Evaluation of oral sustained release enteric coated microbeads of ceftriaxone sodium

Background: Ceftriaxone sodium (CS) is a third generation cephalosporin and belongs to BCS Class III.  This antibiotic cannot be absorbed orally owing to its poor permeability through GI epithelia and its acid labile nature. The purpose of this research was to develop and evaluate microbeads exploiting the pH-sensitive property and biodegradability of calcium alginate for intestinal delivery of CS. Methods: Microbeads of CS entrapped in sodium alginate and sodium carboxymethyl cellulose (CMC) were prepared by ionotropic gelation method using calcium chloride as a crosslinking agent followed by coating with various polymers such as cellulose acetate phthalate, Opadry^®, Eudragit^® L-100 and Eudragit^® S-100. The microbeads were then evaluated for entrapment efficiency using HPLC, in vitro drug release examined in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8), swellability, surface morphology and structure using scanning electron microscopy (SEM) and atomic force microscopy (AFM), and polymer matrix strength and thermal stability using thermogravimetric analysis (TGA). Results: The drug entrapment efficiency of the optimized formulation was determined to be 70 ± 5 %. The drug release was found to be consistent with an erosion-dependent swelling mechanism. Swelling properties of drug-loaded microbeads were found to be in range from 0.86 to 3.35. Microbeads coated with all the coating polymers exhibited sustained release and followed first-order kinetics and the mechanism of diffusion was determined to be non-Fickian. SEM images demonstrated the structure and surface of the microspheres. AFM images demonstrated composition dependent variations in surface texture, morphology, and roughness. TGA thermograms demonstrated the cross-linking efficiency and thermal stability of the microbeads when various polymers were blended with sodium alginate. Conclusion: Sustained release CS microbeads of sodium alginate and sodium CMC were successfully prepared. Parameters such as polymer concentration, calcium chloride concentration, coating polymer concentration, stirring speed and cross-linking time significantly affected entrapment efficiency, surface morphology and in vitro drug release. The use of sodium alginate, sodium CMC and other coating polymers decreased the drug release behavior in gastric conditions to certain degree but sustained the drug release at intestinal pH.