Development of O/W nanoemulsions for ophthalmic administration of timolol.
After an initial screening of ingredients and production methods, nanoemulsions for ocular administration of timolol containing the drug as maleate (TM) or as ion-pair with AOT (TM/AOT) were prepared. The physico-chemical characterization of nanoemulsions, regarding mean diameter, pH, zeta potential, osmolarity, viscosity and surface tension, underlined their feasibility to be instilled into the eyes. Single components and emulsions were tested ex vivo on rabbit corneas to evaluate corneal irritation, that was measured according to opacity test. A marked decrease in corneal opacity was observed using the drug formulated in nanoemulsions rather than in aqueous solutions. Drug permeation and accumulation studies were performed on excised rabbit corneas. An increase in drug permeation through and accumulation into the corneas were observed using TM-AOT compared to TM due to an increase of lipophilicity of the drug as ion-pair. The introduction of chitosan (a positive charged mucoadhesive polymer) into emulsions allowed to increase TM permeation probably due to the interaction of chitosan with corneal epithelial cells.
Dipartimento Scienza e Tecnologia del Farmaco, Università di Torino, via P Giuria 9, 10125 Torino, Italy. marina.gallarate@unito.it
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Gallarate
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Chirio
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Bussano
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Peira
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Battaglia
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Baratta
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Trotta
D060433:Administration, Ophthalmic; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D048271:Chitosan / Q000737:chemistry; D003318:Corneal Opacity / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions / Q000008:administration & dosage / Q000138:chemical synthesis*; D066298:In Vitro Techniques; D036103:Nanotechnology / Q000379:methods; D011817:Rabbits; D012972:Sodium Hydroxide / Q000009:adverse effects; D013386:Succinates / Q000737:chemistry; D013999:Timolol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
C512554:1,4-bis(2-ethylhexyl) sodium sulfosuccinate; D000319:Adrenergic beta-Antagonists; D004655:Emulsions; D013386:Succinates; D012972:Sodium Hydroxide; D013999:Timolol; D048271:Chitosan