Study On The Drug Loading And Releasing Characteristic Of Ethyl Cellulose In Treatment For Restenosis

As a rising technology, slow and controlled release technicque can effectively solve the problems of too quick release and too short effective reaction time of active agents. The advantages of slow and controlled release techicque are of remarkable potential of application in effective and long-term drug delivery.Ethyl cellulose （EC） is an ethyl-substituted cellulose ether, where the glucose units are joined by b-1,4 links. The ethoxyl substitution values of commercial products range from a degree of substitution of 2.2–2.6 ethoxyl groups per anhydrous glucose units. This corresponds to an ethoxyl content of 44.5– 49%. Ethyl cellulose is a non-toxic, stable, compressible, inert, hydrophobic polymer that has been widely used to prepare pharmaceutical dosage forms. The properties of ethyl cellulose sustained release products, including film coated tablets, microspheres, microcapsules and matrix tablets for both soluble and poorly soluble drugs have been reported.In this paper, we chose EC, aspirin and probucol as study subjects. We systematically studied the condition of preparation of drug loaded ethyl cellulose film and microparticles, general mechanism of drug loading behavior and interaction between drug and matrix. Ethyl cellulose is a non-toxic, stable, compressible, inert, hydrophobic polymer that has been widely used to prepare pharmaceutical dosage forms. The properties of ethyl cellulose sustained release products, including film coated tablets, microspheres, microcapsules and matrix tablets for both soluble and poorly soluble drugs have been reported. Three kinds of drugs （probucol and aspirin） loaded ethyl cellulose film were prepared by casting the EC-methyl benzene solution with drugs into the home-made model. The EC films are opaque and have a good property in strength and flexibility. The kind and amount of plasticizer are both one of the most important parameters. With increased amount of plasticizer, the burst release and drug release speed decreased. EC had a good effect on the controlled release of the three drugs, and the effect of probucol was the best one. The release time can last more 30 days and the burst release increased with the increasing initial drug concentration. And the“sandwich type”EC film can inhibit the burst of probucol and make it release delayed. The lag-time can be controlled by changing the amount of the blank layer.A series of low molecular weight EC were prepared and the Mηwas determined. Probucol loaded EC microparticles were prepared by emulsion-solvent evaporation method. Probucol is a hydrophobic drug, which was dissolved in CH2Cl2 with EC and added in SDS water solutions. An O/W emulsion was formed under drastic stirring. The morphological examination of microparticles was preformed by scan electron microscope （SEM）. It shows that these particles were spherical shape and the average diameter decreased with the decreasing molecular weight of EC. When the Mηwas lower than 1.0×10^-4, the particle size was down to nanometer. The encapsulation efficiency of probucol in EC microparticles was above 70% and majority of probucol was physical embedded into the EC microparticles as crystal. The in vitro release of probucol from EC microparticles lasted for over 30 days. The burst release and release speed was mainly depended on drug’s diffusion. With increasing absolute amount of loaded probucol, the release speed increased. EC microparticles have a better effect on the hydrophobic drug probucol than EC film with the same absolute drug loading capacity.In the mixture system of the hydrophilic drug aspirin loaded CS nanoparticles and the hydrophobic drug probucol loaded EC microparticles, the two drugs had no effect with each other on the drug release in vitro. In the blending system of probucol EC microparticles and aspirin chitosan nanoparticles, in vitro release of aspirin and probucol lasted for 48h and over 30 days, respectively. 3¹3 days after the release of aspirin closed to the active drug concentration, an active concentration of probucol have achieved. The results showed that in different period, the principal component of released drugs was different. These offer elementary theoretic basis for the procedure drug delivery for therapy of restenosis.