الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Contamination of NSP is a major public health problem which threatens health of the patients, especially those with compromised immunity. Bacterial, viral and fungal contamination may lead to physical changes such as breaking of emulsions, thinning of creams and fermentation of syrups.
Bacterial isolates that most often contaminate NSP are those ubiquitous organisms which are present in the surrounding environment such as Bacillus spp. and P. aeruginosa.
Safety of NSP is related to the microbial limits and absence of certain microorganisms specified by the pharmacopeia. Therefore, adherence to SOPs and GMP guidelines during manufacturing, and assessment of microbiological quality of NSP is very crucial to ensure safety of the patients.
The present study aimed to:
1. Evaluate the microbiological quality of certain non-sterile pharmaceutical products commonly used in Alexandria.
2. Determine TAMC and TYMC of microorganisms present in each non-sterile pharmaceutical product and compare it with the range specified in USP.
3. Isolate and identify the predominant contaminant microorganisms in non- sterile pharmaceutical products.
4. Compare rates of contamination of non-sterile pharmaceuticals collected from governmental and non-governmental pharmacies.
The present cross-sectional study was conducted over a period of 4 months from the beginning of August to the end of November 2019. It enrolled 21 herbal syrups and 161 non-herbal oral and topical preparations. Samples were collected from governmental and non-governmental pharmacies.
Counting method suitability testing was conducted on each brand to test if any of the examined products had an inhibitory effect on possibly present microorganisms. According to USP, each sample was examined for total bioburden by TAMC and TYMC using spread plate method. Tests for specified microorganisms were conducted for each sample according to route of administration. Oral samples were tested for the presence of E. coli, while topical ones were examined for the presence of S. aureus and P. aeruginosa.
The results of the present study revealed that:
1. Out of 182 examined samples, 79 (43.41%) were tablets, followed by syrups 68 (37.36 %).
2. Half of samples (50.55%) were purchased from governmental pharmacies, and the other half (49.45%) were from non- governmental ones.
3. Out of 182 studied NSP, 176 (96.70%) had an expiry period ranging from 1-4 years, while only 5 (2.75%) samples were to be expired in the same year, and only one sample had expiry date after 5 years.
4. Out of 182 examined samples, 161(88.46%) were non-herbal samples while only 21 (11.54%) were herbal syrup products.
5. Out of 182 examined samples, 31 (17.03%) and 35 (19.23%) had exceeded the maximum acceptable limits of TAMC and TYMC, respectively.
6. Out of 21 herbal pharmaceuticals, 2 (9.52 %) and 3 (14.29 %) had exceeding TAMC and TYMC limits, respectively.
7. Out of 161 non-herbal products, 29 (18.01%) and 32 (19.88%) were off limits of TAMC and TYMC, respectively.
8. Seven (8.86%) out of 79 tablets, 16 (34.04%) out of 47 non-herbal syrups, 2 (25.00%) out of 8 suspensions and 1(25.00%) out of 4 emulsions had passed the maximum acceptable limit of TAMC.
9. Regarding topical products, 3 (30.00%) out of 10 gels and none of creams had passed the permissible limit of TAMC.
10. Out of 79 tablet samples, only 7 (8.86%) had passed the permissible limits of TAMC (>2000 CFU/g), while 11 (23.40%) out of 47 non-herbal syrups had exceeded the TAMC limits with counts ranging from 200-2000 CFU/ml and 5 (10.64%) with counts >2000 CFU/ml. Two suspension samples were off limits, one had count ranging from 200-2000 CFU/ml and the other one had count >2000 CFU/ml. Only one emulsion had an exceeding count ranging from 200-2000 CFU/ml.
11. Regarding TAMC of topical products, the three gel samples that were off limits had counts ranging from 200-2000 CFU/g.
12. The majority of capsule samples, 5 (83.33%) out of 6 had unsatisfactory TYMC compared to the USP specification for oral non-aqueous preparations (>2 x 10² CFU/g), while only 5 (6.33%) out of 79 tables were off limits.
13. Out of 47 non-herbal syrups, 2 (4.26%) had exceeded the TYMC limit with counts > 20 CFU/ml and 14 (29.78%) with counts > 200 CFU/ml, while two (25.00%) out of 8 suspensions had exceeded the limit with count >200 CFU/ml.
14. Regarding TYMC of topical preparations, 3 (30%) out of 10 gels and 1 (14.29%) out of 7 creams were off limits (>2 x 101 CFU/g).
15. Microorganisms had been recovered from only 19 (10.44%) out of 182 tested samples. Two (10.53%) out of these isolates were recovered from herbal products, and 17 (89.47%) were from non-herbal samples.
16. The majority of recovered isolates, 14 (73.68%) out of 19 had been isolated from samples purchased from governmental pharmacies, while the remaining 5 (26.32%) isolates were recovered from samples purchased from non-governmental pharmacies.
17. The majority of recovered isolates, 15 (78.95%) out of 19 were gram negative bacteria, while only 4 (21.05%) were gram positive isolates. All gram- positive isolates were correctly identified as Bacillus spp. by routine biochemical tests.
18. Out of 15 gram-negative isolates, only 4 (26.67%) were correctly identified as P. aeruginosa isolates, while 11 (73.33%) were inconclusively identified by routine biochemical methods.
19. The 11 inconclusive isolates were correctly identified by VITEK® 2 automated system as follows: 3 (27.27%) were Pseudomonas stutzeri, 3 (27.27%) were Stenotrophomonas maltophilia, two (18.19%) were Acinetobacter baumannii complex and the remaining three isolates were Achromobacter denitrificans, Ochrobactrum anthropi and Aeromonas salmonicida.
20. The majority of gram-negative bacterial isolates (53.33%) had been recovered from tablet samples, followed by syrups (26.67%).
21. All four-gram positive bacterial isolates had been recovered from topical products; 2 from gels and 2 from cream samples.
22. Out of 4 P. aeruginosa isolates, 2 (50%) were recovered from tablets and 2 (50%) were from syrups. Two (66.67%) out of 3 Pseudomonas stutzeri isolates were recovered from tablets and one (33.33%) was from syrup.
23. One (33.33%) out of 3 Stenotrophomonas maltophilia isolates was recovered from tablet, one (33.33%) was from syrup and one (33.33%) was from suspension.
24. The only isolate of Achromobacter denitrificans, and the two isolates of Acinetobacter baumannii complex isolates were recovered from tablets.
25. The only one isolate of Ochrobactrum anthropi was recovered from capsule, and one Aeromonads salmonicida isolate was recovered from suspension.
26. There was no significant association between the total bioburden and source of samples, whether purchased from governmental and non-governmental pharmacies, where 20 (21.74%) out 92 pharmaceuticals purchased from governmental pharmacies, and 11(12.22 %) out of 90 products purchased from non-governmental pharmacies were off limits of TAMC. Regarding TYMC, 22 (23.91%) out 92 pharmaceuticals purchased from governmental pharmacies, and 13 (14.44 %) out of 90 products purchased from non-governmental pharmacies were off limits.
27. There was a significant association between TAMC and expiry dates, where 2 (40%) out of 5 samples that would expire in the same year, and 26 (15.30%) out of 170 samples with expiry dates within 1-3 years had exceeded the maximum acceptable limit.
It can be concluded from the present study that:
1. The microbiological quality of the examined samples was satisfactory.
2. Syrups were the most common dosage form to exceed TAMC limit, while capsules were the commonest to exceed TYMC.
3. None of the microorganisms specified by the USP had been isolated from the specified pharmaceuticals according to route of administration.
4. Recovered microorganisms were ubiquitous in nature, such as Bacillus spp., Pseudomonas spp. and Acinetobacter baumannii complex.
5. Oral dosage forms were more contaminated than others.
6. All gram-negative isolates were recovered from oral dosage forms, while gram positives isolates were recovered from topical ones.
7. No significant differences between microbial bioburden of products purchased from governmental and non-governmental pharmacies.
8. There was a significant association between expiry dates and TAMC.
from the results of the present study, the following recommendations are suggested:
1. Manufacturers should be aware to the hazard of microbial contamination of non-sterile drugs and strictly adhere to GMP.
2. USP guidelines should be applied to control the microbial bioburden of NSP.
3. Periodic surveillance of microbiological quality of non-sterile products in the manufacturing companies and pharmacies.
4. Proper counselling should be given to the patient by the pharmacist about the optimum use and storage conditions of medication at home.