Development and characterization of Tc-99m timolol maleate for evaluating efficacy of in situ ocular drug delivery system

In situ gel-forming systems have drawn much attention of current researchers to
overcome the poor bioavailability from the conventional eye drops. The present
work described formulation and pharmacoscintigraphic evaluation of timololmaleate-
loaded chitosan/hydroxy propyl methyl cellulose (HPMC)-based
polymer matrix for enhanced ocular retention. Chitosan and HPMC ratio was
optimized and formulation was characterized for various in vitro parameters.
The ocular retention was studied on New Zealand rabbits by gamma
scintigraphy, which is a very simple and noninvasive technique. For scintigraphy
study, the drug timolol maleate was radiolabeled 99mTc by direct labeling
method using SnCl2·2H2O as reducing agent. The labeling procedure was
optimized to get maximum labeling efficiency (>98%). In vitro stability of the
radiolabeled drug (99mTc-timolol maleate complex) was checked and it was
found to be stable for up to 24 h. Plain drug eliminates rapidly as significant
activity was recorded in kidney and bladder after 2 h of ocular administration. It
was evident from the scintigraphic images and the time–activity curve plotted
from the data that the plain drug solution cleared very rapidly from the corneal
region and reached into systemic circulation via nasolachrymal drainage
system, as significant activity was recorded in kidney and bladder after 2 h of
ocular administration. Developed formulation cleared at a slow rate and
remained at corneal surface for longer time duration. No radioactivity was
observed in systemic circulation after 2 h. Ocular irritation of the developed
formulation was also checked by hen’s egg chorioallantoic membrane test and
formulation was found to be practically nonirritant. The study signified the
potential of gamma scintigraphy in evaluation of novel drug delivery systems in
a noninvasive manner.