Hwan Baek, Sung Joo Hwang, Min Soo Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The purpose of the present study was to fabricate ezetimibe-hydroxypropyl cellulose (HPC) solid dispersion nanoparticles with enhanced dissolution and oral bioavailability using the supercritical antisolvent (SAS) process. We investigated the influence of SAS process parameters (pressure, temperature, and solute concentration) on the formation of ezetimibe-HPC solid dispersion particles. Physico-chemical properties of solid dispersion nanoparticles were characterized by scanning electron microscopy, differential scanning calorimeter, powder X-ray diffraction, a particle size analyzer, and measurements of the specific surface area. The mean particle size of ezetimibe-HPC solid dispersions could be controlled by the solute concentration. Physico-chemical analysis demonstrated that ezetimibe is amorphous in all solid dispersions. The dissolution rate of the solid dispersion nanoparticles was inversely proportional to the mean particle size. Ezetimibe administered in the form of 150.6-nm HPC solid dispersion nanoparticles demonstrated rapid dissolution of up to 95 % of the total amount within 10 min, as well as higher oral bioavailability than the drug introduced in the physical mixture. We also observed 3.2- and 2.0-fold increases in Cmax and AUC0→24 h values, respectively, for ezetimibe administered in the nanoparticle form compared to the drug within the physical mixture. Therefore, these results demonstrated that dissolution and oral absorption of ezetimibe can be enhanced by formulating it in the form of amorphous HPC solid dispersion nanoparticles manufactured using the SAS process.

Original languageEnglish
Pages (from-to)641-649
Number of pages9
JournalJournal of Pharmaceutical Investigation
Volume45
Issue number7
DOIs
Publication statusPublished - 2015 Dec 1

Fingerprint

Nanoparticles
Biological Availability
Particle Size
Ezetimibe
X-Ray Diffraction
Pharmaceutical Preparations
Electron Scanning Microscopy
Powders
hydroxypropylcellulose
Pressure
Temperature

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

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title = "Enhancement of dissolution and bioavailability of ezetimibe by amorphous solid dispersion nanoparticles fabricated using supercritical antisolvent process",
abstract = "The purpose of the present study was to fabricate ezetimibe-hydroxypropyl cellulose (HPC) solid dispersion nanoparticles with enhanced dissolution and oral bioavailability using the supercritical antisolvent (SAS) process. We investigated the influence of SAS process parameters (pressure, temperature, and solute concentration) on the formation of ezetimibe-HPC solid dispersion particles. Physico-chemical properties of solid dispersion nanoparticles were characterized by scanning electron microscopy, differential scanning calorimeter, powder X-ray diffraction, a particle size analyzer, and measurements of the specific surface area. The mean particle size of ezetimibe-HPC solid dispersions could be controlled by the solute concentration. Physico-chemical analysis demonstrated that ezetimibe is amorphous in all solid dispersions. The dissolution rate of the solid dispersion nanoparticles was inversely proportional to the mean particle size. Ezetimibe administered in the form of 150.6-nm HPC solid dispersion nanoparticles demonstrated rapid dissolution of up to 95 {\%} of the total amount within 10 min, as well as higher oral bioavailability than the drug introduced in the physical mixture. We also observed 3.2- and 2.0-fold increases in Cmax and AUC0→24 h values, respectively, for ezetimibe administered in the nanoparticle form compared to the drug within the physical mixture. Therefore, these results demonstrated that dissolution and oral absorption of ezetimibe can be enhanced by formulating it in the form of amorphous HPC solid dispersion nanoparticles manufactured using the SAS process.",
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Enhancement of dissolution and bioavailability of ezetimibe by amorphous solid dispersion nanoparticles fabricated using supercritical antisolvent process. / Ha, Eun Sol; Kim, Jeong Soo; Baek, In Hwan; Hwang, Sung Joo; Kim, Min Soo.

In: Journal of Pharmaceutical Investigation, Vol. 45, No. 7, 01.12.2015, p. 641-649.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Enhancement of dissolution and bioavailability of ezetimibe by amorphous solid dispersion nanoparticles fabricated using supercritical antisolvent process

AU - Ha, Eun Sol

AU - Kim, Jeong Soo

AU - Baek, In Hwan

AU - Hwang, Sung Joo

AU - Kim, Min Soo

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AB - The purpose of the present study was to fabricate ezetimibe-hydroxypropyl cellulose (HPC) solid dispersion nanoparticles with enhanced dissolution and oral bioavailability using the supercritical antisolvent (SAS) process. We investigated the influence of SAS process parameters (pressure, temperature, and solute concentration) on the formation of ezetimibe-HPC solid dispersion particles. Physico-chemical properties of solid dispersion nanoparticles were characterized by scanning electron microscopy, differential scanning calorimeter, powder X-ray diffraction, a particle size analyzer, and measurements of the specific surface area. The mean particle size of ezetimibe-HPC solid dispersions could be controlled by the solute concentration. Physico-chemical analysis demonstrated that ezetimibe is amorphous in all solid dispersions. The dissolution rate of the solid dispersion nanoparticles was inversely proportional to the mean particle size. Ezetimibe administered in the form of 150.6-nm HPC solid dispersion nanoparticles demonstrated rapid dissolution of up to 95 % of the total amount within 10 min, as well as higher oral bioavailability than the drug introduced in the physical mixture. We also observed 3.2- and 2.0-fold increases in Cmax and AUC0→24 h values, respectively, for ezetimibe administered in the nanoparticle form compared to the drug within the physical mixture. Therefore, these results demonstrated that dissolution and oral absorption of ezetimibe can be enhanced by formulating it in the form of amorphous HPC solid dispersion nanoparticles manufactured using the SAS process.

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