Saettone M F, Chetoni P, Cappanera L, Conte U, Finne U, Järvinen K, Salivirta J, Urtti A
Laboratory of Pharmaceutical Technology/Biopharmaceutics, Institute of Pharmaceutical Chemistry, University of Pisa, Italy.
J Ocul Pharmacol. 1993 Spring;9(1):1-12. doi: 10.1089/jop.1993.9.1.
The object of this study was to test whether flat, circular ophthalmic inserts releasing drug only from one side, would show improved activity parameters and reduced systemic absorption. To this purpose, uncoated and one-side coated hydroxypropylcellulose inserts containing timolol were prepared and evaluated. An acrylic copolymer (Eudragit RS) was used as coating material. Timolol release from inserts was studied both in vitro and in vivo. Timolol release in vitro from the coated inserts was much slower than from the uncoated ones, due to the smaller releasing surface area. Compared with timolol eyedrops (0.5%, 50 microliters), administration of 250 micrograms of timolol in uncoated or coated inserts produced a significantly greater hypotensive effect at 6 and 8 hr post instillation in rabbits with artificially increased intraocular pressure. The coated inserts containing 62.5 micrograms of timolol antagonised isoproterenol-induced ocular hypotension significantly more than timolol eyedrops (0.5%, 12.5 microliters) and uncoated inserts containing 62.5 micrograms of timolol. Both uncoated and coated inserts provided a significant sustaining of timolol release in tear fluid and decreased systemic peak concentrations of timolol with respect to the eyedrop control. However, one-side coated inserts failed to show significant improvements with respect to the uncoated samples.
本研究的目的是测试仅从一侧释放药物的扁平圆形眼科插入剂是否会显示出改善的活性参数并减少全身吸收。为此，制备并评估了含噻吗洛尔的未包衣和单侧包衣的羟丙基纤维素插入剂。使用丙烯酸共聚物（尤特奇RS）作为包衣材料。对插入剂中噻吗洛尔的释放进行了体外和体内研究。由于释放表面积较小，包衣插入剂在体外的噻吗洛尔释放比未包衣的插入剂慢得多。与噻吗洛尔滴眼液（0.5%，50微升）相比，向人工升高眼压的兔眼滴入250微克未包衣或包衣插入剂中的噻吗洛尔后6小时和8小时产生的降压作用明显更强。含62.5微克噻吗洛尔的包衣插入剂比噻吗洛尔滴眼液（0.5%，12.5微升）和含62.5微克噻吗洛尔的未包衣插入剂更能显著对抗异丙肾上腺素引起的眼压降低。与滴眼液对照相比，未包衣和包衣插入剂在泪液中均能显著维持噻吗洛尔的释放，并降低噻吗洛尔的全身峰值浓度。然而，单侧包衣插入剂与未包衣样品相比未显示出显著改善。
