Eprosartan loaded mesoporous silica nanoparticles embedded in mucoadhesive buccal films: A strategy for improved bioavailability

Eprosartan is a selective angiotensin receptor blocker used to treat essential hypertension. However, it has a low oral bioavailability of only 13 % as it is categorized as BCS class II and undergoes first-pass metabolism. Therefore, incorporating eprosartan into mesoporous silica nanoparticles (MSNs)-loaded buccal film might augment its bioavailability. The MSNs were formulated using the incipient wetness method, and an I-optimal design was utilized for optimization purposes. The independent variables were the drug-to-mesoporous silica ratio and the type of mesoporous silica. The entrapment efficiency percent (EE %), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and percentage of drug released after 6 h (Q6 %) were assessed. The optimized MSNs formula was assessed by evaluating its morphology, Fourier-transform infrared spectroscopy (FTIR), and thermal analysis. Then, the optimized MSNs formula was embedded into a mucoadhesive buccal film, which was characterized via ex vivo permeation and pharmacokinetics studies. The optimized MSNs formula was spherical and had EE % of 99.50 f 0.54 %, PS of 197.9 f 2.2 nm, PDI of 0.442 f 0.008, ZP of -16.21 f 0.87 mV, and Q6 % of 93.00 f 1.9 %. The FTIR ensured the drug's uptake by the porous structure, while thermal analysis confirmed its amorphous state after loading into MSNs. The MSNs-loaded buccal film augmented the apparent permeability coefficient by 4.88 folds compared to free-drug film. The Cmax and AUC0-t of MSNs-loaded buccal film were 2.88-fold and 2.63-fold, respectively, compared to the oral eprosartan, while the Tmax was shortened to 0.5 h instead of 1 h. This study confirmed the capability of MSNs-loaded buccal film to enhance the bioavailability of eprosartan.