Study Of Potential Drug Carrier Ion-exchange Fiber Drug Delivery System

Ion exchange fiber is a kind of non-crossing ion-exchange material,composed of monofilament with the diameter of 10- 300μm.Unlike ion-exchange resins,ion-exchange fibers consist of a non-cross-linked polymeric framework carrying a positive (anion-exchanger) or a negative(cationic exchanger) fixed electric charge(Helfferich,1955). The ionized groups are covalently attached to the framework,and they are compensated by mobile counter-ions of opposite charge.Drug fiber complexes can be formed through valence bond or adsorption,can improve the drug stability and dissolution velocity.Compared to the traditional ion exchange resin,ion exchange fiber consisted with smaller diameter.It is suggested to have a larger surface area to unit volume ratio,which leads to a higher absorption rate and absorption capacity as compared with the resin.It is easier to covalent with the IEF than IER by electrostatic interactions for larger molecular drug,with the reason that crossing can hinder drug bound and release with the IER.So the IER drug delivery system might exist drawbacks such as low drug loading capacity and low drug releasing amount, while ion exchange fiber can solve these problems.Thus,ion exchange fiber is expected to be developed to be a kind of novel potential drug carrier.The physicochemical properties of ion exchange fiber such as the water content,density, capacity,pKa and swelling ability were investigated.The determination method was established for eight cationic drug and seven anion drug,and the solubilities and partition coefficients were determined,the pKa of the drugs were retrieved.The binding mechanism was identified by SEM,DSC,Infrared spectra and X-ray diffraction,results reveal that the drugs bind to the fiber through chemical interactions not simply physical adsorption.The best fit of experimental data shows that the adsorption kinetics of cationic drug we studied on ion-exchange fiber can be described by second-order model.The calculated rate constant k first decreased then as the concentration increased,which did not allow to the kinetic theory.To solve this problem,a new ion exchange model was propesed which can describe the kinetic ion exchange process successfully.The equilibrium adsorption data of drugs onto ion-exchange fiber was also analyzed by Langmuir and Freundlich models and we also tries to explain the binding mechanism from the viewpoint of thermodynamics.The increase inΔΗ` with the increase of temperature indicated that more efficient adsorption will be reached at lower temperature.The positive values of entropy change(AS~ρ) reflected the affinity of drugs toward ion exchange fiber in aqueous solutions.Two mathematical models based on Donnan theory and ion exchange equilibrium theory taking into account the chemical partition coefficient of D+,Na+ and Cl~- were developed to simulate the drug loading onto ion exchange fiber and releasing process respectively with the aim to gain mechanistic understanding on the factors affecting these two processes.The loading drug concentration,drug solution volume and fiber dose can affect the loading capacity,the partition coefficient and the Donna potential obviously.However for a given amount of drug,the decrease of solution volume(i.e.increase the drug concentration) does not have much effect on the Donna potential,the Donna potential remain almost constant.The sodium chloride concentration,release medium volume and drug-fiber complexes dose can contribute to the drug releasing process.The ration of the solvent in the coating system is acetone:liquid paraffin:Span 85=15:30:55,the EC acetone concentration is 3%containing 10%DBP,10%PEG-400.The coating material and fiber ratio is 1:10,under middle stir velocity at 40°C for 8 h.It had been should showed that the use of 0.8%Avicel RC591 could form suspensions.The gamma scintigraphy was applied in order to assess gastro-retentive behavior of the ion exchange fiber in healthy human volunteer.Results showed that almost all the fibers could retain in the stomach for 2 hours,only slight fibers were excreted to intestine.The result showed that a significant gastro-retentive characteristic of ion exchange fibers.The improved bioavailability of riboflavin and FM from the drug fiber obtained in this study,suggests that the fiber could retain in the stomach.