-
Journal of Pharmaceutical and... Feb 2024To ensure the efficacy, safety, and quality of drugs, several national and international guidelines and regulatory requirements exist. The most important international... (Review)
Review
To ensure the efficacy, safety, and quality of drugs, several national and international guidelines and regulatory requirements exist. The most important international regulatory framework for quality is the collection of the guidelines ICH Q1-Q14 (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use), which form the basis for the development and approval of medicinal products. Additionally, international and national pharmacopoeias and national regulatory authorities like Food and Drug Administration (FDA) and European Directory for the Quality of Medicines and HealthCare (EDQM) have to be considered during the lifecycle of a drug. Further, regular updates and optimization of processes and methods together with periodic audits and inspections of the manufacturing plants help to ensure compliance with the complex regulatory requirements for medicinal products. Although the pharmaceutical world seems to be very well regulated and controlled, several drug recalls per year have to be announced and conducted to remove defect products from the market and protect the patient from any potential health risk. This review article provides an overview of the most common reasons for such recalls presenting several historical and current cases with a detailed discussion of root causes. A specific focus lies on quality issues like drug degradation, impurity and nitrosamine contamination, lack of drug stability, occurrence and transformation of polymorphs, contamination with particulates and foreign matters, amongst others. The role of APIs, excipients and packaging will be discussed as well as the analytical challenges to detect, control and mitigate such quality issues. A final chapter will discuss the current situation and an outlook on emerging topics and future challenges for drug quality.
Topics: Humans; Pharmaceutical Preparations; Drug Packaging; Drug Stability
PubMed: 38103416
DOI: 10.1016/j.jpba.2023.115880 -
Journal of Pharmaceutical Sciences Sep 2023Most N-Nitrosamine compounds are found to be genotoxic in several animal species. Some are classified as probable or possible human carcinogens and very low acceptable... (Review)
Review
Most N-Nitrosamine compounds are found to be genotoxic in several animal species. Some are classified as probable or possible human carcinogens and very low acceptable daily intake has been established such as 96 ng/day for N-nitrosodimethylamine (NDMA) and 26.5 ng/N-nitrosodiethylamine (NDEA). The pharmaceutical industry has considered all processing areas for potential formation or contamination of N-nitrosamine. One risk is the potential contamination of nitrosamine during drug product blister packaging using lidding foils containing nitrocellulose, and different approaches have been used by pharmaceutical companies to evaluate and mitigate this risk. Herein we share a perspective from IQ Consortium N-nitrosamine Working Group on some of the approaches and corresponding results. From these assessments, it was concluded that the risk of nitrosamine contamination during blister packaging is negligible. The approaches shared in this perspective can be incorporated into risk assessment for nitrosamine contamination during drug product packaging at other pharmaceutical companies.
Topics: Animals; Humans; Nitrosamines; Blister; Dimethylnitrosamine; Drug Contamination; Product Packaging; Pharmaceutical Preparations
PubMed: 37478970
DOI: 10.1016/j.xphs.2023.07.014 -
Briefings in Bioinformatics Jul 2023Human prescription drug labeling contains a summary of the essential scientific information needed for the safe and effective use of the drug and includes the...
Human prescription drug labeling contains a summary of the essential scientific information needed for the safe and effective use of the drug and includes the Prescribing Information, FDA-approved patient labeling (Medication Guides, Patient Package Inserts and/or Instructions for Use), and/or carton and container labeling. Drug labeling contains critical information about drug products, such as pharmacokinetics and adverse events. Automatic information extraction from drug labels may facilitate finding the adverse reaction of the drugs or finding the interaction of one drug with another drug. Natural language processing (NLP) techniques, especially recently developed Bidirectional Encoder Representations from Transformers (BERT), have exhibited exceptional merits in text-based information extraction. A common paradigm in training BERT is to pretrain the model on large unlabeled generic language corpora, so that the model learns the distribution of the words in the language, and then fine-tune on a downstream task. In this paper, first, we show the uniqueness of language used in drug labels, which therefore cannot be optimally handled by other BERT models. Then, we present the developed PharmBERT, which is a BERT model specifically pretrained on the drug labels (publicly available at Hugging Face). We demonstrate that our model outperforms the vanilla BERT, ClinicalBERT and BioBERT in multiple NLP tasks in the drug label domain. Moreover, how the domain-specific pretraining has contributed to the superior performance of PharmBERT is demonstrated by analyzing different layers of PharmBERT, and more insight into how it understands different linguistic aspects of the data is gained.
Topics: Humans; Drug Labeling; Information Storage and Retrieval; Learning; Natural Language Processing
PubMed: 37317617
DOI: 10.1093/bib/bbad226 -
Biomedicine & Pharmacotherapy =... Dec 2023Depression is often associated with fatigue/energy loss. However, we lack a detailed understanding of the factors explaining this association. In this study, we...
Depression is often associated with fatigue/energy loss. However, we lack a detailed understanding of the factors explaining this association. In this study, we uncovered that depressed mice have a defect in fat absorption, resulting in weight loss and reduced circulating lipid levels. Si-Ni-San (SNS), a basic formula of traditional Chinese medicine (TCM) for the treatment of depression, was found to not only alleviate depression-like behaviors, but also reverse the weight loss and dietary fat absorption of depressed mice. We found that SNS improved body weight and circulating lipid levels of depressed mice by up-regulating proteins [such as FFA uptake protein (CD36), TAG synthesis proteins (GPAT3, MOGAT2, DGAT1 and DGAT2) and chylomicron packaging proteins (MTP and APOB)] in the fat absorption pathway. Furthermore, cell-based results conducted with LPS-stimulated mouse MODE-K and human Caco-2 cells support that SNS, as well as Sinensetin (SIN) and Nobiletin (NOB), the two active components of the formula, have a role in regulating lipid absorption. Mechanistic studies revealed that SNS reverses body weight and fat absorption defects of depressed mice in part through the NR1D1/BMAL1/DGAT2 axis. These findings advance our understanding of the crosstalk between depression and energy loss, highlight the importance of gut function in disease management, and provide a basis for the application of SNS in the clinical treatment of depression and related disorders.
Topics: Mice; Humans; Animals; Dietary Fats; Disease Models, Animal; Caco-2 Cells; Depression; Body Weight; Weight Loss; 1-Acylglycerol-3-Phosphate O-Acyltransferase
PubMed: 37857252
DOI: 10.1016/j.biopha.2023.115677 -
Clinical Infectious Diseases : An... Nov 2023Manufacturing and formulation of stable, high purity, and high dose bacteriophage drug products (DPs) suitable for clinical usage would benefit from improved process...
Manufacturing and formulation of stable, high purity, and high dose bacteriophage drug products (DPs) suitable for clinical usage would benefit from improved process monitoring and control of critical process parameters that affect product quality attributes. Chemistry, Manufacturing, and Controls (CMC) for both upstream (USP) and downstream processes (DSP) need mapping of critical process parameters (CPP) and linking these to critical quality attributes (CQA) to ensure quality and consistency of phage drug substance (DS) and DPs development. Single-use technologies are increasingly becoming the go-to manufacturing option with benefits both for phage bioprocess development at the engineering run research stage and for final manufacture of the phage DS. Future phage DPs under clinical development will benefit from implementation of process analytical technologies (PAT) for better process monitoring and control. These are increasingly being used to improve process robustness (to reduce batch-to-batch variability) and productivity (yielding high phage titers). Precise delivery of stable phage DPs that are suitably formulated as liquids, gels, solid-oral dosage forms, and so forth, could significantly enhance efficacy of phage therapy outcomes. Pre-clinical development of phage DPs must include at an early stage of development, considerations for their formulation including their characterization of physiochemical properties (size, charge, etc.), buffer pH and osmolality, compatibility with regulatory approved excipients, storage stability (packaging, temperature, humidity, etc.), ease of application, patient compliance, ease of manufacturability using scalable manufacturing unit operations, cost, and regulatory requirements.
Topics: Humans; Bacteriophages; Pharmaceutical Preparations; Excipients
PubMed: 37932112
DOI: 10.1093/cid/ciad555 -
Injury Epidemiology Nov 2023Intentional use of high doses of loperamide has been linked to serious cardiac toxicity. The objective of this study is to investigate the characteristics and trends of...
BACKGROUND
Intentional use of high doses of loperamide has been linked to serious cardiac toxicity. The objective of this study is to investigate the characteristics and trends of loperamide cases reported to United States (US) poison centers and to evaluate the changes in reported loperamide cases following US Food and Drug Administration (FDA) warnings, labeling requirements, and packaging restrictions for loperamide starting in 2016, with an emphasis on intentional exposures.
METHODS
Data from the National Poison Data System were analyzed.
RESULTS
There were 12,987 cases reported to US poison centers from 2010 to 2022, for which, loperamide was the most likely substance responsible for observed clinical effects. Although 46.1% of these cases were associated with minor or no effect, 13.4% resulted in a serious medical outcome, including 59 deaths (0.5%). Eight percent (8.1%) of cases were admitted to a critical care unit and 5.0% were admitted to a non-critical care unit. Among cases with a serious medical outcome, most were associated with loperamide abuse (38.0%), intentional-misuse (15.7%), or suspected suicide (27.5%). The majority (60.0%; n = 33) of fatalities were related to abuse, followed by suspected suicide (20.0%; n = 11) and intentional-misuse (5.5%, n = 3). The rate of loperamide cases per 100,000 US population reported to US PCs decreased from 0.44 in 2010 to 0.36 in 2015 (p = 0.0290), followed by an increase to 0.46 in 2017 (p = 0.0013), and then a trend reversal with a decrease to 0.28 in 2022 (p < 0.0001). The rate of serious medical outcomes related to loperamide increased from 0.03 in 2010 to 0.05 in 2015 (p = 0.0109), which subsequently increased rapidly to 0.11 in 2017 (p < 0.0001), and then demonstrated a trend reversal and decreased to 0.04 in 2022 (p < 0.0001).
CONCLUSIONS
FDA warnings, labeling requirements, and packaging restrictions may have contributed to the observed trend reversal and decrease in reports to US poison centers of loperamide cases related to intentional misuse, abuse, and suspected suicide. This demonstrates the potential positive effect that regulatory actions may have on public health. These findings contribute to the evidence supporting the application of similar prevention efforts to reduce poisoning from other medications associated with intentional misuse, abuse, and suicide.
PubMed: 38001549
DOI: 10.1186/s40621-023-00473-2 -
Journal of Dairy Science Dec 2023The aim of this study was to evaluate the influence of different packaging materials [standard foil: BOPP (biaxially oriented polypropylene)/PET (polyester)/PE...
The aim of this study was to evaluate the influence of different packaging materials [standard foil: BOPP (biaxially oriented polypropylene)/PET (polyester)/PE (polyethylene) for upper layer, and APET (polyethylene terephthalate)/PE for bottom layer; foil 1: PP (polypropylene)/PET/PE/EVOH (ethylene-vinyl alcohol copolymer)/PE upper layer, and PP/PE/EVOH/PE bottom layer; foil 2: PP/PET/PE/EVOH/PE upper layer, and PA (polyamide)/EVOH/PE bottom layer; foil 3: PP/PET/PE upper layer, and PA/EVOH/PE bottom layer; foil 4: PP/PET/PE upper layer, and PA/PE bottom layer; foil 5: PP upper layer, and PP/PP bottom layer] on the quality of 3 different ripening rennet cheeses packed under different modified atmosphere (MAP) conditions as reflected in particular physicochemical, microbiological, and sensorial changes. The changes were monitored during a period of 90 d of storage at 2°C or 8°C. For Gouda cheese, CO content of the headspace of the packages was in the range 35% to 45%, whereas for Maasdamer and Sielski Klasyczny cheeses it was 55% to 65%. Three-way ANOVA showed that the foil type influenced the moisture content of Gouda cheese stored for 90 d at 2°C and for Sielski Klasyczny cheese at 8°C, whereas the moisture content was not dependent on MAP conditions during storage. Moreover, the foil type had a significant effect on free fatty acid changes for Gouda and Sielski Klasyczny cheeses stored at 2°C for 90 d. Sensory attributes changed significantly over storage time at 2°C for all studied cheeses as affected by foil type, whereas there was no effect of MAP conditions. In general, the cheeses packed in standard foil and foil 4 were characterized by the highest values of mean sensory attributes. Time was the most significant factor influencing most changes in physicochemical and sensory attributes of cheeses stored at 2°C and 8°C. The storage temperature did not affect the moisture of the samples during storage. In general, we found an increase in the pH value during storage regardless of storage temperature. It was possible to decrease the thickness of the packaging material from initial 103 and 250 µm (standard foil; lid and bottom, respectively) to 98 and 100 µm (foil 4) without affecting sensory attributes of the product.
Topics: Animals; Cheese; Polypropylenes; Food Packaging; Drug Packaging; Climate
PubMed: 37641356
DOI: 10.3168/jds.2022-22772 -
Bioprocess and Biosystems Engineering Oct 2023Zinc oxide nanoparticles (ZnONPs) have become the widely used metal oxide nanoparticles and drawn the interest of global researchers due to their biocompatibility, low... (Review)
Review
Zinc oxide nanoparticles (ZnONPs) have become the widely used metal oxide nanoparticles and drawn the interest of global researchers due to their biocompatibility, low toxicity, sustainability and cost-effective properties. Due to their unique optical and chemical properties, it emerges as a potential candidate in the fields of optical, electrical, food packaging and biomedical applications. Biological methods using green or natural routes are more environmentally friendly, simple and less use of hazardous techniques than chemical and/or physical methods in the long run. In addition, ZnONPs are less harmful and biodegradable while having the ability to greatly boost pharmacophore bioactivity. They play an important role in cell apoptosis because they enhance the generation of reactive oxygen species (ROS) and release zinc ions (Zn), causing cell death. Furthermore, these ZnONPs work well in conjunction with components that aid in wound healing and biosensing to track minute amounts of biomarkers connected to a variety of illnesses. Overall, the present review discusses the synthesis and most recent developments of ZnONPs from green sources including leaves, stems, bark, roots, fruits, flowers, bacteria, fungi, algae and protein, as well as put lights on their biomedical applications such as antimicrobial, antioxidant, antidiabetic, anticancer, anti-inflammatory, antiviral, wound healing, and drug delivery, and modes of action associated. Finally, the future perspectives of biosynthesized ZnONPs in research and biomedical applications are discussed.
Topics: Zinc Oxide; Nanoparticles; Metal Nanoparticles; Anti-Infective Agents; Antioxidants; Apoptosis
PubMed: 37294320
DOI: 10.1007/s00449-023-02886-1 -
Oman Medical Journal Jul 2023Dyslipidemia is an important risk factor for cardiovascular disease. In developed countries, only 50% of patients with chronic illness adhere to their long-term therapy.... (Review)
Review
OBJECTIVES
Dyslipidemia is an important risk factor for cardiovascular disease. In developed countries, only 50% of patients with chronic illness adhere to their long-term therapy. This article aimed to review the factors affecting adherence to lipid-lowering drugs (LLDs).
METHODS
The searched articles were selected based on the available keywords in the title and abstract with the publication restricted between January 2010 and September 2020. Articles generated from the databases must fulfill both inclusion and exclusion criteria in the present systematic review. Our initial search retrieved 221 literature reviews. After excluding articles with irrelevant topics, a total of 23 articles were chosen for this current review.
RESULTS
The factors were classified based on three main factors: patient-related, medication-related, and healthcare workers-related factors. For patient-related factors, gender, age, number of family members, education level, post-hospitalization, comorbidities and cardiovascular disease risk, follow-up status, occupation, socio-economy, insurance, perception, ethnicity, and health plan were among the factors affecting adherence to LLDs. As for medication-related factors, timing, polypharmacy, duration of treatment, generic medication, intensity of medication, side effects, initiating dose, packaging, drug dosing, and type of drugs were revealed as contributing factors. In the light of healthcare workers, related factors shown were counseling, medication optimization, type of provider, and location of the hospital.
CONCLUSIONS
Recommendations to improve adherence include educating patients on the disease itself and the importance of the treatment, modification of the dosing, timing and type of LLDs, and effective consultations by healthcare workers. Further studies need to be done in Malaysia as there is inadequate research on this topic.
PubMed: 37736054
DOI: 10.5001/omj.2023.67 -
International Journal of Pharmaceutics Jun 2024Mesoporous silica nanoparticles (MSNs) endowed with polymer coatings present a versatile platform, offering notable advantages such as targeted, pH-controlled, and... (Review)
Review
Mesoporous silica nanoparticles (MSNs) endowed with polymer coatings present a versatile platform, offering notable advantages such as targeted, pH-controlled, and stimuli-responsive drug delivery. Surface functionalization, particularly through amine and carboxyl modification, enhances their suitability for polymerization, thereby augmenting their versatility and applicability. This review delves into the diverse therapeutic realms benefiting from polymer-coated MSNs, including photodynamic therapy (PDT), photothermal therapy (PTT), chemotherapy, RNA delivery, wound healing, tissue engineering, food packaging, and neurodegenerative disorder treatment. The multifaceted potential of polymer-coated MSNs underscores their significance as a focal point for future research endeavors and clinical applications. A comprehensive analysis of various polymers and biopolymers, such as polydopamine, chitosan, polyethylene glycol, polycaprolactone, alginate, gelatin, albumin, and others, is conducted to elucidate their advantages, benefits, and utilization across biomedical disciplines. Furthermore, this review extends its scope beyond polymerization and biomedical applications to encompass topics such as surface functionalization, chemical modification of MSNs, recent patents in the MSN domain, and the toxicity associated with MSN polymerization. Additionally, a brief discourse on green polymers is also included in review, highlighting their potential for fostering a sustainable future.
PubMed: 38862066
DOI: 10.1016/j.ijpharm.2024.124314