[Critical influencing factors on quality of traditional Chinese medicine preparations from perspective of process and equipment].

The quality of traditional Chinese medicine preparations is directly related to the safety of patients. Among the various factors, the process and corresponding critical equipment are critical factors influencing the quality of the preparations. To improve the quality of traditional Chinese medicine preparations, this article summarizes and analyzes the problems in the process links and corresponding critical equipment in the manufacturing process of traditional Chinese medicine preparations. Furthermore, a critical quality attribute evaluation system is established based on safety and effectiveness combined with the drug properties, preparation process, and preparation characteristics, providing a basis for the process and equipment improvements aimed at quality enhancement.

[The Applications of qNMR in Drug Quality Control].

NMR is well known as one of the most important methods for elucidating the structure of organic compounds. Furthermore, it has recently been recognized as a powerful tool for quantitative analysis. The quantitative NMR (qNMR) has become an official analytical method described in detail in the Japanese Pharmacopoeia. And today, it is widely applied in drug development. The qNMR method offers many new advantages over traditional and conventional quantitative analysis methods. For example, this method requires only a few milligrams of the analyte and allows absolute quantitation of the analyte without using a qualified reference standard as a control sample. Then, it can be easily applied to most chemicals without expending significant time and resources on method development. In addition, residual solvent can be determined using qNMR methods. The peak area of an NMR spectrum is directly proportional to the number of protons contributing to the resonance. Based on this principle, the residual solvent can be determined by counting the signal corresponding to the residual solvent in the sample solution. We have applied qNMR as an alternative to GC. Thus, qNMR is an innovative and promising analytical technique that is expected to make significant progress in the future. Recently, the analytical research and quality control departments have been working together to expand this technology to a wide range of areas in the pharmaceutical industry.

Social and cultural determinants of antibiotics prescriptions: analysis from a public community health centre in North India.

This paper explores the socio cultural and institutional determinants of irresponsible prescription and use of antibiotics which has implications for the rise and spread of antimicrobial resistance (AMR). This study describes the patterns of prescription of antibiotics in a public facility in India and identifies the underlying institutional, cultural and social determinants driving the irresponsible use of antibiotics. The analysis is based on an empirical investigation of patients' prescriptions that reach the in-house pharmacy following an outpatient department (OPD) encounter with the clinician. The prescription analysis describes the factors associated with use of broad-spectrum antibiotics, and a high percentage of prescriptions for dental outpatient department prescribed as a precautionary measure. This paper further highlights the need for future research insights in combining socio-cultural approach with medical rationalities, to further explore questions our analysis highlights like higher antibiotic prescription, etc., Along with the recommendations for further research.

Eye Drop Quality Issues: Can the FDA See This One Through?

The Food and Drug Administration (FDA) has long suffered from a lack of resources limiting their inspection capacity. They have fallen behind on proactive surveillance inspections of foreign manufacturing sites, relying instead on for-cause inspections after a problem has been discovered. Over-the-counter (OTC) products are especially vulnerable because the FDA considers them lower priority. This issue recently made big news after improperly manufactured OTC eye drops harmed users across the country, in some cases causing blindness. To prevent future harm to Americans, it is imperative that the FDA receives enough resources to keep up with their routine inspections.

Evaluating the Potency of Selected Antibiotic Medications Dispensed in Community Pharmacies in Gwale, Kano, Nigeria.

The worsening of antibiotic resistance is a multifactorial process. One aspect of this is the counterfeiting of antibiotic medications. This is supposed to be particularly high in developing countries, including Nigeria. Therefore, the potency of some antibiotic drugs dispensed in community pharmacies in Gwale, Kano, Nigeria, was investigated in this case study. Three products, each from different manufacturers, with the active ingredients of ceftriaxone, gentamicin, ciprofloxacin, and metronidazole, respectively, were included in this study. By means of a disc-diffusion assay, the effect against the typed strains Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) as well as Clostridium tetani isolated from soil was tested. Clinical isolates of S. aureus and E. coli were also used. While antibiotics, with the exception of ciprofloxacin-containing preparations against C. tetani, showed acceptable efficacy against the typed strains by comparison with the clinical science laboratory references, a predominant failure was observed with the clinical isolates. Thus, the investigated drug preparations can be considered of acceptable quality for the treatment of susceptible bacterial infections. This excludes counterfeits in the sampled preparations. However, the insufficient efficacy against clinical isolates further documents the severity of nosocomial bacteria.

Consumer expectations, drug effects, price and purity of heroin and cocaine purchased at drug consumption rooms.

BACKGROUND: Drug consumption rooms offer heroin and cocaine consumers a secure and hygienic environment including medical and social guidance. Despite the support and mentoring, only sparse information is available about how drug quality, drug prices and user expectations match at these locations. The present study reports analysis of these three parameters in two drug consumption rooms in Luxembourg. METHODS: Drug users were invited to participate in the project by handing in a few milligrams of the product they planned to consume for chemical analysis and filling out a short questionnaire about the price and their expectations. After consumption, they were asked to report the experienced effects. Drug quality was accessed using LC-Q-ToF and HPLC-UV, and a statistical analysis was carried out of the questionnaires that were correctly filled out. RESULTS: A total of 513 drug samples have been analyzed. Most consumers were looking for the relaxing/calming effects of heroin and the stimulating effects of cocaine, but they generally overestimated heroin potency and underestimated cocaine potency. No strong correlation based on Spearman's ρ between drug user estimations, drug prices and drug quality was found. CONCLUSION: To the best of our knowledge, this study is the first to combine drug analysis with heroin and cocaine user feedback about expectation, drug prices and drug effects. The analytical results were of great interest for users and the staff working at the drug consumption rooms. They may be a strong supplementary communication tool for health care workers when discussing effects and risks of highly toxic substance consumption.

Radiothermal Emission of Nanoparticles with a Complex Shape as a Tool for the Quality Control of Pharmaceuticals Containing Biologically Active Nanoparticles.

It has recently been shown that the titer of the SARS-CoV-2 virus decreases in a cell culture when the cell suspension is irradiated with electromagnetic waves at a frequency of 95 GHz. We assumed that a frequency range in the gigahertz and sub-terahertz ranges was one of the key aspects in the "tuning" of flickering dipoles in the dispersion interaction process of the surfaces of supramolecular structures. To verify this assumption, the intrinsic thermal radio emission in the gigahertz range of the following nanoparticles was studied: virus-like particles (VLP) of SARS-CoV-2 and rotavirus A, monoclonal antibodies to various RBD epitopes of SARS-CoV-2, interferon-α, antibodies to interferon-γ, humic-fulvic acids, and silver proteinate. At 37 °C or when activated by light with λ = 412 nm, these particles all demonstrated an increased (by two orders of magnitude compared to the background) level of electromagnetic radiation in the microwave range. The thermal radio emission flux density specifically depended on the type of nanoparticles, their concentration, and the method of their activation. The thermal radio emission flux density was capable of reaching 20 µW/(m2 sr). The thermal radio emission significantly exceeded the background only for nanoparticles with a complex surface shape (nonconvex polyhedra), while the thermal radio emission from spherical nanoparticles (latex spheres, serum albumin, and micelles) did not differ from the background. The spectral range of the emission apparently exceeded the frequencies of the Ka band (above 30 GHz). It was assumed that the complex shape of the nanoparticles contributed to the formation of temporary dipoles which, at a distance of up to 100 nm and due to the formation of an ultrahigh strength field, led to the formation of plasma-like surface regions that acted as emitters in the millimeter range. Such a mechanism makes it possible to explain many phenomena of the biological activity of nanoparticles, including the antibacterial properties of surfaces.

Analysis of the problems of drug sampling and testing programme under tripartite system reform in China.

RATIONALE: To ensure that quality medicines are available to the populace. AIM AND OBJECTIVE: To provide a new perspective for drug sampling and testing using a risk-based approach globally, and provide a reference for improving the efficiency of the drug sampling and testing programme in China. METHOD: This study used a combination of theoretical analysis and problem analysis. First, we analysed the high-risk drugs that should be given attention to theoretically in the drug sampling testing programme based on the healthcare reform in China. Second, this study leveraged on data on the sampling and testing of drugs extracted from self-constructed data by the China Food and Drug Administration (CFDA). The integrated and structured data sets were used to conduct an innovative analysis that identifies the actual content of the drug sampling and testing programme and contrasts them with the theoretical content to understand the problems. This study used quantitative and qualitative approaches for data analysis. RESULTS: Following analysis, we discovered that there is still a big gap between the reality of drug sampling and testing in China and the ideal state of the objective requirements of healthcare reforms. The major sources of risk are the retail pharmacies or hospital pharmacies in the distribution chain of drugs; however, the CFDA sampled mostly drugs from drug manufacturers. Additionally, the CFDA did not sample adequate essential medicines, bid-winning drugs (especially those with large price drops in centralized procurement), biological products and other high-risk drug varieties. The high-risk drugs produced by companies or enterprises with a history of noncompliance, especially bid-winning enterprises in centralized procurement, were not sampled. CONCLUSION: We suggest that the major content of drug sampling and testing in China should focus on the link of drug utilization, varieties of drugs with large price drops in centralized procurement and bid-winning enterprises with a history of noncompliance.

Quantification of Grapiprant and Its Stability Testing under Changing Environmental Conditions.

Grapiprant is a new analgesic and anti-inflammatory drug belonging to the piprant class, approved in 2016 by the FDA Veterinary Medicine Center for the treatment of pain and inflammation associated with osteoarthritis in dogs. It acts as a highly selective antagonist of the EP4 receptor, one of the four prostaglandin E2 (PGE2) receptor subtypes. It has been shown to have anti-inflammatory effects in rat models of acute and chronic inflammation and clinical studies in people with osteoarthritis. The current state of knowledge suggests the possibility of using it in oncological therapy. The manuscript presents the development of conditions for the identification and quantitative determination of grapiprant by thin-layer chromatography with densitometric detection. The optimal separation of the substance occurs using silica gel 60F254 chromatographic plates and the mobile phase containing ethyl acetate-toluene-butylamine. Validation (according to ICH requirements) showed that the developed method is characterized by straightness of results in a wide concentration range with the limit of detection of 146.65 µg/mL. The %RSD values of the precision and accuracy confirm the sensitivity and reliability of the developed procedure. Next, the method was used for quantification of grapiprant in a pharmaceutical preparation, and for stability studies under various environmental conditions. Additionally, the mass studies were carried out on the stressed samples using the UPLC-MS/MS method. The degradation products were primarily characterized by comparing their mass fragmentation profiles with those of the drug. The results indicated a potential degradation pathway for grapiprant.

Recent developments in microfluidic paper-based analytical devices for pharmaceutical analysis.

In the last decade, due to the global increase in diseases, drugs for biomedical applications have increased dramatically. Therefore, there is an urgent need for analytical tools to monitor, treat, investigate, and control drug compounds in diverse matrices. The new and challenging task has been looking for simple, low-cost, rapid, and portable analytical platforms. The development of microfluidic paper-based analytical devices (µPADs) has garnered immense attention in many analytical applications due to the benefit of cellulose structure. It can be functionalized and serves as an ideal channel and scaffold for the transportation and immobilization of various substances. Microfluidic technology has been considered an effective tool in pharmaceutical analysis that facilitates the quantitative measurement of several parameters on cells or other biological systems. The µPADs represent unique advantages over conventional microfluidics, such as the self-pumping capability. They have low material costs, are easy to fabricate, and do not require external power sources. This review gives an overview of the current designs in this decade for µPADs and their respective application in pharmaceutical analysis. These include device designs, choice of paper material, and fabrication techniques with their advantages and drawbacks. In addition, the strategies for improving analytical performance in terms of simplicity, high sensitivity, and selectivity are highlighted, followed by the application of µPADs design for the detection of drug compounds for various purposes. Moreover, we present recent advances involving µPAD technologies in the field of pharmaceutical applications. Finally, we discussed the challenges and potential of µPADs for the transition from laboratory to commercialization.

FDA Approaches in Monitoring Drug Quality, Forces Impacting the Drug Quality, and Recent Alternative Strategies to Assess Quality in the US Drug Supply.

Since the US Food and Drug Administration (FDA) began monitoring the quality of pharmaceutical manufacturing by enforcing current good manufacturing practices roughly 60 years ago, forces related to the global economy have changed, rendering the task of monitoring quality more difficult. Alternative strategies by groups like Valisure, LLC, and the University of Kentucky Drug Quality Study to monitor the quality of the currently circulated US drug supply through end-product testing and screening have resulted in several concerning findings. Given the successful approaches of identifying quality defects in pharmaceuticals by non-regulatory bodies, and considering the changing landscape and pressures on manufacturing, the FDA, large buying groups, and the US Department of Defense should consider these alternative strategies as a means to augment current regulatory activities.

Development of single- and multiplex immunoassays for rapid detection and quantitation of amodiaquine in ACT drugs and rat serum.

Amodiaquine (AQ) is a commonly used antimalarial drug, and N-desethyl-AQ (N-DEAQ) is an active metabolite of AQ. Given the significance of drug quality in the management of malaria cases, this study aims to develop antibody-based assays for the detection and quantitation of AQ without the need for sophisticated equipment. Two monoclonal antibodies (mAbs) against AQ, designated as JUN7 and TE7, were selected, which showed 72.7% and 9.5% cross-reactivity to N-DEAQ, respectively. These mAbs showed <0.1% cross-reactivity to other commonly used antimalarial drugs. An indirect competitive enzyme-linked immunosorbent assay (icELISA) based on JUN7 showed a 50% inhibitory concentration (IC50) of 0.16 ng/mL and a working range of 0.06-0.46 ng/mL. A lateral flow immunoassay (LFIA) based on JUN7 was also developed with a working range of 2.58-30.86 ng/mL. The icELISA and LFIA were applied for the quantification of AQ in commercial drugs, and the results were comparable to those determined using high-performance liquid chromatography. In addition, a combination dipstick for simultaneous, qualitative analysis of AQ and artesunate was developed. All immunoassays based on JUN7 can be applied for quality control of AQ-containing artemisinin-based combination therapies. As TE7 showed low cross-reactivity to N-DEAQ, an icELISA based on TE7 was developed with an IC50 of 0.38 ng/mL and a working range of 0.14-1.67 ng/mL. The TE7 icELISA was applied for the study of pharmacokinetics of AQ in rat serum after intragastric administration, and the results were consistent with those of previous studies.

Meeting report: an exploration into the scientific and regulatory aspects of pharmaceutical drug quality in the United States.

INTRODUCTION: The University of Florida College of Pharmacy, Department of Pharmaceutical Outcomes and Policy hosted a seminar 6-7 March 2021, on the quality of pharmaceutical products in the United States. This meeting report summarizes the topics presented at the seminar and highlights the expert opinions offered by the presenters. AREAS COVERED: The seminar, held virtually due to the COVID-19 pandemic, included slide presentations and faculty-moderated panel discussions from experts in the field. These experts from regulatory, academic, and private sectors discussed bioequivalence standards, existing and emerging efforts to promote quality in brand and generic manufacturing, as well as market-based solutions throughout the drug supply chain. EXPERT OPINION: The time spent understanding bioequivalence standards during the seminar felt especially important and relevant in our current pandemic environment, given the present need to have confidence in the science of drug development and to advocate for the safety of pharmaceuticals. Also an important point to emphasize from the seminar, was that every stakeholder along the drug supply chain has a responsibility to do their part to maintain its quality. And those in attendance, many of whom were students of healthcare sciences, were encouraged to be leaders in their fields and develop strategies to advance innovative improvements.

Pharmaceutical enterprises drug quality strategy Moran analysis considering government supervision and new media participation.

The improvement of drug quality requires not only the supervision of government, but also the participation of new media. Therefore, this paper considers the impact of government regulation and new media reports on pharmaceutical enterprises, constructs a Moran Process evolutionary game model, and analyzes the evolution trajectory of pharmaceutical enterprises' choice of drug quality improvement strategy and drug cost reduction strategy. We obtain the conditions for the two strategies to achieve evolutionary stability under the dominance of external factors and the dominance of expected returns. To verify the theoretical results, we conduct a numerical simulation by the software MATLAB 2021b. The results show that, first of all, when the government penalty is high, the drug quality improvement strategy tends to become an evolutionary stable solution, increasing the penalty amount will help promote the improvement of drug quality. What's more, when the government penalty is low and the new media influence is low, the drug cost reduction strategy is easier to dominate. The higher the new media influence, the higher the probability that pharmaceutical enterprises choose the drug quality improvement strategy. Thirdly, when the number of pharmaceutical enterprises is lower than a threshold, the drug quality improvement strategy is easier to dominate. Finally, the drug quality improvement strategy is dominant when the quality cost factor is low and the government penalty is high, the drug cost reduction strategy is dominant when the quality cost factor is high and the government penalty is low. Above all, this paper provides countermeasures and suggestions for the drug quality improvement of pharmaceutical enterprises in practice.

Analysis of Traditional Chinese Medicine regulation in Canada / 国际中医中药杂志

This paper analyzes the laws, regulations and concre measures of Traditional Chinese Medicine (TCM) in Canada, so as to provide reference for TCM products to enter Canada, and for the establishment of TCM regulation system and the improvement of its detailed rules in China. The regulation of TCM in Canadian, on the one hand, supervision is to provide guidance for the protection of consumers' rights and interests, including the guidance of rational drug use and rational purchase for consumers; on the other hand, it is to supervise enterprises, including the safety, effectiveness and quality certification of TCM products, labeling and packaging requirements, as well as the site certification of product manufacturing, packaging, labeling and import. The Ministry of health of Canada takes evidence as the core of evaluation, and ensures the safe and effective use of TCM products in Canada through product and site licensing evaluation. In the supervision of TCM, relevant departments in China should further strengthen the protection of consumers' drug rights and interests, strengthen the construction of TCM registration evidence system, and pay attention to the risk management of drug production quality.

A New Paradigm for Ensuring Digital Drug Care Quality Monitoring Based on Ontology Tools.

Systematizing and conceptualizing of the components of the patient's diagnosis at definite Clinical Situations are the important steps in constructing the medical electronic platforms to monitor the drug treatment quality and to realize the process of risk-management of drug care. The risk-management is a hard and expensive process for the non-profit hospitals. The Information technologies have a high potential for solving these problems. The conceptual schemes to construct the multimodal medical electronic platform were discussed. The Information Space of Clinical Practice, Information Field for formulating the detailed patient's diagnosis at the definite Clinical Situations, Information Environment for the components of the detailed patient's diagnosis were described.

Fruits of Vitex doniana sweet: toxicity profile, anti-inflammatory and antioxidant activities, and quantification of one of its bioactive constituents oleanolic acid.

BACKGROUND: Vitex doniana Sweet fruit, an under-utilised crop specie of Ghana, has not been validated for its ethnomedical use in managing inflammatory conditions. Therefore, the study sought to investigate its anti-inflammatory and antioxidant activities as well as isolate and quantify one of its active constituents. MATERIALS AND METHODS: In-vivo anti-inflammatory activity of the methanol fruit extract was evaluated using the carrageenan-induced oedema model in chicks. The in-vitro antioxidant property was also investigated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The acute and subacute toxicity studies of the fruit extract were evaluated in rodent models. RESULTS: No signs of autonomic and central nervous system stimulation/depression were recorded. The LD50 by oral route, was estimated to be beyond 3000 mg/kg. Subacute studies revealed an increase in red blood cell and lymphocyte counts. Liver enzymes, serum proteins and bilirubin levels did not significantly increase. The crude extracts at doses of 10, 30 and 100 mg/kg inhibited paw oedema considerably. The ethyl acetate fraction showed the highest antioxidant activity (IC50 = 99.35 ± 0.77 µg/mL). Oleanolic acid, isolated from the ethyl acetate extract, showed significant anti-inflammatory and antioxidant activities. A sensitive high-performance liquid chromatography method for the detection and estimation of oleanolic acid, as a biomarker compound for V. doniana fruit, was developed and validated for quality assurance purposes. CONCLUSION: The extract of V. doniana fruits possesses considerable anti-inflammatory and antioxidant properties and was non-toxic under laboratory conditions.

Evaluation of the In-Vitro Dissolution Permeation Systems 1 (IDAS1) as a potential tool to monitor for unexpected changes in generic medicaments in poorly regulated markets.

Panama, like most Latin American countries, has insufficient regulatory safeguards to ensure the safety and efficacy of all pharmaceutical products in the market, a situation that results in a two-tier system, where affluent citizens can afford innovator products while poor citizens must consume 'generics' of uncertain quality. Given that one lot of each drug product is analyzed every five years during registration while commercial lots are not, and since most products are not bioequivalent but simply copies or similars, there is a concern that commercial and registration lots of these 'generics' may not be of the same quality. The objective of this study was to assess the ability of various in vitro quality control tests to detect difference among five amlodipine products available in the Panamanian market: four 'generics', made in various countries, and the innovator, made in Germany and used as reference listed drug in Panama (Pan-RLD). The innovator manufactured in the United States (US-RLD) was used to compare the two RLDs. The Content Uniformity test, 30-min Dissolution test and multiple-pH Dissolution Profiles did not show any difference among the products. However, the in vitro dissolution absorption system 1 (IDAS1) showed a statistically significant difference in the amount dissolved between Pan-RLD and three out of the four 'generics', and significantly lower permeated amount for all the 'generics' compared with Pan-RLD; only US-RLD was similar to Pan-RLD. Thus, IDAS1 showed promise as a potential tool that authorities in weakly regulated markets can use to monitor for possible lot-to-lot product changes, which can help improve the quality of pharmaceutical products available to their entire populations. The significance of the similarity between the innovators made in Germany and the United States and their difference from the 'generics' (manufactured in other countries) is not known but deserves investigation.

Quality of Drug in Health Facilities: A Cross-sectional Study.

BACKGROUND: Poor quality drugs result minor to detrimental effect on human health. The drug should be of standard quality and should be used appropriately in order to meet its therapeutic efficacy. This study aims to assess the quality of drug in Nepal. METHODS: A cross sectional study was conducted in randomly selected 88 health facilities in Nepal from 10th April to 30th June 2016. Selective medicines were collected from both private licensed pharmacies and selected public health facilities. Face to face interview with health facility in-charge of selected health facilities was carried out along with the direct observation of the medicine storage room. The collected medicine samples were dispatched to two laboratories for in-vitro analysis. The labels of the collected medicine were analyzed. The obtained data were entered in Epidata version 3.1, cleaned in Microsoft excel 2007 and analyzed in SPSS version 20. RESULTS: Out of 172 brands, nine brands of medicines were found substandard. Information regarding storage conditions, direction for use and category of the drug were lacking in the label of some brands of medicines. Some selected health facilities were found not meeting major requirements for drug storage: protection from sunlight, moisture, heat, well ventilation and proper sanitation. CONCLUSIONS: Few drugs were found to be substandard in Nepalese market from both public and private sectors. Adequate labeling and proper storage condition of medicines in health facilities were lacking.