Title:Formulation and Evaluation of Canagliflozin Hemihydrate-loaded Nanostructured Lipid Carriers Using Box-Behnken Design: Physicochemical Characterization, Ex-vivo Analysis, and In-vivo Pharmacokinetics
Volume: 19
Issue: 4
Author(s): Ravindra Kamble, Mohit Kumar, Vaibhav Shinde, Chellampillai Bothiraja, Amol Muthal and Ashwin Mali*
Affiliation:
- Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune,
Maharashtra, India
Keywords:
Canagliflozin hemihydrate, nanostructured lipid carriers, Box-Behnken design, in-vitro release, ex-vivo permeability, bioavailability.
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 CGNloaded
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 in vitro drug release study in simulated intestinal
fluid (pH 6.8) showed significant CGN release from CGN-NLCs compared to CGN dispersion.
Further, the ex vivo intestinal permeability and in vivo 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.
