Mucoadhesive microdiscs engineered for ophthalmic drug delivery: effect of particle geometry and formulation on preocular residence time.
OBJECTIVE
To test the hypothesis that mucoadhesive microdiscs formulated in a rapidly dissolving tablet can increase preocular residence time.


METHODS
Microparticles smaller than 10 mum in diameter were fabricated by emulsification with poly(lactic-co-glycolic acid) as a core material and, in some cases, poly(ethylene glycol) as a mucoadhesion promoter. To examine the effect of particle geometry, microparticles were also cut to have flat surfaces (i.e., microdiscs) and were compared with spherical particles (i.e., microspheres). In vitro mucoadhesion of microparticles was tested on a mucous layer under shear stress, mimicking the human blink. The resultant microparticles were also formulated in two dosage forms, an aqueous suspension and a dry tablet, to test the effect of formulation on the retention capacity of microparticles on the preocular space of rabbits in vivo.


RESULTS
Mucoadhesive microdiscs adhered better to the simulated ocular surface than did other types of microparticles. When a dry tablet embedded with mucoadhesive microdiscs was administered in the cul-de-sac of the rabbit eye in vivo, these microdiscs exhibited longer retention than the other formulations tested in this study. More than 40% and 17% of mucoadhesive microdiscs remained on the preocular surface at 10 minutes and 30 minutes after administration, respectively. Fluorescence images from the eye surface showed that mucoadhesive microdiscs remain for at least 1 hour in the lower fornix.


CONCLUSIONS
This study demonstrated that mucoadhesive microdiscs formulated in a dry tablet can achieve a prolonged residence time on the preocular surface and thus are a promising drug delivery system for ophthalmic applications.
Choy
Young Bin
YB
School of Chemical and Biomolecular Engineering and Center for Drug Design, Development and Delivery, Georgia Institute of Technology, Atlanta, Georgia 30332-0100, USA.
Park
Jung-Hwan
JH
McCarey
Bernard E
BE
Edelhauser
Henry F
HF
Prausnitz
Mark R
MR
D000268:Adhesiveness; D000287:Administration, Topical; D000818:Animals; D001672:Biocompatible Materials; D003228:Conjunctiva / Q000187:drug effects / Q000648:ultrastructure; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D005128:Eye Diseases / Q000188:drug therapy*; D006801:Humans; D019344:Lactic Acid; D008297:Male; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008904:Miniaturization; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D013499:Surface Properties
D001672:Biocompatible Materials; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid