Fabrication, solid state characterization and bioavailability assessment of stable binary amorphous phases of Ritonavir with Quercetin

Swapnil J. Dengale, Syed Sajjad Hussen, B. S.M. Krishna, Prashant B. Musmade, G. Gautham Shenoy, Krishnamurthy Bhat

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Abstract

In the current study, Quercetin (QRT) was characterized for thermodynamic and kinetic parameters and found as an excellent glass former. QRT was paired with Ritonavir (RTV) (BCS class-IV antiretroviral) to form stable amorphous form and pharmacologically relevant combination. Binary amorphous forms of RTV and QRT in molar ratios 1:1, 1:2 and 2:1 were prepared by solvent evaporation technique and characterized by XRPD, DSC and FTIR. The prepared binary phases were found to become amorphous after solvent evaporation which was confirmed by disappearance of crystalline peaks from X-ray diffractograms and detecting single Tg in DSC studies. The physical stability studies at 40°C for 90 days found RTV:QRT 1:2 and RTV:QRT 2:1 phases stable, while trace crystallinity was detected for 1:1 M ratio. The temperature stability of RTV:QRT 1:2 and RTV:QRT 2:1 amorphous forms can be attributed to phase solubility of both components where the drug in excess acts as a crystallization inhibitor. Except for RTV:QRT 1:2 ratio, there was no evidence of intermolecular interactions between two components. Almost 5 fold increase in the saturation solubility was achieved for RTV, compared to crystalline counterpart. While for QRT, the solubility advantage was not achieved. In vivo oral bioavailability study was conducted for 1:2 binary amorphous form by using pure RTV as a control. Cmax was improved by 1.26 fold and Tmax was decreased by 2 h after comparing with control indicating improved absorption. However no significant enhancement of oral bioavailability (1.12 fold after comparing with control) was found for RTV.

Original languageEnglish
Pages (from-to)329-338
Number of pages10
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume89
DOIs
Publication statusPublished - 2015

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Ritonavir
Quercetin
Biological Availability
Solubility
Fourier Transform Infrared Spectroscopy
Crystallization
Thermodynamics
Glass
X-Rays

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science

Cite this

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title = "Fabrication, solid state characterization and bioavailability assessment of stable binary amorphous phases of Ritonavir with Quercetin",
abstract = "In the current study, Quercetin (QRT) was characterized for thermodynamic and kinetic parameters and found as an excellent glass former. QRT was paired with Ritonavir (RTV) (BCS class-IV antiretroviral) to form stable amorphous form and pharmacologically relevant combination. Binary amorphous forms of RTV and QRT in molar ratios 1:1, 1:2 and 2:1 were prepared by solvent evaporation technique and characterized by XRPD, DSC and FTIR. The prepared binary phases were found to become amorphous after solvent evaporation which was confirmed by disappearance of crystalline peaks from X-ray diffractograms and detecting single Tg in DSC studies. The physical stability studies at 40°C for 90 days found RTV:QRT 1:2 and RTV:QRT 2:1 phases stable, while trace crystallinity was detected for 1:1 M ratio. The temperature stability of RTV:QRT 1:2 and RTV:QRT 2:1 amorphous forms can be attributed to phase solubility of both components where the drug in excess acts as a crystallization inhibitor. Except for RTV:QRT 1:2 ratio, there was no evidence of intermolecular interactions between two components. Almost 5 fold increase in the saturation solubility was achieved for RTV, compared to crystalline counterpart. While for QRT, the solubility advantage was not achieved. In vivo oral bioavailability study was conducted for 1:2 binary amorphous form by using pure RTV as a control. Cmax was improved by 1.26 fold and Tmax was decreased by 2 h after comparing with control indicating improved absorption. However no significant enhancement of oral bioavailability (1.12 fold after comparing with control) was found for RTV.",
author = "Dengale, {Swapnil J.} and Hussen, {Syed Sajjad} and Krishna, {B. S.M.} and Musmade, {Prashant B.} and {Gautham Shenoy}, G. and Krishnamurthy Bhat",
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T1 - Fabrication, solid state characterization and bioavailability assessment of stable binary amorphous phases of Ritonavir with Quercetin

AU - Dengale, Swapnil J.

AU - Hussen, Syed Sajjad

AU - Krishna, B. S.M.

AU - Musmade, Prashant B.

AU - Gautham Shenoy, G.

AU - Bhat, Krishnamurthy

PY - 2015

Y1 - 2015

N2 - In the current study, Quercetin (QRT) was characterized for thermodynamic and kinetic parameters and found as an excellent glass former. QRT was paired with Ritonavir (RTV) (BCS class-IV antiretroviral) to form stable amorphous form and pharmacologically relevant combination. Binary amorphous forms of RTV and QRT in molar ratios 1:1, 1:2 and 2:1 were prepared by solvent evaporation technique and characterized by XRPD, DSC and FTIR. The prepared binary phases were found to become amorphous after solvent evaporation which was confirmed by disappearance of crystalline peaks from X-ray diffractograms and detecting single Tg in DSC studies. The physical stability studies at 40°C for 90 days found RTV:QRT 1:2 and RTV:QRT 2:1 phases stable, while trace crystallinity was detected for 1:1 M ratio. The temperature stability of RTV:QRT 1:2 and RTV:QRT 2:1 amorphous forms can be attributed to phase solubility of both components where the drug in excess acts as a crystallization inhibitor. Except for RTV:QRT 1:2 ratio, there was no evidence of intermolecular interactions between two components. Almost 5 fold increase in the saturation solubility was achieved for RTV, compared to crystalline counterpart. While for QRT, the solubility advantage was not achieved. In vivo oral bioavailability study was conducted for 1:2 binary amorphous form by using pure RTV as a control. Cmax was improved by 1.26 fold and Tmax was decreased by 2 h after comparing with control indicating improved absorption. However no significant enhancement of oral bioavailability (1.12 fold after comparing with control) was found for RTV.

AB - In the current study, Quercetin (QRT) was characterized for thermodynamic and kinetic parameters and found as an excellent glass former. QRT was paired with Ritonavir (RTV) (BCS class-IV antiretroviral) to form stable amorphous form and pharmacologically relevant combination. Binary amorphous forms of RTV and QRT in molar ratios 1:1, 1:2 and 2:1 were prepared by solvent evaporation technique and characterized by XRPD, DSC and FTIR. The prepared binary phases were found to become amorphous after solvent evaporation which was confirmed by disappearance of crystalline peaks from X-ray diffractograms and detecting single Tg in DSC studies. The physical stability studies at 40°C for 90 days found RTV:QRT 1:2 and RTV:QRT 2:1 phases stable, while trace crystallinity was detected for 1:1 M ratio. The temperature stability of RTV:QRT 1:2 and RTV:QRT 2:1 amorphous forms can be attributed to phase solubility of both components where the drug in excess acts as a crystallization inhibitor. Except for RTV:QRT 1:2 ratio, there was no evidence of intermolecular interactions between two components. Almost 5 fold increase in the saturation solubility was achieved for RTV, compared to crystalline counterpart. While for QRT, the solubility advantage was not achieved. In vivo oral bioavailability study was conducted for 1:2 binary amorphous form by using pure RTV as a control. Cmax was improved by 1.26 fold and Tmax was decreased by 2 h after comparing with control indicating improved absorption. However no significant enhancement of oral bioavailability (1.12 fold after comparing with control) was found for RTV.

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JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

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