Department of Pharmaceutics, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar- 751003, Odisha, India.
Daru. 2022 Jun;30(1):39-47. doi: 10.1007/s40199-021-00428-2. Epub 2022 Jan 7.
Macitentan blocks endothelin receptors in order to control the pulmonary arterial hypertension (PAH). Oral administration of macitentan is associated with painful urination and troubled breathing.
Formulated macitentan hydrogel film was used for examining the control of intraocular pressure, and the effect of surfactant and cosurfactant was studied.
Macitentan 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.
The 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.
Developed macitentan hydrogel film containing Transcutol (MT) could have a high potential for the control and management of ocular hypertension after topical application.
马西替坦通过阻断内皮素受体来控制肺动脉高压（PAH）。马西替坦口服给药与尿痛和呼吸困难有关。
本文使用已成型的马西替坦水凝胶膜来考察其对眼压的控制作用，并研究了表面活性剂和共溶剂的作用。
本文在羟丙甲纤维素（HPMC）基质系统中制备了马西替坦眼用膜制剂，使用不同的表面活性剂/共溶剂系统，并在兔眼结膜囊内给药后监测眼压。
该膜的固态特性表明马西替坦无定形化，且未观察到主要不相容性问题。表面活性剂、共表面活性剂和亲水性共溶剂系统的组合显著改善了药物释放和黏膜组织渗透。与其他膜相比，PEG 和 Transcutol 的存在显著提高了 MP 和 MT 的离体角膜渗透。与其他制剂相比，Transcutol（MT）分别显著提高了 MP 和 MT 的角膜渗透。Transcutol（MT）通过改善囊泡双层流动性和降低黏膜组织屏障来促进跨角膜扩散，从而显著提高了 MP 和 MT 的角膜渗透。由于平衡的液体渗透和聚合物链松弛速率，在药物释放和角膜渗透中观察到扩散和侵蚀控制行为的组合。MP 和 MT 膜用于进一步的体内研究，以实现对眼压的有效和持久控制。体内研究表明，在正常眼压兔模型中，眼压降低了约 23%。该膜成功地将眼压降低了 3 小时。
开发含有 Transcutol（MT）的马西替坦水凝胶膜具有通过局部给药控制和管理眼高压的巨大潜力。
