Role of Porous Carriers in the Biopharmaceutical Performance of Solid SMEDDS of Canagliflozin.
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% RH.


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.
['Singh|Dilpreet|D|', 'Tiwary|Ashok K|AK|', 'Bedi|Neena|N|']
D017607:Aluminum Compounds D000818:Animals D001682:Biological Availability D000068896:Canagliflozin D003102:Colloids D004337:Drug Carriers D065546:Drug Liberation D004655:Emulsions D007413:Intestinal Mucosa D008208:Lymphatic System D017616:Magnesium Compounds D010316:Particle Size D010330:Patents as Topic D016062:Porosity D051381:Rats D017640:Silicates
canagliflozin bioavailability Solubility lymphatic uptake microemulsion solid carriers.