Survey to Identify Substandard and Falsified Tablets in Several Asian Countries with Pharmacopeial Quality Control Tests and Principal Component Analysis of Handheld Raman Spectroscopy

Abstract

The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market.

Substandard and Falsified Medicines in Myanmar

“…Further, there were sporadic reports concerning Myanmar in 2001 and 2008 [7,8]. Therefore, we started a survey in Myanmar in 2014 [9,10], and followed that with the present in 2015. Because the number of patients with long-term diseases in developing countries is increasing [11], not only on anti-microbials, but also on medicines against chronic or life-style related diseases are important.…”

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

“…Moisture absorption because of poor storage conditions, such as high temperature and high humidity, might be one of the causes of quality deterioration. It has been reported that tablets contain a large amount of high specific gravity ingredients, even in falsified medicines that may be manufactured in a sloppy manner ( Kakio et al, 2018 ). The poor dissolution in RXM tablets might be because of the manufacturing process.…”

“…It is pointed out by heads of state and the WHO that universal health coverage (UHC, Good Health and Well-being) as described in Sustainable Development Goal 3.8 (SDGs) cannot be achieved without ensuring the quality of medicines. In many countries, especially low- and middle-income countries (LMICs), medicine regulation authorities, manufacturers, and researchers are struggling to prevent the distribution of SFMs ( Lon et al, 2006 , Amin and Kokwaro, 2007 , Gaudiano et al, 2007 , Khan et al, 2010 , Khan et al, 2011a , Khan et al, 2011b , Binagwaho et al, 2013 , Yoshida et al, 2014 , Otte et al, 2015 , Petersen et al, 2017 , Yong et al, 2015 , Kakio et al, 2017 , Khuluza et al, 2017 , Kakio et al, 2018 , Pisani et al, 2019 , Tabernero et al, 2019 , Schäfermann et al, 2020 ). However, the prevalence of SFMs is currently increasing globally, especially in LMICs, where the proportion of SFMs has reached 10.5% of the pharmaceutical market ( WHO, 2018 ).…”

Emerging Trends in Clinical Tropical Medicine Research

“…Cash-Goldwater et al 11 Infection risk factors Brucellosis confirmed by blood culture, or 4-fold rise in microagglutination was confirmed or probable in 9% of febrile patients, mostly who attend animals but were not suspected by medical providers. Kakio et al 12 Medication quality Studies of dissolution and use of handheld Raman spectrophotometer device were useful in detecting substandard or falsified medications using the antihypertensive candesartan as a test product. Fauver et al 13 Xenosurveillance PCR detected Trypanosoma brucei gambiense, Bacillus anthracis, Middle East respiratory syndrome-related Coronavirus, and Zika virus in the blood of Anopheles gambiae mosquitoes fed on blood containing these pathogens.…”