Studies On Sustained Release Of Water-insoluble Drug From Alcogels

Ionic liquids, as an environmentally-friendly green solvent, represent one of themajor challenges in the field of moden chemistry. A novel hydrogel was synthesizedby incorporation of ionic liquid. The hydrogel has a good compatibility with variousalcoholic solutions and water, it displays remarkably good drug loading potential. Itpossesses a potential application in controlled durg deliveyr system.In this study, the amino acid ionic liquid formed by glycine and strong alkalinesolution which was exchanged by l-ethyl-3-methyl-imidazolium through strong-baseanion exchange resin have been investigated. A novel hydrogel was prepared byfree-radical polymerization with acrylamide(Am) as monomers, ammonium persulfateas initiator, N,N′-methylene bisacrylamide as crosslinking agent in the amino acidionic liquid. The particle size distribution of gel was351.311um. The swellingproperty of the hydrogel was studied by gravimetrical method. It was found that theequilibrium liguid content (ELC) of the gels increased as the polarity(ε) of thesolvents increase.Chloramphenicol was used as the model drug, drug loading was studied byimmersing the gel in the drug solution, then the amount of drug loading was measuredspectrophotometrieally. The influences of the categorical of solvent, temperature,concentration of solutions on the drug loading of the hydrogels were studied in detail.It was found that in various solvent which the drug concentrations were constant,more chloramphenicol was absorbed because of higher solvent uptake. When ethanolas solvent prepared the same concentration of drug solutions, drug loading wasincreased with the increase of temperature. And the equilibrium swelling of the gelincreased with increasd in temperature. Increasing drug concentrations in the swellingmedium(such as water or ethanol) results in a increase in the drug loading, a linearrelationship was obtained between drug concentrations in the swelling medium anddrug loading，but The equilibrium swelling of the medium almost not change.In vitro release experiments, chloramphenicol was used as the model drug. The loaded hydrogels were dried under vacuum at room temperature, then the swellingproperty of the loaded hydrogels were studied by gravimetrical method, the drugrelease was performed under static conditions by immersing samples in medium, thesolid-state properties of the loaded hydrogel samples were characterized by X-raydiffraction (XRD) and differential scanning calorimetry (DSC), the drug–polymerinteractions were characterized by Fourier transforminfrared (FT-IR). The effect ofdifferent factors on cumulate drug release of chloramphenicol from driedpolymer-drug conjugate hydrogels has been investigated. It was found that the moredrug loading in the hydrogel were, the faster the release rate. And it showed thatdifferent drug loading change the drug release kinetics and mechanism. At0.011g/gdrug loading, the release equation was Q=0.0906t0.5+0.0248, and the release curvefollows Higuchi equation, the results of XRD and DSC showed that the drug was in anamorphous state in the hydrogel, n was0.4431, and the release driving forces wasdiffusion. At0.11g/g drug loading, the release equation was Ln(1-Q)=-0.0119t-0.1875,the release curve follows the first order kinetics, the drug was also in an amorphousstate in the hydrogel, n was0.5842, and the release mechanism was AnomalousTransport, it might be controlled by diffusion and swelling. At the drug loading of0.58g/g and1.13g/g, the release equation were Q=0.0126t+0.0191andQ=0.007t+0.0122respectively, the release curve follows Zero-order kinetics, the drugwas in crystallization state in the hydrogel, n were1.0778and1.024, and the releasemechanism was Case II, it might be controlled by swelling and dissolution. FT-IRsuggested that there might be a hydrogen bond present between the hydrogel andchloramphenicol. In addition, the results showed that the release rate increased as thetemperature of the release medium increased. The release rate was varying with thecounter-ion species, it was Kcl＞Nacl＞Mgcl2＞Cacl2＞Alcl3, and the release ratedecreased with increasing the ionic strength of the release medium. Moreover, as thepH of the release medium increases, the release rate was faster. The effect of therelease medium on release rate were: Artificial intestinal juice＞artificial gastric juice＞artificial tears＞normal saline. Besides, there was a close correlation between the release rate and the ELC of the dried polymer-drug conjugate hydrogels.These results indicate that the novel hydrogel has a promising future as a devicefor the sustained drug release delivery of poorly water soluble drugs.