Ocular powder: dry topical formulations of timolol are well tolerated in rabbits.
OBJECTIVE
Although eye drops are the most common form of ocular drugs, they have several limitations. Drug absorption into the eye is, in general, less than 5%, addition of preservatives is often necessary, and many drugs cannot be formulated as eye drops. Formulating ocular drugs as powder may solve these problems. The aim of this study was to investigate ocular irritation in rabbits following powder administration.


METHODS
Timolol maleate (TM) powder was administered to pigmented lop rabbits. Both pure TM powder and freeze-dried with PVP-polymer (2.4% of mass) were tested in 1.0- and 0.1-mg doses. Additionally, 4 rabbits received 0.1 mg of the pure powder 3 times a day for 8 d. Redness of the bulbar conjunctiva and the amount of discharge was rated from photographs (0-3 points, randomized and masked evaluation). The 8-d experiment additionally included examination with a slit lamp and examination of hematoxylin-eosin stained sections of eyes with light microscopy.


RESULTS
No serious or irreversible signs of irritation were noted. Doses of 1.0 mg were more irritating than 0.1-mg doses. There was no detectable difference in irritation between pure or freeze-dried powder. Slit-lamp examination, surface photographs and histology showed a negligible difference between drug and control eyes following the 8-d experiment.


CONCLUSIONS
The results suggest that 0.1 mg of timolol powder does not irritate the eye and that testing topical timolol powder in humans is feasible.
Hardarson
Sveinn Hákon
SH
Department of Ophthalmology, University of Iceland, National University Hospital, Reykjavík, Iceland.
Sigurdsson
Hákon Hrafn
HH
Níelsdóttir
Gudrún Eva
GE
Valgeirsson
Jón
J
Loftsson
Thorsteinn
T
Stefánsson
Einar
E
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005123:Eye / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects*; D005240:Feasibility Studies; D005260:Female; D008297:Male; D011208:Powders / Q000008:administration & dosage* / Q000009:adverse effects; D011817:Rabbits; D011859:Radiography; D015203:Reproducibility of Results; D013999:Timolol / Q000008:administration & dosage* / Q000009:adverse effects
D011208:Powders; D013999:Timolol