Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain.
Invest Ophthalmol Vis Sci. 2011 Jun 1;52(6):3548-56. doi: 10.1167/iovs.10-6338.
To assess the in vitro tolerance and in vivo efficacy of new unpreserved formulations of timolol maleate (TM) in aqueous solutions of bioadhesive polymers used for dry eye treatment and to compare them with three traditional TM formulations: unpreserved Timabak (Thea, Madrid, Spain), benzalkonium chloride (BAK)-preserved Timoftol (Frosst Laboratories, Madrid, Spain), and BAK-preserved Timolol Sandoz (Frosst Laboratories).
New formulations were composed of TM (0.5%) and carboxymethyl cellulose (0.5%), hyaluronic acid (0.2%), or hydroxypropylmethyl cellulose (0.3% or 0.5%). In vitro tolerance was determined in human corneal-limbal epithelial cells and normal human conjunctival cells. The ocular hypotensive effect was evaluated measuring IOP in rabbit eyes for 8 hours.
In all cases, cell survival after exposure to the formulations was greater in the new unpreserved TM formulations than in the traditional TM solutions (BAK-preserved and unpreserved). In addition, the new formulations were demonstrated to maintain the hypotensive effect of TM in different magnitudes. The maximum hypotensive effect was reached by TM 0.5% in carboxymethyl cellulose 0.5% (32.37%).
The results demonstrated that new unpreserved formulations of TM with bioadhesive polymers decreased IOP in rabbits and reached values closer to those reached by traditional solutions. Furthermore, new formulations presented a significantly higher in vitro tolerance than the same compound in traditional formulations. Although unpreserved formulations are usually more expensive, preservative-free antiglaucoma eye drops should improve compliance and adherence in the medical treatment of glaucoma. Bioadhesive polymers could be part of antiglaucoma formulations to reduce ocular toxicity, improve drug efficacy, and protect the ocular surface in long-term therapies.
评估新型马来酸噻吗洛尔（TM）未加防腐剂制剂在用于干眼症治疗的生物黏附聚合物水性溶液中的体外耐受性和体内疗效，并将其与三种传统 TM 制剂进行比较：未加防腐剂的 Timabak（西班牙马德里 Thea 公司）、苯扎氯铵（BAK）保存的 Timoftol（西班牙马德里 Frosst 实验室）和 BAK 保存的 Timolol Sandoz（西班牙马德里 Frosst 实验室）。
新制剂由 TM（0.5%）和羧甲基纤维素（0.5%）、透明质酸（0.2%）或羟丙基甲基纤维素（0.3%或 0.5%）组成。在人角膜缘上皮细胞和正常人类结膜细胞中测定体外耐受性。通过测量兔眼 8 小时内的眼压来评估眼压低作用。
在所有情况下，与传统 TM 溶液（BAK 保存和未保存）相比，新的未加防腐剂 TM 制剂暴露后细胞存活率更高。此外，新制剂被证明以不同程度维持 TM 的降压作用。最大降压作用是 TM 0.5%在羧甲基纤维素 0.5%（32.37%）中达到的。
结果表明，具有生物黏附聚合物的新型马来酸噻吗洛尔未加防腐剂制剂降低了兔眼内压，并达到了更接近传统溶液的水平。此外，新制剂的体外耐受性明显高于传统制剂中的相同化合物。尽管未加防腐剂的制剂通常更昂贵，但不含防腐剂的青光眼滴眼液应该可以提高青光眼治疗中的顺应性和依从性。生物黏附聚合物可作为青光眼制剂的一部分，以降低眼毒性、提高药物疗效并在长期治疗中保护眼表面。
