Ceftriaxone (CTX) is a widely used injectable third-generation cephalosporin that exhibits broad-spectrum antibacterial activity. Unfortunately, the oral route of this drug suffers different encumbrances, such as instability in the upper part of the GIT and enzymatic degradation, as well as poor permeability. There is no reported tablet dosage form for this drug. In this respect, the authors investigated the possibility of developing an enteric-coated oral tablet of CTX that would be helpful for better patient compliance. The tablet consists of directly compressed core of CTX, citric acid (CA), sodium chloride (NaCl), and two biopolymers-chitosan (CH), a permeation enhancer, and silicified microcrystalline cellulose (SMCC), a wicking agent. Both biopolymers are naturally occurring polysaccharides that are biodegradable in the colon and able to incorporate acid labile drugs. CA is a pH modulator to protect CTX from protease enzymes, while NaCl is a translocation enhancer that helps drug penetration. The enteric coat of the core was shellac (SH) with plasticizer glycerol tristearate (GTS) and CA that was applied by direct compression (dry coating). The solventless heat curable coat resulted in an enteric-coated tablet that complies with the USP pharmacopeia. The optimized formula was further subjected to in vitro release and stability studies, as well as ingredient compatibility. In vivo oral bioavailability of the enteric-coated tablets in rabbits gave promising results (absolute bioavailability of about 80%). Synergistically, all ingredients together augmented oral bioavailability of CTX. This developed formula could be a perspective delivery system for those drugs intended to be absorbed from the colon such as peptides and peptide-like drugs.
Keywords: ceftriaxone; chitosan; colon targeting; enteric coated; shellac.