-
Yakugaku Zasshi : Journal of the... 2021We have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug... (Review)
Review
We have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug Information Office of our hospital, we found a large discrepancy between the description of perinatal drugs in package inserts in Japan and the description of the Pregnancy Risk Category according to the U.S. Food and Drug Administration. In the Japan Environment and Children's Study (JECS), we determined the proportion of drug and supplement use among 97464 pregnant women. We clarified that prescriptions of antihypertensive drugs for pregnant women increased during the second half of pregnancy, while prescriptions of anti-epileptic and anti-anxiety drugs decreased after pregnancy using a claims database. A survey of pharmacists and pharmacy students revealed a lack of awareness of effective folic acid intake to reduce the risk of neural tube defects in infants. The percentage of pre-pregnancy folic acid supplementation among pregnant women participating in the Babies and their Parents' Longitudinal Observation in Suzuki Memorial Hospital on Intrauterine Period (BOSHI) study, the JECS, and the Tohoku Medical Megabank (TMM) Birth and Three-Generation (BirThree) cohort study was 6.3-18.0%. As a result of close examination of the records of inquiries to the Drug Information Office of our hospital, and of cases in which our lactation plan sheet was applied, it was found that there were discrepancies between the information on the drug package insert and the information on Medications & Mother's Milk, etc. in Japan. The results obtained have been clinically applied in daily practice and we are continuing our research while taking measures.
Topics: Abnormalities, Drug-Induced; Adult; Awareness; Breast Feeding; Cohort Studies; Databases, Factual; Dietary Supplements; Drug Information Services; Drug Labeling; Female; Folic Acid; Humans; Infant, Newborn; Japan; Neural Tube Defects; Pharmacists; Pregnancy; Prescription Drugs; Safety; Surveys and Questionnaires; Young Adult
PubMed: 33790112
DOI: 10.1248/yakushi.20-00184 -
Advanced Drug Delivery Reviews Nov 2023Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical... (Review)
Review
Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical excipients, food additives, emulsifiers in cosmetics, and as household/industrial detergents. This review outlines the interaction of surfactant-type excipients present in oral pharmaceutical dosage forms with the intestinal epithelium of the gastrointestinal (GI) tract. Many surfactants permitted for human consumption in oral products reduce intestinal epithelial cell viability in vitro and alter barrier integrity in epithelial cell monolayers, isolated GI tissue mucosae, and in animal models. This suggests a degree of mis-match for predicting safety issues in humans from such models. Recent controversial preclinical research also infers that some widely used emulsifiers used in oral products may be linked to ulcerative colitis, some metabolic disorders, and cancers. We review a wide range of surfactant excipients in oral dosage forms regarding their interactions with the GI tract. Safety data is reviewed across in vitro, ex vivo, pre-clinical animal, and human studies. The factors that may mitigate against some of the potentially abrasive effects of surfactants on GI epithelia observed in pre-clinical studies are summarised. We conclude with a perspective on the overall safety of surfactants in oral pharmaceutical dosage forms, which has relevance for delivery system development.
Topics: Animals; Humans; Excipients; Drug Compounding; Pharmaceutical Preparations; Intestines; Surface-Active Agents
PubMed: 37739041
DOI: 10.1016/j.addr.2023.115086 -
International Journal of Pharmaceutics Jan 2023Three-dimensional (3D) printing is an emerging technology with great potential in pharmaceutical applications, providing innovative solutions for both patients and... (Review)
Review
Three-dimensional (3D) printing is an emerging technology with great potential in pharmaceutical applications, providing innovative solutions for both patients and pharmaceutical industry. This technology offers precise construction of the structure of dosage forms and can benefit drug product design by providing versatile release modes to meet clinical needs and facilitating patient-centric treatment, such as personalized dosing, accommodate treatment of specific disease states or patient populations. Utilization of 3D printing also facilitates digital drug product development and manufacturing. Development of 3D printing at early clinical stages and commercial scale pharmaceutical manufacturing has substantially advanced in recent years. In this review, we discuss how 3D printing accelerates early-stage drug development, including pre-clinical research and early phase human studies, and facilitates late-stage product manufacturing as well as how the technology can benefit patients. The advantages, current status, and challenges of employing 3D printing in large scale manufacturing and personalized dosing are introduced respectively. The considerations and efforts of regulatory agencies to address 3D printing technology are also discussed.
Topics: Humans; Technology, Pharmaceutical; Drug Industry; Drug Delivery Systems; Printing, Three-Dimensional; Pharmaceutical Preparations
PubMed: 36509225
DOI: 10.1016/j.ijpharm.2022.122480 -
Molecular Therapy : the Journal of the... Aug 2023Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is...
Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is still a major unmet clinical need. We recently discovered the destabilization of the AMP-activated protein kinase (AMPK) complex in adipose tissue as a key event in cachexia-related adipose tissue dysfunction and developed an adeno-associated virus (AAV)-based approach to prevent AMPK degradation and prolong cachexia-free survival. Here, we show the development and optimization of a prototypic peptide, Pen-X-ACIP, where the AMPK-stabilizing peptide ACIP is fused to the cell-penetrating peptide moiety penetratin via a propargylic glycine linker to enable late-stage functionalization using click chemistry. Pen-X-ACIP was efficiently taken up by adipocytes, inhibited lipolysis, and restored AMPK signaling. Tissue uptake assays showed a favorable uptake profile into adipose tissue upon intraperitoneal injection. Systemic delivery of Pen-X-ACIP into tumor-bearing animals prevented the progression of cancer cachexia without affecting tumor growth and preserved body weight and adipose tissue mass with no discernable side effects in other peripheral organs, thereby achieving proof of concept. As Pen-X-ACIP also exerted its anti-lipolytic activity in human adipocytes, it now provides a promising platform for further (pre)clinical development toward a novel, first-in-class approach against cancer cachexia.
Topics: Animals; Humans; Adipose Tissue; AMP-Activated Protein Kinases; Cachexia; Neoplasms; Peptides; Pharmaceutical Preparations; Quality of Life
PubMed: 37408309
DOI: 10.1016/j.ymthe.2023.06.020 -
Sensors (Basel, Switzerland) Feb 2022All pharmaceutical drugs, vaccines, cosmetic products, and many medical breakthroughs must first be approved through clinical research and trials before advancing to... (Review)
Review
All pharmaceutical drugs, vaccines, cosmetic products, and many medical breakthroughs must first be approved through clinical research and trials before advancing to standard practice or entering the marketplace. Clinical trials are sets of tests that are required to determine the safety and efficacy of pharmaceutical compounds, drugs, and treatments. There is one pre-phase and four main clinical phase requirements that every drug must pass to obtain final approval. Analytical techniques play a unique role in clinical trials for measuring the concentrations of pharmaceutical compounds in biological matrices and monitoring the conditions of patients (or volunteers) during various clinical phases. This review focuses on recent analytical methods that are employed to determine the concentrations of drugs and medications in biological matrices, including whole blood, plasma, urine, and breast milk. Four primary analytical techniques (extraction, spectroscopy, chromatography, and electrochemical) are discussed, and their advantages and limitations are assessed. Subsequent to a survey of evidence and results, it is clear that microelectromechanical system (MEMS) based electrochemical sensor and biosensor technologies exhibit several notable advantages over other analytical methods, and their future prospects are discussed.
Topics: Biosensing Techniques; Clinical Trials as Topic; Electrochemical Techniques; Humans; Pharmaceutical Preparations
PubMed: 35214505
DOI: 10.3390/s22041592 -
AIMS Public Health 2021Geriatrics as an educational topic has been a high priority in current health care. The innovative Age-Friendly health system with the 4Ms structure (what Matters most,...
BACKGROUND
Geriatrics as an educational topic has been a high priority in current health care. The innovative Age-Friendly health system with the 4Ms structure (what Matters most, Medication, Mentation, Mobility) needs to be integrated into oral health and dental services training. The purpose of this study is to respond to one question: are the graduating general dentists trained and prepared to treat medically vulnerable elderly in communities?
METHODS
All pre-doctorate dental students from first year to fourth year were invited to voluntarily respond to an online survey provided on Qualtrics. The survey provided examples of two broken molar teeth that need extraction. First, students were asked how comfortable they felt extracting the two molars based on the x-rays. Then, the question was repeated to evaluate if they felt comfortable with extracting the teeth in a patient with one chronic condition and related medication(s). Finally, the students were again questioned whether they feel comfortable to provide the same service to medically vulnerable patients with multiple health conditions and polypharmacy.
RESULTS
The majority of students who participated in this study said they were comfortable with extracting the teeth of patients without any chronic condition. However, many more chose to refer medically vulnerable patients with multiple chronic conditions and polypharmacy to a specialist.
CONCLUSIONS
Dental education in many U.S. dental schools may provide adequate education and create competent general dentists. Yet, the competency and confidence required for dentists to be able to treat older adults with multiple health conditions and using prescribed or over-the-counter medication is insufficient.
PubMed: 34786428
DOI: 10.3934/publichealth.2021054 -
European Journal of Pharmaceutical... May 2023Bilayer tablets offer various drug release profiles for individual drugs incorporated in each layer of a bilayer tablet, which is rarely achievable by conventional... (Review)
Review
Bilayer tablets offer various drug release profiles for individual drugs incorporated in each layer of a bilayer tablet, which is rarely achievable by conventional tablets. These tablets also help avoid physicochemical incompatibilities between drugs and excipients. Successful manufacturing of such more complex dosage forms depends upon screening of material attributes of API and excipients as well as optimization of processing parameters of individual unit operations of the manufacturing process that must be strictly monitored and controlled to obtain an acceptable drug product quality and performance in order to achieve safety and efficacy per regulatory requirements. Optimizing formulation attributes and manufacturing processes during critical stages, such as blending, granulation, pre-compression, and main compression, can help avoid problems such as weight variation, segregation, and delamination of individual layers, which are frequently faced during the production of bilayer tablets. The main objective of this review is to establish the basis for the implementation of Quality by Design (QbD) system principles for the design and development of bilayer tablets, encompassing the preliminary and systematic risk assessment of critical material attributes (CMAs) and critical process parameters (CPPs) with respect to in-process and finished product critical quality attributes (CQAs). Moreover, the applicability of the QbD methodology based on its purpose is discussed and complemented with examples of bilayer tablet technology.
Topics: Excipients; Tablets; Drug Liberation; Technology, Pharmaceutical; Drug Compounding
PubMed: 36828037
DOI: 10.1016/j.ejps.2023.106412 -
Molecules (Basel, Switzerland) Jan 2023Central nervous system (CNS) disorders are a therapeutic area in drug discovery where demand for new treatments greatly exceeds approved treatment options. This is... (Review)
Review
Central nervous system (CNS) disorders are a therapeutic area in drug discovery where demand for new treatments greatly exceeds approved treatment options. This is complicated by the high failure rate in late-stage clinical trials, resulting in exorbitant costs associated with bringing new CNS drugs to market. Computer-aided drug design (CADD) techniques minimise the time and cost burdens associated with drug research and development by ensuring an advantageous starting point for pre-clinical and clinical assessments. The key elements of CADD are divided into ligand-based and structure-based methods. Ligand-based methods encompass techniques including pharmacophore modelling and quantitative structure activity relationships (QSARs), which use the relationship between biological activity and chemical structure to ascertain suitable lead molecules. In contrast, structure-based methods use information about the binding site architecture from an established protein structure to select suitable molecules for further investigation. In recent years, deep learning techniques have been applied in drug design and present an exciting addition to CADD workflows. Despite the difficulties associated with CNS drug discovery, advances towards new pharmaceutical treatments continue to be made, and CADD has supported these findings. This review explores various CADD techniques and discusses applications in CNS drug discovery from 2018 to November 2022.
Topics: Computer-Aided Design; Ligands; Drug Design; Psychotropic Drugs; Pharmaceutical Preparations
PubMed: 36770990
DOI: 10.3390/molecules28031324 -
European Cells & Materials Mar 2021The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic... (Review)
Review
The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic strategies for preventing disease progression and reducing tooth loss. A technical expert panel (TEP) was established of 11 medical specialists, including periodontists and bone specialists that followed the PRISMA-ScR model to perform the scoping review and considered for eligibility both pre-clinical and clinical studies published in the English language up to September 2020. 716 items were initially found. After duplicate removal and screening of articles for eligibility criteria, 25 articles published between 2001 and 2019 were selected. Only studies concerning teriparatide, strontium ranelate, sclerostin antibodies and DKK1 antibodies met the eligibility criteria. In particular, only for teriparatide were there both clinical studies and experimental studies available, while for other bone anabolic drugs only animal studies were found. Available evidence about the use of bone anabolic drugs in periodontology demonstrates beneficial effects of these agents on biological pathways and histological parameters involved in periodontal tissue regeneration that suggest relevant clinical implications for the management of periodontitis.
Topics: Animals; Bone and Bones; Humans; Periodontitis; Pharmaceutical Preparations
PubMed: 33733451
DOI: 10.22203/eCM.v041a20 -
Ultrasonics Sonochemistry Jan 2022This study determined the influence of diacylglycerol (DAG) pre-emulsion on the gel properties and microstructure of golden thread surimi gels. DAG emulsion stabilized...
This study determined the influence of diacylglycerol (DAG) pre-emulsion on the gel properties and microstructure of golden thread surimi gels. DAG emulsion stabilized using sodium caseinate was pre-emulsified through ultrasound. The average particle size of DAG pre-emulsion decreased from 1324.15 nm to 41.19 nm, with notable improvements in apparent viscosity and storage stability. The surimi gels with different amounts (0%, 1%, 3%, 5%, and 7% w/w) of DAG pre-emulsion were prepared under heat induction. The whiteness of the composite gels markedly increased with the incorporation of DAG pre-emulsion. The peak T value of immobilized water, the gel strength, and water-holding capacity increased gradually, but it slightly decreased with the addition of 7% pre-emulsion. The curve of G' and G″ kept climbing as the concentration of pre-emulsion, and the microstructure of the gel network tended to become denser and more orderly. Principal component analysis (PCA) of electronic nose results showed that the surimi gels containing pre-emulsion could be clearly distinguished from the control group. In conclusion, the addition of 5% DAG pre-emulsion to surimi not only improved gel properties to the highest extent but also be compensated for lipid loss during the rinsing of surimi.
Topics: Diglycerides; Emulsions; Fish Products; Gels; Ultrasonics; Water
PubMed: 35042162
DOI: 10.1016/j.ultsonch.2022.105915