ArticleDaru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences2022
Management and control of intraocular pressure applying macitentan hydrogel film formulation: improved effect of surfactant and cosurfactant system.
Article in Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMacitentan blocks endothelin receptors in order to control the pulmonary arterial hypertension (PAH). Oral administration of macitentan is associated with painful urination and troubled breathing.
objectivesFormulated macitentan hydrogel film was used for examining the control of intraocular pressure, and the effect of surfactant and cosurfactant was studied.
methodsMacitentan ocular film formulation has been prepared in hydroxypropyl methylcellulose (HPMC) matrix system using different surfactant/co-surfactant system, and intraocular pressure was monitored on normotensive rabbit eyes after application in the cul-de-sac.
resultsThe solid state characterization of the film indicated amorphisation of macitentan and no issues regarding major incompatibility was observed. Combination of surfactant, co-surfactant and hydrophilic co-solvent systems in the said films markedly improved the drug release and mucosal tissue permeation. Presence of PEG and Transcutol significantly improved ex vivo corneal permeation of MP and MT respectively compared to other films. Transcutol (MT) exhibited greatest difference among the formulations by improving the vesicular bilayer fluidity and reducing the mucosal tissue barrier facilitating the transcorneal diffusion. A combination of diffusion and erosion control behavior was observed in drug release and corneal permeation of the films due to the balanced liquid penetration and polymeric chain relaxation rate. MP and MT films were used for further in vivo studies to achieve possible effective and prolonged control of intraocular pressure. In vivo study has revealed the reduction in intraocular pressure upto about 23 % when tested on normotensive rabbit model. The films has managed to lower the IOP upto 3 h.
conclusionDeveloped macitentan hydrogel film containing Transcutol (MT) could have a high potential for the control and management of ocular hypertension after topical application.
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