Structure Optimization And Character Adjustment Of Transdermal Drug Delivery Systems Via Electrospun Technology

Transdermal drug delivery system (TDDS) can avoid the first-pass effect in liver andthe deactivation of model drugs in intestinal tract. TDDS will result in a constantplasma concentration, extending the time of effective drug concentration, bettercompliance, and drug safety. TDDS is a complicated system which involves pressuresensitive adhesive matrix, model drug and transdermal enhancer. Today, there is noeffect approach in coordinating the interactions among PSA matrix, model drug andtransdermal enhancer to improve the compatibility between patient’s skin and TDDS. Inthis study, electrospun technology is introduced into the design of novel transdermalpatches.Adding Poly (vinyl pyrrolidone)(PVP) in cellulose acetate (CA) electrospunprecursor solution improved the electrospunability of original CA solutions. Ibuprofen(IBU) was loaded into the CA/PVP electrospun fibers. The distribution state of IBU wasdetected via DSC and XRD, and results suggested that IBU was in an “amorphousstate”. FTIR studies showed that new hydrogen bonds generated between IBU andfibrous matrix. Such secondary interaction and nano-structures of composite fibersimproved the compatibility between IBU and fibrous matrix, which effectively inhibitedIBU from separating crystals out off from the medicated fibrous matrix. The high IBUconcentration in fibrous matrix endowed the medicated fibers good in vitro IBU releaseand transdermal permeation profiles. Combination the IBU-loaded CA/PVP fibrous matand PSA, a novel Drug-in-fibers transdermal patch was prepared. Amorphous IBU wasencapsulated in the CA/PVP fibers, which avoided IBU crystals to destroy the adhesiveproperties of PSA, and improved the thermalstability of the new patch. However, thedual-hindrance of fibrous matrix and PSA made the Drug-in-fibers patch have a poorrelease profile. To improve the release profile of IBU from Drug-in-fibers, aDrug-in-adhesive/fibers type patch was designed. It was fabricated by combiningmedicated PSA and IBU-loaded CA/PVP fibrous mat, which made this kind of patchendowed the fast IBU release rate of drug-in-adhesive and the good thermalstability ofDrug-in-fibers.To enhance the breathability and water-repellence of traditional patch, aheterogeneous HPSA-PVP/c-PVA composite membrane was fabricated by electrospun method. This bistratal membrane had breathability and water-repellence. IBU wasencapsulated in the HPSA-PVP/c-PVA composite membrane. DSC and XRD resultsillustrated that such composite membrane could inhibit IBU from re-crystallization for along period. In sum, the good re-crystallization inhibition, breathability,water-repellence and adhesive properties of such membrane provided a novel approachin transdermal patch design.In this study, coaxial electrospun method provided a new solution on inhibition there-crystallization of model drugs with strong crystallinity. To fabricate the “core-shell”fibers,15wt%CA/acetone/N, N-dimethyl acetamide solution was selected as the corematerial, and15wt%PVP/alcohol solution was used as the shell material. Transmissionelectron microscope results suggested that such “core-shell” fibers had the similarstructure with a “pencil”. ART molecules were encapsulated in the core of the coaxialfibers, which prevented ART from re-crystallization for a long period. In vitro releasestudies illustrated that an erosion-diffusion manner was observed, which released ARTat a slow and continuous rate. Ex vivo permeation study suggested that the “core-shell”fibers improved the permeation profile of ART.The study of electrospun technology in TDDS illustrated that such approach hadgood functionality and application values in the structure optimization and the propertymodulation of TDDS design. Studies in this text provided theoretical basis in improvingthe biocompatibility, thermolstability and breathability of novel patch, and providednew insight in TDDS design.