The Fifth Generation Electrospun Structural Nanofiber-based Solid Dispersion Of Poorly Soluble Drugs

Improving solubility and membrane permeation absorption of the poorly water-soluble drug,enhancing its efficacy and reducing side effects have been one of the important and difficult problems in pharmacy.Among the investigated chemical and physical methods,amorphous solid dispersion are occupying increased share portion continuously.The fifth generation solid dispersion can furnish both improved dissolution behavior base on the physicochemical property of carrier material and also programmed drug controlled release profiles with an intentional tailor on components and their spatial distributions within the structural nanofiber.High-voltage electrospinning technology(electrospinning)is one of the most promising methods for industrial production of nanofibers.Electrospinning process as "top-down" technology manufacturing nanofiber is feasible,flexible,controllable process to fabricate fibers.Electrospinning can one-step prepare solid dispersions with micro/nano structure fibers effectively through the nozzle structure design macroscopically.The collected nanofibers often assemble into non-woven fabrics randomly with 3D continuous network structure,huge surface area and large porosity.These unique properties make electrospinning nanofibers a perfect candidate for solid dispersion,and the technology is an advanced technology for creating solid dispersions.Traditional electrospinning process can be a highly effective way to produce monolithic polymeric films that have a diameter in the range of 100-1000 nm.Size as small as 100 nm or an even monolayer is very difficult to create by using the electrospinning process directly.Compared with monolithic nanofibers,the sheath thickness of a core-shell nanofiber can be easily adjusted to less than 100 nm using the coaxial process.In particular,the exploitation of modified coaxial process can provide a series of protocols to realize this goal.All types of solutions can be used as the shell fluids(e.g.solvent,surfactant,solution with functional ingredients)in modified coaxial process regardless of their electrospinnability,which means the increasing possibilities for functional material design and development.This topic is preparation of the fifth generation of solid dispersions that core-shell nanofibers with ultra-thin shell,improving the dissolution rate of poorly water-soluble drug and development of fast-dissolving delivery system.Firstly,electrospinning windows of hydrophilic polyvinylpyrrolidone(PVP)and hydrophobic polycaprolactone(PCL)have been explored.Preparing PVP solution with different molecular weights and PCL solution with different concentrations,then fabricating monolithic nanofiber using single-fluid electrospinning process.Optimize electrospinning parameters via morphology observation.Secondly,core-shell nanofibers with ultra-thin shell were designed and prepared using modified coaxial process.A poorly water-soluble drug such as quercetin/tamoxifen citrate(TC)was selected as a model drug.Design of two systems:PVP-PVP with quercetin nanofiber membrane;PCL-PVP with TC nanofiber membrane.The effects of load,surfactant and core-shell fluid rate ratio on fiber morphology were evaluated.Functional characterization was further studied.PVP-PVP with quercetin nanofiber membrane:with the increase of drug content,the bead string structure in the membrane gradually decreases,and the different surface active agents have a certain influence on the morphology of the fibers.PCL-PVP with TC nanofiber membrane:with the increase of drug content,the average diameter of nanofibers decreased;the average diameter of nanofibers decreased with the increase of the rate of the sheath relatively.The properties of the fibers in the two systems are characterized.Evaluation via SEM and TEM demonstrated that nanofiber has linear and fine morphology,and the size of sheath was less than 100 nm.XRD and FTIR results showed that the crystallized model drug was distributed in the polymeric matrix amorphously and that quercetin/TC and PVP K10 have good compatibility.In vitro dissolution tests suggested that the core-shell nanofibers with ultra-thin shell released the drug in the dissolution medium immediately(1 min).On the choice of drug,quercetin and tamoxifen citrate(TC)are model drugs.Quercetin is a plant-based drug and tamoxifen citrate is a synthetic drug,this study can provide a new method of developing the fast-dissolving delivery system of herb medicine or weatern medicine.On the choice of technology,a modified coaxial process as a advanced technology fabricate core-shell nanofibers with ultra-thin shell successfully,model drug distributed in ultra-thin shell,providing a new idea to develop fast-dissolving delivery system.At the same time,the nanofiber itself to macro(axial)and micro(radial)combined naturally.These materials can furnish both advantages of solid products that convenient package and transportation and obtained the pharmacodynamic and pharmacokinetic characteristics of nano drug delivery system,thereby promising applicability and potential of structural nanofiber in future.