Simultaneous improvement of solubility and permeability by fabricating binary glassy materials of Talinolol with Naringin

Solid state characterization, in-vivo in-situ evaluation

Ainampudi Teja, Prashant B. Musmade, Amol B. Khade, Swapnil J. Dengale

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Abstract

The aim of the current study was to prepare binary amorphous forms of Talinolol (TLN) by using Naringin (NRG) as a stabilizing agent. The secondary objective of this study was to study the effect of P-gp inhibitor NRG on the P-gp probe drug TLN. The binary amorphous samples were prepared by quench cooling technique in the molar ratios TLN:NRG (1:1), TLN:NRG (1:2), TLN:NRG (2:1). The prepared samples were characterized by DSC, FTIR and XRD. Amorphicity of the prepared binary amorphous samples was confirmed by spotting diffuse halo in the diffractograms and further corroborated by detecting glass transition event (Tg) in the thermograms of the respective samples. The Tgs for all prepared systems were found above room temperature, the highest being 45.43 °C. The systems were found physically stable at 25 °C and 40 °C at dry conditions for 60 days. The temperature stability of prepared amorphous forms may be attributed to strong intermolecular hydrogen bond interaction between TLN and NRG, which was confirmed by Gordon-Taylor calculations and FTIR data. The solubility of TLN in amorphous form was increased by approximately 9-fold as compared to its crystalline counterpart. The in-vivo bioavailability study conducted on wistar rats demonstrated 5.4-fold increase in the AUC0-t value for TLN as compared to its crystalline counterpart. Further to learn the contribution of P-gp inhibition by NRG on the permeability of TLN, In-vitro single pass perfusion studies were conducted on the ileum of wistar rats. The permeability of TLN in rat ileum in the presence of NRG was significantly increased to 3.16 × 10-5 cm/s as compare to control value 2.48 × 10-5 cm/s. The current study demonstrated the ability of binary amorphous technology to simultaneously overcome both the BCS barriers i.e. solubility and permeability.

Original languageEnglish
Pages (from-to)234-244
Number of pages11
JournalEuropean Journal of Pharmaceutical Sciences
Volume78
DOIs
Publication statusPublished - 14-08-2015

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talinolol
Solubility
Permeability
Fourier Transform Infrared Spectroscopy
Ileum
Wistar Rats
naringin
Metrorrhagia

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

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title = "Simultaneous improvement of solubility and permeability by fabricating binary glassy materials of Talinolol with Naringin: Solid state characterization, in-vivo in-situ evaluation",
abstract = "The aim of the current study was to prepare binary amorphous forms of Talinolol (TLN) by using Naringin (NRG) as a stabilizing agent. The secondary objective of this study was to study the effect of P-gp inhibitor NRG on the P-gp probe drug TLN. The binary amorphous samples were prepared by quench cooling technique in the molar ratios TLN:NRG (1:1), TLN:NRG (1:2), TLN:NRG (2:1). The prepared samples were characterized by DSC, FTIR and XRD. Amorphicity of the prepared binary amorphous samples was confirmed by spotting diffuse halo in the diffractograms and further corroborated by detecting glass transition event (Tg) in the thermograms of the respective samples. The Tgs for all prepared systems were found above room temperature, the highest being 45.43 °C. The systems were found physically stable at 25 °C and 40 °C at dry conditions for 60 days. The temperature stability of prepared amorphous forms may be attributed to strong intermolecular hydrogen bond interaction between TLN and NRG, which was confirmed by Gordon-Taylor calculations and FTIR data. The solubility of TLN in amorphous form was increased by approximately 9-fold as compared to its crystalline counterpart. The in-vivo bioavailability study conducted on wistar rats demonstrated 5.4-fold increase in the AUC0-t value for TLN as compared to its crystalline counterpart. Further to learn the contribution of P-gp inhibition by NRG on the permeability of TLN, In-vitro single pass perfusion studies were conducted on the ileum of wistar rats. The permeability of TLN in rat ileum in the presence of NRG was significantly increased to 3.16 × 10-5 cm/s as compare to control value 2.48 × 10-5 cm/s. The current study demonstrated the ability of binary amorphous technology to simultaneously overcome both the BCS barriers i.e. solubility and permeability.",
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AU - Teja, Ainampudi

AU - Musmade, Prashant B.

AU - Khade, Amol B.

AU - Dengale, Swapnil J.

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N2 - The aim of the current study was to prepare binary amorphous forms of Talinolol (TLN) by using Naringin (NRG) as a stabilizing agent. The secondary objective of this study was to study the effect of P-gp inhibitor NRG on the P-gp probe drug TLN. The binary amorphous samples were prepared by quench cooling technique in the molar ratios TLN:NRG (1:1), TLN:NRG (1:2), TLN:NRG (2:1). The prepared samples were characterized by DSC, FTIR and XRD. Amorphicity of the prepared binary amorphous samples was confirmed by spotting diffuse halo in the diffractograms and further corroborated by detecting glass transition event (Tg) in the thermograms of the respective samples. The Tgs for all prepared systems were found above room temperature, the highest being 45.43 °C. The systems were found physically stable at 25 °C and 40 °C at dry conditions for 60 days. The temperature stability of prepared amorphous forms may be attributed to strong intermolecular hydrogen bond interaction between TLN and NRG, which was confirmed by Gordon-Taylor calculations and FTIR data. The solubility of TLN in amorphous form was increased by approximately 9-fold as compared to its crystalline counterpart. The in-vivo bioavailability study conducted on wistar rats demonstrated 5.4-fold increase in the AUC0-t value for TLN as compared to its crystalline counterpart. Further to learn the contribution of P-gp inhibition by NRG on the permeability of TLN, In-vitro single pass perfusion studies were conducted on the ileum of wistar rats. The permeability of TLN in rat ileum in the presence of NRG was significantly increased to 3.16 × 10-5 cm/s as compare to control value 2.48 × 10-5 cm/s. The current study demonstrated the ability of binary amorphous technology to simultaneously overcome both the BCS barriers i.e. solubility and permeability.

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