Preparation And In Vitro Release Characteristics Of Controlled Release Microspheres Of Cefepime Diydrochloride

Sustained-release and controlled-release preparations represent the most rapidly advancing areas of science. Such preparations offer numerous advantages compared to conventional dosage forms including improved efficacy, reduced toxicity, improved patient compliance and reduced the total dose of the drug. Carboxymethylchitosan is a kind of water soluble chitosan derivative with good biocompatibility and antibacterial property, and has been proved safe and biodegradable. Cefepime dihydrochloride (Maxipimg) belongs to the fourth generation of cephalosporins. It has broad-spectrum antibacterial property and stable to (3-lactamases. The market share of Maxipime increase gradually at home and abroad in recent yeas.In this paper, O-carboxymethylchitosan (OCMC) microspheres containing an antibiotic drug cefepime dihydrochloride (CD) have been successfully prepared by emulsion crosslinking using glutaraldehyde. Single factor experiments were applied to study the effects of various influencing factors on preparation of microspheres. The results showed that the main influencing factors which effect the drug loading and drug encapsulation efficiency of CD-OCMC were the OCMC concentration in the aqueous phase, mass ratio of CD to OCMC, the dosage of crosslinker (v(GA)/m(OCMC)) and the Span80concentration in the organic phase.The central composite design-response surface methodology was used to optimize process variables after single factor experiments. The main influencing factors were listed as independent variables and the dependent variables were drug-loading and encapsulation efficiency. Then multiple linear regression and second-order polynomial model were fitted individually and stepwise regression was used to simplify model. Models with high multiple correlation coefficients were obtained. According to the fitting model, response surfaces that showed the relationships between the response variable and independent variables were generated. Surface plots and contour lines which based on the mathematical models were drawn using the statistical program SAS9.2. The optimal values are as follows:the OCMC concentration is2.7%, mass ratio of CD to OCMC is0.665, v(GA)/m(OCMC) is8mL/g, the Span80concentration is4%. Verification experiments were carried out at the conditions, and the result showed that central composite design-response surface methodology can be successfully used to predict the relation of the dependent variables and the four independent variables. According to these conditions, the microspheres are spherical in shape. The mean diameter is7μm and the span is1.52. The drug loading and drug encapsulation efficiency of CD-loaded microspheres are21.4%±0.5%and41.3%±0.7%respectively.The microspheres prepared at the optimal conditions was used in drug release studies. And in vitro release behaviors of the microspheres were studied in phosphate buffer solution (pH=7.3), HC1media (pH=1.2) and0.9%sodium chloride solution. The results showed that the microspheres proved to be successful in prolonging drug release up to10days or more, and the in vitro release profiles were found to be biphasic with a burst release followed by a gradual release phase, and followed the Higuchi matrix model.