Azithromycin loaded on hydrogels of carbomer: chemical stability and delivery properties

Hydrogels of carbomer (C) and azithromycin (AZI) were prepared by neutralizing with AZI 50% of the carboxylic groups of 0.25% C(974) and C(934) dispersions. The hydrogels exhibit pH close to 8 and are physically stable. Titration with NaCl revealed a high degree of counterion condensation C-AZI. The release of AZI in a Franz cell was almost negligible when the receptor compartment was filled with water but was increased about 20 times as water is replaced by NaCl solution. Two analytical methods were used to evaluate the effect of the counterionic condensation on the chemical stability of AZI, a microbial assay and an HPLC method. Degradation of AZI in buffered aqueous solution was used as reference. The stability of AZI was significantly improved in the hydrogels retaining more than 75% of the initial concentration along a period of 18-20 months evaluated and the self life (t(90)) of the drug was increased 27 and 20 times over the reference. The improvement of AZI stability could be attributed to the high degree of counterion condensation in which drug molecules remain associated to the macromolecular phase having a high negative electrokinetic potential and higher viscosity and lower kinetic energy than those in the fluid phase.