Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop.
Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop.
复制标题
他克莫司/羟丙基-β-环糊精滴眼剂的开发和表征。
DOI：
10.3390/pharmaceutics13020149
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发表时间：
2021-01-23
期刊：
影响因子：
5.4
通讯作者：
Otero-Espinar FJ
中科院分区：
文献类型：
--
作者：
García-Otero X;Díaz-Tomé V;Varela-Fernández R;Martín-Pastor M;González-Barcia M;Blanco-Méndez J;Mondelo-García C;Bermudez MA;Gonzalez F;Aguiar P;Fernández-Ferreiro A;Otero-Espinar FJ
葡萄膜炎是一种视力炎症性疾病，在发展中国家发病率很高。目前，市售治疗仍然有限，通常进行重新配制，以获得他克莫司滴眼液作为皮质类固醇难治性眼病的治疗替代品。这项工作的目的是开发一种粘膜粘附，无毒和稳定的局部眼用制剂，可以安全地在医院药房制备。以他克莫司/羟丙基-β-环糊精（HPβCD）为包合物，制备了4种不同的眼用制剂。相溶解度图、核磁共振（NMR）和分子模拟研究表明，他克莫司/HPβCD形成1：1和1：2包合物，用40%（w/v）HPβCD水溶液可获得0.0 2%（w/v）的他克莫司浓度。制剂在pH、渗透压和安全性方面也显示出良好的眼科性质。稳定性研究证明这些制剂在冷藏条件下至少稳定3个月。离体生物粘附和体内眼部持久性显示出良好的粘膜粘附特性，与临床环境中使用的参考药物混合物相比，眼部持久性更高（用40%（w/v）HPβCD和Liquifilm®配制的滴眼液的t1/2为86.2 min，而参考制剂为46.3 min）。因此，这些新型滴眼剂作为葡萄膜炎治疗的安全替代方案以及包括用于局部眼部施用的新药的通用组合物具有很高的潜力。
Uveitis is a vision inflammatory disorder with a high prevalence in developing countries. Currently, marketed treatments remain limited and reformulation is usually performed to obtain a tacrolimus eye drop as a therapeutic alternative in corticosteroid-refractory eye disease. The aim of this work was to develop a mucoadhesive, non-toxic and stable topical ophthalmic formulation that can be safely prepared in hospital pharmacy departments. Four different ophthalmic formulations were prepared based on the tacrolimus/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes’ formation. Phase solubility diagrams, Nuclear Magnetic Resonance (NMR) and molecular modeling studies showed the formation of 1:1 and 1:2 tacrolimus/HPβCD inclusion complexes, being possible to obtain a 0.02% (w/v) tacrolimus concentration by using 40% (w/v) HPβCD aqueous solutions. Formulations also showed good ophthalmic properties in terms of pH, osmolality and safety. Stability studies proved these formulations to be stable for at least 3 months in refrigeration. Ex vivo bioadhesion and in vivo ocular permanence showed good mucoadhesive properties with higher ocular permanence compared to the reference pharmacy compounding used in clinical settings (t1/2 of 86.2 min for the eyedrop elaborated with 40% (w/v) HPβCD and Liquifilm® versus 46.3 min for the reference formulation). Thus, these novel eye drops present high potential as a safe alternative for uveitis treatment, as well as a versatile composition to include new drugs intended for topical ophthalmic administration.
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影响因子：
2.9
作者：
Chu DS;Johnson SJ;Mallya UG;Davis MR;Sorg RA;Duh MS
通讯作者：
Duh MS
影响因子：
2.8
作者：
Dutescu, Ralf M.;Panfil, Claudia;Schrage, Norbert
通讯作者：
Schrage, Norbert
DOI：
10.1136/bjophthalmol-2013-304453
发表时间：
2014-08
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Fukushima A;Ohashi Y;Ebihara N;Uchio E;Okamoto S;Kumagai N;Shoji J;Takamura E;Nakagawa Y;Namba K;Fujishima H;Miyazaki D
通讯作者：
Miyazaki D
影响因子：
--
作者：
Baranowski P;Karolewicz B;Gajda M;Pluta J
通讯作者：
Pluta J
影响因子：
17.8
作者：
de Smet, Marc D.;Taylor, Simon R. J.;Lightman, Sue
通讯作者：
Lightman, Sue