Solubility of simvastatin and lovastatin in mixtures of dichloromethane and supercritical carbon dioxide

Dong Joon Oh, Byung Chul Lee, Sung Joo Hwang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The phase behavior of simvastatin and lovastatin drugs, which are well-known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dichloromethane (DCM) and supercritical carbon dioxide (CO 2) was investigated to present a guideline for establishing operating conditions in the particle formation of the drugs by a supercritical antisolvent recrystallization process utilizing DCM as a solvent and CO 2 as an antisolvent. The solubilities of the statin drugs in the DCM + CO2 mixtures were determined as functions of temperature, pressure, and solvent composition by measuring the cloud points of the ternary mixtures of simvastatin + DCM + CO2 and lovastatin + DCM + CO2 at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility data of simvastatin and lovastatin are presented in the mixtures of DCM + CO2 with the DCM mole fractions between 0.18 and 0.34 at temperatures from 303.25 K to 333.25 K and at pressures up to about 45 MPa. The ternary mixtures exhibited the cloud point phase behavior of a typical lower critical solution temperature phase behavior. The solubility of the drug increased as the DCM composition in solution and the system pressure increased at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature. Simvastatin was more soluble than lovastatin in the mixtures of DCM + CO2.

Original languageEnglish
Pages (from-to)1273-1279
Number of pages7
JournalJournal of Chemical and Engineering Data
Volume52
Issue number4
DOIs
Publication statusPublished - 2007 Jul 1

Fingerprint

Lovastatin
Simvastatin
Methylene Chloride
Dichloromethane
Carbon Dioxide
Carbon dioxide
Solubility
Phase behavior
Pharmaceutical Preparations
Carbon Monoxide
Temperature
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Chemical analysis
Phase equilibria

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

@article{c9a3aae3cd4c42c988bce26ae3d34c5c,
title = "Solubility of simvastatin and lovastatin in mixtures of dichloromethane and supercritical carbon dioxide",
abstract = "The phase behavior of simvastatin and lovastatin drugs, which are well-known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dichloromethane (DCM) and supercritical carbon dioxide (CO 2) was investigated to present a guideline for establishing operating conditions in the particle formation of the drugs by a supercritical antisolvent recrystallization process utilizing DCM as a solvent and CO 2 as an antisolvent. The solubilities of the statin drugs in the DCM + CO2 mixtures were determined as functions of temperature, pressure, and solvent composition by measuring the cloud points of the ternary mixtures of simvastatin + DCM + CO2 and lovastatin + DCM + CO2 at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility data of simvastatin and lovastatin are presented in the mixtures of DCM + CO2 with the DCM mole fractions between 0.18 and 0.34 at temperatures from 303.25 K to 333.25 K and at pressures up to about 45 MPa. The ternary mixtures exhibited the cloud point phase behavior of a typical lower critical solution temperature phase behavior. The solubility of the drug increased as the DCM composition in solution and the system pressure increased at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature. Simvastatin was more soluble than lovastatin in the mixtures of DCM + CO2.",
author = "Oh, {Dong Joon} and Lee, {Byung Chul} and Hwang, {Sung Joo}",
year = "2007",
month = "7",
day = "1",
doi = "10.1021/je700019h",
language = "English",
volume = "52",
pages = "1273--1279",
journal = "Journal of Chemical & Engineering Data",
issn = "0021-9568",
publisher = "American Chemical Society",
number = "4",

}

Solubility of simvastatin and lovastatin in mixtures of dichloromethane and supercritical carbon dioxide. / Oh, Dong Joon; Lee, Byung Chul; Hwang, Sung Joo.

In: Journal of Chemical and Engineering Data, Vol. 52, No. 4, 01.07.2007, p. 1273-1279.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Solubility of simvastatin and lovastatin in mixtures of dichloromethane and supercritical carbon dioxide

AU - Oh, Dong Joon

AU - Lee, Byung Chul

AU - Hwang, Sung Joo

PY - 2007/7/1

Y1 - 2007/7/1

N2 - The phase behavior of simvastatin and lovastatin drugs, which are well-known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dichloromethane (DCM) and supercritical carbon dioxide (CO 2) was investigated to present a guideline for establishing operating conditions in the particle formation of the drugs by a supercritical antisolvent recrystallization process utilizing DCM as a solvent and CO 2 as an antisolvent. The solubilities of the statin drugs in the DCM + CO2 mixtures were determined as functions of temperature, pressure, and solvent composition by measuring the cloud points of the ternary mixtures of simvastatin + DCM + CO2 and lovastatin + DCM + CO2 at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility data of simvastatin and lovastatin are presented in the mixtures of DCM + CO2 with the DCM mole fractions between 0.18 and 0.34 at temperatures from 303.25 K to 333.25 K and at pressures up to about 45 MPa. The ternary mixtures exhibited the cloud point phase behavior of a typical lower critical solution temperature phase behavior. The solubility of the drug increased as the DCM composition in solution and the system pressure increased at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature. Simvastatin was more soluble than lovastatin in the mixtures of DCM + CO2.

AB - The phase behavior of simvastatin and lovastatin drugs, which are well-known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dichloromethane (DCM) and supercritical carbon dioxide (CO 2) was investigated to present a guideline for establishing operating conditions in the particle formation of the drugs by a supercritical antisolvent recrystallization process utilizing DCM as a solvent and CO 2 as an antisolvent. The solubilities of the statin drugs in the DCM + CO2 mixtures were determined as functions of temperature, pressure, and solvent composition by measuring the cloud points of the ternary mixtures of simvastatin + DCM + CO2 and lovastatin + DCM + CO2 at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility data of simvastatin and lovastatin are presented in the mixtures of DCM + CO2 with the DCM mole fractions between 0.18 and 0.34 at temperatures from 303.25 K to 333.25 K and at pressures up to about 45 MPa. The ternary mixtures exhibited the cloud point phase behavior of a typical lower critical solution temperature phase behavior. The solubility of the drug increased as the DCM composition in solution and the system pressure increased at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature. Simvastatin was more soluble than lovastatin in the mixtures of DCM + CO2.

UR - http://www.scopus.com/inward/record.url?scp=34547686077&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547686077&partnerID=8YFLogxK

U2 - 10.1021/je700019h

DO - 10.1021/je700019h

M3 - Article

VL - 52

SP - 1273

EP - 1279

JO - Journal of Chemical & Engineering Data

JF - Journal of Chemical & Engineering Data

SN - 0021-9568

IS - 4

ER -