Oral Delivery of Transferrin Coated Rivastigmine Microspheres for Alzheimer’s Disease Therapy

Rivastigmine hydrogen tartrate (RHT) is a first-line drug used for Alzheimer’s disease treatment. But RHT has high solubility and gastric hurdles which interfere with its bioavailability profile via oral route. To overcomes these issue RHT loaded transferrin-tagged microsphere was synthesized by using the solvent injection method. QbD (Quality by Design) systematic-based approaches used for the optimization of the microsphere using Box Behnken Design (BBH). Factor screening study accomplished on the basis of the result of the preliminary batches for particle size, uniformity, and Entrapment Efficiency (EE%). Transferrin coating on the surface of the microsphere takes place by electrostatic attraction physical absorption method. This coating was confirmed by the SEM-based elemental analysis method EDX (Energy Dispersive X-ray). BSA protein assay shows 67.10% coating of the Transferrin (Tf). DSC and FTIR characterization studies give surety regarding the compatibility of the drug and excipient and there is no interaction observed. Morphological Study of the Microsphere demonstrated smooth surfaces with a spherical appearance. In-vitro examination exhibits sustain release pattern of drug release and follow the Higuchi model of drug kinetics. In-vivo pharmacokinetic study revealed significant increases in the blood plasma level of the drug entrapped in C-MS as compared to the free drug solution. Ex-vivo permeability informed that C-MS indicates 80.92% cumulative permeability comparatively higher than U-MS and free drugs. The whole study points out that significant increment in the bioavailability of the RHT noted for rivastigmine coated microsphere (U-MS), which can effectively use for management of the Alzheimer’s disease.