Development and In vivo Evaluation of Cefdinir Nanosus-pension for Improved Oral Bioavailability

Abstract

Cefdinir belongs to III generation cephalosporins and is an oral extended spectrum antibiotic. It is a BCS class IV drug, with low solubility resulting in a low oral bioavailability of about 21% for capsules and 25% for suspension. The aim of this work was to develop cefdinir nanosuspension to improve the oral bioavailability. Nanosuspensions were prepared by using single stabilizer and combination of two stabilizers by employing high speed homogenization followed by sonication method and the prepared nanosuspensions were characterized. Initially, the drug excipient compatibility was checked by Differential Scanning Calorimeter (DSC). In trial experiments, tween80 concentration was varied from 0.25 to 0.75% and homogenization time was varied from 2.5 min to 10 min, and 0.5% surfactant concentration was found optimal. Further, trials were conducted with SLS and poloxamer 188 at the same concentration to know the role of stabilizers. Trials were also done by preparing cefdinir nano-suspensions with different techniques for comparative studies and their size and poly dispersity indices (PDI) were found. The mean size and zetapotential (ZP) of nanosuspensions, prepared by high speed homogenization followed by sonication varied from 541.7 to 947.2 and-13.7mV to -22.4mV respectively. Results of saturation solubility and dissolution studies were used to optimize the nanosuspension. Optimized nanosuspension showed improved saturation solubility, dissolution rate and oral bioavailability by 1.752 fold when compared to marketed suspension and found to be stable at RT for 2 months.The bioavailability improvement was significant at a level of P value < 0.05 when student unpaired t-test was used. Hence, cefdinir nanosuspension formulation holds a great promise in improving dissolution rate and oral bioavailability.