Preparation and evaluation of acetazolamide liposomes as an ocular delivery system

The aim of this work was to formulate a liposomal preparation of acetazolamide to be applied topically, and to evaluate the in vitro and in vivo performance of the prepared liposomes. Acetazolamide liposomes were prepared using the reverse evaporation technique. Neutral, positively-charged, and negatively-charged liposomes were evaluated for their entrapment efficiency, drug release, and in vivo activity. Drug release from liposomes was studied using the membrane diffusion technique. Carbonic anhydrase inhibition activity was determined by the pH stat method, and compared to spectrophotometric determination of acetazolamide. The prepared liposomes were tested for their effect on the intraocular pressure (IOP) in rabbits. The percent entrapment efficiency was 29.27, 41.06 and 49.58% for negatively-charged, neutral and positively-charged liposomes, respectively. The proportion of drug released after 9 h was 13.36, 33.8 and 26.7%, for negatively-charged, neutral and positively-charged liposomes, respectively. There was a good correlation between the percent of inhibition of carbonic anhydrase activity and the amount of drug released from the liposomes as determined spectrophotometrically. Two acetazolamide formulations produced a marked decrease in the IOP. (C) 1997 Elsevier Science B.V.