Yes, the drops are small.

GENERAL DROP SIZE INFO - NOT TRAVATAN

Indian Journal of Pharmacology 1993; 25: 163 - 164 SHORT COMMUNICATION
DROP VOLUME OF COMMERCIAL ANTI-GLAUCOMA EYE DROPS

AVTAR LAL*
Department of Pharmacology,
Mahatma Gandhi Institute of Medical Sciences,
Sevagram - 442 102,
Accepted for publication: January 02, 1993.
Summary Seventy six bottles of 19 different brands of anti- glaucoma eye
drops (pilocarpine 1, 2, 4 %
and timolol 0.25, 0.5 %) were tested for total volume, total number of
drops, drop volume,
drops/ml, and duration of therapy, by using a 10 ml glass cylinder with 0.1
ml graduations and
a mechanical counter. The range of the drop volume for pilocarpine 1% was
55.3 - 55.4 µl:
pilocarpine 2% was 41 .O - 54.4 µl; pilocarpine 4% was 47.8 - 47.8 µl and
timolol 0.25% was
38.7 - 55.2 µl; timolol 0.5% was 35.9 - 55.6 µ l . Ten out of 19 brands of
antiglaucoma eye
drops had total volume less than the labelled amount. The drop volume of
the commercial
anti- glaucoma eye drops is more than optimal.
Key words Glaucoma pilocarpine timolol drop volume
Eye drops are the predominant method of ocular
drug delivery system. The volume of the human tear
film is approximately 7-l 0 ~l.~-~ When some solution
is instilled into the eye it can hold about 30 p13-5
and the remaining part of the instilled fluid spills out
onto the cheeks. A part of it is also drained into the
nasolacrimal duct, .where it is absorbed producing
systemic side effects.2~3~6-8
In glaucoma, as the anti-glaucoma eye drops have
to be used for a long duration, the large drop volume
of these eye drops will cause nuisance and systemic
toxicity, in addition to increasing the cost of therapy.
The present study was undertaken to examine empirically
the drop volume, total volume, total number
of drops, drops/ml, and total duration of therapy of
these eye drops because no such study has been
reported previously.
MATERIALS AND METHODS
Seventy-six samples of 19 different brands of commercial
anti- glaucoma eye drops (pilocarpine 1, 2,
4 % and timolol 0.25, 0.5 %) were tested at room
temperature (33-35°C). The seal of each bottle was
opened and the solution was transferred to a standardized
plastic bottle, the dropper tip dimension of
which was equal to that of commercial anti-glaucoma
eye dropper tips, This was done for the sake of
accuracy and uniformity. The bottle was held upside
down and was pressed with the thumb and fingers
to such an extent that only single drop fell. The
pressure on the bottle was released after that. By
using a counter the drops were counted as they fell
into a 10 ml glass cylinder (Corning, with 0.1 ml
* Present address: Dr. Avtar Lal, Department of Pharmacology,
University College of Medical Sciences, Shahdara, Delhi.- 110 095.
graduation). The volume of the cylinder was
measured after every 20 drops. In this way, the total
volume and the total number of drops in each bottle
was measured. The same bottle and the cylinder
were used throughout the study and in between the
trials these were cleaned with deionised distilled
water and were dried before use.
The drop volume (µl) = measured volume of the
container (µl) + total number of drops in the container.
The number of the drops/ml = number of the
drops in the container + measured volume of the
container (ml).
For calculating the duration of therapy, it was assumed
that pilocarpine was used one drop in each
eye 4 times a day and timolol was used one drop
in each eye twice a day, and compliance was optimal.
Duration of therapy for pilocarpine (days) = Total
number of drops of pilocarpine + 4. Duration of
therapy for timolol (days) = Total number of drops
of timolol + 4. The results were expressed as range
for each drug.
RESULTS
The labelled volume of all medications were 5 ml
except one brand of pilocarpine (Carpomiotic 2%)
which is being supplied as 10 ml bottle. The total
volume, total number of drops, drops/ml, drops size,
and the duration of therapy varied widely (Table 1).
The drop volume of pilocarpine 1% ranged from 55.3
µ l to 55.4 µl; pilocarpine 2% (5 ml bottle) ranged
from 41 .O µl to 44.7 µl; pilocarpine 2% (10 ml bottle)
ranged from 54.4 µ l to 54.5 µl; pilocarpine 4% ranged
DROP VOLUME OF EYE DROPS 164
Table 1. The number of brands (N), labelled volume, measured total volume,
drops/ml, drop volume, total number of drops in bottle,
and duration of therapy for anti-glaucoma eye drops (pilocarpine and
timolol). The results are expressed in range.
Medications N Labelled Total volume Drops/ml Drop volume Total drops in
Duration of
volume (ml) (ml) (µl) b o t t l e therapy
(days)
Pilocarpine 1% 1 5 4.6 - 4.7 18.3 - 18.4 55.3 - 55.4 85 - 86 10.6 - 10.7
Pilocarpine 2% 2 5 4.8 - 5.0 22.3 - 24.4 41 .0 - 44.7 108 - 123 13.5 - 15.3
Pilocarpine 2% 1 10 9.4 - 9.5 18.3 - 18.4 54.4 - 54.5 173 - 174 18.3 - 18.4
Pilocarpine 4% 1 5 4.8 - 4.9 20.9 - 20.9 47.8 - 47.8 103-104 12.9 - 13.0
Timolol 0.25% 7 5 4.8 - 5.4 18.1 - 26.0 38.7 - 55.2 90 - 134 22.5 - 33.5
Timolol 0 . 5 % 7 5 4.9 - 5.4 18.0 - 28.0 35.9 - 55.6 89 - 142 22.2 - 35.5
from 47.8 µl to 47.8 µl; timolol 0.25% ranged from
38.7 µl to 55.2 µl; timolol 0.5% ranged from 35.9 µl
to 55.6 µl (Table 1). One brand of pilocarpine 1%
had a volume of 4.6 ml. Though, minimum overfilling
is a common goal of the pharmaceutical industry to
ensure the delivery of at least the labelled amount,
10 brands out of 19 had a total volume less than the
labelled amount.
DISCUSSION
There are some important implications of using eye
drops having smaller drop volume i.e., less than 30
µ l because under normal conditions an eye can hold
only 30 µ l of the instilled fluid.3-5 It has been reported
that a 15 µl drop volume of clonidine eye drop
decreased the intra-ocular pressure equivalent to
that produced by 70 µl drop, without causing any
systemic hypotension.g File and PattonlO found that
20 µ l drop of pilocarpine 0.5% caused a miotic
response that was essentially equivalent to that obtained
with 50 µ l drop. In our laboratory, we found
that 10 µl drop of phenylephrine 10% produced the
pupillary dilatation more than that of 40 µl or 80 µ l
drops in rabbits.”
It is also true that if the drop volume is smaller, the
number of drops per bottle volume would be more
and would cover a longer duration. The smaller drop
volume will not only make the therapy cost-effective
but will decrease the side effects and enhance the
therapeutic response.3,6-11 The optimal volume of
the drop should be in the range of 15 - 30 µl.¹ 121g-11
But, the drop volumes of the commercial eye drops
were more than optimal in the present study (Table
1). The bigger drop of the anti-glaucoma eye drops
can be made in the desired range by alterations in
the physical characters of the medications and by
decreasing the eye dropper tip dimension.’ This will
greatly diminish the cost of topical glaucoma therapy
and will also improve the therapeutic index.
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