Microbiological Quality of Semi-Solid Pharmacy compounded Topical Preparations

 

Sana Soheilian¹, Fatemeh Zeraati², Iraj Khodadadi³, Mahmoud Farshchian⁴, Marzieh Mosaed⁵, Mohamad Ali Seif Rabiei⁶, Shabnam Pourmoslemi⁷

¹Department of  Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

²Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

³Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

⁴Department of Dermatology, Hamadan University of Medical Sciences, Hamadan, Iran

⁵Vice Chancellor for Food and Drug, Hamadan University of medical sciences, Hamadan, Iran

⁶Department of Community Medicine, Hamadan Medical School, Hamadan University of Medical Sciences, Hamadan, Iran

 

ABSTRACT:

Pharmacy compounded topical preparations can be a favorable environment for microbial growth because of variable manufacturing condition and absence of antimicrobial agents in their formulations. In the present study evaluation of microbiological quality of three semi-solid pharmacy compounded topical preparations was performed according to United States Pharmacopeia (USP) acceptance criteria for non-sterile topical pharmaceuticals. Preparations were purchased from five different pharmacies in Hamedan, Iran and studied for total aerobic microbial count (TAMC), total yeast and mold count (TYMC) and presence of objectionable specified microorganisms. TAMC and TYMC were investigated using pour plate counting method and selective differential culture media combined with biochemical tests were used for detection of specified microorganisms in the preparations. Sixty percent of preparations were unacceptable due to at least one of the investigated items; TAMC, TYMC and presence of objectionable specified microorganisms. Half of the preparations had unacceptable TAMC, in 10% TYMC was above the acceptable range and four preparations were contaminated with Staphylococcus aurous (S. aurous) and Escherichia coli (E. coli). Other specified microorganisms were not detected. Results of this study showed unacceptable microbiological quality of pharmacy compounded topical preparations that can put consumers, especially those with compromised immunity, at serious risk.  A direct relationship was observed between the pharmacies and microbiological quality of their preparations, indicating the importance of implementing hygiene and good compounding practice in the preparation process.

 

 

 

 

 

INTRODUCTION:

With the development of commercial manufacturing, pharmacies gradually transitioned into dispensing of standardized drug products manufactured by the pharmaceutical industry.¹ However, there are certain circumstances in which pharmacy compounded drugs may be necessary for patients with certain therapeutic needs, for example patients with documented allergy to a drug ingredient, or to fulfill medical needs of individuals that cannot be met with commercially available products.^2,3,4

 

Topical preparations such as creams and ointments are widely used in the form of pharmacy compounded products. These products can be a favorable environment for microbial growth because of moisture content and absence of antimicrobial agents in their formulations. Although not expected to be sterile, they must be free of virulent pathogens and their content of aerobic microorganisms should be in a certain range.^5,6 For instance, USP suggests 10² cfu/g for TAMC and 10¹ cfu/g for TYMC, along with absence of objectionable microorganisms, S. aurous and Pseudomonas aeroginosa (P. aeroginosa) as the microbial quality standard for topical preparations.⁷ Presence of microorganisms irrespective of being objectionable or non-pathogenic can bring about changes in physical characteristics of topical preparations, including breaking of emulsions, thinning of creams, appearance of turbidity or deposit and change in odor and color of the product, all identified as quality defects.^8,9 There are also reports about disease outbreaks caused by contaminated topical preparations, which in some cases have involved patient deaths.^10,11

 

According to the importance of microbial quality of topical preparations, several studies have been conducted on pharmaceutical industry manufactured or pharmacy compounded topical preparations. Okeke and Laminara studied microbial quality of skin moisturizing products in a tropical developing country and found out that 16.3% of samples had TAMC more than 10³ cfu/g at the time of purchase and E. coli, Staphylococcus spp., Pseudomonas spp. and Bacillus spp. were the most commonly recovered bacteria. Following use for 14 days, TAMC of samples and proportion of E.coli and other gram negative bacteria increased. Authors suggested that organic constituents of these products, particularly in the absence of preservatives enhance survival and growth of microorganisms in containers stored under ambient tropical condition.¹² In another study Behravan and coworkers investigated type and incidence of predominant microorganisms in both unused and used cosmetic creams manufactured by eight different manufacturers in Iran. Results of this study showed that 17% of unused and 10% of used creams did not contain viable microorganisms. TAMCs were mainly in the range of 10²-10³ cfu/g and gram positive bacilli were the most frequent isolated genus, followed by S.aurous and E.coli. Level of contamination was highly related to the manufacturer.¹³ In a study performed by Abdollahi and coworkers on 5 pharmacy compounded semisolid skin preparations, samples were collected from 10 different pharmacies in Kerman, Iran and investigated for TAMC and type of present microorganisms. Results showed that 96% of samples contained viable microorganisms, from them 86% had more than 10² cfu/g TAMCs. Predominant microorganisms were gram positive bacilli, S. aurous, E. coli and P. aeroginosa. Only 30% and 14% of samples were acceptable according to USP acceptance criteria for absence of specified objectionable microorganisms and TAMC, respectively. Frequency of contamination was significantly related to the type of preparations, especially their water content and the pharmacy from which samples were purchased.¹⁴

 

According to the above mentioned studies, microbiological contamination is a major concern for topical preparations, especially when compounded in the pharmacies.^15,16 In the present study microbiological quality of three pharmacy compounded topical preparations were investigated. Preparations were purchased from 5 different pharmacies in Hamedan, Iran and studied for TAMC, TYMC (total yeast and mold count) and presence of 5 specified microorganisms; S. aurous, E. coli, P. aeroginosa, Candida albicans (C. albicans) and Aspergillus niger (A. niger), usually categorized as objectionable microorganisms. Results were reported as acceptable or unacceptable according to USP acceptance criteria for topical pharmaceuticals.

 

MATERIAL AND METHODS:

Microorganisms, chemicals and regents:

S. aurous (ATCC 6538), E.coli (ATCC 8739), P. aeroginosa (ATCC 9027), C.albicans (ATCC 10231) and A. niger spores (ATCC 16404) with relative PTCC numbers were supplied from Persian Type Culture Collection (PTCC) in the form of lyophilized microorganisms. They were cultured according to the supplier’s direction and preserved in deep freezer (-80 °C) for further studies.

 

Soybean casein digest agar (SCDA), soybean casein digest broth (SCDB), cornmeal agar and bismuth sulfite agar (BSA) culture media were supplied from Himedia (India). Lactose broth (LB), sabouraud dextrose agar (SDA), sabouraud dextrose broth (SDB) and cetrimide agar were purchased from Merck, Germany and Eosin Methylene Blue (EMB) Agar and mannitol salt agar (MSA) were from Conda (Spain).

 

Pharmacy compounded topical preparations:

Three semisolid topical preparations with higher rate of administration by dermatologists, including urea + eucerin, fluocinolone + eucerin and salicylic acid + betamethasone + eucerin, were purchased from 5 different pharmacies in Hamedan. This was performed using dermatologist’s prescriptions and pharmacies were not aware of the researchers’ intention. Sampling was repeated after 2 months from the same pharmacies.

 

Sample size and sample preparation:

Sample size was estimated 30 according to equation (1) which is used for determining sample size in cross-sectional studies. Three pharmacy compounded topical preparations were purchased from 5 different pharmacies, 2 times with 14 days interval. Each sample was investigated twice, immediately after purchase and 14 days later. Samples were kept at room temperature in a dark place in the 14 days interval.

 

N= z (1-α/2)² * p*q / d²                                                 equation (1)

 

In this formula α and d represent type I error and precision, respectively and are considered 0.05. p=0.96 represents expected prevalence of proportion which is derived from a previous study on pharmacy compounded semi-solid preparations conducted in Kerman, Iran.¹⁴ Since 95% level of confidence was used for this study, z value is 1.96.

 

Emulsified samples were prepared by dispersing 10g of preparations in 90 ml sterile normal saline containing (0.25-2 g) tween 80. Heating to maximum temperature of 45°C was used when needed to improve homogeneity of the mixture.  Further dilution was performed by transferring 10 mL of the emulsified sample to a 100 ml volumetric flask and adjusting the volume by normal saline.

 

Suitability of the test:

These tests were performed to investigate the ability of microbiological tests used in this study for recovering, identification and enumeration of microorganisms present in the products. Standard suspensions of S. aurous, E.coli, P. aeroginosa, C.albicans and A.niger spores in peptone water were prepared from their fresh cultures. Turbidity of each suspension was adjusted to one-half McFarland barium sulfate standard and further diluted to 1.5 × 10⁵ cfu/ml. Inoculation of preparations were performed by adding 20 µL of microorganisms suspensions to 20 ml of emulsified samples to contain 150 cfu/ml of test microorganisms. Control samples were also prepared by adding 20 µL of microorganisms’ suspensions to 20 ml normal saline. Control and inoculated samples were cultured in duplicate using (SCDA) medium for bacteria and (SDA) medium for C. albicans and A. niger using pour plate method. Enumeration of colonies was performed after 24 hours incubation at 35°C for bacteria and 2-7 days at 25°C for C. albicans and A. niger.

 

Suitability of selective and differential media used for determining specified microorganisms was investigated by inoculating the surface of each medium with relative specified microorganism. Inoculums from standard suspension of S. aurous, E. coli, P. aeroginosa, C. albicans and A. niger were transferred on MRS agar, EMB agar, cetrimide agar, cornmeal agar and SDA, respectively. Microbial growth was investigated after incubating the petri dishes for 24 hours at 35°C for bacteria and 2-5 days at 25°C for C. albicans and A. niger.

 

Sterility of culture media and diluents was approved by incubating them for at least 1 week and monitoring them for any signs of microbial growth.

 

TAMC and TYMC enumeration:

Three serial 10 fold dilutions of preparations were prepared according to the method described in sample preparation section. Pour plate method for determining the number of microorganisms present in each dilution was performed in duplicate plates. In pour plate method, 1 ml of sample was transferred to a sterile petri dish and 15-20 ml culture medium at the temperature of 45 °C was added. After mixing the contents of petri dish, culture medium was allowed to solidify at room temperature. Petri dish was then incubated upside down at 32.5±2.5 °C for bacteria and 20-25°C for mold/yeast. SCDA and SDA culture media were used for bacterial and mold/yeast count, respectively.

 

After 7 days of incubation, plates relevant to the dilution that contained 30-300 bacterial colonies or not more than 100 mold/yeast colonies were chosen. TAMC and TYMC were determined by multiplying the average number of colonies by the dilution factor.

 

Detection of specified microorganisms:

Pre-enrichment:

Pre-enrichment is enriching a sample by introducing nutrient culture media to resuscitate stressed and injured microorganisms and increase the number of cells into a detectable number. Low water content and presence of various ingredients in formulation of topical preparations attenuate growth of microorganisms while they are still alive. Pre-enrichment of samples can revitalize these microorganisms and prepare them for growth on selective differential culture media in the next step.

 

Pre-enrichment of preparations for specified bacteria was performed by transferring 10 g samples of the preparations to SCDB and LB culture media and incubating them at 32.5±2.5 °C for 24-48 hours. A 10 g sample of each preparation was also transferred to SDB culture medium and incubated at 20-25°C for 4 day in order to resuscitate possible specified molds/yeasts.

 

 

 

Test for S. aurous:

Inoculums of pre-enriched samples in SCDB were transferred on MSA culture medium and incubated at 32.5±2.5 °C for 24-48 hours. Absence of yellow colonies surrounded by yellow zones on MSA was interpreted as absence of S. aurous in the preparations. In the case of growth of colonies, gram staining and coagulase test were performed. For coagulase test, suspicious colonies were separately transferred to test tubes containing 0.5 ml horse plasma and incubated in 37°C water bath. Positive and negative control samples were also prepared and test tubes were monitored for plasma coagulation until 24 hours. When no coagulation was observed, preparations were considered free of S. aurous.¹⁷

 

Test for P. aeruginosa:

Inoculums of pre-enriched samples in SCDB were transferred on cetrimide agar culture medium and incubated at 32.5±2.5 °C for 24-48 hours. Absence of typical yellow-green colonies with fluorescence under 254 nm was interpreted as absence of P. aeroginosa in the preparations.¹⁸ In the case of growth of colonies, gram staining and oxidase test were performed. For oxidase test, suspicious colonies were transferred on N, N-dimethyl-p-phenylenedihydrochloride impregnated paper strips. When dark-blue color of the reagent was not changed to pink and then purple, oxidase test was considered negative.

 

Test for Salmonella species:

Inoculums of pre-enriched samples in LB were transferred on BSA culture medium and incubated at 32.5±2.5 °C for 48 hours. Absence of typical black colonies with metallic sheen was interpreted as absence of salmonella species in the preparations.

 

Test for E. coli:

Inoculums of pre-enriched samples in LB were transferred on EMB agar culture medium and incubated at 32.5±2.5 °C for 24-48 hours. Absence of typical dark, blue-black colonies with a metallic green sheen was interpreted as absence of E.coli in the preparations.

 

Test for C. albicans:

Inoculums of pre-enriched samples in SDB were transferred on cornmeal agar culture medium using an inoculating loop and streaked lightly. Cultures were covered by sterile cover glasses and incubated at 20-25 °C for 24 hours. In the case of presence of C. albicans in the samples, pseudomyceliums, chlamydospores and blastospores would be produced and observed by bright-field microscopy.

 

Test for A. niger:

Inoculums of pre-enriched samples in SDB were transferred on SDA culture medium and incubated at 20-25 °C for 3-5 days. In the case of growth of molds, detection of A. niger was performed according to macroscopic and microscopic characteristics of colonies and comparison with a standard culture. Size, color and texture of colonies are among the most important macroscopic features. Microscopic features such as shape and size of conidia, vesicles and hyphae should also be noted.

 

Data Analysis and Statistical Assessment:

Descriptive statistic analysis of results was performed by SPSS 16. Independent Sample T-Test was utilized to compare TAMC and TYMC of preparations in day 0 and day 14, (95% confidence interval, p=0.05). 

 

RESULTS:

Suitability tests:

Results of suitability tests for sample preparation and pour plate method used for determining TAMC and TYMC of preparations are shown in Table 1.

 

Table 1. Results of suitability tests               

Microorganisms	urea+eucerin		fluocinolone+eucerin		salicylic acid + betamethasone+ eucerin
	Mean recovered microorganisms ±SD (n=2)	Percent of recovery*	Mean recovered microorganisms ±SD (n=2)	Percent of recovery	Mean recovered microorganisms ±SD (n=2)	Percent of recovery
S. aurous	153 ± 5.6	96.2%	179.5 ± 10.6	92.5%	145 ± 4.2	88.9%
P. aeroginosa	150.5 ± 6.3	80%	166 ± 2.8	95.4%	155 ± 10.6	88.3%
E. coli	135 ± 4.2	75.8%	170 ± 7.1	89.9%	135.5 ± 6.4	87.9%
C. albicans	17 ± 1.4	80.9%	23.5 ± 4.9	81%	14 ± 2.8	86.7%
A. niger	132 ± 8.5	84.6%	138 ± 4.2	84.6%	152 ± 4.9	84.2%

*percent of recovered microorganisms from preparations compared with the recovered number from standard samples

 

In this study determining the possible specified microorganisms was performed using selective differential culture media and some biochemical tests. As another part of suitability tests, inoculums of standard specified microorganisms were cultured on selective differential culture media. Results showed growth of microorganisms’ colonies with their as anticipated morphological characteristics. Incubating diluents and culture media used for sample preparation and counting method for 14 days showed no signs of microbial growth and proved their sterility.

 

TAMC and TYMC enumeration and presence of specified microorganisms:

Tables 2-4 show results of TAMC and TYMC enumeration of the preparations, purchased 2 times from the same pharmacies (group A and B) and each one analyzed twice (day 0 and day 14). TAMC and TYMC amounts were compared with USP acceptance criteria for topical preparations and results are shown as acceptable or unacceptable (A or U, respectively) in the tables. In the case of detection of specified microorganisms in the preparations, they are specified in the tables. Contamination with specified microorganisms makes the preparation unacceptable regardless of its TAMC and TYMC.

 

From 30 preparations analyzed immediately after purchase, 22 items contained viable aerobic bacteria and 18 items contained mold/yeasts.

 

Table 2. TAMC and TYMC amounts for urea+eucerin preparations

Pharmacies

Group A

Group B

Day 0

Day 14

Day 0

Day 14

Mean TAMC ± SD

Mean TYMC ± SD

A/U

Mean TAMC ± SD

Mean TYMC ± SD

A/U

Mean TAMC ± SD

Mean TYMC ± SD

A/U

Mean TAMC ± SD

Mean TYMC ± SD

A/U

1

5 ± 7.1

0

A

30 ± 2.8

0

A

100 ± 2.8

0

A

10 ± 0

0

A

2

0

0

A

30 ± 1.4

0

A

0

0

A

115 ± 3.5

0

U

3

1080 ± 5.6

115 ± 2.1

U

150 ± 2.8

0

U

150 ± 1.4

0

U

65 ± 0.7

0

A

4

85 ± 0.71

20 ± 2.8

U*

50 ± 1.4

0

A

0

0

A

50 ± 0

0

A

5

0

0

U#

50 ± 0

0

A

120 ± 1.4

0

U

70 ± 1.4

0

U*

*growth on MSA and coagulase positive

 #growth on EMB agar

 

Table 3. TAMC and TYMC amounts for fluocinolone+eucerin preparations

Pharmacies

Group A

Group B

Day 0

Day 14

Day 0

Day 14

Mean TAMC ± SD

Mean TYMC ± SD

A/U

Mean TAMC ± SD

Mean TYMC ± SD

A/U

Mean TAMC ± SD

Mean TYMC ± SD

A/U

Mean TAMC ± SD

Mean TYMC ± SD

A/U

1

80 ± 2.8

120 ± 4.2

U*

90 ± 4.2

20 ± 2.8

U

180 ± 1.4

0

U

85 ± 2.1

15 ± 0.7

U

2

120 ± 1.4

430 ± 9.9

U

95 ± 0.7

275 ± 6.4

U

180 ± 1.4

0

U

30 ± 2.8

10 ± 1.4

A

3

70 ± 2.8

530 ± 11.3

U

55 ± 2.1

45 ± 3.5

U

650 ± 9.9

35 ± 0.7

U

590 ± 5.6

0

U

4

120 ± 2.8

65 ± 2.1

U

60 ± 2.8

0

A

450 ± 5.6

110 ± 4.2

U

30 ± 1.4

30 ± 0

U

5

405 ± 2.1

95 ± 4.9

U*

350 ± 7.1

65 ± 2.1

U

790 ± 8.5

5 ± 0.7

U

5 ± 3.5

0

A

*growth on MSA and coagulase positive

 

Table 4. TAMC and TYMC amounts for salicylic acid + betamethasone+ eucerin

Pharmacies

Group A

Group B

Day 0

Day 14

Day 0

Day 14

Mean TAMC ± SD

Mean TYMC ± SD

A/U

Mean TAMC ± SD

Mean TYMC ± SD

A/U

Mean TAMC ± SD

Mean TYMC ± SD

A/U

Mean TAMC ± SD

Mean TYMC ± SD

A/U

1

5 ± 0.7

5 ± 0.7

A

15 ± 0.7

5 ± 0.7

A

65 ± 2.1

5 ± 0.7

A

0

85 ± 0.7

A

2

70 ± 2.8

35 ± 0.7

U

35 ± 2.1

0

A

20 ± 1.4

10 ± 0

A

105 ± 3.5

65 ± 3.5

U

3

0

5 ± 0.7

A

0

5 ± 0.7

A

0

75 ± 0.7

A

5 ± 0.7

90 ± 2.8

U

4

0

0

A

80 ± 1.4

25 ± 0.7

U

0

15 ± 0.7

A

95 ± 2.1

0

A

5

130 ± 2.1

0

U

0

5 ± 0.7

A

15 ± 2.1

125 ± 3.5

U

0

65 ± 2.1

U

 

Microbiological quality of preparations in days 0 and 14.:

Comparing the results of TAMC and TYMC enumeration in days 0 and 14 was performed using Independent Sample T-Test (95% confidence interval, p=0.05). Based on results shown in Table 5, significant difference between TAMC and TYMC of days 0 and 14 were observed in one and four items, respectively.

 

 

Table 5. p values obtained from comparing TAMC and TYMC of preparations in days 0 and 14

Preparations	Pharmacies	P value*
		Group A		Group B
		TAMC	TYMC	TAMC	TYMC
urea+eucerin	1	0.77	ND	0.14	ND
	2	0.09	ND	0.14	ND
	3	0.03	0.08	0.08	ND
	4	0.2	0.5	0	ND
	5	ND#	ND	0.07	ND
fluocinolone+eucerin	1	0.81	0.11	0.11	0.09
	2	0.27	0.2	0.09	0.42
	3	0.61	0.11	0.53	0.02
	4	0.17	0.14	0.06	0.23
	5	0.48	0.57	0.06	0.42
salicylic acid + betamethasone+ eucerin	1	0.29	1	0.14	0.007
	2	0.3	0.02	0.19	0.27
	3	ND	1	0.42	0.6
	4	0.08	0.04	0.1	0.09
	5	0.08	0.42	0.5	0.17

*with 95% confidence interval, p value<0.05 indicates significant difference between the results and p value≥0.05 indicates absence of any significant difference between results of two studied groups

 

DISCUSSION:

Suitability tests showed that recovery of selected microorganisms from the three preparations were more than 80% in almost all cases. This means that sample preparation and pour plate method used for TAMC and TYMC enumeration can provide accurate total count of the microorganisms present in the preparations. Growth of specified microorganisms on their selective differential culture media means that in case of contamination of the preparations with specified microorganisms, they can be detected.

 

Based on results of this study, 60% of preparations did not fulfill USP acceptance criteria for topical preparations immediately after purchase (day 0). Half of the unacceptable items had TAMC larger than10² cfu/g. Three of thirty items had unacceptable TYMC (10 cfu/g) and in four items a specified microorganism was found. In the previous study on microbiological quality of pharmacy compounded topical preparations in Kerman, 86% of samples had TAMCs above 10² cfu/g and 14% were contaminated with specified objectionable microorganisms.¹⁴ Although in the present study preparations with unacceptable TAMCs constituted 50% of tested preparations, rate of contamination with specified microorganisms was the same. We also investigated TYMC as an important item in microbiological quality of non-sterile preparations that was in unacceptable range for 10% of preparations. 

According to growth on MSA, coagulation of horse plasma and observing gram positive cocci clusters in gram staining; three preparations were recognized as contaminated with S. aurous. Culture of urea+eucerin preparation purchased from pharmacy 5 on EMB agar resulted in growth of gram negative bacilli with distinct characteristics of E. coli colonies on this culture medium, that are characteristics of E. coli. Previous studies on industry manufactured and pharmacy compounded topical preparations showed gram positive bacilli, S. aurous and E. coli the most predominant bacteria in these preparations.^12-14 Both S. aurous and E.coli are human pathogens that can cause serious health problems for consumers of these preparations especially those with compromised immune system like elderly, children and consumers of immunosuppressive drugs.¹⁹ The most probable source of these bacteria in pharmacy compounded preparations is people involved in compounding them.²⁰ S. aurous can be part of normal flora in some individuals without showing signs of illness; many are also asymptomatic carriers of E.coli.²¹ Therefore, employing proper sanitation by the personnel involved in compounding process is the most effective way to reduce risk of contamination with these bacteria.^20,22

 

Comparing the results showed that except in a number of cases, there was not a significant difference in TAMC and TYMC count of preparations between days 0 and 14. It can be concluded that ingredients of the preparations do not have major antimicrobial effect to decrease TAMC and TYMC in the 14 days interval; they also do not provide a suitable environment for the present microorganisms to grow and increase TAMC and TYMC in this time.

 

Comparing pharmacies about microbial quality of their preparations showed that all the preparations of pharmacy 5 were unacceptable immediately after purchase. The only case of contamination with E.coli was urea+eucerin preparation purchased from this pharmacy and one out of three cases of contamination with S. aurous was its fluocinolone+eucerin preparation. This can be the result of poor hygiene and inadequate facility and equipment used for compounding the preparations. Previous studies have also shown a direct relation between the source pharmacy and microbial quality of pharmacy compounded preparations.¹⁴ Preparations obtained from pharmacy 3 with 33.3% unacceptable items had the best microbiological quality.

 

Comparing the preparations showed that percent of unacceptable items for urea + eucerin, fluocinolone+eucerin and salicylic acid + betamethasone + eucerin preparations were 50, 90 and 30, respectively. Salicylic acid + betamethasone+ eucerin preparations had the lowest TAMC and TYMC range and did not contain any of the specified microorganisms. Type and composition of preparations can affect their susceptibility to microbiological contamination. High water content and ingredients that can be used as nutrient source can increase the risk of contamination.^23,24 On the other hand ingredients like salicylic acid with known antimicrobial and antifungal properties decrease the risk of microbiological contamination.^25,26

 

Results of this study showed unacceptable microbiological quality of pharmacy compounded topical preparations that can put consumers, especially those with compromised immunity, at serious risk.  A direct relationship was observed between the pharmacies and microbiological quality of their preparations, indicating the importance of implementing hygiene and good compounding practice in the preparation process. Authors suggest that informing pharmacies and regulatory authorities about the results of this study will result in developing policies to improve the microbiological quality of pharmacy compounded preparations.

 

ACKNOWLEDGEMENTS:

We would like to express our special thanks to the Deputy of Research and Technology development and Vice Chancellor for Food and Drug, Hamadan University of medical sciences. This study has been adapted from a Pharm.D thesis at Hamadan University of Medical Sciences.

 

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Received on 31.10.2018         Modified on 15.11.2018

Accepted on 19.12.2018      © RJPT All right reserved