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Journal of Separation Science May 2020Polyethylene glycols are synthetic polymers composed of repeating oxyethylene subunits, which have been known for non-toxic, non-immunogenic, non-antigenic, good... (Review)
Review
Polyethylene glycols are synthetic polymers composed of repeating oxyethylene subunits, which have been known for non-toxic, non-immunogenic, non-antigenic, good solubility in water and therefore approved for pharmaceutical applications. Recently, attachment or amalgamation of polyethylene glycols to therapeutic small molecules, peptides, proteins, or nanoparticles has become a mature technology for the sake of improving their pharmacokinetic and pharmacological profiles, also referred to as PEGylation. By comparison, there are only a few PEGylated pharmaceuticals have been registered for further clinical trials and even less was approved for marketing. High failure rate of PEGylated pharmaceuticals in pre-clinical and clinical trials could be majorly attributed to their unclear pharmacokinetic behaviors. Therefore, the in vivo fate of the PEGylated pharmaceuticals for the various routes of administration needs to be thoroughly investigated An accurate in vivo pharmacological study thereof highly depends on the precise detection of polyethylene glycols as well as their fragments in biological matrixes. The goal of this review is to highlight the analytical methods that were developed and applied to evaluate the polyethylene glycols in pharmaceutical ingredients and excipients, which bring us closer to bridging the gap between the development of polyethylene glycol-based drug delivery systems and their clinical application.
Topics: Drug Delivery Systems; Humans; Pharmaceutical Preparations; Polyethylene Glycols
PubMed: 32077620
DOI: 10.1002/jssc.201901340 -
Expert Opinion on Drug Metabolism &... Jun 2024Advances in the accessibility of manufacturing technologies and iPSC-based modeling have accelerated the overall progress of organs-on-a-chip. Notably, the progress in... (Review)
Review
INTRODUCTION
Advances in the accessibility of manufacturing technologies and iPSC-based modeling have accelerated the overall progress of organs-on-a-chip. Notably, the progress in multi-organ systems is not progressing with equal speed, indicating that there are still major technological barriers to overcome that may include biological relevance, technological usability as well as overall accessibility.
AREAS COVERED
We here review the progress in the field of multi-tissue- and body-on-a-chip pre and post- SARS-CoV-2 pandemic and review five selected studies with increasingly complex multi-organ chips aiming at pharmacological studies.
EXPERT OPINION
We discuss future and necessary advances in the field of multi-organ chips including how to overcome challenges regarding cell diversity, improved culture conditions, model translatability as well as sensor integrations to enable microsystems to cover organ-organ interactions in not only toxicokinetic but more importantly pharmacodynamic and -kinetic studies.
Topics: Humans; Lab-On-A-Chip Devices; Animals; COVID-19; Pharmacokinetics; Pharmaceutical Preparations; Models, Biological; Microphysiological Systems
PubMed: 38832686
DOI: 10.1080/17425255.2024.2362183 -
International Journal of Pharmaceutics Apr 2022The combination of two or more active pharmaceutical ingredients in the same dosage form - fixed-dose combination products - for topical administration represents a... (Review)
Review
The combination of two or more active pharmaceutical ingredients in the same dosage form - fixed-dose combination products - for topical administration represents a promising therapeutic approach for treating several pathologies, including pain. The pre-clinical development of fixed-dose combination products aims to characterize the interactions between the different APIs and ensure that the final medicinal product has the required safety characteristics. To this end, there are several regulatory accepted in vitro tests to assess the safety of medicinal products intended for cutaneous administration. In turn, the evaluation of anti-inflammatory activity should be based on models described in the scientific literature, as there are no models fully validated by competent entities. Therefore, this work presents the information regarding accepted in vitro tests to assess the safety of topical products and the most used methods to assess anti-inflammatory activity. Additionally, a new approach to select a fixed-dose combination product with the potential to enhance the therapeutic effects of the individual active pharmaceutical ingredients is rationalized by integrating the overall effects on several targets relevant for inflammation and pain management in one numeric index.
Topics: Administration, Topical; Anti-Inflammatory Agents; Drug Combinations; Humans; Pain; Pharmaceutical Preparations
PubMed: 35219825
DOI: 10.1016/j.ijpharm.2022.121621 -
BMJ Open Apr 2022This study aimed to evaluate a biometric palm vein authentication system to prevent medication administration errors in psychiatric hospitals. (Observational Study)
Observational Study
OBJECTIVES
This study aimed to evaluate a biometric palm vein authentication system to prevent medication administration errors in psychiatric hospitals.
DESIGN
This is a pre-post observational study.
SETTING
Conventionally, the medication was distributed after a double check. We developed and introduced a new medication administration cart in two psychiatric hospitals in Japan, in which each patient-specific drug box had to be electronically opened only by palm vein authentication.
PARTICIPANTS
A total of 3444 and 3523 patients were present 18 months before and after introducing the cart, respectively. Of the 212 nurses recruited, 28 were excluded due to a lack of experience with the conventional medication administration system and incomplete questionnaires.
PRIMARY AND SECONDARY OUTCOME MEASURES
The primary outcome was the efficacy of this system by comparing the incidence of medication administration errors before and after introducing the cart. The secondary outcome was a survey regarding nurses' attitudes toward this system.
RESULTS
After introduction of the new system, the number of medication errors due to misidentification of persons relative to the total number of admitted patients was significantly reduced from 6/3444 to 2/3523 (p<0.0001). Among 184 nurses, 182 responded that anxiety regarding administration errors was either reduced or unchanged using this system. Male nurses reported a greater increase in work burden than female nurses (OR=3.11, 95% CI=1.44 to 6.72). Nurses working in chronic care wards reported greater time pressure than nurses working in emergency wards (OR=3.33, 95% CI=1.16 to 9.57). Nurses working in dementia care wards reported a greater patient care burden than nurses working in emergency wards (OR=5.67, 95% CI=1.22 to 26.27).
CONCLUSIONS
This new system might have potential for reducing the patient misidentification risk during medication without increasing the anxiety experienced by nurses concerning administration errors. However, system usability and efficiency must be improved to reduce additional work burden, time pressure and patient care burden.
Topics: Biometry; Female; Hospitals, Psychiatric; Humans; Male; Medication Errors; Medication Systems; Patients; Pharmaceutical Preparations
PubMed: 35487740
DOI: 10.1136/bmjopen-2021-055107 -
International Journal of Pharmaceutics Dec 2021While continuous manufacturing (CM) of pharmaceutical solid-based drug products has been shown to be advantageous for improving the product quality and process... (Review)
Review
While continuous manufacturing (CM) of pharmaceutical solid-based drug products has been shown to be advantageous for improving the product quality and process efficiency in alignment with FDA's support of the quality-by-design paradigm (Lee, 2015; Ierapetritou et al., 2016; Plumb, 2005; Schaber, 2011), it is critical to enable full utilization of CM technology for robust production and commercialization (Schaber, 2011; Byrn, 2015). To do so, an important prerequisite is to obtain a detailed understanding of overall process characteristics to develop cost-effective and accurate predictive models for unit operations and process flowsheets. These models are utilized to predict product quality and maintain desired manufacturing efficiency (Ierapetritou et al., 2016). Residence time distribution (RTD) has been a widely used tool to characterize the extent of mixing in pharmaceutical unit operations (Vanhoorne, 2020; Rogers and Ierapetritou, 2015; Teżyk et al., 2015) and manufacturing lines and develop computationally cheap predictive models. These models developed using RTD have been demonstrated to be crucial for various flowsheet applications (Kruisz, 2017; Martinetz, 2018; Tian, 2021). Though extensively used in the literature (Gao et al., 2012), the implementation, execution, evaluation, and assessment of RTD studies has not been standardized by regulatory agencies and can thus lead to ambiguity regarding their accurate implementation. To address this issue and subsequently prevent unforeseen errors in RTD implementation, the presented article aims to aid in developing standardized guidelines through a detailed review and critical discussion of RTD studies in the pharmaceutical manufacturing literature. The review article is divided into two main sections - 1) determination of RTD including different steps for RTD evaluation including experimental approach, data acquisition and pre-treatment, RTD modeling, and RTD metrics and, 2) applications of RTD for solid dose manufacturing. Critical considerations, pertaining to the limitations of RTDs for solid dose manufacturing, are also examined along with a perspective discussion of future avenues of improvement.
Topics: Excipients; Pharmaceutical Preparations; Technology, Pharmaceutical
PubMed: 34748808
DOI: 10.1016/j.ijpharm.2021.121248 -
Physical Review. E Jun 2020T-cell receptors (TCR) are key proteins of the adaptive immune system, generated randomly in each individual, whose diversity underlies our ability to recognize...
T-cell receptors (TCR) are key proteins of the adaptive immune system, generated randomly in each individual, whose diversity underlies our ability to recognize infections and malignancies. Modeling the distribution of TCR sequences is of key importance for immunology and medical applications. Here, we compare two inference methods trained on high-throughput sequencing data: a knowledge-guided approach, which accounts for the details of sequence generation, supplemented by a physics-inspired model of selection; and a knowledge-free variational autoencoder based on deep artificial neural networks. We show that the knowledge-guided model outperforms the deep network approach at predicting TCR probabilities, while being more interpretable, at a lower computational cost.
Topics: Amino Acid Sequence; Deep Learning; Ligands; Models, Biological; Receptors, Antigen, T-Cell
PubMed: 32688532
DOI: 10.1103/PhysRevE.101.062414 -
American Journal of Health Promotion :... Mar 2023Evaluate if there is a(n): 1) reduction in health risk behaviors and 2) association between health and wellness initiative participation and claims costs decreases...
PURPOSE
Evaluate if there is a(n): 1) reduction in health risk behaviors and 2) association between health and wellness initiative participation and claims costs decreases overtime.
DESIGN
Health risk behavior change consisted of the analysis of pre (2009) - post (2019) measures of health questionnaire participants. The medical and pharmaceutical claims costs evaluation consisted of a time-series (2016-2019) design with a comparison group.
SETTING
A large mid-western university with a health system.
SAMPLE
The health risk behavior sample ranged from 5215-5399, depending on the variable of interest. The medical and pharmaceutical costs sample used a cohort of participants (participating all 4 years, n=11114) and non-participants (not participating all 4 years, n=4776).
INTERVENTION
Comprehensive employee health and well-being initiative.
MEASURES/ANALYSIS
McNemar's tests were used to identify bivariate associations between 2009 and 2019 health risks. The claims cost analysis used propensity score matching based on select demographics and linear mixed-effects regression modeling.
RESULTS
Results show statistically significant (P > .001) improvements (ranging from -2.1% to -12.5%) in 7 of 8 health risk behaviors. 2016 and 2019 claims costs have a lower statistically significant (P > .001) percent increase for participants (32.6%) compared to non-participants (47.5%).
CONCLUSION
Employers, may consider implementing a comprehensive health and wellness program as part of their strategy to assist in health behavior risk reduction and health care cost containment.
Topics: Humans; Universities; Health Promotion; Delivery of Health Care; Health Behavior; Pharmaceutical Preparations; Health Care Costs
PubMed: 36121212
DOI: 10.1177/08901171221127987 -
Physical Review. E Mar 2020The molecular mechanism of specific interactions between double stranded DNA molecules has been investigated for many years. Problems remain in how confinement, ions,...
The molecular mechanism of specific interactions between double stranded DNA molecules has been investigated for many years. Problems remain in how confinement, ions, and condensing agents change the interactions. We consider how the orientational alignment of DNAs contributes to the interactions via free energy simulations. Here we report on the effective interactions between two parallel DNA double helices in 150-mM NaCl solution using all atom models. We calculate the potential of mean force (PMF) of DNA-DNA interactions as a function of two coordinates, interhelical separation of parallel double helices and relative rotation of a DNA molecule with respect to the other about the helical axis. We generate the two-dimensional PMF to better understand the effective interactions when a DNA molecule is in juxtaposition with another. The analysis of the ion and solvent distributions around the DNA and particularly in the interface region shows that certain alignments of the DNA pair enhance the interactions. At local free energy minima in distance and alignment, water molecules and Na^{+} ions form a hydrogen bonded network with the phosphates from each DNA. This network contributes an attractive energy component to the DNA-DNA interactions. Our results provide a molecular mechanism whereby local DNA-DNA interactions, depending on the helical orientation, give a potential mechanism for stabilizing pairing of much larger lengths of homologous DNA that have been seen experimentally. The study suggests an atomically detailed local picture of relevance to certain aspects of DNA condensation or aggregation.
Topics: DNA; Molecular Dynamics Simulation; Nucleic Acid Conformation; Rotation
PubMed: 32289903
DOI: 10.1103/PhysRevE.101.032414 -
International Journal of Offender... Jul 2021Drug Court Treatment (DCT) Programs seek to integrate substance abuse treatment into the criminal justice system by providing a structured environment for offenders who...
Drug Court Treatment (DCT) Programs seek to integrate substance abuse treatment into the criminal justice system by providing a structured environment for offenders who engage in treatment in lieu of incarceration. DCT has shown successes in reducing drug/alcohol use, recidivism, and cost, but the impact of DCT on non-substance-related mental health outcomes is less clear. This study evaluated mental health correlates within a DCT sample through analyses of participants' pre-entry and pre-graduation Minnesota Multiphasic Personality Inventory-Second Edition (MMPI-2) profiles. When diagnostic information was available, mood disorders had the highest comorbidity with alcohol/substance use diagnoses. Comparisons across administrations of the MMPI-2 indicated significant differences among mean scores on 6 Clinical scales, and mean profile elevation scores significantly decreased. Results suggest a significant presence of mental health comorbidities in DCT programs, and significant mental health improvements were seen for graduates, suggesting the utility of DCT for treating mental health problems in addition to substance use.
Topics: Humans; MMPI; Mental Disorders; Mental Health; Pharmaceutical Preparations; Recidivism; Substance-Related Disorders
PubMed: 32538260
DOI: 10.1177/0306624X20928031 -
American Journal of Health-system... Nov 2023With the implementation of a new electronic health record (EHR) system across Mayo Clinic, a project was approved to standardize and converge 9 region-specific...
PURPOSE
With the implementation of a new electronic health record (EHR) system across Mayo Clinic, a project was approved to standardize and converge 9 region-specific large-volume infusion pump (LVP) drug libraries for Baxter SIGMA Spectrum pumps.
SUMMARY
The objectives of the project were to (1) develop recommendations for identified variances in practice, (2) consolidate regional drug libraries into a converged enterprise library, (3) improve the drug library management process, and (4) maintain or exceed previous Dose Error Reduction System (DERS) compliance for infusions administered. Harmonization efforts with infusion pumps decreased the number of drug libraries maintained, reduced content maintenance time, and increased readiness for smart infusion pump-EHR interoperability. Seven of the 8 regions for which change in DERS compliance was assessed showed improved compliance relative to baseline in the 30-day postwashout period. Furthermore, when comparing pre- and postimplementation DERS compliance, the number of regions meeting the minimum compliance rate of 95% increased from 5 to 6 regions.
CONCLUSION
The project improved the drug library management process, allowed for DERS compliance to be accurately compared across regions, and ensured that patients across the enterprise receive the same standard of care with the administration of intravenous medications.
Topics: Humans; Pharmaceutical Preparations; Medication Errors; Infusions, Intravenous; Infusion Pumps; Reference Standards
PubMed: 37527506
DOI: 10.1093/ajhp/zxad172