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The AAPS Journal Jul 2014This review further clarifies the concept of pharmaceutical quality by design (QbD) and describes its objectives. QbD elements include the following: (1) a quality... (Review)
Review
This review further clarifies the concept of pharmaceutical quality by design (QbD) and describes its objectives. QbD elements include the following: (1) a quality target product profile (QTPP) that identifies the critical quality attributes (CQAs) of the drug product; (2) product design and understanding including identification of critical material attributes (CMAs); (3) process design and understanding including identification of critical process parameters (CPPs), linking CMAs and CPPs to CQAs; (4) a control strategy that includes specifications for the drug substance(s), excipient(s), and drug product as well as controls for each step of the manufacturing process; and (5) process capability and continual improvement. QbD tools and studies include prior knowledge, risk assessment, mechanistic models, design of experiments (DoE) and data analysis, and process analytical technology (PAT). As the pharmaceutical industry moves toward the implementation of pharmaceutical QbD, a common terminology, understanding of concepts and expectations are necessary. This understanding will facilitate better communication between those involved in risk-based drug development and drug application review.
Topics: Chemistry, Pharmaceutical; Drug Design; Drug Industry; Humans; Pharmaceutical Preparations; Quality Improvement; Technology, Pharmaceutical
PubMed: 24854893
DOI: 10.1208/s12248-014-9598-3 -
Nordic Journal of Psychiatry Sep 2018Ethnopharmacology relates to the study of substances used medicinally by different ethnic or cultural groups or handling of, drugs-based ethnicity or pharmacogenetics. (Review)
Review
BACKGROUND
Ethnopharmacology relates to the study of substances used medicinally by different ethnic or cultural groups or handling of, drugs-based ethnicity or pharmacogenetics.
AIMS
To review the key aspects of ethnopharmacology.
METHOD
This lecture gives an overview of the relationship between geography, culture, pharmacogenomics and prescribing.
RESULTS
Although the majority of antipsychotics, antidepressants and mood-stabilisers are widely and cheaply available in generic forms, prescription rates can vary. Clozapine is one such example with prescribing-rates ranging from less than 10 patients per 100,000 people to nearly 180 patients/100,000 people. Pharmacogenetic studies of antipsychotics and antidepressants concern gene polymorphisms that may affect both, pharmacodynamic or pharmacokinetic properties. Considerable genetic and ethnic variability has been seen for the P450 microsomal enzymes CYP 2D6 and 1A2.
CONCLUSIONS
With accelerated global mobility and increased understanding of medicinal substances at molecular level, understanding of ethnopharmacology will become increasingly important in routine clinical practice.
Topics: Ethnopharmacology; Humans; Pharmacogenetics; Polymorphism, Genetic
PubMed: 30688173
DOI: 10.1080/08039488.2018.1525636 -
Current Opinion in Pharmacology Apr 2021The focus here was on the pharmacological and clinical pharmacological issues pertaining to the vast range of drugs (e.g. synthetic cannabimimetics, synthetic opioids,... (Review)
Review
The focus here was on the pharmacological and clinical pharmacological issues pertaining to the vast range of drugs (e.g. synthetic cannabimimetics, synthetic opioids, novel stimulants, novel psychedelics, PCP/ketamine-like compounds, prescribed medicinal compounds and popular psychotropic herbs/plants) discussed by Internet-based enthusiasts of new/novel psychoactive substances (NPS), 'e-psychonauts'. Currently ongoing related in silico studies, followed by further in vitro and in vivo/preclinical studies, will hopefully provide important findings in terms of which molecules within each given NPS class may present with higher levels of receptor affinities, and hence clinical potency. Understanding the pharmacological characteristics/potency of those novel recreational molecules will hopefully help in predicting related NPS diffusion, morbidity and possible lethality data.
Topics: Analgesics, Opioid; Humans; Pharmaceutical Preparations; Psychopharmacology; Psychotropic Drugs
PubMed: 33774473
DOI: 10.1016/j.coph.2021.02.008 -
Expert Opinion on Drug Delivery Apr 2017Medicine diversion for recreational use is a constant concern for health authorities. Parachuting, also refered to as bombing, is used in order to increase the expected... (Review)
Review
Medicine diversion for recreational use is a constant concern for health authorities. Parachuting, also refered to as bombing, is used in order to increase the expected effect, to accelerate time-to-onset and to create mixtures of medicines and substances. Aeras covered: Firstly, we analyzed all available scientific literature (PRISMA) and internet forums without any limiting timeframe. Secondly, we collected cases of parachuting reported in the west of France by the addictovigilance and poison control centres. Our study confirms the reality of this emerging issue associated with a higher medical risk (60% of intoxication cases were moderate-to-severe in our study). The substances involved in parachuting were primarily stimulants, with a majority of MDMA, although the use of diverted medication and psychotropes is also of concern. Expert opinion: Parachuting is a dangerous way of using substances and of diverting medicines. This type of administration gives users a certain pharmacokinetic latitude to 'play' with respect to substances and medicines. Medicine abuse deterrent formulations do not seem to be sufficient in preventing diversions. This dangerous method of using substances and of diverting medicines should drive pharmaceutical companies to innovate in the interest of public health and safety.
Topics: Central Nervous System Agents; Chemistry, Pharmaceutical; Humans; Pharmaceutical Preparations; Substance-Related Disorders
PubMed: 27546356
DOI: 10.1080/17425247.2016.1222371 -
Drug and Alcohol Dependence Jul 2015Substance-related disorders (SRDs) are a major cause of morbidity and mortality worldwide. Family, twin, and adoption studies have demonstrated the substantial... (Review)
Review
BACKGROUND
Substance-related disorders (SRDs) are a major cause of morbidity and mortality worldwide. Family, twin, and adoption studies have demonstrated the substantial heritability of SRDs. To determine the impact of genetic variation on risk for SRD and the response to treatment, researchers have conducted a number of secondary data analyses and quasi-experimental studies that target one or more candidate gene variants.
METHODS
This review examines studies in which candidate polymorphisms were examined as mediator variables to identify pharmacogenetic effects on subjective responses to drug administration or cues or outcomes of medication trials for SRDs. Efforts to use a meta-analytic approach to quantify these effects are premature because the number of available studies using similar methods and outcomes is limited, so the present review is qualitative.
RESULTS
Findings from these studies provide preliminary evidence of clinically relevant pharmacogenetic effects. However, independent replication of these findings has been sparse.
CONCLUSIONS
Although this growing body of literature has produced conflicting results, improved statistical controls may help to clarify the findings. Additionally, the use of empirically derived sub-phenotypes (i.e., which serve to differentiate distinct groups of affected individuals) may also help to identify genetic mediators of pharmacologic response in relation to SRDs. The identification of genetic mediators can inform clinical care both by identifying risk factors for SRDs and predicting adverse events and therapeutic outcomes associated with specific pharmacotherapies.
Topics: Behavior, Addictive; Humans; Pharmacogenetics; Polymorphism, Genetic; Substance-Related Disorders
PubMed: 25819021
DOI: 10.1016/j.drugalcdep.2015.03.003 -
Therapeutic Delivery Jul 2023The effectiveness of pharmaceutical drugs depends not only on their active components and manufacturing processes, but also on the role played by pharmaceutical... (Review)
Review
The effectiveness of pharmaceutical drugs depends not only on their active components and manufacturing processes, but also on the role played by pharmaceutical excipients. The traditional definition of excipients as inactive and cost-effective substances has evolved significantly. They are now recognized as essential elements of drug formulations, constituting 80-90% of the final product. The rapid advancements in delivery systems, along with scientific, regulatory, financial and technological developments in biopharmaceutics, have generated renewed interest in the use and functionality of excipients, especially in solid dosage forms. This review focuses on the categorization of excipients according to the International Pharmaceutical Excipient Council (IPEC) and the establishment of guidelines for evaluating the safety of a new proposed excipient.
Topics: Excipients; Chemistry, Pharmaceutical; Drug Compounding; Biopharmaceutics; Pharmaceutical Preparations
PubMed: 37464784
DOI: 10.4155/tde-2023-0026 -
British Medical Journal Nov 1963
Topics: Appetite Depressants; Chlorphentermine; Pharmacology; Substance-Related Disorders; Toxicology
PubMed: 14056912
DOI: 10.1136/bmj.2.5367.1269 -
International Journal of Pharmaceutics Jul 2016Both biopharmaceutics classification system (BCS) and topical drug classification system (TCS) are based on sound scientific principles with the aim of providing... (Review)
Review
Both biopharmaceutics classification system (BCS) and topical drug classification system (TCS) are based on sound scientific principles with the aim of providing biowaiver and reducing regulatory burden without lowering the quality requirements and standards of approval for the drug products. BCS is based on the solubility and permeability properties of the active pharmaceutical ingredient (API, or drug substance) whereas the TCS is based on the qualitative and quantitative composition of the dosage form and the in vitro release rate of the active ingredient as key decision tools. Both BCS and TCS take drug release and dissolution as their guiding principle for providing biowaiver, increasing the availability and affordability of safe and effective medicines to the consumers and at the same time maintaining the drug product quality.
Topics: Biological Availability; Biopharmaceutics; Chemistry, Pharmaceutical; Drug Liberation; Excipients; Humans; Permeability; Pharmaceutical Preparations; Solubility; Therapeutic Equivalency
PubMed: 27208656
DOI: 10.1016/j.ijpharm.2016.05.032 -
The Alkaloids. Chemistry and Biology 2013This review article is a tribute to the numerous chemists whose relentless effort for the last quarter of a century resulted in the isolation, identification, and... (Review)
Review
This review article is a tribute to the numerous chemists whose relentless effort for the last quarter of a century resulted in the isolation, identification, and finally the chemical synthesis of a family of bis-steroidal pyrazine alkaloids of marine origin. In the task of defeating cancer, the search for bioactive substances among the naturally occurring compounds is, without any doubt, a preferential approach. The remarkable contribution of Petitt, Fusetani, and their coworkers allowed to discover this family of marine alkaloids that emerge as potential therapeutic anticancer agents, although there is still a long way to go. The challenging and dangerous task of collecting living organisms from deep-waters was followed by a laborious isolation, elucidation of the complicated structures and biological tests. The outcome of this paramount effort was the identification of 45 compounds that stand, to date, as some of the most potent anticancer agents. The intriguing structures of the isolated alkaloids drew the attention of synthetic chemists, valiant enough to undertake the challenging task of synthesizing some of the most active members of the family. Fuchs, Heathcock, Winterfeldt, Suarez, Shair, and their associates pioneered in the establishment of feasible synthetic routes for the preparation of some of the naturally occurring compounds and a large number of synthetic analogs, allowing to establish SAR criteria that have guided the design of new synthetic analogs. Numerous analogs have been prepared to investigate the mechanism of action of bis-steroidal pyrazines, e.g. cephalostatin analogs bearing a strained spiroketal moiety. However, the mechanism of action and the biological target of these compounds remain far from being understood. Therefore, the rational design of simpler, yet highly active analogs seems at the current stage elusive. It is still 1 to clear why these compounds need to be dimeric to show high biological activity. Furthermore, it is not known whether the central pyrazine ring is simply a linker or has some additional function. This could be tested by examining the biological activity of steroidal dimers with other linkers, e.g. with a benzene ring. Such analogs have been actually prepared but without functional groups necessary for biological activity. The clinical trials of cephalostatins have got stuck due to a shortage of material. There is an urgent need to provide highly active, yet not too complex analogs, which could be available in substantial amounts for advanced pharmacological studies.
Topics: Alkaloids; Animals; Chemistry, Pharmaceutical; Chordata, Nonvertebrate; Molecular Structure; Phenazines; Spiro Compounds; Steroids; Urochordata
PubMed: 24712099
DOI: 10.1016/b978-0-12-407774-4.00002-9 -
Journal of Veterinary Pharmacology and... Nov 2021Metabolomics is the large-scale study of low-molecular-weight substances in a biological system in a given physiological state at a given time point. Metabolomics can be... (Review)
Review
Metabolomics is the large-scale study of low-molecular-weight substances in a biological system in a given physiological state at a given time point. Metabolomics can be applied to identify predictors of inter-individual variability in drug response, provide clinicians with data useful for decision-making processes in drug selection, and inform about the pharmacokinetics and pharmacodynamics of a drug. It is, therefore, an exceptional approach for gaining new understanding effects in the field of comparative veterinary pharmacology. However, the incorporation of metabolomics into veterinary pharmacology and toxicology is not yet widespread, and this is probably, at least in part, a result of its highly multidisciplinary nature. This article reviews the potential applications of metabolomics in veterinary pharmacology and therapeutics. It integrates key concepts for designing metabolomics studies and analyzing and interpreting metabolomics data, providing solid foundations for applying metabolomics to the study of drugs in all veterinary species.
Topics: Animals; Metabolomics; Pharmacology
PubMed: 33719079
DOI: 10.1111/jvp.12961