ONE POT DEVELOPMENT OF LIPID BASED QUERCETIN SPHERICAL AGGLOMERATES FOR BIOAVAILABILITY ENHANCEMENT: IN-VITRO AND IN-VIVO ASSESSMENTS

RAKESH MISHRA; SHWETA KULKARNI; AKASH AHER

doi:10.22159/ijap.2023v15i3.47266

Authors

RAKESH MISHRA Department of Pharmaceutics, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India https://orcid.org/0000-0002-8520-1412
SHWETA KULKARNI Department of Pharmaceutics, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India https://orcid.org/0000-0003-4350-1465
AKASH AHER Department of Pharmaceutics, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India https://orcid.org/0009-0003-6160-4377

DOI:

https://doi.org/10.22159/ijap.2023v15i3.47266

Keywords:

Quercetin, Spherical crystallization, Anti-solvent precipitation, Solubility, Permeability, Gelucire 43/01, lipid based agglomerates

Abstract

Objective: Quercetin, a wonder flavanoid despite numerous pharmacological actions, has limited clinical applications due to solubility and permeability issues and additionally having shorter biological half life. The goal of the current work was to design Quercetin lipid-based spherical crystals, to improve its oral bioavailability and sustain its in-vivo plasma levels.

Methods: An anti-solvent precipitation method was employed to prepare Quercetin spherical agglomerates using ethanol and distilled water as good and bad solvents respectively. As bridging liquid chloroform, dichloromethane, hexane and gelucire 43/01, compritol 888 as lipid carrier were screened. The drug to lipid polymer proportion and stirring speed effect were optimized by 3-level, 2-factor, experimental design. Numerical optimization function was employed to identify the optimum level of independent variables. Spectroscopic, micromeritic, surface morphology, size distribution, saturated solubility, in-vitro dissolution, in-vivo pharmackokinetic and stability studies were performed.

Results: Surface morphology studies indicated the agglomeration of Quercetin needle like fragments into spherical shape which further showed smooth surfaces due to entrapment of QC in lipid carrier. The spherical agglomerates of Quercetin showed four-fold improvement in aqueous solubility compared to pure drug and showed 92.13% release in 8 hours. The optimised formulation showed a 3.69-fold enhancement in relative bioavailability contrast to marketed preparation in an in-vivo pharmacokinetic analysis in male Wistar rats.

Conclusion: The obtained lipid-based spherical crystals of Quercetin with enhanced bioavailability could be effectively used for its various potential pharmacological applications. The designed system can also be utilized to deliver other phytochemicals with poor bioavailability due to limited solubility and permeability.

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Objective: Quercetin, a wonder flavanoid despite numerous pharmacological actions, has limited clinical applications due to solubility and permeability issues and additionally having shorter biological half life. The goal of the current work was to design Quercetin lipid-based spherical crystals, to improve its oral bioavailability and sustain its in-vivo plasma levels.

Methods: An anti-solvent precipitation method was employed to prepare Quercetin spherical agglomerates using ethanol and distilled water as good and bad solvents respectively. As bridging liquid chloroform, dichloromethane, hexane and gelucire 43/01, compritol 888 as lipid carrier were screened. The drug to lipid polymer proportion and stirring speed effect were optimized by 3-level, 2-factor, experimental design. Numerical optimization function was employed to identify the optimum level of independent variables. Spectroscopic, micromeritic, surface morphology, size distribution, saturated solubility, in-vitro dissolution, in-vivo pharmackokinetic and stability studies were performed.

Results: Surface morphology studies indicated the agglomeration of Quercetin needle like fragments into spherical shape which further showed smooth surfaces due to entrapment of QC in lipid carrier. The spherical agglomerates of Quercetin showed four-fold improvement in aqueous solubility compared to pure drug and showed 92.13% release in 8 hours. The optimised formulation showed a 3.69-fold enhancement in relative bioavailability contrast to marketed preparation in an in-vivo pharmacokinetic analysis in male Wistar rats.

Conclusion: The obtained lipid-based spherical crystals of Quercetin with enhanced bioavailability could be effectively used for its various potential pharmacological applications. The designed system can also be utilized to deliver other phytochemicals with poor bioavailability due to limited solubility and permeability.