Preparation and characterization of simvastatin/hydroxypropyl-β-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process

Seoung Wook Jun, Min Soo Kim, Jeong Soo Kim, Hee Jun Park, Sibeum Lee, Jong Soo Woo, Sung Joo Hwang

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

In the present study, the practically insoluble drug, simvastatin (SV), and its inclusion complex with hydroxypropyl β-cyclodextrin (HP-β-CD) prepared using supercritical antisolvent (SAS) process were investigated to improve the aqueous solubility and the dissolution rate of drug, thus enhancing its bioavailability. Inclusion complexation in aqueous solution and solid state was evaluated by the phase solubility diagram, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The phase solubility diagram with HP-β-CD was classified as AL-type at all temperatures investigated, indicating the formation of 1:1 stoichiometric inclusion complex. The apparent complexation constants (K1:1) calculated from phase solubility diagram were 774, 846 and 924 M-1 at 25, 37 and 45 ± 0.5 °C, respectively. No endothermic and characteristic diffraction peaks corresponding to SV was observed for the inclusion complex in DSC and PXRD. FT-IR study demonstrated the presence of intermolecular hydrogen bonds between SV and HP-β-CD in inclusion complex, resulting in the formation of amorphous form. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably increased in inclusion complex, compared with the physical mixture and drug alone. Moreover, SV/HP-β-CD inclusion complex performed better than SV in reducing total cholesterol and triglyceride levels. This could be primarily attributed to the improved solubility and dissolution associated with inclusion complex between drug and HP-β-CD. In conclusion, SAS process could be a useful method for the preparation of the inclusion complex of drug with HP-β-CD and its solubility, dissolution rate and hypolipidemic activity were significantly increased by complexation between SV and HP-β-CD.

Original languageEnglish
Pages (from-to)413-421
Number of pages9
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume66
Issue number3
DOIs
Publication statusPublished - 2007 Jun 1

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Simvastatin
Cyclodextrins
Solubility
Differential Scanning Calorimetry
Fourier Transform Infrared Spectroscopy
Pharmaceutical Preparations
Powders
X-Rays
Electron Scanning Microscopy
Biological Availability
Hydrogen
Triglycerides
Cholesterol
Temperature

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science

Cite this

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title = "Preparation and characterization of simvastatin/hydroxypropyl-β-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process",
abstract = "In the present study, the practically insoluble drug, simvastatin (SV), and its inclusion complex with hydroxypropyl β-cyclodextrin (HP-β-CD) prepared using supercritical antisolvent (SAS) process were investigated to improve the aqueous solubility and the dissolution rate of drug, thus enhancing its bioavailability. Inclusion complexation in aqueous solution and solid state was evaluated by the phase solubility diagram, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The phase solubility diagram with HP-β-CD was classified as AL-type at all temperatures investigated, indicating the formation of 1:1 stoichiometric inclusion complex. The apparent complexation constants (K1:1) calculated from phase solubility diagram were 774, 846 and 924 M-1 at 25, 37 and 45 ± 0.5 °C, respectively. No endothermic and characteristic diffraction peaks corresponding to SV was observed for the inclusion complex in DSC and PXRD. FT-IR study demonstrated the presence of intermolecular hydrogen bonds between SV and HP-β-CD in inclusion complex, resulting in the formation of amorphous form. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably increased in inclusion complex, compared with the physical mixture and drug alone. Moreover, SV/HP-β-CD inclusion complex performed better than SV in reducing total cholesterol and triglyceride levels. This could be primarily attributed to the improved solubility and dissolution associated with inclusion complex between drug and HP-β-CD. In conclusion, SAS process could be a useful method for the preparation of the inclusion complex of drug with HP-β-CD and its solubility, dissolution rate and hypolipidemic activity were significantly increased by complexation between SV and HP-β-CD.",
author = "Jun, {Seoung Wook} and Kim, {Min Soo} and Kim, {Jeong Soo} and Park, {Hee Jun} and Sibeum Lee and Woo, {Jong Soo} and Hwang, {Sung Joo}",
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Preparation and characterization of simvastatin/hydroxypropyl-β-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process. / Jun, Seoung Wook; Kim, Min Soo; Kim, Jeong Soo; Park, Hee Jun; Lee, Sibeum; Woo, Jong Soo; Hwang, Sung Joo.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 66, No. 3, 01.06.2007, p. 413-421.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Preparation and characterization of simvastatin/hydroxypropyl-β-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process

AU - Jun, Seoung Wook

AU - Kim, Min Soo

AU - Kim, Jeong Soo

AU - Park, Hee Jun

AU - Lee, Sibeum

AU - Woo, Jong Soo

AU - Hwang, Sung Joo

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N2 - In the present study, the practically insoluble drug, simvastatin (SV), and its inclusion complex with hydroxypropyl β-cyclodextrin (HP-β-CD) prepared using supercritical antisolvent (SAS) process were investigated to improve the aqueous solubility and the dissolution rate of drug, thus enhancing its bioavailability. Inclusion complexation in aqueous solution and solid state was evaluated by the phase solubility diagram, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The phase solubility diagram with HP-β-CD was classified as AL-type at all temperatures investigated, indicating the formation of 1:1 stoichiometric inclusion complex. The apparent complexation constants (K1:1) calculated from phase solubility diagram were 774, 846 and 924 M-1 at 25, 37 and 45 ± 0.5 °C, respectively. No endothermic and characteristic diffraction peaks corresponding to SV was observed for the inclusion complex in DSC and PXRD. FT-IR study demonstrated the presence of intermolecular hydrogen bonds between SV and HP-β-CD in inclusion complex, resulting in the formation of amorphous form. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably increased in inclusion complex, compared with the physical mixture and drug alone. Moreover, SV/HP-β-CD inclusion complex performed better than SV in reducing total cholesterol and triglyceride levels. This could be primarily attributed to the improved solubility and dissolution associated with inclusion complex between drug and HP-β-CD. In conclusion, SAS process could be a useful method for the preparation of the inclusion complex of drug with HP-β-CD and its solubility, dissolution rate and hypolipidemic activity were significantly increased by complexation between SV and HP-β-CD.

AB - In the present study, the practically insoluble drug, simvastatin (SV), and its inclusion complex with hydroxypropyl β-cyclodextrin (HP-β-CD) prepared using supercritical antisolvent (SAS) process were investigated to improve the aqueous solubility and the dissolution rate of drug, thus enhancing its bioavailability. Inclusion complexation in aqueous solution and solid state was evaluated by the phase solubility diagram, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The phase solubility diagram with HP-β-CD was classified as AL-type at all temperatures investigated, indicating the formation of 1:1 stoichiometric inclusion complex. The apparent complexation constants (K1:1) calculated from phase solubility diagram were 774, 846 and 924 M-1 at 25, 37 and 45 ± 0.5 °C, respectively. No endothermic and characteristic diffraction peaks corresponding to SV was observed for the inclusion complex in DSC and PXRD. FT-IR study demonstrated the presence of intermolecular hydrogen bonds between SV and HP-β-CD in inclusion complex, resulting in the formation of amorphous form. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably increased in inclusion complex, compared with the physical mixture and drug alone. Moreover, SV/HP-β-CD inclusion complex performed better than SV in reducing total cholesterol and triglyceride levels. This could be primarily attributed to the improved solubility and dissolution associated with inclusion complex between drug and HP-β-CD. In conclusion, SAS process could be a useful method for the preparation of the inclusion complex of drug with HP-β-CD and its solubility, dissolution rate and hypolipidemic activity were significantly increased by complexation between SV and HP-β-CD.

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