Purpose: To evaluate the
efficacy and systemic side effects of a novel once-a-day timolol 0.1% eye gel
(Nyolol Gel®, Nyogel 0.1%®, Timosan®)
formulated with an innovative mucoadhesive vehicle, containing a combination of
carbomer and PVA, with a traditional timolol 0.5% solution.
Method: A phase I,
randomised, double-masked, two-period, two-week, cross-over study in 24 healthy
volunteers. The tests used: measurement of IOP; aqueous humour flow; exercise
test (ergometry); analyses of haemodynamic characteristics and pulmonary
function test; plasma concentration of timolol.
Results: Aqueous timolol
0.5% decreased peak heart rate in exercise test by 19,0 beats/min, which was
statistically significant from the reduction of only 4,6 beats/min for the
timolol 0.1% gel group. The two formulations differed significantly also in
their capability to change haemodynamic parameters in rest. The novel
mucoadhesive gel formulation did not change these parameters whereas the
aqueous solution was seen to decrease heart rate and the heamodynamic response
to body position. The maximum plasma concentration of timolol was about 10 fold
lower after timolol 0.1% gel as compared to aqueous timolol 0.5%. There was no
statistical difference between the once-a-day timolol 0.1% gel and the
traditional twice-a-day timolol 0.5% solution in their capability to decrease
IOP or aqueous humour production.
Conclusions: The results
indicate that by using a mucoadhesive vehicle that enhances timolol’s corneal
penetrability, it is possible to 1) reduce the concentration of active timolol
to 0.1% while maintaining its IOP-lowering efficacy; 2) to reduce the
applications to only once daily; 3) to improve the efficacy/systemic side effect
ratio. The present type of test pattern is a valuable tool when new drugs and
formulations are designed.