Public Perception toward E-commerce of Medicines and Comparative Pharmaceutical Quality Assessment Study of Two Different Products of Furosemide Tablets from Community and Illicit Online Pharmacies.

BACKGROUND: E-commerce of medicines has been extensively spread worldwide. Many reasons influence consumers to purchase their medical needs through the Internet, including low cost, availability, accessibility, and time saving. However, most of these medicines are substandard and counterfeit. AIM: To assess the perception of people in the UAE about purchasing medicines from online sources and to evaluate the quality of furosemide tablets from two different sources including illegal online source.
MATERIALS AND METHODS: A cross-sectional study was conducted on 528 participants in the UAE. The questionnaire included three parts to assess the public perception and experience toward purchasing medicines from online sources. Furosemide tablets, purchased from the UAE market and an illegal online source, were physically and chemically studied to assess their quality according to the British Pharmacopoeia (2018).
RESULTS: The survey results revealed that less than 10% of participants have purchased their medicines from online sources and mostly they were nonprescription products (78%). Most common motives for online purchasing were either unavailability in the local pharmacies (43%) or lower cost compared to that in local market (43%). The opinion of participants toward purchasing of online medicines was negative. On the other hand, the experimental analysis showed that online furosemide had failed to pass the chemical assay test (91.0% ± 0.8), which makes it a substandard product.
CONCLUSION: This study showed that few consumers had considered purchasing pharmaceutical products from online sources as a feasible way to save money and time. However, most of them were in doubt about their quality, which encourages health-care providers to guide patients to government-supported websites if required. The study also showed that the quality of online medicines is questionable, indicating that these products are not equally effective as the medicines purchased from a local pharmacy.

Introduction

Online purchasing of pharmaceutical products has become a popular phenomenon and has continuously spread out almost all over the world since 1999.[1] Online pharmacies are classified into three categories: click-and-mortar pharmacies that are online branches of local community pharmacies, legal websites of authorized distributors that provide delivery services to patients from neighboring pharmacies, and illegal Internet sites where state health authorities have no control on their products.[2] The latter type of online pharmacies is the most precarious one and most of the products they sell are substandard and counterfeit. Despite a rigorous ban on illegal websites from international (e.g., Interpol) and local authorities (e.g., the US Food and Drug Administration), more than 30,000 of illicit online pharmacies still operate their businesses worldwide to sell fake pharmaceutical products through websites and social media platforms. The UAE Ministry of Health and Prevention has warned that online trade of medical products is strictly prohibited in the country as 90% of the drugs sold online are from unknown sources and most of them are substandard and counterfeit according to the World Health Organization (WHO).[3] Despite these medications pose danger and threat to public health, purchasing medications through online sources has increased as it is considered by many consumers a more convenient, faster, and less costly than the traditional way.[4] The risk of consuming substandard and counterfeit medications is related to illegal online pharmacies that provide medications from unknown sources and offer them without prescriptions, which increases the risk of drug abuse. Although health organizations are always warning about fake online drugs, awareness of patients is still somehow low.[5] In addition, patients who have no health insurance usually look for a source that is more affordable for prescription medicines, especially those online websites that provide the feasibility in buying medications. Other reasons that promote online purchasing of medical products are providing accessibility to many pharmaceutical products and the high rate of privacy for patients who want to hide their medical condition.[2] One of the perilous consequences of purchasing medications from uncertain online sources is the possibility of causing serious conditions. This is likely because of the lack of patient knowledge and physician or pharmacist counseling. According to a study conducted in the University of Pécs, Hungary, the majority of patients were unaware about the legal and illegal online pharmacies, especially those who order some prescription medications without the consultation of the physician or pharmacist.[5]

Any product can be counterfeited, and research reports indicate that around 1% of the prescription medications sold in the United States and Europe and 30% sold in parts of Asia, Africa, and Latin America are counterfeit.[6] However, medications purchased via unknown distribution channels, such as the Internet websites, have higher chances to be counterfeit. According to WHO, up to 60% of medications purchased through Internet could be counterfeit or substandard, and more than 50% of medications purchased online from sites that concealed their actual physical address were found to be counterfeit. Therefore, it becomes a necessity to teach patients and advise them to purchase their medications from trusted and reliable sources.[7] Pharmacists can play an important role in assuring patients’ safety by combating these fake and illegal pharmaceutical products, and counsel their patients about the danger of purchasing their medicines from illegal online sources. Research and quality control assessment of online-marketed drugs are limited. The aim of this work was to conduct two types of studies. First, a cross-sectional study was performed to perceive the people’s opinions about online purchasing of medications from various groups of society in the UAE. Second, we conducted a quality assessment study of two products of a popular antihypertensive drug, furosemide tablets, used as a diuretic, purchased from the UAE market and online sources. All tests carried out in this study were according to the British Pharmacopoeia (BP) 2018 specifications.[8] The analysis involved both physical and chemical quality control tests. Physical testing included dissolution, disintegration, hardness, friability, and weight variation, whereas chemical testing involved identification and assay of the active ingredient.

Materials and Methods

Cross-sectional study

Study design

This descriptive, quantitative, cross-sectional study was conducted from March 3, 2018, to March 10, 2018, among the UAE population. A questionnaire was used to assess the participants’ perception about purchasing their medicines from online sources.

Selection criteria

Inclusion criteria included the following:

UAE residents.

Aged 18 years or above.

Willing to participate.

Sample size

Over 1500 persons from both genders of different age groups and various demographic, educational, and cultural backgrounds were requested to participate in answering this voluntary questionnaire. Sample size was determined based on certain statistical calculations, taking in account the statistical variables and the type of outcomes such as margin of error and confidence level. The expected response rate was approximately 35% by 528 participants from all the Emirates.

Data collection

The questionnaire used for data collection comprised 13 different questions divided into three parts. The first section focused on sociodemographic data such as age, gender, nationality, and level of education. The second section aimed to investigate the practice and experience of purchasing medications from online sources among the public. The third section was the core of this study designed to assess the knowledge and behavior of participants toward purchasing medicines through online sources.

Statistical analysis

Data from questionnaires were analyzed using Microsoft Excel (Redmond, Washington, USA). A descriptive approach was carried out for data analysis, where frequencies and percentages were calculated and displayed as pie and bar charts.

Ethical approval

This study was approved by the ethics committee at Ajman University (UG 2018.1.1). The study was voluntary and each respondent’s personal information was kept confidential. Participants were informed about the objectives of the study, and the process of gathering information was anonymous.

Experimental study

The first product of furosemide tablets was purchased from a local community pharmacy in the Emirate of Ajman, UAE. The product is legally authorized by the drug authorities in the country. The other product of furosemide tablets was ordered online using Google search engine. The product label did not mention the manufacturer name, but it indicated that the product originated from Philippines. Both products, which are still not expired, were stored at room temperature away from direct sunlight. Phosphate buffer (pH 5.8), used for dissolution testing, was prepared by mixing sufficient quantities of disodium hydrogen phosphate dihydrate and potassium dihydrogen phosphate purchased from Sigma-Aldrich (St. Louis, Missouri, USA). The pH was adjusted with analytical reagent grade sodium hydroxide used in this work was from Sigma-Aldrich. Water used for dilution and solution preparations was prepared by Milli-Q reverse osmosis Millipore (Bedford, Massachusetts, USA). A sensitive digital analytical balance from OHAUS (Parsippany, New Jersey, USA), dissolution apparatus II and disintegration tester from Erweka (Heusenstamm, Germany), and ultraviolet (UV)-Visible spectrophotometer model UV-1800 from Shimadzu (Kyoto, Japan) were used in the experiments.

Quality control tests were carried out based on the BP (2018)[8] on furosemide 40mg tablets from two different sources (local pharmacy in the UAE and online source). They were composed of physical and chemical tests. Physical tests include weight variation, disintegration, dissolution, friability, and hardness, whereas chemical tests included the identification and assay tests. Final results are reported as average values ± standard deviation.

Weight variation test

As the average weight of furosemide tablets is between 80 and 250mg, they should meet the BP (2018) requirements for weight variation as the following: (1) No more than two tablets deviate by more or less than 7.5% of the average tablets weight and (2) None of the tablets deviate by more than the double of that percentage. The test was carried out by weighing out 20 tablets collectively and individually to assess the tablet individual weights as per the BP (2018) specifications.[8]

Disintegration test

Six tablets were inserted inside the vessels of the disintegration apparatus. Distilled water was used as the medium and the temperature was set at 37°C. As per the BP (2018) specifications,[8] all tablets should disintegrate completely within 30min. If one or two tablets failed the test, it should be repeated with another 12 tablets. At least 16 of 18 tablets should pass the test, otherwise, the product fails the test.

Dissolution test

Six furosemide tablets containing less than 100mg were used to comply the BP (2018) requirements with dissolution apparatus II. At stage one (S1) of dissolution and according to the BP (2018),[8] for a drug to pass the test, at least 80.0% (Q + 5.0%) of the active ingredient should be dissolved within 45min, where the term Q is the quantity of active substance dissolved in a specified time. In this test, the medium used was 900mL of phosphate buffer (pH, 5.8) per vessel. The temperature was set at 37°C and the paddles rotate at 50rpm. A gap of 2min between the insertions of tablets was kept to have enough time for withdrawing a sample for further analysis. A sample of 10–20mL was withdrawn from each vessel at 0, 15, 30, 45, and 60min and filtered. Later, each sample was diluted with the medium to get an expected concentration of 0.001% w/v of furosemide. Later, the absorbance was measured spectrophotometrically at 277nm.

Friability test

Ten tablets were weighed collectively and considered as the initial weight (Wi). Those tablets were rotated inside the friabilator/friability tester at 25rpm for 4min. After that, the tablets were removed from the friabilator and cleaned for any fragments to be reweighed and recorded as the final weight (Wf). The percentage weight loss should not exceed 1.0% as per the BP (2018) specifications.[8] The friability was calculated by the following equation:

Hardness test

Ten tablets were placed between two platens (jaws) of the machine separately. The machine was calibrated to measure the load applied to break each tablet. All tablets should be broken at nearly similar load and the average load was calculated in kilopound (kp).

Identification and assay

Identification and assay tests were carried out according to the monograph of furosemide tablets in the BP (2018).[8] Identification test was performed by measuring the absorbance of the diluted sample solution using the UV-Vis spectrophotometer in the range from 200 to 400nm wavelength. The product passes the test if two peaks of maximum absorbance wavelengths at 228 and 271nm are shown. Assay test was carried out by crushing 20 tablets using a mortar and pestle. A quantity equivalent to 0.2g of furosemide was shaken with 300mL of 0.1 M NaOH in a 500-mL volumetric flask for 10min. The volume was made up to 500mL by 0.1 M NaOH, and the contents were filtered. Five millimeter from the resulting solution were diluted to 250mL with 0.1 M NaOH. Then, the absorbance of each solution was measured at 271nm taking 580 as a value of A (1%, 1cm). These procedures were replicated 15 times for each product, and the average values and standard deviations were calculated. According to the BP (2018), the percentage content must not be less than 95.0% and not more than 105.0% for the drug to pass the test. Statistical significance was calculated by t-test: paired two sample for means (P = 0.05) to assess the difference between UAE and online furosemide tablets results of the assay.

Results and Discussion

Sociodemographic characteristics

This cross-sectional study was conducted in the UAE in January 2018 to assess the practice and perception of purchasing medications from online sources. The responses received from this study were 528 as expected (response rate of approximately 35%). Majority of the participants were females (75%, n = 397), and 77% (n = 408) of the respondents were highly educated. Half of the participants were of the age 18–25 years (50%, n = 262) as shown in Table 1.

Table 1

Demographic characteristics of the participants (n = 528)

Demographic	Sample size (n)	Percentage
Gender
Male	131	25%
Female	397	75%
Age group (years)
12–17	22	4%
18–25	262	50%
26–35	85	16%
36–45	73	14%
˃45	86	16%
Educational level
University level or higher	120	77%
Students	408	23%

Practice and experience of purchasing online medications

Overall, only one-tenth of the participants (10%, n = 51) had already purchased their medications from online sources [Figure 1], which is consistent with the previous studies reported in literature about the tendency of patients to purchase online medications.[19] Nonprescription or over the counter (OTC) medicines were the most commonly purchased medicines from online sources (78%) as shown in Figure 2. Furthermore, the majority of the participants were using online sources for food supplementations (41%) and weight loss products (31%) as shown in Figure 3. Likewise, complementary medicines and supplements were purchased by all participants as previously reported in literature.[9] The main reasons for purchasing online medications were the low price (43%) and the nonavailability of certain medications in local pharmacies (43%) [Figure 4]. This was also consistent with the previous studies where the shortage of some drugs and low prices encourage patients to go for online drugs.[91011] Among the people who had already purchased their needs from online sources (n = 51), approximately half of them experienced a little improvement after using online medications (51%, n = 26), whereas 35% (n = 18) noticed a remarkable improvement [Figure 5]. In addition, almost half of the participants (45%) would reorder online medications in future [Figure 6]. Also, previous study revealed that Internet-based sildenafil improved patients’ satisfactions without any side effects, and the rates of requesting refill were high among the patients.[12]

Figure 1

Prevalence of people purchasing online medications in the UAE

Figure 2

The most purchased medications from online sources in the UAE

Figure 3

Common medical conditions/drug classes for online purchasing in the UAE

Figure 4

Reasons for purchasing online medications in the UAE

Figure 5

Participants’ health condition improvement after using online medications

Figure 6

Participants’ attitudes about considering online ordering of medications in the future

Behavior and knowledge of participants toward purchasing online-based medicines

Overall, more than half of the total participants (61%, n = 321) were unsure about the quality of the purchased online medications and only few participants (5%, n = 26) believed in high quality of online medications [Figure 7]. On the other hand, about half of the participants (45%, n = 237) would never purchase online medications in the future, whereas only 20% (n = 106) would do that [Figure 8]. Moreover, majority of the participants (78%, n = 411) were unaware about the law of UAE that considers purchasing medications from online sources as illegal [Figure 9].

Figure 7

Assessment of the quality of the online medicines among the participants

Figure 8

Participants’ opinions about purchasing recommending others to online medications

Figure 9

Participant awareness on illegality of trading medications through Internet in the UAE

Tablets of the UAE furosemide showed an average weight of 0.1662g (±0.0014) with a relative standard deviation (RSD) not exceeding 0.8424%, whereas those of online furosemide showed a smaller average weight (0.1610 ± 0.0020g) with a 1.2422% RSD. None of the 40 tablets (UAE and online furosemide tablets) deviated by more or less than 7.5%. Therefore, furosemide tablets from the UAE and online sources passed the BP (2018) requirements of weight uniformity Table 2.[8]

Table 2

Weight variation results of the UAE and online furosemide tablets

Parameter	UAE furosemide	Online furosemide
Average weight (g)	0.1662	0.1610
SD	0.0014	0.0020
RSD (%)	0.8424	1.2422
Allowed range (±7.5%)	0.1537–0.1787	0.1489–0.1731
No. of deviated tablets	None	None
Accepted/rejected BP 2018	Accepted	Accepted

SD = standard deviation, RSD = relative standard deviation

Figure 10 represents the time required for drug release from furosemide tablets of both UAE and online source. Furosemide tablets from the UAE showed the fastest disintegration time at 10.0 ± 1.4s, whereas online furosemide tablets had a delayed disintegration time of 75.0 ± 1.9s. Both UAE and online furosemide tablets comply with the BP (2018) specifications that specify all tablets disintegrate completely within less than 30min.[8]

Figure 10

Disintegration test results of the UAE and online furosemide tablets

The dissolution test was carried out by using dissolution apparatus II. It can be seen that after 15.0min, the dissolution of the UAE furosemide tablets was higher (101.4% ± 2.3%) compared to the dissolution of online furosemide (92.6% ± 1.5%). After that, the dissolution of the UAE furosemide tablets reached a plateau with a dissolution percentage of approximately 106.3% ± 1.6%, whereas dissolution rate of online furosemide tablets was fluctuating between 97.0% and 110.1% with high standard deviation. Results of dissolution for both furosemide products were in accordance to the BP (2018) specifications of dissolution test;[8] in which not less than 80.0% of the active ingredient should be dissolved within 45–60min. In addition to that, a significant difference (P < 0.05) was observed in the dissolution patterns of both products as shown in Table 3 and Figure 11.

Table 3

Dissolution test results of the UAE and online furosemide tablets

Source	Time (min)	% Dissolved amount	SD
UAE	0	0.0	0.0
	15	101.4	2.3
	30	106.5	1.2
	45	106.3	0.9
	60	106.4	2.7
Online	0	0.0	0.0
	15	92.6	1.5
	30	97.0	5.6
	45	110.1	3.0
	60	109.7	4.2
P value	0.00574

SD = standard deviation

Figure 11

Dissolution test results of the UAE and online furosemide tablets

The friability test was carried out to evaluate the ability of tablets to withstand breaking during shipping, handling, and packaging. As per the BP (2018), not more than 1.0% of tablets weight should be lost after tumbling.[8] The percentages weight loss of the UAE and online furosemide was 0.61% and 0.27, respectively, which indicates that both products passed the friability test.

The load needed for the UAE furosemide tablets to break was 6.13 kp, whereas that for online furosemide product was 7.14 kp.

Identification test

UV spectrophotometric spectra of both products showed two UV absorbance maxima at around 228 and 271nm, which confirm the identity of furosemide as specified by the BP (2018) specifications for furosemide identification test.[8]

Assay test

The UV-Vis spectrophotometer assay results of the UAE furosemide tablets showed a percentage content of 100.2% ± 0.7%. On the other hand, online furosemide represented only 91.0% ± 0.8% of the drug content. Therefore, the UAE furosemide was accepted, whereas the online furosemide did not pass the test as per the BP (2018) specifications where the percentage of active ingredients must be between 95.0% and 105.0%.[8] Moreover, a high significant difference was observed between the assay results of both UAE and online furosemide tablets when applied paired two sample t-test for mean values (P = 0.05). These results show that the furosemide tablet product from online source is substandard and could result in treatment failure of hypertension.

Conclusion

This study focused on an important health issue, which is the purchasing of medications from illegal online sources. There was a dilemma of quality, safety, and efficacy of the online-sold pharmaceutical preparations, and very limited studies discussed the quality assessment of the online medications and the potential risk of these products. The findings of this study revealed that some online medications are substandard and counterfeit and may not contain the exact labeled amount stated by the manufacturer. Therefore, if there is any shortage of some medications in the local pharmacies and if patients would seek them from online sources, then health-care providers should take an action in guiding their patients to the trusted websites.

Financial support and sponsorship

This study received funds from the College of Pharmacy and Health Sciences at Ajman University to support the purchasing of materials.

Conflicts of interest

There are no conflicts of interest.