Herrero-Vanrell R, Fernandez-Carballido A, Frutos G, Cadórniga R
Departamento de Farmacia y Technología Farmacéutica, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
J Ocul Pharmacol Ther. 2000 Oct;16(5):419-28. doi: 10.1089/jop.2000.16.419.
The aim of this work was to evaluate how the addition of mucoadhesive polymers to aqueous solutions affects the ocular response of tropicamide (0.2%; w/v). The polymer solutions tested were carboxymethylcellulose sodium salt (CMC-Na; 1%; w/v), hyaluronic acid sodium salt (HA-Na; 0.1%; w/v) and polyacrylic acid (PAA; 0.2%; w/v). Polymeric solutions were compared to a nonviscous formulation (AS). In vitro mucoadhesion measurements were expressed as a percentage of the adhesion force mucin-mucin, considering this one as 100% mucoadhesion. The values ofmucoadhesion obtained were 172%, 127%, 103% and 87.6% for formulations with CMC, PAA, HA and AS, respectively. The mydriatic response of tropicamide was determined in adult male New Zealand rabbits, weighing 1.7-2 Kg, by pupil diameter measurements at different times after instillation. The area under the mydriatic response-time curve (AUC 0-6 hr) was interpreted as an indication of the bioavailability of tropicamide in each vehicle. The AUC 0-6 hr was related to the in vitro mucoadhesion for each formulation. Tropicamide solutions with CMC-Na and PAA resulted in mucoadhesion and AUC 0-6 hr values approximately 1.9 and 1.4 times higher than AS. Although the solution with HA-Na was less mucoadhesive than PAA, the hyaluronic acid solution resulted in a higher AUC mydriasis/time value. Formulations with HA-Na and PAA presented values of surface tension close to that observed in the lacrimal fluid, with the Imax (maximum pupil diameter) being higher than for CMC-Na and AS. Greater than 90% of the mydriatic effect disappeared 4.5 hr after instillation for PAA and AS. Nevertheless, the mydriatic effect remained up to 5.5 hr for HA-Na and CMC-Na. HA-Na solution enhanced the bioavailability oftropicamide, presenting a value of mucoadhesion similar to the reference mucin-mucin.
本研究的目的是评估向水溶液中添加粘膜粘附聚合物如何影响托吡卡胺（0.2%；w/v）的眼部反应。所测试的聚合物溶液为羧甲基纤维素钠盐（CMC-Na；1%；w/v）、透明质酸钠盐（HA-Na；0.1%；w/v）和聚丙烯酸（PAA；0.2%；w/v）。将聚合物溶液与非粘性制剂（AS）进行比较。体外粘膜粘附测量值以粘蛋白-粘蛋白粘附力的百分比表示，将其视为100%粘膜粘附。对于含CMC、PAA、HA和AS的制剂，获得的粘膜粘附值分别为172%、127%、103%和87.6%。通过在成年雄性新西兰兔（体重1.7-2千克）滴入后不同时间测量瞳孔直径，确定托吡卡胺的散瞳反应。散瞳反应-时间曲线下面积（AUC 0-6小时）被解释为每种载体中托吡卡胺生物利用度的指标。AUC 0-6小时与每种制剂的体外粘膜粘附有关。含CMC-Na和PAA的托吡卡胺溶液导致的粘膜粘附和AUC 0-6小时值分别比AS高约1.9倍和1.4倍。虽然含HA-Na的溶液比PAA的粘膜粘附性小，但透明质酸溶液导致更高的AUC散瞳/时间值。含HA-Na和PAA的制剂表面张力值接近泪液中的观察值，Imax（最大瞳孔直径）高于CMC-Na和AS。对于PAA和AS，超过90%的散瞳作用在滴入后4.5小时消失。然而，对于HA-Na和CMC-Na，散瞳作用可持续至5.5小时。HA-Na溶液提高了托吡卡胺的生物利用度，其粘膜粘附值与参考粘蛋白-粘蛋白相似。
