BACKGROUND: Application of timolol maleate (TM) in a conventional dosage form (solution) into the eye results in almost 80% of the instilled dose being lost either through spillage or due to drainage into the nasolacrimal duct. Later results in systemic side-effects especially in patients suffering from heart diseases or bronchial asthma thus limiting the usefulness of TM for the control of glaucoma. Earlier we had reported on the development of a mucoadhesive coated niosomal system for TM (TM REV(bio)) containing 0.25% TM. Presently we establish and report the pharmacokinetic and pharmacodynamic superiority of the developed ocular formulation of TM. METHODS: Aqueous humor concentration of TM in male albino rabbits, after instillation of one drop of TM solution (TMS) or TMREV(bio) was measured using the microdialysis method. RESULTS: Peak concentration of drug in aqueous humor from TMREV(bio) (12.46 microg/ml achieved at 60 min) was almost 1.7 times that of the control drug solution (TMS, 0.25%; 7.2 microg/ml). An important observation was that the high drug concentrations achieved upon TMREV(bio) administration were maintained for up to 2 h. AUC for TMREV(bio) formulation was 2.34 times that of the TMS. CONCLUSIONS: This study confirms a sustained and controlled effect of the developed formulation.
BACKGROUND: Application of timolol maleate (TM) in a conventional dosage form (solution) into the eye results in almost 80% of the instilled dose being lost either through spillage or due to drainage into the nasolacrimal duct. Later results in systemic side-effects especially in patients suffering from heart diseases or bronchial asthma thus limiting the usefulness of TM for the control of glaucoma. Earlier we had reported on the development of a mucoadhesive coated niosomal system for TM (TM REV(bio)) containing 0.25% TM. Presently we establish and report the pharmacokinetic and pharmacodynamic superiority of the developed ocular formulation of TM. METHODS: Aqueous humor concentration of TM in male albino rabbits, after instillation of one drop of TM solution (TMS) or TMREV(bio) was measured using the microdialysis method. RESULTS: Peak concentration of drug in aqueous humor from TMREV(bio) (12.46 microg/ml achieved at 60 min) was almost 1.7 times that of the control drug solution (TMS, 0.25%; 7.2 microg/ml). An important observation was that the high drug concentrations achieved upon TMREV(bio) administration were maintained for up to 2 h. AUC for TMREV(bio) formulation was 2.34 times that of the TMS. CONCLUSIONS: This study confirms a sustained and controlled effect of the developed formulation.
Authors: George A Baklayan; Erin C Collins; Tim Thetford; Arnel Soriano; Clara K Song; John Han Journal: J Ocul Pharmacol Ther Date: 2008-10 Impact factor: 2.671
Authors: I Bravo-Osuna; V Andrés-Guerrero; P Pastoriza Abal; I T Molina-Martínez; R Herrero-Vanrell Journal: Drug Deliv Transl Res Date: 2016-12 Impact factor: 4.617
Authors: Jose Navarro-Partida; Carlos Rodrigo Castro-Castaneda; Francisco J Santa Cruz-Pavlovich; Luis Abraham Aceves-Franco; Tomer Ori Guy; Arturo Santos Journal: Pharmaceutics Date: 2021-05-09 Impact factor: 6.321