1. Introduction
ny compounded form of pharmaceutical product made in pharmacies, hospital or factory may be contaminated with microbes. This contamination can originate from raw materials or during production. Hence, it is important to study the physical and chemical properties and stability of compounded drugs. Microbial contamination of compounded and health products has been considered from the past and for this reason, in pharmaceutical pharmacopoeias, some restrictions have been put on such products. For such specific products, it is necessary that they be free of contaminating microorganisms [3]. Small drug particles in semi-solid form of pharmaceutical compounds may dissolve in the continuous phase and join larger particles (e.g. Ostwald ripening). To examine the tendency of Ostwald ripening during the production stage, it is possible to study the room temperature cycle up to 40° C. [9].
The particle size of compounded products is affected by the viscosity and concentration of their ingredients [10]. The pH of a semi-solid form may be related to multiple failure modes in the drug product. The pH effect of topical drug forms in the living organism (in vivo) on the skin is not well known [11]. One of the goals of quality assurance programs is to establish systems that can ensure the uniformity of the properties of medications in all doses or packages, and on the other hand, to ensure their safety when consumed. The assurance about uniformity (effectiveness) and health of the medications are related to the stability of the compounded product.
Therefore, it is important to pay attention to the stability and properties of these products. In this regard, various tests have been performed to evaluate the efficacy and safety of dermatological drugs, including assessment of the amount of active ingredients in the formulation, the uniformity of dosage forms, pH, the amount of water content, microbial constraints, viscosity and particle size [2]. Due to the importance of physicochemical and microbial properties of the compounded medications produced in urban pharmacies, this study aimed to investigate their physicochemical properties and microbial contamination.
2. Methods and Materials
This is an experimental field study. 63 prescribed compounded medications with specific formulation (Table 1) containing an oxidizing substance (hydroquinone), a substance with the ability to change the pH of the product (salicylic acid), and an antioxidant (vitamin C) were collected from 63 pharmacies in Yazd city in the spring 2017, and experimental studies on the study variables continued until the fall 2017. According to Pharmacopoeia guidelines, the numbers of microbes including Pseudomonas aeruginosa, Staphylococcus aureus, Candida sp., and Escherichia coli that are not allowed in topical drugs were counted using the spread plate technique.
To measure the viscosity, 1 gram of each sample was placed in the viscometer (Brookfield, USA) at room temperature and then, it was measured at 10 rpm. In order to test the physicochemical properties of the samples, one gram of each sample was poured into a 10-cc beaker and placed on a heater, using a magnet to create a uniform flow and increase the temperature. In the end, the temperature at which the samples underwent phase change was measured using a thermometer. The amount of hydroquinone in each sample was measured in milligrams per gram of cream with a spectrophotometer at a wavelength of 293 nm where methanol was used as a blank.
3. Results
According to Table 2, only one sample contaminated with Staphylococcus aureus was found, and microbial contamination by Pseudomonas aeruginosa and Escherichia coli did not occur outside the designated range, and 15 samples had fungal infection (candida albicans) (Figure 1).
One month after the samples were stored in ideal conditions, 22.2% of them showed discoloration. After a few weeks, 31.7% had discoloration and 23.8% showed creaming phenomenon (Figure 2).
In terms of particle size distribution, 22.2% of the samples had a 10-20 μm particle size, 33.3%, 20-30 μm; 23.8%, 30-40 μm; 12.6%, 40-50 μm; and 7.9% were in a range of 50-60 μm. Moreover, 12.6% of the samples underwent phase change and creaming at a temperature of 30-40° C, 77.7% at 40-50° C, and 9.5% at 50-60° C. The maximum viscosity of the semi-solid product was between 2,500 and 3,000 centipoise (29 samples). Hydroquinone in 50% of the samples was more than one gram; in 35%, between 0.9 and 1 g, and in 15% it was less than 0.9 g.
4. Discussion
Elmorsy and Hafez [12] in a study on various cosmetic brands found bacterial and fungal-microbial contamination in 22.6% of the samples. The products were contaminated with pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. In study conducted in Poland by Glogowski et al. [19] on the viscosity of salicylic acid and boric acid inside the ointment formulation, they concluded that the formulation containing salicylic acid had better viscosity. Kumar et al [21] in a study to determine the amount of lidocaine in the ointment formulation by spectrophotometer at a wavelength of 263 nm, found that its amount was 98.7%. Jeon et al. [11] found out that changing the pH of any topical cream could influence the effect of the cream on the skin and its other features.
5. Conclusion
One of the limitations of this study was the lack of uniform conditions in pharmacies for making the study drugs. According to the results obtained from particle size and physicochemical properties, the related principles during the production of compounded medications should be observed more. Numerous factors such as increased awareness, adherence to principles, more use of preservatives, use of moisturizing creams (which contain significant preservatives) and use of alcohol as a solvent in the study samples, can reduce the rate of contamination in compounded drugs made in pharmacies.
Ethical Considerations
Compliance with ethical guidelines
This study considered all the rules related to pharmaceutical research and obtained an ethical approval (Code: IR.SSU.MEDICINE.REC.1396.85) from the Medical University of Yazd.
Funding
This study received financial support from the Deputy for Research of Shahid Sadoughi University of Medical Sciences.
Authors' contributions
All authors contributed in preparing this article.
Conflicts of interest
The authors declared no conflict of interest.
Acknowledgements
The authors would like to thank Dr. Masoud Heidarinejhad and all those had cooperation in conducting this study.
References
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