Influence of Preparation Methods on Physicochemical and Pharmacokinetic Properties of Co-amorphous Formulations

The Case of Co-amorphous Atorvastatin: Naringin

Athira Nair, Raghava Varma, Karthik Gourishetti, Krishnamurthy Bhat, Swapnil Dengale

Research output: Contribution to journalArticle

Abstract

Purpose: The goal of the study was to investigate the influence of processing methods on the physicochemical and pharmacokinetic properties of co-amorphous materials. Methods: Co-amorphous formulations of atorvastatin (ATV) and naringin (NRG) in the molar ratio 1:1 were prepared by quench cooling (ANQC), solvent evaporation (ANSE), and ball milling (ANBM) and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (XRPD), and Fourier transform infrared spectroscopy (FTIR). Further, the performance of prepared co-amorphous formulations was evaluated in vitro and in vivo. Results: All processing methods yielded homogeneous co-amorphous formulation, which was confirmed by single glass transition (Tg) event and diffuse halo in DSC and XRPD, respectively. Irrespective of processing method employed, all co-amorphous formulations were found stable at 30 °C for 90 days in dry conditions (under vacuum). Significant improvement in the solubility of ATV was observed in ANQC and ANSE co-amorphous formulations, highest being 56-fold for the later. ATV from ANSE formulation showed highest drug release (97%), while surprisingly ANQC showed significantly lower ATV release as compared to the physical mixture. Amongst three preparation methods, solubility advantage of ANSE could translate into efficacious pharmacokinetic parameters, where the improvement in ATV exposure (AUC 0-t) and plasma concentration (Cmax) were found 4.5-fold and 7-fold, respectively, as compared to the physical mixture. Conclusion: It was concluded that the preparation methods of co-amorphous formulations have a profound effect on physical properties like stability, physicochemical properties like solubility, dissolution rate, and pharmacokinetic properties like AUC and Cmax.

Original languageEnglish
JournalJournal of Pharmaceutical Innovation
DOIs
Publication statusPublished - 01-01-2019

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Pharmacokinetics
Solubility
Differential Scanning Calorimetry
Area Under Curve
Fourier Transform Infrared Spectroscopy
Vacuum
Powders
Glass
naringin
Atorvastatin Calcium
X-Rays

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

Cite this

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title = "Influence of Preparation Methods on Physicochemical and Pharmacokinetic Properties of Co-amorphous Formulations: The Case of Co-amorphous Atorvastatin: Naringin",
abstract = "Purpose: The goal of the study was to investigate the influence of processing methods on the physicochemical and pharmacokinetic properties of co-amorphous materials. Methods: Co-amorphous formulations of atorvastatin (ATV) and naringin (NRG) in the molar ratio 1:1 were prepared by quench cooling (ANQC), solvent evaporation (ANSE), and ball milling (ANBM) and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (XRPD), and Fourier transform infrared spectroscopy (FTIR). Further, the performance of prepared co-amorphous formulations was evaluated in vitro and in vivo. Results: All processing methods yielded homogeneous co-amorphous formulation, which was confirmed by single glass transition (Tg) event and diffuse halo in DSC and XRPD, respectively. Irrespective of processing method employed, all co-amorphous formulations were found stable at 30 °C for 90 days in dry conditions (under vacuum). Significant improvement in the solubility of ATV was observed in ANQC and ANSE co-amorphous formulations, highest being 56-fold for the later. ATV from ANSE formulation showed highest drug release (97{\%}), while surprisingly ANQC showed significantly lower ATV release as compared to the physical mixture. Amongst three preparation methods, solubility advantage of ANSE could translate into efficacious pharmacokinetic parameters, where the improvement in ATV exposure (AUC 0-t) and plasma concentration (Cmax) were found 4.5-fold and 7-fold, respectively, as compared to the physical mixture. Conclusion: It was concluded that the preparation methods of co-amorphous formulations have a profound effect on physical properties like stability, physicochemical properties like solubility, dissolution rate, and pharmacokinetic properties like AUC and Cmax.",
author = "Athira Nair and Raghava Varma and Karthik Gourishetti and Krishnamurthy Bhat and Swapnil Dengale",
year = "2019",
month = "1",
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language = "English",
journal = "Journal of Pharmaceutical Innovation",
issn = "1872-5120",
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T1 - Influence of Preparation Methods on Physicochemical and Pharmacokinetic Properties of Co-amorphous Formulations

T2 - The Case of Co-amorphous Atorvastatin: Naringin

AU - Nair, Athira

AU - Varma, Raghava

AU - Gourishetti, Karthik

AU - Bhat, Krishnamurthy

AU - Dengale, Swapnil

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: The goal of the study was to investigate the influence of processing methods on the physicochemical and pharmacokinetic properties of co-amorphous materials. Methods: Co-amorphous formulations of atorvastatin (ATV) and naringin (NRG) in the molar ratio 1:1 were prepared by quench cooling (ANQC), solvent evaporation (ANSE), and ball milling (ANBM) and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (XRPD), and Fourier transform infrared spectroscopy (FTIR). Further, the performance of prepared co-amorphous formulations was evaluated in vitro and in vivo. Results: All processing methods yielded homogeneous co-amorphous formulation, which was confirmed by single glass transition (Tg) event and diffuse halo in DSC and XRPD, respectively. Irrespective of processing method employed, all co-amorphous formulations were found stable at 30 °C for 90 days in dry conditions (under vacuum). Significant improvement in the solubility of ATV was observed in ANQC and ANSE co-amorphous formulations, highest being 56-fold for the later. ATV from ANSE formulation showed highest drug release (97%), while surprisingly ANQC showed significantly lower ATV release as compared to the physical mixture. Amongst three preparation methods, solubility advantage of ANSE could translate into efficacious pharmacokinetic parameters, where the improvement in ATV exposure (AUC 0-t) and plasma concentration (Cmax) were found 4.5-fold and 7-fold, respectively, as compared to the physical mixture. Conclusion: It was concluded that the preparation methods of co-amorphous formulations have a profound effect on physical properties like stability, physicochemical properties like solubility, dissolution rate, and pharmacokinetic properties like AUC and Cmax.

AB - Purpose: The goal of the study was to investigate the influence of processing methods on the physicochemical and pharmacokinetic properties of co-amorphous materials. Methods: Co-amorphous formulations of atorvastatin (ATV) and naringin (NRG) in the molar ratio 1:1 were prepared by quench cooling (ANQC), solvent evaporation (ANSE), and ball milling (ANBM) and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (XRPD), and Fourier transform infrared spectroscopy (FTIR). Further, the performance of prepared co-amorphous formulations was evaluated in vitro and in vivo. Results: All processing methods yielded homogeneous co-amorphous formulation, which was confirmed by single glass transition (Tg) event and diffuse halo in DSC and XRPD, respectively. Irrespective of processing method employed, all co-amorphous formulations were found stable at 30 °C for 90 days in dry conditions (under vacuum). Significant improvement in the solubility of ATV was observed in ANQC and ANSE co-amorphous formulations, highest being 56-fold for the later. ATV from ANSE formulation showed highest drug release (97%), while surprisingly ANQC showed significantly lower ATV release as compared to the physical mixture. Amongst three preparation methods, solubility advantage of ANSE could translate into efficacious pharmacokinetic parameters, where the improvement in ATV exposure (AUC 0-t) and plasma concentration (Cmax) were found 4.5-fold and 7-fold, respectively, as compared to the physical mixture. Conclusion: It was concluded that the preparation methods of co-amorphous formulations have a profound effect on physical properties like stability, physicochemical properties like solubility, dissolution rate, and pharmacokinetic properties like AUC and Cmax.

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