RESUMO
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.
Assuntos
Medicamentos Genéricos/química , Bangladesh , Comércio , Contaminação de Medicamentos/economia , Contaminação de Medicamentos/legislação & jurisprudência , Contaminação de Medicamentos/estatística & dados numéricos , Embalagem de Medicamentos/economia , Embalagem de Medicamentos/normas , Medicamentos Genéricos/economia , Medicamentos Genéricos/normas , Controle de QualidadeRESUMO
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.
Assuntos
Medicamentos Falsificados/análise , Modelos Químicos , Análise Espectral Raman , Medicamentos Falsificados/química , Fluconazol/análise , Fluconazol/química , Análise dos Mínimos Quadrados , Citrato de Sildenafila/análise , Citrato de Sildenafila/química , Comprimidos , Tadalafila , Dicloridrato de Vardenafila/análise , Dicloridrato de Vardenafila/químicaRESUMO
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.
RESUMO
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.
Assuntos
Medicamentos Falsificados/análise , Disponibilidade de Medicamentos Via Internet/normas , Controle de Qualidade , Agentes Urológicos/análise , Dicloridrato de Vardenafila/análise , Medicamentos Falsificados/química , Medicamentos Falsificados/economia , Humanos , Japão , Disponibilidade de Medicamentos Via Internet/economia , Análise de Componente Principal , Citrato de Sildenafila/análise , Análise Espectral Raman , Comprimidos , Tadalafila/análise , Agentes Urológicos/química , Agentes Urológicos/economia , Agentes Urológicos/normas , Dicloridrato de Vardenafila/químicaRESUMO
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.
Assuntos
Preparações de Ação Retardada/normas , Composição de Medicamentos/normas , Omeprazol/normas , Camboja , Cromatografia Líquida de Alta Pressão , Indústria Farmacêutica , Microscopia Eletrônica de Varredura , Mianmar , Vigilância de Produtos Comercializados , Tomografia Computadorizada por Raios XRESUMO
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.