The effect of micronization method on characterization and deposition profiles of different dry powder formulations of cefotaxime sodium

Abstract

Aerosol therapy is used as an alternative to systemic treatments to treat symptoms of the disease locally and to avoid the use of large doses of drugs that result in severe side effects in other organs. Cefotaxime sodium, as a third generation of cephalosporins, has a high degree of stability in the presence of (beta)-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria. The aim of this study was to compare the effect of two methods of micronization: spray drying and jet milling on the characterization and deposition profile of different formulations of cefotaxime as a dry powder inhalation. The powder properties of the samples were examined by laser diffraction, scanning electron micrography, differential scanning calorimetery, Karl fisher water content, helium densitometer and X-ray diffraction analysis. Deposition profiles of formulations were determined using Twin Stage Impinger with a Spinhaler(r) at a flow rate of 60L/min. An amorphous form of the drug obtained when spray drying was used. However, spray dried particles were larger than jet milled particles, these particles exhibited improved aerodynamic properties. Fine particle fractions of the drug aerosolized from the formulations ranged from 12.98 up to 30.57%. The highest fine particle fraction was obtained by formulation containing spray dried drug and lactose (63–90μm) as a carrier with drug/carrier ratio 2:1. In addition, use of lactose carrier enhanced the deposition profiles of all formulations.