University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.
Graefes Arch Clin Exp Ophthalmol. 2010 Oct;248(10):1467-72. doi: 10.1007/s00417-010-1383-0. Epub 2010 May 2.
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.
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.
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.
This study confirms a sustained and controlled effect of the developed formulation.
马来酸噻吗洛尔（TM）以常规剂型（溶液）滴注入眼，大约有 80%的滴注剂量会由于溢出或通过鼻泪管引流而损失。这会导致全身性副作用，特别是在患有心脏病或支气管哮喘的患者中，从而限制了 TM 用于控制青光眼的用途。我们之前曾报道过开发一种含有 0.25%TM 的黏附性包衣的尼莫司汀脂质体系统（TMREV(bio)）。目前，我们建立并报告了开发的 TM 眼部制剂的药代动力学和药效学优势。
使用微透析法测量雄性白化兔滴注一滴 TM 溶液（TMS）或 TMREV(bio)后房水中 TM 的浓度。
从 TMREV(bio)（60 分钟时达到 12.46 微克/毫升）获得的房水中药物的峰值浓度几乎是对照药物溶液（TMS，0.25%；7.2 微克/毫升）的 1.7 倍。一个重要的观察结果是，在 TMREV(bio)给药后达到的高药物浓度可以维持长达 2 小时。TMREV(bio)制剂的 AUC 是 TMS 的 2.34 倍。
这项研究证实了开发的制剂具有持续和受控的作用。
