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Evaluation of Antimicrobial Effectiveness of Ophthalmic Drops Sold in Nigeria Pharmacy Stores and Market Places

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© © All Rights Reserved
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EVALUATION OF ANTIMICROBIAL EFFECTIVENESS OF OPHTHALMIC DROPS


SOLD IN NIGERIA PHARMACY STORES AND MARKET PLACES

Article · February 2017

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“Evaluation of antimicrobial effectiveness of ophthalmic drops sold in Nigeria pharmacy stores and market places”

ISSN No. 2394-3971

Original Research Article


EVALUATION OF ANTIMICROBIAL EFFECTIVENESS OF OPHTHALMIC DROPS
SOLD IN NIGERIA PHARMACY STORES AND MARKET PLACES
1
Oluwayemisi A. Olorode (PhD, MLS)* 2Ogba M. Ofonime (PhD, MLS) and
1
Azere E. Orowo (BPharm)
1
Department of Pharmaceutical Microbiology and Biotechnology, Niger Delta University,
Wilberforce Island, Bayelsa State.
2
Department of Medical Laboratory Science, University of Calabar, Nigeria.

Submitted on: January 2017


Accepted on: February 2017
For Correspondence
Email ID:

Abstract
Eye drops are sterile liquids for instillation into the conjunctiva sac worldwide; they are
formulated and packaged in order to maintain their sterility throughout the period of use. This
study was conducted to evaluate the pharmaceutical quality and antimicrobial effectiveness
ophthalmic drops offered for sale in Nigeria. A total of thirty-three (33) sterile eye drops of 11
different brands (3 of each) were examined; these include Gentamicin, Chloramphenicol,
Ciprofloxacin, Betaxolol, Betamethasone, Artificial tears, Hypromellose, Diclofenac, and
Timolol were purchased in pharmacy stores and the other two which are natural drops were
purchased from the market and bus vendor (Oster and Quick action). A standardized (using 0.5
Mac Farland turbidity standard) clinical isolates of Escherichia coli, Pseudomonas aeruginosa,
and Staphylococcus aureus were added (according to British and United State Pharmacopoeia) to
newly opened eye drops and stored at room temperature away from light. At 1hour, 3days,
7days, 14days, 21days and 28days samples were collected, plated and the number of viable
microorganisms was counted after 48hrs incubation at 37oC. Seven 7 (Gentamicin,
Betamethasone, Chloramphenicol, Hypromellose, Artificial tears, Ciprofloxacin and Medico Research Chronicles, 2017
Betaxolol)out of the test eye drops had significant antimicrobial activity with their anti-infective
having the highest rapidity in bactericidal activity; Timolol and Diclofenac showed a reduced
and poor antimicrobial activity. The findings had shown 77.8 of the test eye drops passed the
antimicrobial effectiveness test while 22.2% failed. Quick action and Oster were found to
contain heavy microbial growth. In conclusion, the ophthalmic drops offered for sale in Nigeria
from approved medicine stores are of acceptable standard.

Keywords: Ophthalmic drops, Antimicrobial effectiveness, Escherichia coli, Pseudomonas


aeruginosa and Staphylococcus aureus

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Introduction multiple dosage eye drop formulations as


Eye drops (ophthalmic drops) are a popular repeated use can lead to contamination.
dosage formulation meant for instillation to These eye drops are mostly packaged in
the conjunctival sac. They have been used plastic containers with droppers and patients
successfully for the treatment of various eye are advised to avoid touching the tip with
infections and are either prescribed by an their fingers and the eyes (conjunctiva sac)
ophthalmologist or sold over the counter. to which they are being instilled thus to
The use of eye drops is widespread in all prevent contamination of the product with
regions of the world especially during the micro-organisms present in the fingers and
harmattan or dry season like in Nigeria, conjunctiva sac. The use of contaminated
where dust particles, as well as other eye drops may lead to a range of eye
irritants, are easily blown into the eye. They diseases, some easily treated while others
contain medicaments dissolved or suspended may lead to blurred vision or permanent loss
in aqueous or oily vehicles. Depending on of sight. These reasons, therefore, demand
the condition being treated, they may the use of antimicrobial preservatives in the
contain steroids, antihistamines, formulation of eye drops at a concentration
sympathomimetics, beta receptor blockers, that will impede microbial growth without
parasympathomimetics, parasympatholytics, causing irritation to the ocular tissues of the
prostaglandins, non-steroidal anti- patient/user. A preservative is a substance
inflammatory drugs (NSAID’s), antibiotics, that is added to products such as foods,
antifungal or topical anesthetics. Eye drops pharmaceuticals, paints, biological samples,
do not sometimes have medications in them wood, beverages, etc. to prevent
and are only lubricating and tear replacing decomposition by microbial growth or by
solutions. Since eye drops are formulations undesirable chemical changes. In general,
meant to be instilled into the conjunctiva sac preservation is implemented in two modes,
of the eyes, there is a need for them to be chemical and physical. Chemical
sterile (totally free from microbial preservation entails adding chemical
contaminants). For eye drop products, the compounds to the product while physical
requirement for sterility should be preservation may entail refrigeration and
maintained throughout the period of their drying (Msgati and Titus,2012).The
use. This is because while in use microbial preservatives used in ophthalmic drops (eye Medico Research Chronicles, 2017
contamination may lead to product drops) include; phenylmercuric nitrate or
degradation or result in ocular infections acetate, benzalkonium chloride,
(Samadi et al., 2013). chlorhexidine acetate, thiomersal, para
They are convenient and easily administered hydroxybenzoate, EDTA, chlorobutanol,
without causing irritation to the eye. A benzyl alcohol, phenyl ethyl alcohol at in
major disadvantage of eye drops is its use concentrations. These preservatives are
imprecise dosage as there is the danger of added to multidose eye-drops to inhibit
instilling more than or less than the required microbial contamination and may also act
dose. Another disadvantage of eye drops is synergistically with other preservatives or
the rather high possibility of contamination with other components of the formula to
with micro-organism as well as foreign enhance the total effects for microbial
matters. Contamination with control. Their inclusion should be at a
microorganisms is frequently seen in concentration that is effective but non-toxic

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to humans. The single most dominant factor premises in Yenagoa, Bayelsa state, Nigeria.
characteristic of all ophthalmic products is a These include preparations of Gentamicin
specification on sterility not only after sulfate, Chloramphenicol, Timolol,
preparation but throughout the period of use. Betaxolol hydrochloride, Hypromellose,
This is a legal requirement that dates back to Diclofenac sodium, Artificial tears, and
1955 (Marchese et al.,2001) and is still in Betamethasone eye drops from different
force today. Despite this requirement, manufacturers. Two (2) of the brands of eye
extensive researches have not been done on drops (3 from each brand) were purchased
the quality and antimicrobial effectiveness from medicine vendors one from a
of commercially available eye drops marketplace and the other from a bus vendor
purchased and used by patients. This study in Port Harcourt, Rivers state. The eye drops
helps to evaluate the effectiveness of were; Quick action® natural eye drop and
antimicrobial preservatives used in eye Oster ® eye drop. Both of them are locally
drops sold in Bayelsa and Rivers states, produced and they contain natural
Nigeria. ingredients. The prices of the study eye drop
ranged from #200 to #1300 (Nigerian
Materials and Method money). Each container label was noted for
Study setting the following: Contents, Manufacturer,
The study was carried out in Bayelsa state, Manufacturing and Expiry dates,
Nigeria and most of the eye drops were preservatives used and batch number.
purchased in her capital city, Yenagoa.
Bayelsa is a state in southern Nigeria in the Materials used
core Niger Delta region, between Delta state Sterile McCartney bottles, syringes (2ml
and Rivers state. The four main languages and5ml), sterile pipette, cotton wool, Petri
spoken are Izon, Nembe, Epie-Atissa and dishes, wire loop, autoclave, dryer,
Ogbia. Like the rest of Nigeria, English is incubator, foil paper, water bath, beakers,
the official language. Bayelsa has a riverine colony counter, sterile hockey stick,
and estuarine setting and a lot of her analytical balance.
communities are almost completely
surrounded by water hence making these Media used
communities inaccessible by road. Two of Nutrient agar, Nutrient broth, freshly Medico Research Chronicles, 2017
the eye drops used was purchased in Rivers prepared 0.5Mcfarland standards and
state, Nigeria. Her capital city is Port- thioglycollate medium (serving as
Harcourt and the state is bounded on the neutralizer) were used.
south by the Atlantic Ocean, to the North by
Imo, Abia and Anambra states, to the east by Preparation of inoculum for the challenge
Akwa Ibom state and to the west by Bayelsa test
and Delta states. Reference strains of microorganisms used
were from medical samples culture
Eye drops used collections maintained in pharmaceutical
A total of 33 eye drops of 11 different microbiology laboratory, faculty of
brands (3 from each brand) were used in this pharmacy, Niger Delta University and these
study. Nine (9) brands of the eye drops were include inoculums of Pseudomonas
purchased from registered pharmacy aeruginosa, Escherichia coli, and

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Staphylococcus aureus. The inoculums of drop. The inoculated product was then
the study organisms were taken from maintained at 20−25°c (room temperature)
nutrient agar slope culture and subculture in away from light, throughout the test period.
nutrient broth and incubated at 37oC At 1hour, 3 days, 7 days, 14 days, 21 days
overnight. The inoculum was then streaked and 28 days interval, 1ml of the sample were
on nutrient agar plates to get discrete withdrawn and inoculated into 9ml
colonies. The identity of each thioglycollate medium to neutralize the
microorganism was reassessed using colony preservative before plating out on nutrient
morphology and biochemical tests. Three to agar in duplicates and incubated at 37°c for
five colonies were then picked using a 48hours to determine the number of viable
sterile wire loop and transferred into sterile organisms on each plate using the colony
saline to obtain a microbial count of about counter and the mean value were computed
1*108 colony forming a unit (CFU) per ml from the number of colonies formed on
on comparison with the turbidity of
0.5Macfarland standard previously prepared. Results
Properties of the eye drops
Negative control test Table 1.0 showed the properties of the study
The negative control test was carried out by eye drops. Most of the products have their
plating out 0.1ml of each eye drop on manufacturing date, expiry date, batch
nutrient agar of each eye drop before the number and NAFDAC number clearly stated
inoculation of the microorganism to on the package. The exceptions to this were
determine the initial microbial load. The products J (the manufacturing date, expiry
plates were then incubated for 24hours after date, batch number and NAFDAC number
which the colony forming units were then was not indicated on the package), K (batch
enumerated. number and NAFDAC number not
indicated) and D (NAFDAC number not
Challenge test of the eye drops with the indicated). The eye drops were all within
microorganisms their expiry date and the volumes ranged
The eye drops were transferred aseptically from 5-15ml. From the nine(9) brands of eye
into sterile McCartney bottles and capped. drops, six (6) (Products A, B, D,E,F, and G)
Challenging organisms of 0.15ml, 0.1ml, contained benzalkonium chloride as Medico Research Chronicles, 2017
and 0.05ml (equivalent to 1% of the total preservative ranging from 0.01%-0.02%
volume of the 15ml,10ml, and 5ml eye with product D having a combination of
drops) was inoculated into each eye drop so benzalkonium chloride (0.01%) and
that for a brand of eye drop of 3 one disodium edetate (0.05%) as a preservative.
contained Pseudomonas aeruginosa, the Product C contained thiomersal (0.02mg/ml)
other Staphylococcus aureus, and the third as preservative while Product I contained
Escherichia coli. The eye drops were then phenylmercuric nitrate (0.001%). On the
mixed thoroughly to obtain even distribution other hand, Products H, J and K’s specific
of the microorganism throughout the eye preservative used was not stated.

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Results
Table1: Shows Properties of the Different Brands of Eye drops
Duration
Product Country of Mfd Expiry Batch Nafdac Volume
Content Preservative after
code manufacture date date number number (ml)
first opening

A Gentamicin Benzalkonium chloride (0.02%) India Jun-14 May-17 Yes Yes 10ml 1 month
sulphate
B Betaxolol HCl Benzalkonium chloride (0.1mg) Belgium May-13 Aug-16 Yes Yes 5ml 1 month
C Chloramphenicol Thiomersal (0.02mg/ml) India Oct-13 Sep-16 Yes Yes 10ml 28 days
D Artificial tears Benzalkonium chloride (0.01%), Belgium Jul-14 Jun-17 Yes No 15ml Nil
disodium edetate (0.05%)
E Ciprofloxacin Benzalkonium chloride (0.01 %) Nigeria Jul-13 Jun-16 Yes Yes 10ml 1 month
F Hypromellose Benzalkonium chloride (0.01%) United Jul-14 Jul-17 Yes Yes 10ml 28 days
kingdom
G Timolol Benzalkonium chloride (0.01%) India Sep-14 Aug-17 Yes Yes 10ml 28 days
H Betamethasone + Nil Nigeria Nov-14 Oct-17 Yes Yes 10ml 28 days
neomycin
I Diclofenac Phenylmecuric nitrate (0.001%) India Feb-14 Jan-17 Yes Yes 10ml 1 month
sodium

Medico Research Chronicles, 2017


J Oster natural eye Nil Nigeria Nil Nil no No 10ml 2 months
drop
K Quick action Nil Nigeria Feb-15 Feb-18 No No 10ml 1 month
natural eye drop

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Table2 shows the result of the negative hours. All the eye drops were found to be
control test of the eye drops when cultured sterile with the exception of Oster and Quick
on nutrient agar and incubated at 37◦c for 24 action eye drops.

Table 2: Negative control test of the eye drops

Product code Eye drop brand Number Colony forming


Examined unit/ml

A Gentamicin 1 0
2 0
3 0
B Betaxolol 1 0
2 0
3 0
C Chloramphenicol 1 0
2 0
3 0
D Artificial tears 1 0
2 0
3 0
E Ciprofloxacin 1 0
2 0
3 0
F Hypromellose 1 0
2 0
3 0
G Timolol 1 0
2 0
3 0
H Betamethasone 1 0
2 0 Medico Research Chronicles, 2017
3 0
I Diclofenac 1 0
2 0
3 0
J Oster eye drop 1 >10⁵
2 >10⁵
3 >10⁵
K Quick action 1 >10⁵
2 >10⁵
3 >10⁵

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TABLE 3: Negative Control Test of the Eye drops


Product code Eye drop brand Number examined Colony
forming unit/ml

A Gentamicin 1 0
2 0
3 0
B Betaxolol 1 0
2 0
3 0
C Chloramphenicol 1 0
2 0
3 0
D Artificial tears 1 0
2 0
3 0
E Ciprofloxacin 1 0
2 0
3 0
F Hypromellose 1 0
2 0
3 0
G Timolol 1 0
2 0
3 0
H Betamethasone 1 0
2 0
3 0
I Diclofenac 1 0
2 0
3 0
J Oster eye drop 1 >10⁵ Medico Research Chronicles, 2017
2 >10⁵
3 >10⁵
K Quick action 1 >10⁵
2 >10⁵
3 >10⁵
Figures 1.0 to 6.0 depict bar charts of the aureus against the study eye drops listed
challenge tests of ophthalmic drops to the above, while figure 3.0 depicted the graph of
test organisms. Figure 1.0 shows the bar Pseudomonas aeruginosa against the study
chart of Escherichia coli against the study eye drops. Figures 4.0 to 6.0 expressed the
brands of eye drops, Gentamycin, graph of Escherichia coli, Staphylococcus
Chloramphenicol, Ciprofloxacin, Timolol, aureus and Pseudomonas aeruginosa
Betaxolol, Betamethasone, Hypromellose, challenge test against the Quick action and
Artificial tears, Quick action, Oster. Figure Oster respectively.
2.0 showed the bar chart of Staphylococcus

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Figure 1: Showing Challenge test of Ophthalmic drops to Escherichia coli

Medico Research Chronicles, 2017

Figure 2: showing challenge test of the ophthalmic drops to Staphylococcus aureus

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Figure 3: showing challenge test of the ophthalmic drops to Pseudomonas aeruginosa

Note: From the bar charts (1, 2 and 3), a charts for Oster® and Quick action® eye
growth batch pattern is observed at 1 hour, 3 drops is due to the high number of colony
days, 7 days, 21 days and 28 days when the forming units observed relative to the other
eye drops are inoculated with the test eye drops, hence the need for a separate bar
organisms. It should be noted however that chart to show the microbial growth pattern
the supposed no growth value as seen in the for these eye drops.

Medico Research Chronicles, 2017

Figure 4: Showing challenge test of Quick action and Oster eye drops to Escherichia coli

Olorode O. A.. et al., Med. Res. Chron., 2017, 4 (1), 109-122 117
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Figure 5: showing challenge test of Quick action and Oster eye drops to Staphylococcus aureus

Medico Research Chronicles, 2017

Figure 6.0: Showing challenge test of Quick action and Oster eye drops to Pseudomonas
aeruginosa

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Discussion responsible for its activity on E. coli, S.


The antimicrobial preservative efficacy of aureus, and Ps. aeruginosa observed during
the eye drops challenged with Escherichia the challenge test. Artificial tears challenged
coli, Staphylococcus aureus, and with E. coli and S. aureus showed no growth
Pseudomonas aeruginosa is shown in Table from the 7th day and no growth at the 14th
3 and the negative control test is shown in day challenged with Ps. aeruginosa and no
Table 2. The negative control test of the eye recovery of the microorganism by the 28th
drops without inoculation of the day which is in compliance with the No
microorganism showed that the eye drops recovery (N.R) term of British
were sterile with the exception of the natural Pharmacopoeia (BP) ‘A’ criteria which
eye drops (Quick action ® and Oster ® eye requires no recovery of viable cells after the
drops) which showed a high level of 28 days. Hypromellose eye drop also
microbial contamination. showed no growth from the 14th day with no
The eye drop products used for evaluation in recovery of viable cells on the 28th day
this study were purchased in Yenagoa, when challenged with the test organisms.
Bayelsa state and Port- Harcourt, Rivers Betaxolol eye drop challenged with
state. It should be noted that the same eye Escherichia coli showed no growth at the 7th
drop brands are available and on sale day to the 28th day while challenged with
throughout the country. Staphylococcus aureus and Pseudomonas
From the antimicrobial preservative aeruginosa there was no growth from the
challenge test carried out, it was observed 14th day onwards.
that the anti-infective eye drops Diclofenac eye drop challenged with the
(Gentamicin, Chloramphenicol and micro-organism showed microbial presence
Ciprofloxacin eye drops) exhibited rapid even after a 14th day. The active ingredient
bactericidal activity showing no growth at 1 (Diclofenac) does not possess any
hour, 3days, 7days, 14 days, 21 days and 28 antimicrobial activity and the preservative
days this is consistent with a study carried employed in its formulation (phenylmercuric
out by Akinkunmi (2013). These results are nitrate 0.001%) may not possess adequate
not unexpected since gentamicin, antimicrobial activity against the selected
chloramphenicol and ciprofloxacin are bacteria used in this study. It should also be
antimicrobial agents with broad spectrum noted that the recommended concentration
activities against a wide range of bacteria of phenylmercuric nitrate as preservative
including S. aureus, Pseudomonas sp, system in eye drops is 0.002% according to Medico Research Chronicles, 2017
Proteus and many coliform bacilli the British pharmacopeia (2005) and United
(Rosenthal et al., 2006). This produces a states pharmacopeia (2012) hence the
synergistic effect with the preservative concentration of the preservative used in this
against any invading microorganism eye drop formulation falls below the
(Akinkunmi, 2013). The Betamethasone eye recommended standard and may be
drop also exhibited this property although responsible for its poor activity against the
the preservative used in its formulation was study organisms. Timolol eye drop had
not stated on the label. This eye drop, Escherichia coli, Staphylococcus aureus and
however, is a combination formulation Pseudomonas aeruginosa, growth except on
containing Betamethasone (0.1%w/v) and 14 days, but re-growth of bacteria cells on
Neomycin (0.5% w/v). Neomycin is an 28 days. This pattern previously documented
aminoglycoside and has excellent activity for Pseudomonas aeruginosa by Akers and
against Gram-negative and good activity Taylor (1990 and T I P 2015), occurs for a
against Gram-positive bacteria. This broad variety of reasons; of these, the loss of
spectrum of activity of Neomycin may be preservative stability/activity, mutational or
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physiological adaptive changes of the dropper back into the container after use,
microbial cells and the selection of more may again contaminate the container
resistant survivors have to be considered. In (Rahman et al., 2006). Previous studies on
Pseudomonas aeruginosa and other preserved eye drops by Schein et al (1992)
Pseudomonas spp the genetic ability to have found high contamination rates in beta
synthesize an alginate based biofilm playing blockers, steroid drops, and ocular lubricants
an important role in cell adhesion and in the and concluded that acetylcysteine,
protection against the inhibitory effects of hypromellose and prednisolone drops are
antibacterial agents is extensively described prone to contamination even in the presence
(Williams, 2011; Nicole, 2014). Natural eye of preservatives (David and Malik 2009).
drops (Oster and Quick action) only showed The requirement on the efficacy of
a reflection of their negative control test. antimicrobial preservation in the USP for
There was heavy microbial growth from 1 bacteria requires not less than 1 log
hour to the 28th day when challenged with reduction from the initial count after 7 days
the test organisms. and not less than 3 log reductions from the
Ophthalmic products are required to be initial count after 14 days and no increase
packaged in such a way that they will retard from the 14 days count after 28 days (USP
contamination. This is because multi-dose 29, 2006). The results obtained from this
containers may be opened and closed and study showed that the Gentamicin,
used many times by the consumer. During Chloramphenicol, Ciprofloxacin, Artificial
administration, the pipette attached to the tears, Betamethasone+neomycin,
cap of the bottle comes completely out of Hypromellose and Betaxolol eye drops had
the container and this exposes the contents significant activity against the test
of the bottle. Previous studies on preserved organisms due to the preservative system
eye drops have concluded that pathogenic employed in their formulation and intrinsic
Gram-negative bacteria are more likely to antimicrobial activity of their active
grow in the bottle reservoir than Gram- ingredient. The preservative systems
positive organisms which are mainly employed in Timolol and Diclofenac eye
commensals in the environment (Sunita, drops did not possess adequate antimicrobial
2013; Schein et al., 1992; Geyer et al., activity against the test organisms.
1995). All the study eye drops have their Conclusion
tips attached to the bottle. This is of a great In conclusion, seven (7) out of the 9 study
advantage of the old types of eye drops brands of eye drops (Gentamicin, Medico Research Chronicles, 2017
container that comprised a dropper Chloramphenicol, Ciprofloxacin,
separately packaged from the main Betamethasone, Artificial tears,
container. These old container types have Hypromellose and Betaxolol eye drops)
been reported to encourage contamination were of appropriate microbial quality since
during use leading to serious ocular they were shown to have complied with
infections (Stevens and Matheson, 1992). official requirements with respect to sterility
Spillage of the contents can also increase the and demonstrated ability to effectively kill
chance of contamination. Poor technique in microbes as required. Timolol and
administering the drops is a further risk Diclofenac had weak preservatives. Quick
factor for contamination especially if action and Oyster did not meet the sterility
patients are self-administering in an standard. Since 77.8% of the test eye drops
outpatient setting. Elderly patients with showed significant antimicrobial
provision and co-ordination may effectiveness, while 22.2% showed poor
inadvertently touch their eyes or skin with antimicrobial effectiveness profile, it can be
the pipette dropper and on insertion of the concluded that eye drops offered for sale
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and use in Nigerian pharmacy stores are of • David, P.F and Malik Y.K. (2009).
acceptable microbial quality and possessed Preservatives in topical ophthalmic
good antimicrobial profile. medications; historical and clinical
Recommendations perspectives. Expert Rev Opthalmol
For quality to be maintained throughout the 2009; 4(1) 59-64
use of the products, it is recommended that • Greyer, O. Bottom, E J. Podos, S. M.
patients should adhere to standard guidelines 1995. Microbial contamination of
of using eye drops. Each eye drop product medications used to treat glaucoma. Br J
should not be used by more than one person, Ophthalmol Vol. 7 pages 337 – 379
the tip of the bottle should not come in • Marchese, A. Bozzolasco M. Gualco, L.
contact with the hands or eye or other Schito G. C. and Debbia, E. A. 2001.
objects and the eye drops should be stored as Evaluation of Spontaneous
recommended to avoid contamination and Contamination of Ocular Medications.
assurance of sterility of the eye drop product Chemotherapy. Vol 47 pages 304- 308
throughout its period of use. The regulatory Msagati, A and Titus A.M. (2012).The
agency in Nigeria, National Agency for chemistry of food additives and
Food and Drug Administration and Control preservatives. Retrieved from
(NAFDAC), should checkmate the illicit http:/www.eblib.com
manufacture and sale of natural eye drop • Nicole Vu, Kevin Nguyen, and Thomas
products in the country as those encountered CK (2014). The essentials of United
in the course of this study (Quick action ® states pharmacopeia chapter 51
and Oster ® eye drops). The dates of antimicrobial effectiveness testing and
manufacture, expiry is also important and its application in pharmaceutical
should be specified, this would give an idea compounding. International journal of
about the timeframe, the wholesomeness of pharmaceutical compounding Vol. 18.
the product can be assured and the general No 2;123-130
public should purchase NAFDAC registered • Rahman, M. O. Tejwani, D. Wilson, J.
products. A. Butcher, I. and Ramaesh, K. 2006.
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