Formulation, Development and Optimization of Intranasal Microspheres of Rivastigmine Tartrate

Abstract

Rivastigmine tartrate (RIVA) is an anti-cholinesterase inhibitor which is used in the treatment of dementia of Alzheimer’s disease, which has oral bioavailability (36%) due to extensive hepatic first pass metabolism. To overcome this drawback, novel, intranasal microspheres of RIVA was developed. Microspheres were formulated by using chitosan as polymer and span 80 as an emulsifier by emulsion crosslinking method. The preliminary studies were done to optimize various process parameters. The prepared batches were evaluated for % entrapment efficiency (% EE), particle size and particle size distribution, in-vitro drug release, in-vitro drug permeability, % drug loading and % mucoadhesion. 23 full factorial design was used, to optimize the key process parameters like drug to polymer ratio, stirrer speed and crosslinking time. From the optimization of designed batches, it was found the results of batch D8 was within the acceptable range (% EE 73.77, % Drug release at 8 hr 70.53). To prepare once a day dose, it was decided to coat the microspheres by emulsion solvent evaporation method using Eudragit RS PO to sustain the drug release. The evaluation of coated microspheres showed that batch C2 gave controlled drug release up to 24 hr. Scanning electron microscopy studies of coated and uncoated microspheres were done, in both cases, good Sphericity and smooth surface was found. Prepared microspheres should be stored in cool and dry place to maintain their quality.