Formulation and Optimization of Rivastigmine-Loaded PLGA and Chitosan Nanoparticles for Transdermal Delivery

Abstract

Rivastigmine (RVT) is anti-Alzheimer with low bioavailability and with short elimination half-life due to significant first-pass metabolism. RVT is a hydrophilic drug because it has low permeability tothe skin. Therefore, in the present study, RVT-loaded polymeric nanoparticles (NPs) were formulated to improve drug permeation through the transdermal route. A polymeric nanoparticle of RVT was prepared (using the factorial design) and characterized using the biodegradable polymers, Poly (lactic-co-glycolic) acid (PLGA) and Chitosan (CH) as carriers.PLGA NPs were prepared by the nano-precipitation method, while CH NPs were prepared by the ionic gelation method. The effect of formulation variables on particle size (PS), PDI, and percentage entrapment efficiency (%EE) of NPs were studied using factorial design and were optimized based on the responses' desirability, i.e., minimum particle size and PDI and maximum entrapment efficiency. The optimized PLGA NPs showed PS of 291.3nm, PDI of 0.296, and %EE of 75.31%, whereas CH NPS showed PS of 339.3 nm, PDI of 0.264, and %EE of 83.91%. DSC thermograms indicated that RT was dispersed as an amorphous state in both PLGA and CH NPs. TEM and SEM studies indicated that the NPs were spherical and smooth. In vitro release studies showed 52.7±1.07 and 75.02±0.97% release from PLGA NPs and CH NPs in 24 h, respectively, whereas from drug solution 92.21±1.11% with 2h.Optimized NPs were incorporated in the patch, and in vitro permeation studies were performed across the pork ear skin.The steady-state flux of PLGA and CH NPs merged patch, i.e., PPN and PCN, was 223.64 and 265.18µg/cm2.h respectively, whereas for pure RVT containing patch (PD) was shown to be 55.01µg/cm2. h after 24 hrs. Results indicated that the flux of PPN and PCN was 4.06 and 4.82 fold higher than PD. Proposed comparative studies of developed patches with marketed patches showed that the developed patch of drug-loaded in polymeric nanoparticles could be a potential alternative for exiting sold Exelon® patch.