To improve the poor compatibility among different components of Drug-in-adhesive type patch, two novel plasters (Drug-in-fiber and Drug-in-adhesive/fiber) were developed based on ibuprofen (IBU)-loaded fiber mats. These fibrous mats were fabricated via electrospinning of cellulose acetate/poly(vinylpyrrolidone) composites in a binary solvent of N,N-dimethyl acetamide/acetone. Physical status studies suggested that Drug-in-fiber could inhibit IBU re-crystallization, but the active ingredients were released at a relatively slow rate due to the dual-resistance of fiber mat and adhesive matrix. To overcome this shortcoming, Drug-in-adhesive/fiber was designed by coupling medicated hydrophilic pressure sensitive adhesive and IBU-loaded fiber mat. This method endowed Drug-in-adhesive/fiber a fast IBU release rate and high permeated drug amount though simulative skins. This design separated enhancer from adhesive matrix, which guaranteed Drug-in-adhesive/fiber excellent adhesion forces. Hence, the plasters based on medicated fiber mats improved the compatibility among patch components.