Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro , in silico , and in-vivo study

Abstract

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (−18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ’s antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.

Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1β Signaling Pathways

“…When examined using transmission electron microscopy (TEM), the ZnO-NPs appeared predominantly spherical, with particle sizes ranging from 50 to 70 nm. 19 , 35

Figure 3 ( A ) Determination of size and shape of green ZnO-NPs by TEM ( B ) FTIR spectra of the biosynthesized ZnO nanoparticles using Althaea Officinali s extract and ( C ) EDX of Zinc Oxide nanoparticles made by Althaea Officinalis .

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“…TNF-α, released early in the inflammatory response, plays a role in regulating the levels of IL-6. 19 , 48 , 49 Similarly, IL-1β is an alarm-phase cytokine that is associated with various clinical symptoms related to wounds. Macrophages release IL-10, a significant cytokine that reduces inflammation and modulates the immune system.…”

“…We evaluated the dynamic size of the particles in the solution by monitoring the electrophoretic mobility of the samples and using dynamic light scattering (DLS) at a 90-degree scattering angle and a 25-degree Celsius temperature. 18 , 19 …”

“…Eight months after the formulation was developed, the tests were carried out, with each test being run in triplicate using 30-gram samples. 18 , 19 …”

“…Additionally, the solution was supplemented with 0.005 mg/mL of bovine pituitary extract and 5 ng/mL of epidermal growth factor to the final concentration. 18 , 19 …”