Udenafil is a BCS class II drug with very low aqueous solubility (approximately 0.0798
mg/ml) and is used in urology to treat erectile dysfunction. It shows low oral bioavailability
(approximately 38?) due to lower solubility and intestinal first pass metabolism. A drug
having low solubility in gastro-intestinal tract cannot be absorbed completely and needs to be
formulated in a special formulation.Current work was carried out to develop and evaluate
supersaturated self emulsifying drug delivery system (Super-SMEDDS) of udenafil in order
to attain enhanced solubility and dissolution properties with improved oral
bioavailability.The solubility of Udenafil was checked in different oils, surfactants, and
cosurfactants and ternary phase diagrams were constructed to evaluate the microemulsion
domain. The Udenafil SMEDDS was prepared using Oleic acid (oil), Cremophor RH40
(surfactant), and polyethylene glycol 400 (cosurfactant). In order to produce the formulation
comparable with the available marketed tablet the Super-SMEDDS formulations were
developed where drug loading was increased to 100mg in preconcentrates. Developed
formulations were evaluated for particle size distribution, zeta potential, polydispersity index,
and subjected to in vitro release studies and ex vivo permeability studies. The optimized
formulation produced fine microemulsion with globule size of 158.8 ± 2.15nm,
polydispersibility index in range of 0.369±0.06 and zeta potential value of -37±4mV. Freeze
thaw cycling, centrifugation test, dilution study showed that optimized formulation is
thermodynamically stable. In vitro dissolution studies of Super-SMEDDS against UDL API
and Udzire tablet (100mg) carried out in dissolution media 0.1N HCl and pH 6.8 showed a dramatic improvement in the in vitro dissolution profiles. Results of ex vivo studies indicate
nearly three folds improvement in permeability of drug solution. Developed formulations
were found to be promising and may result in improved therapeutic performance.
Keywords: Super-SMEDDS, Udenafil, Erectile dysfunction, Cremophor RH40, Oleic acid,
polyethylene glycol 400
Abbreviations: Supersaturated self emulsifying drug delivery system (Super-SMEDDS),
Udenafil(UDL), Simulated gastric fluid (SGF), Simulated intestinal fluid (SIF), % transmittance
(%T), Oleic Acid (OLA), Krebs-Ringer-phosphate-buffer (KRPB), Liquid SMEDDS (LSMEDDS), Cremophor RH40 Cr-RH40, Polyethylene Glycol (PEG 400)
Publication date: 01/10/2021
https://ijbpas.com/pdf/2021/October/MS_IJBPAS_2021_OCT_SPCL_1047.pdf
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https://doi.org/10.31032/IJBPAS/2021/10.10.1047
