Objective: The aim of the present investigation entails the development of solid SMEDDS
for improving the oral bioavailability of canagliflozin using porous carriers. The previous patent
(WO2017046730A1) was based on enhanced solubility of canagliflozin through co-crystal formation.
Methods: Preconcentrates were prepared by employing Lauroglycol (80 mg), Tween 80 (300 mg) and
Transcutol P (120 mg) and successfully adsorbed onto various hydrophilic and hydrophobic carriers.
The prepared solid SMEDDS were characterized for various parameters to determine the optimized
formulation. In vitro, ex vivo and in vivo studies were carried out to determine drug release kinetics,
permeation and absorption rate, respectively. Stability of the formulation was investigated at 45°C/75%
Results: The solid preconcentrates prepared with hydrophobic carriers exhibited desired attributes in a
uniform range. Neusilin adsorbed solid SMEDDS (S(N)SMEDDS) portrayed enhanced amorphization
in XRD and DSC studies and found to be physically compatible in FTIR studies. SEM revealed colloidal
particles having spherical morphology with negligible aggregation. Ex vivo permeation rate of the
drug across excised intestinal segments (duodenum, jejunum, ileum and colon) was observed to be 3.72,
5.85, 4.51 and 3.0-fold, respectively, as compared to pure drug. TEM of reconstituted SMEDDS indicated
nano-sized globules with negligible coalescence. Enhanced in vitro dissolution rate of optimized
solid SMEDDS manifested in bioavailability enhancement of 167.54% and 188.98%, as compared to
pure drug and marketed product. These studies further substantiate the lymphatic uptake of SMEDDS
through chylomicron flow blocking approach. Establishment of Level A IVIVC showed a uniform correlation
between the in vitro dissolution efficiency and in vivo pharmacokinetic parameters.
Conclusion: The present investigation reveals the immense potential of solid SMEDDS in augmenting
the oral bioavailability profile of poorly water-soluble drug canagliflozin.