REDUCTION OF CARDIOVASCULAR SIDE-EFFECTS ASSOCIATED WITH OCULAR ADMINISTRATION OF METIPRANOLOL BY INCLUSION IN POLYMERIC NANOCAPSULES

被引:21
作者
LOSA, C [1 ]
ALONSO, MJ [1 ]
VILA, JL [1 ]
ORALLO, F [1 ]
MARTINEZ, J [1 ]
SAAVEDRA, JA [1 ]
PASTOR, JC [1 ]
机构
[1] FAC FARM SANTIAGO DE COMPOSTELA,FARM GALEN LAB,CAMPUS UNIV,E-15706 SANTIAGO,SPAIN
来源
JOURNAL OF OCULAR PHARMACOLOGY | 1992年 / 8卷 / 03期
关键词
D O I
10.1089/jop.1992.8.191
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
A new formulation of metipranolol base for ophthalmic administration was developed consisting of a colloidal suspension of polyepsiloncaprolactone nanocapsules with an oily core (Migliol 840) in which the drug is dissolved. Physicochemical properties of the nanocapsules show that the polymer coating around the oily droplets causes an important reduction of the droplet size, with no significant modification of the surface charge noted. When this formulation was administered to rabbits, a reduction of intraocular pressure similar to that seen with commercial eye drops was observed. Nevertheless, the evaluation of the cardiovascular side effects clearly showed lower conjunctival absorption of the encapsulated drug compared with the commercial drops. The direct (bradycardia) and the indirect evaluation (based on the study of the influence on the hypotensive and positive chronotropic effects of isoprenaline) showed that blockage of beta-adrenoreceptors was reduced greatly by the topical administration of the new formulation.
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页码:191 / 198
页数:8
相关论文
共 13 条
[1]  
Patton T.F., Robinson J.R., Quantitative precorneal disposition of topically applied pilocarpine nitrate in rabbit eyes, J. Pharm. Sci, 65, pp. 1295-1301, (1976)
[2]  
Kaila T., Salminen L., Huupponen R., Systemic absorption of topically applied ocular timolol, J. Ocul. Pharmacol, 1, pp. 79-83, (1985)
[3]  
Munroe W.P., Rindone J.P., Kershner R.M., Systemic side effects associated with the ophthalmic administration of timolol, Drug Intell. Clin. Pharm, 19, pp. 85-89, (1985)
[4]  
Chang S.-C., Bundgaard H., Buur A., Lee V.H.L., Improved corneal penetration of timolol by prodrugs as a means to reduce systemic drug load, Invest. Ophthalmol. Vis. Sci, 28, pp. 487-491, (1987)
[5]  
Bundgaard H., Improved ocular delivery of pilocarpine and timolol through prodrugs, 5th Int. Conf. Pharm. Tech., Paris, 1, pp. 52-60, (1989)
[6]  
Losa C., Calvo P., Castro E., Vila Jato J.L., Alonso M.J., Improvement of ocular penetration of amikacin sulphate by association to poly(butylcyanoacrylate) nanoparticles, J. Pharm. Pharmacol, 43, pp. 548-552, (1991)
[7]  
Diepold R., Kreuter J., Himber J., Gurny R., Lee V.H.L., Robinson J.R., Saettone M.F., Schnaudigel O.E., Comparison of different models for the testing of pilocarpine eyedrops using conventional eyedrops and a novel depot formulation (nanoparticles), Graefe's Arch. Clin. Exp. Ophthalmol, 227, pp. 188-193, (1989)
[8]  
Marchal-Heussler L., Maincent P., Hoffman M., Spittler J., Couvreur P., Antiglaucomatous activity of betaxolol chlorhydrate sorbed onto different isobutylcyanoacrylate nanoparticles preparations, Int. J. Pharm, 58, pp. 115-122, (1990)
[9]  
Fessi H., Devissaguet J.P., Puisieux F., Procédé de préparation de systèmes colloïdaux dispersibles d'une substance sous forme de nanocapsules, Eur. Pat. Appl. NQ 0274, 961, (1988)
[10]  
Moffat A.C., Metipranolol, Clarke's Isolation and Identification of Drugs, (1986)