Nasal Mucoadhesive Microspheres of Lercanidipine with Improved Systemic Bioavailability and Antihypertensive Activity

Purpose
The current study entails the design, development, and optimization of nasal mucoadhesive microspheres of lercanidipine with improved systemic bioavailability for the management of hypertension.

Methods
Mucoadhesive microspheres of lercanidipine were prepared by solvent evaporation and polymerization method using bovine serum albumin (BSA) as the carrier and glutaraldehyde as the chelating agent. For screening the material and process variables, Taguchi design revealed the major influence of BSA concentration and glutaraldehyde volume as the critical factors for the preparation of microspheres. These factors were systematically optimized using Central Composite design to evaluate the particle size, entrapment efficiency, and in vitro drug release from the microspheres as the response variables.

Results
The optimized microspheres were prepared using 4.4% BSA and 0.25-mL glutaraldehyde, and stirring speed at 1500 rpm, which exhibited particle size of 34 μm, entrapment efficiency of 88.6%, Q6h of 94.67%, T60% of 3.2 h, and bioadhesion efficiency of 93.2%. In vivo pharmacokinetics in rabbits showed remarkable superiority of the optimized nasal microspheres (p < 0.001) with nearly eightfold improvement in the drug absorption parameters vis-à-vis the pure drug lercanidipine. Accelerated stability studies for 6 months demonstrated nearly similar drug release profiles at different time intervals, indicating the robustness of the optimized formulation.

Conclusions
In a nutshell, the present studies resulted in the successful development of optimized lercanidipine microspheres for nasal delivery.