Screening and quantification of undeclared PGF2α analogs in eyelash-enhancing cosmetic serums using LC-MS/MS.

In recent years, cosmetics deemed equivalent to pharmaceutical products containing prostaglandin F2α (PGF2α) analogs have been distributed overseas in the form of eyelash serums that can be purchased via the internet. The purpose of this study was to investigate the presence or absence of PGF2α analogs in eyelash serums procured in Japan via the internet to elucidate the actual composition. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurement system was developed for the determination of 14 PGF2α analogs in cosmetic serums. In total, 64 eyelash serum samples were purchased from 34 websites. After pretreatment, eyelash serum samples were screened for PGF2α analogs using the LC-MS/MS system. Products containing PGF2α analogs were subjected to quantification of these compounds. Of the 64 products, four were found to contain bimatoprost, among which, three did not indicate their contents on their package labels. In contrast, no samples were found to contain latanoprost, travoprost, or tafluprost, which are prescribed for glaucoma treatment. Additionally, eight products contained other PGF2α analogs, which have not been used as pharmaceuticals. The ease of access to cosmetic serums containing PGF2α analogs via online purchases presents a risk of serious side effects, particularly when consumers are not informed of their contents on the packages. This issue requires serious consideration to avoid the incorporation of pharmaceutical substances into cosmetic products.

A comprehensive analysis of selected medicines collected from private drug outlets of Dhaka city, Bangladesh in a simple random survey.

Comprehensive data are needed to prevent substandard and falsified (SF) medicines as they pose a major risk to human health. To assess the quality of selected medicines, samples were collected from random private drug outlets of Dhaka North and South City Corporation, Bangladesh. Sample analysis included visual observation of the packaging, authenticity of the samples, legitimacy and registration verification of the manufacturer, physicochemical analysis, and price. Chemical analysis of the samples was performed using a portable Raman spectroscopy and high-performance liquid chromatography according to the pharmacopoeia. Several discrepancies were noted in the visual observation of samples. Among the 189 collected samples of esomeprazole (ESM), cefixime (CFIX), and amoxicillin-clavulanic acid (CVA-AMPC), 21.2% were confirmed to be authentic, 91.3% manufacturers were confirmed legitimate, and 2.1% of all samples were unregistered. Chemical analysis of the samples revealed that 9.5% (95% CI 5.7-14.6) of samples were SFs. Falsified samples and quality variation in the same generic branded samples were both detected by Raman spectroscopic analysis. Overall, sample prices were satisfactory relative to the international reference price. This study documents the availability of poor-quality medicines, demonstrating the need for immediate attention by the national medicine regulatory authority.

Small-scale dissolution test screening tool to select potentially substandard and falsified (SF) medicines requiring full pharmacopoeial analysis.

The purpose of this study was to design a convenient, small-scale dissolution test for extracting potential substandard and falsified (SF) medicines that require full pharmacopoeial analysis. The probability of metronidazole samples complying with the US Pharmacopoeia (USP) dissolution test for immediate-release tablet formulations was predicted from small-scale dissolution test results using the following criteria: (1) 95% confidence interval lower limit (95% CIlow) of the average dissolution rate of any n = 3 of n = 24 units of each sample, and (2) average and minimum dissolution rates for any n = 3 of n = 24 units. Criteria values were optimized via bootstrap sampling with Thinkeye data-mining software. Compliant metronidazole samples in the USP first-stage and second-stage dissolution test showed complying probabilities of 99.7% and 81.0%, respectively, if the average dissolution rate of n = 3 units is equal to or greater than the monograph-specified amount of dissolved drug (Q; 85% of labeled content for metronidazole). The complying probabilities were 100.0% and 79.0%, respectively, if the average dissolution rate of n = 3 units is 91% or higher and the minimum dissolution rate is 87% or higher. Suitable compliance criteria for the small-scale dissolution test are: average dissolution rate of n = 3 units is Q + 6% or more and minimum dissolution rate is Q + 2% or more.

Patient safety and public health concerns: poor dissolution rate of pioglitazone tablets obtained from China, Myanmar and internet sites.

BACKGROUND: Poor quality medicines have serious implications for public health. The aim of this study was to explore the quality of the antidiabetic pioglitazone, using samples collected in China and Myanmar, and samples purchased online. METHODS: In this cross-sectional study, we examined samples (n = 163) collected from hospitals in Shanghai, China in 2012 (n = 44), products purchased via the internet and imported into Japan in 2013 (n = 59), and samples purchased in shops in Yangon, Myanmar in 2015 (n = 60). Collected samples were subjected to visual inspection, authenticity investigation and quality testing (potency, content uniformity and dissolution test) by high-performance liquid chromatography. Samples were rated as compliant or non-compliant based on the relevant pharmacopoeial acceptance criteria. RESULTS: Visual inspection of all samples revealed compliant products. However, responses from manufacturers during authenticity investigation were poor. Among the n = 44 samples from China, one was non-compliant in the potency test. Among the n = 59 samples personally imported into Japan, 38% of generic samples were found to be non-compliant. In Myanmar, 13.3% of samples were non-compliant. Non-compliant samples predominantly failed in the dissolution test. All non-compliant samples were generic. CONCLUSIONS: Despite the apparent satisfactory outcome on the samples from China, pioglitazone samples collected in Myanmar and purchased online for personal import into Japan included many substandard products, which failed quality assessment predominantly because of poor dissolution. Internet providers did not comply with Japanese regulations in various respects.

Substandard and Falsified Medicines in Myanmar.

Background: substandard and falsified medicines (SFMs) are a threat to public health. The availability of SFMs in Myanmar was reported by the World Health Organization (WHO) in 1999, but there have been few systematic surveys on falsified medicines in Myanmar since then. The aim of this study is to examine the extent of SFMs for sale in Myanmar. Methods: target medicines were tablets of candesartan, metformin, and pioglitazone, and infusions of ciprofloxacin and levofloxacin. Samples were collected from hospitals, pharmacies, and wholesalers located in the Mandalay region in 2015. We carried out observation testing, authenticity investigation, and quality testing to search for SFMs, and analyzed the relationship between SFMs and the price and store type. Results: There were no falsified medicines found in the authenticity check, though there remained a problem due to low response rates from manufacturers and regulatory authorities. In the quality test, some tablets of metformin and pioglitazone made in India failed the dissolution test. Conclusions: although no serious problems were found, some substandard medicines were detected. Regular surveys to monitor SFMs are therefore recommended, together with further regulatory guidance to improve conditions in all medicine manufacturers, distributors, and pharmacies.

A Cross-Sectional Investigation of the Quality of Selected Medicines for Noncommunicable Diseases in Private Community Drug Outlets in Cambodia during 2011-2013.

Although the issue of substandard and falsified medicines is quite well known, most research has focused on medicines used to treat communicable diseases, and relatively little research has been carried out on the quality of medicines for noncommunicable diseases (NCDs). This study was designed to assess the quality of seven widely used medicines for NCDs in Cambodia during 2011-2013. Medicines were collected from private community drug outlets in Phnom Penh (urban area), by stratified random sampling and in Battambang, Kandal, Kampong Speu, and Takeo (rural areas) by convenience sampling. Samples were subsequently analyzed by visual inspection, authenticity investigation, and pharmacopoeial analysis by high-performance liquid chromatography. Various discrepancies were observed in visual inspection of packages and medicines. Of 372 tablet/capsule samples from 64 manufacturers in 16 countries, the manufacturers confirmed 107 (28.8%) as authentic; the authenticity of other samples could not be verified. Three hundred sixty-four (97.8%) samples were registered in Cambodia. Among all samples, 23.4% (95% CI 19.2-28.0) were noncompliant in one or more of the quality tests: 12.9% (95% CI 9.7-16.7) contained an amount of active pharmaceutical ingredient outside the permitted range, including some showing extreme deviations, 14% (95% CI 10.6-17.9) failed because of content variation, and 10.8% (95% CI 7.8-14.4) failed to meet pharmacopoeial reference ranges in dissolution tests. Pharmaceutical quality appeared to be unrelated to storage conditions. Although no sample was obviously falsified, there is a high prevalence of substandard medicines for NCDs in Cambodia, indicating the need for focused regulatory action, including collaborative initiatives with manufacturers.

The health consequences of falsified medicines- A study of the published literature.

OBJECTIVES: To analyse and present the literature describing the health consequences of falsified medicines, focusing on mortality and morbidity, as well as the scale of the issue, the geographic extent, the medicines affected, and the harm caused at both the individual and population levels. METHODS: We searched for articles in PubMed, using pre-optimized keywords '(counterfeit OR fake OR bogus OR falsified OR spurious) AND (medicine OR drug)'. Searches up to February 2017 yielded 2006 hits, of which 1791 were full-length articles in English. Among them, we found 81 papers that qualitatively or quantitatively described 48 incidents in which falsified medicines caused patients to suffer serious adverse effects, injury, symptoms or death. RESULTS: The distribution of incidents was examined according to the economic status of the countries involved, regional location in the world, therapeutic category of the medicines, number of incidents and victims by year, and characteristics of the falsified medicines. Among the 48 reported incidents, 27 (56.3%) occurred in developing countries and 21 (43.7%) in developed countries. These incidents involved a total of approximately 7200 casualties including 3604 deaths. CONCLUSIONS: Despite the poor quality of much of the reported data, the results of this study indicate that all types of medications have been targeted for falsification, and falsified medicines have had a serious impact on the health of both adults and children worldwide, with similar numbers of incidents in developing and developed countries.

An Investigation into the Quality of Medicines in Yangon, Myanmar.

Many poor-quality medicines are supplied to patients mainly in developing countries. No systematic survey on counterfeit medicines has been conducted in Myanmar since 1999. The purpose of this study was to investigate the current situation of substandard or counterfeit medicines in Myanmar. Samples of oral medicines, cefuroxime axetil (CXM), donepezil hydrochloride (DN) and omeprazole (OM), and injections, ceftriaxone sodium (CTRX), and gentamicin sulfate (GM), were collected from pharmacies, hospitals, and wholesalers in Yangon, Myanmar in 2014. Authenticity and quality were verified. There were 221 (94%) foreign medicines among 235 collected samples. Five samples of GM and 1 DN sample were not registered with the Food and Drug Administration, Myanmar. In quality analysis, 36 samples out of 177 (20.3%) did not pass quantity tests, 27 samples out of 176 (15.3%) did not pass content uniformity tests, and 23 out of 128 samples (18.0%) did not pass dissolution tests. Three of the unregistered GM samples failed in both identification and microbial assay tests. Counterfeit GM is being sold in Yangon. Also, the quality of OM is a matter of concern. Poor-quality medicines were frequently found among the products of a few manufacturers. Regular surveys to monitor counterfeit and substandard medicines in Myanmar are recommended.

Quality of omeprazole purchased via the Internet and personally imported into Japan: comparison with products sampled in other Asian countries.

OBJECTIVE: To evaluate the quality of omeprazole personally imported into Japan via the Internet and to compare the quality of these samples with previously collected samples from two other Asian countries. METHODS: The samples were evaluated by observation, authenticity investigation and pharmacopoeial quality analysis. Quality comparison of some selected samples was carried out by dissolution profiling, Raman spectroscopy and principle component analysis (PCA). RESULTS: Observation of the Internet sites and samples revealed some discrepancies including the delivery of a wrong sample and the selling of omeprazole without a prescription, although it is a prescription medicine. Among the 28 samples analysed, all passed the identification test, 26 (93%) passed the quantity and content uniformity tests and all passed the dissolution test. Dissolution profiling confirmed that all the personally imported omeprazole samples remained intact in the acid medium. On the other hand, six samples from two of the same manufacturers, previously collected during surveys in Cambodia and Myanmar, frequently showed premature omeprazole release in acid. Raman spectroscopy and PCA showed significant variation between omeprazole formulations in personally imported samples and the samples from Cambodia and Myanmar. CONCLUSIONS: Our results indicate that the pharmaceutical quality of omeprazole purchased through the Internet was sufficient, as determined by pharmacopeial tests. However, omeprazole formulations distributed in different market segments by the same manufacturers were of diverse quality. Measures are needed to ensure consistent quality of products and to prevent entry of substandard products into the legitimate supply chain.

Erroneous formulation of delayed-release omeprazole capsules: alert for importing countries.

BACKGROUND: Poor drug quality is a matter of serious concern, especially in countries where drug regulation and law enforcement are constrained by limited resources. This study was carried out to investigate the cause of quality failure of omeprazole in Cambodia in 2010 and Myanmar in 2014. METHODS: We conducted pharmacopoeial quantity, content uniformity and dissolution tests of 156 samples of omeprazole capsules collected in Cambodia in 2010 and Myanmar in 2014. High failure rates were found, especially in dissolution testing, and detailed investigation of several unacceptable samples was carried out by means of in-vitro dissolution profiling, scanning electron microscopy (SEM) and X-ray computed tomography (X-ray CT) to identify the cause of failure. RESULTS: Dissolution profiling with and without the acid stage showed that acid caused premature omeprazole release, indicating that the enteric coating of the omeprazole granules was ineffective. SEM examination of two failed samples revealed cracked and broken granules mixed with apparently intact omeprazole granules in the capsule. X-ray CT examination indicated that some granules of failed samples completely lacked enteric coating, and others had incomplete and non-uniform enteric coating or malformation. CONCLUSIONS: Omeprazole capsules collected in Myanmar and Cambodia showed high failure rates in pharmacopoeial tests, especially dissolution tests. Some samples were found to have ineffective or absent enteric coating of the granules, resulting in premature dissolution and degradation in acidic conditions. This is a potentially serious public health issue that needs to be addressed by regulatory authorities in Cambodia and Myanmar, possibly through a collaborative initiative with manufacturers.