Background:
Carvedilol (CD), a non-selective beta-blocker, is indicated for the management
of mild to moderate congestive heart failure. After oral administration, CD is rapidly absorbed
with an absolute bioavailability of 18-25% because of low solubility and extensive first-pass metabolism.
Objective:
The present investigation focused on enhanced oral delivery of CD using supersaturated
self-emulsifying drug delivery (SEDDS) system.
Methods:
Optimized SEDDS consisted of a blend of Oleic acid and Labrafil-M2125 as an oil-phase,
Cremophor-RH40, polyethylene glycol-400 and HPMC-E5 as a surfactant, co-surfactant and supersaturation
promoter respectively. Formulations were characterized for physical characteristics, invitro
release in simulated and biorelevant dissolution media, intestinal permeability and bioavailability
studies in Wistar rats. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis,
scanning electron microscopy (SEM) studies were used to confirm the crystalline nature and
shape of the optimized formulation.
Results:
DSC and XRD, SEM studies showed that the drug was in amorphous form, and droplets
were spherical in shape. Dissolution studies clearly showed distinct CD release in compendial and
biorelevant dissolution media. The results from permeability and in-vivo studies depicted 2.2-folds
and 3.2-folds increase in permeability and bioavailability, respectively from supersaturated SEDDS
in comparison with control.
Conclusions:
The results conclusively confirmed that the SEDDS formulation could be considered as
a new alternative delivery vehicle for the oral supply of CD.
Lay Summary:
Carvedilol (CD) is a non-selective antihypertensive drug with poor oral bioavailability.
Previously, various lipid delivery systems were reported with enhanced oral delivery. We developed
suprsaturable SEDDS formulation with immediate onset of action. SEDDS formulation was developed
and optimized as per the established protocols. The optimized SEDDS formulation was stable
over three months and converted to solid and supersaturated SEDDS. The results from permeability
and in-vivo studies demonstrated an enhancement in permeability and bioavailability from supersaturated
SEDDS in comparison with control. The results conclusively confirmed that the SEDDS formulation
could be considered as a new alternative delivery vehicle for the oral administration of CD.
Toward Biorelevant Dissolution: Application of a Biphasic Dissolution Model as a Discriminating Tool for HPMC Matrices Containing a Model BCS Class II Drug