Combining ion-pair strategy and percutaneous permeation enhancers to develop sustained-release paliperidone patch

In this study, a sustained-release paliperidone (PAL) patch was developed using a combination of ion-pair strategy and percutaneous permeation enhancers (PPEs). The ion-pair strategy was used to improve drug-adhesive miscibility and control drug release. PPEs were used to break SC barrier function to facilitate drug skin permeation. The in vitro skin permeation experiments using single-factor experiments and Box-Behnken design gave the optimized formulation, a 55 μm adhesive thickness patch with 7 % ( w/w ) PAL-LA (Lauric acid), 9.7 % ( w/w ) Plurol® Oleique CC 497 (POCC). Moreover, the pharmacokinetic study confirmed its potential in sustained-release transdermal patch with longer MRT 0-t (18.35 ± 3.11 h) and higher BA (63.14 %) than the gavage group ( C max  = 6.64 ± 2.61 μg/mL, MRT 0-t  = 2.88 ± 1.06 h, BA = 45.70 %) without significant increasing C max . The mechanism study revealed that forming ion-pairs effectively modulated drug’s physicochemical properties and doubly ionic H-bond strength to improve drug miscibility in patches. To summarize, a sustained-release patch of PAL was successfully developed, which provided a strategy for sustained-release patches with good drug-polymer miscibility, drug controlled-release, and feasible drug utilization features.