DESIGN AND EVALUATION OF ZERO-ORDER DRUG-RELEASING RIVASTIGMINE TRANSDERMAL SYSTEMAbstract
Rivastigmine is used for the treatment of mild to moderate dementia of the Alzheimer’s type. Transdermal delivery of Rivastigmine is preferable to improve gastrointestinal tolerability. A novel transdermal system with zero-order release kinetics was developed following a hybrid technique in a combination of the micro reservoir and adhesive dispersion system. The transdermal system was prepared by incorporating rivastigmine in adhesive matrix layer in which rivastigmine-loaded microspheres were dispersed. Microspheres were prepared by spray drying using poly-e-caprolactone and maltodextrin (1:1 ratio) as carriers in various drug: polymer ratios. Microspheres with1:2 drug: polymer ratio (A1) showed desired particle size, yield, assay and in-vitro drug release and were found to be suitable for designing the transdermal system. A1 was dispersed into silicon adhesive layer during the preparation of the patch with a calculated amount of rivastigmine. Transdermal patch with 18 mg rivastigmine was optimized by evaluating ratios of adhesive matrix and microsphere content following DOE where 13 formulations were evaluated for various physical and chemical properties. 5 among 13 formulations were found to be satisfactory and subjected for in-vitro drug release studies. 4 among 5 formulations have shown satisfactory drug release; hence, they were also subjected for ex-vivo permeation studies. In-vitro release kinetic data and ex-vivo permeation data resulted best with the formulation comprising 150 mg of silicon adhesive containing 11.33 mg of Rivastigmine and 20 mg of microspheres containing 6.67 mg of rivastigmine (F5). F5 was subjected for stability as per ICH guidelines and was found stable up to six months at accelerated conditions.