| Arbidol Hydrochloride (AH) was selected as a new antiviral drug for the treatment and prophylaxis of influenza and other acute respiratory viral infections(ARVI). At the same time, AH had the immunomodulating activity, capacity of inducing interferon and antioxidant property. AH was absorbed into blood very quickly after oral administration. The duration of drug efficiency however, was relative short and there existed lower bioavailability. Therefore AH bioadhesive sustained release microspheres were prepared in order to prolong gastrointestinal location time and enhance bioavailability.In the investigations of the pharmaceutical preformulation, the physicochemical properties of AH were studied. The ionization constant (pKa) was determined as 6.73. The molar solution enthalpy ( SH) of AH in water was 56.32kJ/mol. The solubility of AH was significantly influenced by the same ion effect and dependent on pH, The apparent partition coefficient in oil and water of AH was also dependent on pH, and the maximum value appeared at pH6.8. The release rate of AH in water fit Hixson-Crowell model, and the release rate constant was 1.15h-1. The UV absorption properties and the stabilities of AH were studied.In addition, the absorption kinetics was obtained by using the in situ perfusion method in rats. It was showed that the upper and middle part of the small intestine was the preferred absorption segment. The absorption rate constant (ka) were 0.26,0.19,0.10,0.07 h-1 at duodenum, jejunum, ileum and colon respectively. The absorption of AH fit the passive transport mechanism and first order kinetics. The pharmacokinetics in rabbit of AH was studied. TheABSTRACTresult indicated that AH was absorbed into blood quickly after oral administration suspension(20, 40 , 80mg/kg), and the plasma concentration-time fit single compartment first order absorption model.The viscosities of Cb series were extremely large in the solution with pH between 5.0 and 12.0. Cb swelled quickly to achieve equilibrium in artificial gastric and intestinal juice. The adhesive forces of Cb series to gastric mucosa were higher than those to intestinal mucosa, and the order was Cb971p>Cb940 >Cb934p>Cb974p. Cb934p had the lowest transfer rate in stomach and intestine. The gastric eliminate half-life of Cb934p was 7.3h. In brief, it is appropriate for Cb934p to be accepted as the bioadhesive material.The solvent evaporation method was used to prepare AH bioadhesive sustained release microspheres with Ethylcellulose (Ec) as matrix material and Cb934p as bioadhesive material. The effects of instrument variables, process variables and formulation variables on the properties of microspheres (e.g. micrometric properties, release percent and bioadhesion) were investigated. The instrument variables (the shape of vessels, the diameter ratio of paddle to vessels and the position of the paddle) directly affected the formation of microspheres. The stirring rate mainly affected the diameter, release rate and bioadhesion of microspheres. The temperature of the solvent evaporation was the key factor, which affected all the properties of the microspheres. The duration of solvent evaporation mainly affected the release of drug from microspheres. The ratio of ethanol to liquid paraffin, the ratio of drug to excipients and the concentration of emulsifier remarkably affected all the properties of microspheres. The ratio of Cb to EC mainly affected the drug release and bioadhesion of microspheres. While the viscosity and concentration of EC and the amount of hole-inducer mainly affected the release rate of microsppheres.Orthogonal design was used to optimize the formulation and process. By investigating the micrometric properties, bioadhesion and release rates of 3 batches of samples, it was found that the microspheres obtained had the advantages of high encapsulation rate, good sphericity, suitable bioadhesion and fine reproducity of the release rate. The microsphere-forming process, release mechanism and bioadhesive mechanism were explored.The pharmac...
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