title: Improvement of acetazolamide ocular permeation using ascorbyl laurate nanostructures as drug delivery system.
abstract: OBJECTIVE
  To evaluate the performance of 6-O-Lauryl-l-ascorbic acid nanostructures (coagels) as vehicles for acetazolamide (AZM) in ophthalmic administration by in vitro and in vivo experimental tests.
  
  
  METHODS
  The systems of coagel + AZM were evaluated in terms of their in vitro release (dialysis membrane), permeability (isolated cornea), pharmacological effectiveness [intraocular pressure (IOP)-reduction in normotensive rabbits], and potential irritant effects.
  
  
  RESULTS
  The results concerning AZM permeation were better when vehiculized in coagels compared with ringer solution, which was evident from the AZM steady-state flux and P(app) values (J=1.43 μg/min and P(app)=3.04 cm.s(1)). As a consequence of this increase in permeation, the coagel-AZMs were more effective in lowering the IOP, according to the results obtained from the in vivo assays. Coagels loaded with 0.4% (W/W) of AZM showed a higher hypotensive effect in rabbits compared with the commercial formulation AZOPT(®) (brinzolamide 1%), mainly due to the prolonged effect of the former. In all cases, the intensity of irritation was time dependent. The sodium lauryl sulphate solution (2%) used as a positive control produced serious injury 30 min postadministration. This effect caused irritation, which decreased slowly and even at 180 min, the discomfort was still considerable. However, in the case of coagels, a mild-to-moderate effect was observed.
  
  
  CONCLUSIONS
  The incorporation of AZM in coagels seems to improve the ocular bioavailability of this drug. Coagel-AZM 0.4% showed a higher hypotensive effect, with a mild-to-moderate irritant effect. These systems could be administrated in human beings, although more detailed studies still need to be carried out.
authors: Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, UNITEFA-CONICET, Córdoba, Argentina.
authors: Luis I
authors: LI
authors: Tártara
authors: Daniela A
authors: DA
authors: Quinteros
authors: Verónica
authors: V
authors: Saino
authors: Daniel A
authors: DA
authors: Allemandi
authors: Santiago D
authors: SD
authors: Palma
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D001682:Biological Availability; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D003315:Cornea / Q000378:metabolism*; D003956:Dialysis; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D007429:Intraocular Pressure / Q000187:drug effects; D049329:Nanostructures / Q000737:chemistry*; D009883:Ophthalmic Solutions; D010539:Permeability; D011817:Rabbits
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D004337:Drug Carriers; D009883:Ophthalmic Solutions; C006641:ascorbyl monolaurate; D000086:Acetazolamide; D001205:Ascorbic Acid