Carvedilol (CVD) is a non-selective β and α adrenoreceptor blocker, useful in treating hypertension, angina pectoris, congestive heart failure (CHF), and coronary artery diseases. CVD is a poorly water-soluble drug with low oral bioavailability, which may lead to frequent dosing and poor patient compliance for long-term treatment. To improve its bioavailability, we fabricated intranasal administration of CVD-loaded cationic nanoliposomal (NLPs) in situ gel using a simplex lattice design. About 98% of the drug was released from optimized CVD NLPs within 24 h, but in situ nasal gel showed a sustained drug release up to 96 h. The intranasally administered CVD liposomal in situ gel showed a 6.94-fold increase in Cmax and a 5-fold increase in relative bioavailability compared to an oral drug suspension. GastroPlus™ software was utilized to simulate the in vivo drug-absorption profile of the nasal gel via the nasal route of rabbits (experimental) with the plasma drug concentration profile via the intravenous (IV) route of rabbits (predicted). The simulated (IV) and observed (Intranasal) plasma concentration-time profile of CVD was found to be superimposable. The enhanced bioavailability of CVD NLPs in situ gel reveals the potential of cationic NLPs as an alternative carrier for intranasal administration.
By Sweta Kar & Sandeep Kumar Singh