Detection Method of Falsified Medicines by Using a Low-Cost Raman Scattering Spectrometer Combined with Soft Independent Modeling of Class Analogy and Partial Least Squares Discriminant Analysis.

There are many reports of falsified medicines that may cause harm to patients. A rapid and simple method of identifying falsified medicines that could be used in the field is required. Although Raman scattering spectroscopy has become popular as a non-destructive analysis, few validation experiments on falsified medicines that are actually distributed on the market have been conducted. In this study, we validated a discriminant analysis using an ultra-compact, portable, and low-cost Raman scattering spectrometer combined with multivariate analysis. The medicines were three types of erectile dysfunction therapeutic tablet and one type of antifungal tablet: tadalafil (Cialis), vardenafil hydrochloride (Levitra), sildenafil citrate (Viagra), and fluconazole (Diflucan), which is sometimes advertised as female Viagra. For each medicine, the authentic standard product and products obtained by personal import via the internet (genuine or falsified) were used. Discriminant analyses were performed on the Raman spectra combined with soft independent modeling of class analogy (SIMCA) and partial least squares discriminant analysis (PLS-DA). It was possible to identify all falsified samples by SIMCA using the standard product model for all four products. Using the PLS-DA using the PLS models of the four standard products, falsified Levitra and Diflucan samples were classified correctly, although some falsified Cialis and all Viagra samples also belonged to the standard class. In this study, SIMCA might be more suitable than PLS-DA for identifying falsified medicines. A spectroscopic module that combines the low-cost Raman scattering spectroscopy with SIMCA might contribute to the rapid identification of falsified medicines in the field.

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.

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.

Study on health hazards through medicines purchased on the Internet: a cross-sectional investigation of the quality of anti-obesity medicines containing crude drugs as active ingredients.

BACKGROUND: Weight-loss medicines, including crude drugs and herbal supplements disguised as diet-aid products, are readily obtainable and distributed widely, especially in Southeast Asia. Even if such products are unapproved or prescription-only medicines, consumers can purchase them through an agency or directly on the Internet. We evaluated the quality and safety of herbal products purchased on the Internet to reveal their influence on public health. METHODS: Diet-aid products containing Bukuryo (Poria sclerotium), Bakumondo (Ophiopogonis tuber), or Daio (rhubarb rhizome) were purchased through websites that did not provide physical addresses or which advertised misleading medicines (e.g., unapproved Cialis 100 mg tablets, Viagra 100 mg tablets) on websites. We carefully noted details in the descriptions on package inserts or accompanying product characteristics and analyzed the ingredients using qualitative and quantitative methods, namely high-performance liquid chromatography equipped with a photodiode array detector. We requested the respective manufacturers to authenticate their products through a structured questionnaire. RESULTS: We purchased 15 items from 15 Internet sites and imported all 15 items to Japan. One item stated to contain rhubarb rhizome was identified as a prescription medicine; the others were dietary supplements and not medicines. Even though we did not analyze the constituents of all crude drugs, we found some active ingredients in the items. Sibutramine was detected in items confirmed to be supplements, including those containing Poria sclerotium and Ophiopogonis tuber. Each capsule contained ≈ 12 mg of sibutramine, which is the daily dose for anti-obesity medicines. Sibutramine is not approved for use in Japan and its sale has been suspended in Europe and the USA owing to serious adverse effects on the circulatory system. CONCLUSIONS: Our findings indicate that dietary supplements containing injurious ingredients are distributed to Japanese consumers and potentially to a broader international audience, and that purchasing them through unreliable websites bears potential health risks. To avoid potential adverse events, there should be adequate alerts about the risks of taking products without appropriate indications.

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.

Perceptions and practices of pharmaceutical wholesalers surrounding counterfeit medicines in a developing country: a baseline survey.

BACKGROUND: Recent investigations by the Ministry of Health of Cambodia suggest that counterfeit medicines have been introduced into the pharmaceutical market in tampered packaging. To further explore this possibility, an interview survey was conducted at the wholesaler level to investigate the medicinal supply chain in Cambodia. METHODS: Managing executives of 62 (83.8%) registered wholesalers of modern medicines in Cambodia were interviewed in 2009 on their knowledge of, perception on, and practices related to counterfeiting issues through a semi-structured questionnaire. RESULTS: According to our findings, 12.9% of the wholesalers had encountered counterfeit medicine. However, they demonstrated a variety of perceptions regarding this issue. A majority (59.7%) defined counterfeit medicines as medicines without registration, while other definitions included medicines that were fraudulently manufactured, medicines without a batch/lot number, those containing harmful ingredients or a reduced amount of active ingredients, and expired medicines. Additionally, 8.1% responded that they did not know what counterfeit medicines were.During procurement, 66.1% of the wholesalers consider whether the product is registered in Cambodia, while 64.5% consider the credibility and quality of the products and 61.3% consider the reputation of the manufacturers. When receiving a consignment, 80.6% of wholesalers check the intactness of medicines, 72.6% check the specification and amount of medicines, 71% check Cambodian registration, 56.5% check that the packaging is intact, 54.8% check batch and lot numbers, 48.4% check the dates of manufacture and expiration, and 9.7% check analytical certificates.Out of 62 wholesalers, 14.5% had received medicines that arrived without packages or were separated from their packaging and had to be repacked before distribution. Significant statistical association was found between wholesalers who received medicines separately from their packs/containers and who consider their belief on reliability of pharmaceutical products of certain manufacturing country during procurement (Chi-square: 12.951, P = 0.002). When wholesalers divide medicines from larger packs into smaller ones, 54.8% use packaging purchased from local markets. CONCLUSION: A number of wholesalers think counterfeit medicines are medicines without registration, and/or do not have any uniform ideas on the issue and what to do, when they find or suspect counterfeits. Furthermore, their strict adherence to anti-counterfeiting measures is urgently needed.

Quality assessment of Diflucan® tablets distributed online: Diflucan® distributed online.

Background: Falsified medical products have been reported worldwide. Falsified medicines with poor quality are a potential health hazard. Some Internet sites advertise fluconazole (Diflucan®), an antifungal medicine used to treat deep mycoses, as "female Viagra®." Aim: The aim of this study was to investigate the authenticity and quality of Diflucan® tablets distributed on the Internet. Methods: We ordered Diflucan® tablets via the Internet and evaluated them by visual observation, authenticity investigation, quality evaluation (quantity of the active pharmaceutical ingredient, content uniformity, and dissolution), and near-infrared and Raman scattering spectroscopy. Results: We obtained 11 samples of Diflucan® tablets from all 11 Japanese Internet sites identified in our search. Of 11 sites, 7 advertised fluconazole as having effects on female sexual function. Ten of the Diflucan® samples were confirmed as genuine and one sample was falsified. The genuine Diflucan® samples met the specifications of all quality evaluations. The packaging, size, and color of the falsified Diflucan® sample obtained in this study differed from the authentic Diflucan® tablet. The falsified Diflucan® sample obtained in this study did not contain fluconazole and instead contained what appeared to be sildenafil citrate. The spectra of the falsified Diflucan® tablet obtained in this study differed from the authentic Diflucan® tablet in near-infrared and Raman scattering spectroscopy. Conclusion: We confirmed that one falsified Diflucan® tablet was distributed online. Thus, continued measures against falsified medicines are required.

Quality and Authenticity of Metformin Tablets Circulating on Japanese Websites.

BACKGROUND: Low-quality medicines and falsified medicines represent long-standing problems in developing countries. In Southeast Asia, the circulation of low-quality diabetes drugs (metformin) has been confirmed. It is possible that low-quality metformin has entered Japan via personal import through the Internet. This study evaluated the pharmaceutical quality and authenticity of metformin tablets obtained via the Internet in Japan. METHODS: In total, 33 samples of 500-mg metformin tablets and 7 samples of extended-release/sustained-release tablets (500, 750, and 1,000 mg) were purchased via personal import in January 2017. Confirmation of a prescription was never requested purchase. The obtained samples were subjected to visual observations and authenticity investigations. Additionally, quantitative analysis, content uniformity and dissolution tests were performed using HPLC-PDA. RESULTS: Our authenticity investigations revealed that seven samples were genuine products, whereas the authenticity of the remaining 33 samples was unclear. Referring to United States Pharmacopeia 2014 for validation, four samples failed quality testing, five samples failed content uniformity testing, and two samples failed dissolution testing. CONCLUSIONS: Our findings illustrate that metformin tablets of poor-quantity and unregistered/unlicensed doses are available online and that it is important to increase consumer awareness about the presence of these medicines on the Internet to prevent the purchase of substandard medicines.

Clarification of the internal structure and factors of poor dissolution of substandard roxithromycin tablets by near-infrared chemical imaging.

The spread of substandard and falsified medicines has become a global problem, especially in low- and middle-income countries (LMICs). Previously, we found that some tablets containing the same active ingredient had large differences in their dissolution even though their contents were comparable. In this study, we investigated the poor dissolution of roxithromycin tablets using near-infrared chemical imaging (NIR-CI) to visualize the internal tablet structure. Roxithromycin tablets collected in LMICs and the pioneer product Rulid® as a reference were cut to a flat surface for analysis. NIR spectral data were normalized, and a principal component analysis was performed to create a tablet internal structure image. For Rulid®, the differences between the spectra with high and low scores were small, and well-defined aggregation of ingredients was not observed. However, large differences in the scores were found for roxithromycin tablets manufactured in some LMICs, and non-uniformity of ingredient distribution and aggregation were observed. Additionally, some pharmaceutical excipients, such as starch or magnesium stearate, were found in certain aggregates by comparing NIR spectra. The NIR-CI results showed some excipients existed as large aggregates, which indicated that the ingredients were not evenly mixed in the roxithromycin tablet, and this contributed to its poor dissolution.

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.

Prevalence of counterfeit anthelminthic medicines: a cross-sectional survey in Cambodia.

OBJECTIVES: To assess the prevalence of counterfeit anthelminthic medicines in Cambodia, and to determine influential factors. METHODS: Commonly used anthelminthic medicines were collected from private drug outlets. Medicines were carefully observed including their registration labelling, and their authenticity was investigated with the manufacturers and the Medicines Regulatory Authorities. Samples were analysed by High-Performance Liquid Chromatography at the National Health Product Quality Control Centre, Cambodia. RESULTS: Two hundred and three samples of anthelminthics were collected from 137 drug stores. Domestic products constituted 36.9%. Of 196 samples which were verified for registration, 15.8% were not registered. Of 165 samples successfully investigated for their authenticity, 7 (4.2%) were identified as counterfeit. All of these medicines were purchased in open packs or containers, and most of them were foreign manufactured and/or without registration. CONCLUSION: The results of our survey urge strict implementation of drug registration and vigilance on the availability of unregistered medicines to combat counterfeit medicines in Cambodia.

Discrimination of Falsified Erectile Dysfunction Medicines by Use of an Ultra-Compact Raman Scattering Spectrometer.

Substandard and falsified medicines are often reported worldwide. An accurate and rapid detection method for falsified medicines is needed to prevent human health hazards. Raman scattering spectroscopy has emerged as a non-destructive analysis method for the detection of falsified medicines. In this laboratory study, Raman spectroscopy was performed to evaluate the applicability of the ultra-compact Raman scattering spectrometer (C13560). Principal component analysis (PCA) was also performed on the Raman spectra. This study analyzed tadalafil (Cialis), vardenafil (Levitra), and sildenafil (Viagra) tablets. We tested the standard product and products purchased from the internet (genuine or falsified). For Cialis and Levitra, all falsified tablets were identified by the Raman spectra and PCA score plot. For Viagra, the Raman spectra of some falsified tablets were almost comparable to the standard tablet. The PCA score plots of falsified tablets were dispersed, and some plots of falsified tablets were close to the standard tablet. In conclusion, C13560 was useful for the discrimination of falsified Cialis and Levitra tablets, whereas some falsified Viagra tablets had Raman spectra similar to that of the standard tablet. The development of detection methods that can be introduced in various settings may help prevent the spread of falsified products.

Falsified vardenafil tablets available online.

It is often reported that falsified medicines have harmful effects on patients both Japan and abroad. In this study, we purchased vardenafil tablets on the internet and investigated their quality and authenticity using visual observations, authenticity investigations, non-destructive tests (handheld NIR and Raman spectroscopy), and quality analyses (active ingredient content and tablet dissolution rate). We used genuine 20-mg Levitra tablets that were sold in Japan and tablets from Bayer AG (Germany) as controls. In April 2015, we obtained 28 samples from 15 websites on the internet. Our authenticity investigations revealed that 11 (40%) were genuine products and 17 (60%) were falsified products. Handheld NIR and Raman results revealed that the falsified products had different spectra to the genuine products. Principal component analysis of the NIR and Raman spectra showed variation among the falsified products. The 11 genuine products were of good quality, and the 17 falsified products were of poor quality. The falsified products contained sildenafil (the active ingredient of Viagra) or tadalafil (the active ingredient of Cialis) instead of vardenafil. Our results show that falsified Vardenafil tablets are sold on the internet and that it is important to prevent illegal internet sales and increase consumer awareness of the presence of falsified medicines.

Falsified tadalafil tablets distributed in Japan via the internet.

The adverse health effects of falsified medicines for erectile dysfunction have been reported in Japan. We purchased tadalafil (Cialis) tablets online and assessed their authenticity and quality. Of the 45 samples we tested, nine were genuine, 23 were falsified, nine were unregistered/unlicensed samples, and the authenticity of four samples could not be ascertained. Observation of packaging and tablet size, weight, and color revealed differences between some genuine and falsified samples. All genuine samples contained the active pharmaceutical ingredient tadalafil at adequate quantities, while falsified samples contained sildenafil (Viagra). Some falsified samples contained insufficient quantities of tadalafil. All unregistered/unlicensed samples contained neither tadalafil nor sildenafil. Some falsified samples did not dissolve/disintegrate sufficiently. The status of most samples was detectable by Raman scattering and near-infrared spectroscopy. Restricting consumer access to falsified medicines can prevent undesirable health effects.

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.

Antimicrobial therapy for water-associated wound infections in a disaster setting: gram-negative bacilli in an aquatic environment and lessons from Banda Aceh.

INTRODUCTION: As members of the Japan Disaster Relief (JDR) team in Banda Aceh, three of the authors treated 1,891 patients following the tsunami of 2004. Of the 367 cases with traumatic injuries, 216 cases required antimicrobial therapy. The medical services were continued by the Japan Self-Defense (JSD) Medical Team until mid-March 2005. Of the 216 cases initially treated by JDR, 54 required prolonged antimicrobial therapy for persistent symptoms despite repeated debridement. The aim of this study is to recommend an appropriate antimicrobial therapy for water-associated wound infections in the absence of laboratory services in disaster settings following tsunami. METHODS: The JDR and JSD treatment records were analyzed retrospectively. In August 2006, 19 months after the tsunami, the authors investigated pathogens in natural aquatic habitats in the affected area in Banda Aceh. At the same time, interviews with tsunami survivors were performed to determine the influential factors that facilitated wound infections after the tsunami. RESULTS: From the 49 water samples tested, Aeromonas sp., Vibrio sp., Klebsiella sp., and Proteus sp. were isolated from 24, 16, 15, and six samples, respectively. Regardless of the genus, almost all of the isolated gram-negative bacilli were sensitive to ciprofloxacin and gentamicin. CONCLUSIONS: From the microbiological test results and analyses of the medical records and interviews, the researchers recommend the following regimen when clinical microbiological tests are not available: initial treatment with beta"lactam penicillins for three days, followed, if the first antimicrobial is not effective, by ciprofloxacin or any other relevant new quinolones, with the addition of gentamicin if necessary.

A Cross-Sectional Investigation for Verification of Globalization of Falsified Medicines in Cambodia, Indicated by Tablets of Sildenafil Citrate.

Medicine falsification is a global issue. Viagra, an erectile dysfunction therapeutic (EDT) medicine consisting primarily of sildenafil citrate, is the most commonly falsified medicine worldwide. Recently falsified EDTs have been reported multiple times in developing countries. The globalization of falsified EDTs has become a concern. In the present study, we selected sildenafil citrate tablets as an indicator and examined samples from a developing country, Cambodia, to investigate the availability of falsified sildenafil tablets in Cambodia and verify the current globalization status of falsified medicines from the standpoint of a developing country. Six samples of the originator Viagra, and 68 samples of generic sildenafil products were purchased from private drug outlets and wholesalers in Phnom Penh, Svay Rieng, and Battambang. The samples' manufacturers were contacted to authenticate the samples. The quantities and dissolution rates of active ingredients were measured by a high-performance liquid chromatography system with photodiode array. Five generic samples were strongly suspected to be falsified medicines because of their extremely low quality; however, there was little distribution and no falsified medicine alleged to be produced by the originator of Viagra, which charges high prices. That finding indicates that falsification reflects local economic circumstances.

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.