RT Journal Article
T1 Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop
A1 García Otero, Xurxo
A1 Díaz Tomé, Victoria
A1 Varela Fernández, Rubén
A1 Martín Pastor, Manuel
A1 González Barcia, Luis
A1 Blanco Méndez, José
A1 Mondelo García, Cristina
A1 Álvarez Bermúdez, María José
A1 González García, Francisco
A1 Aguiar Fernández, Pablo
A1 Fernández Ferreiro, Anxo
A1 Otero Espinar, Francisco Javier
K1 Tacrolimus
K1 Hydroxypropyl-β-cyclodextrin
K1 Topical ophthalmic administration
K1 Eye drops
K1 Uveitis
K1 PET/CT imaging
AB 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
PB MDPI
YR 2021
FD 2021
LK http://hdl.handle.net/10347/24467
UL http://hdl.handle.net/10347/24467
LA eng
NO Pharmaceutics 2021, 13(2), 149; https://doi.org/10.3390/pharmaceutics13020149
NO This research was partially supported by the Spanish Ministry of Science, Innovation and Universities (RTI2018-099597-B-100), the ISCIII (PI17/00940, RETICS Oftared, RD16/0008/0003 and RD12/0034/0017) and by Xunta de Galicia, grant numbers GPC2013/015 and GRC2017/015
DS Minerva
RD 22 abr 2026