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image of Formulation and Evaluation of Canagliflozin Hemihydrate-loaded Nanostructured Lipid Carriers Using Box-Behnken Design: Physicochemical Characterization, Ex-vivo Analysis, and In-vivo Pharmacokinetics

Abstract

Introduction

Type 2 Diabetes Mellitus (T2DM) is a prevalent metabolic disease significantly impacting healthcare, characterized by increased blood glucose levels from the average level due to insulin resistance or a lack of insulin production. Canagliflozin Hemihydrate (CGN) is one of the drugs of choice in the treatment of the disease. However, CGN belongs to BCS class IV making it difficult to formulate into suitable dosage form. The purpose of the present study was to systematically optimize and explore the potential of Nanostructured Lipid Carriers (NLCs) to improve the solubility and bioavailability of CGN.

Methods

The emulsification and ultrasonication methods were used for the preparation of CGN-loaded NLCs (CGN-NLCs) by employing the Box-Behnken design. The solid lipid to liquid lipid ratio (X1), surfactant concentration (X2), and sonication time (X3) were independent variables, while particle size (Y1) and entrapment efficiency (EE) (Y2) were selected as dependent variables.

Results

The optimized batch showed particle size, zeta potential, Polydispersity Index (PDI), and EE of 221.2 ± 2.25 nm, -37 mV, 0.268 ± 0.024, and 98.2 ± 1.62%. The TEM revealed a homogeneous spherical shape of CGN-NLCs. Further, the DSC and XRD studies revealed reduced crystallinity with complete encapsulation of CGN in NLCs. The drug release study in simulated intestinal fluid (pH 6.8) showed significant CGN release from CGN-NLCs compared to CGN dispersion. Further, the intestinal permeability and pharmacokinetic study showed a 1.33-fold and 3.81-fold increase in permeability and bioavailability along with improvement in Cmax, Tmax, and [AUC]0–24 as compared to CGN dispersion.

Conclusion

Thus, the prepared CGN-NLCs could be a better viable option for T2DM with improved therapeutic efficacy.

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2025-04-11
2025-11-07

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Formulation and Evaluation of Canagliflozin Hemihydrate-loaded Nanostructured Lipid Carriers Using Box-Behnken Design: Physicochemical Characterization, Ex-vivo Analysis, and In-vivo Pharmacokinetics
Bentham Science Publishers ; https://doi.org/10.2174/0126673878343297250325060051
/content/journals/raddf/10.2174/0126673878343297250325060051
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  • Article Type:     Research Article
Keywords: Box-Behnken design ; ex-vivo permeability ; nanostructured lipid carriers ; in-vitro release ; Canagliflozin hemihydrate ; bioavailability

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