Formulation of Pregabalin-Loaded Trimethyl Chitosan Microspheres for Nasal Drug Delivery: In vitro, ex vivo and in vivo Characterization

Background:

Polar drugs make it difficult to cross nasal cells. Trimethyl Chitosan (TMC) microspheres help absorption by opening junctions, increasing drug retention. Pregabalin absorbs well orally but delays crossing the brain, limiting emergency seizure treatment. The present study aimed to develop pregabalin-loaded TMC microspheres for intranasal administration in epilepsy.

Materials and Methods:

The microspheres were prepared by ionotropic gelation method using TMC and glutaraldehyde by varying the formulation and processing parameters and have been characterized for the physicochemical, drug release and pharmacodynamic properties.

Results:

The microspheres' particle size was 10.71- 22.85 μm with a positive zeta potential of 25.1. At 0.6% TMC, particle size was 14.05±1.24 μm, increasing to 22.85±1.48 μm at 1% TMC concentration, suitable for administration in the nasal cavity without the risk of passing to the lower respiratory tract. TP3 batch (1:1 pregabalin: TMC ratio) had 91.64% entrapment efficiency. Over 90% of drug release was achieved in in vitro and ex vivo studies using sheep nasal mucosa. The bioadhesion potential measured on sheep nasal mucosa reached 86.29±1.41%. Moreover, the excised sheep nasal mucosa exhibited no morphological toxicity, indicating a high level of biocompatibility. The microspheres significantly delayed the commencement of clonic convulsion (210 s) and presented complete protection (100%) against pentylenetetrazol-induced seizures in mice.

Conclusion:

Pregabalin-loaded TMC microspheres were a promising approach for incorporating hydrophilic drugs and have great potential for nasal administration of pregabalin.