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Current Pharmaceutical Design 2020Cocrystallization is a widely accepted and clinically relevant technique that has prospered very well over the past decades to potentially modify the physicochemical... (Review)
Review
Cocrystallization is a widely accepted and clinically relevant technique that has prospered very well over the past decades to potentially modify the physicochemical properties of existing active pharmaceutic ingredients (APIs) without compromising their therapeutic benefits. Over time, it has become an integral part of the pre-formulation stage of drug development because of its ability to yield cocrystals with improved properties in a way that other traditional methods cannot easily achieve. Cocrystals are solid crystalline materials composed of two or more than two molecules which are non-covalently bonded in the same crystal lattice. Due to the continuous efforts of pharmaceutical scientists and crystal engineers, today cocrystals have emerged as a cutting edge tool to modulate poor physicochemical properties of APIs such as solubility, permeability, bioavailability, improving poor mechanical properties and taste masking. The success of cocrystals can be traced back by looking at the number of products that are getting regulatory approval. At present, many cocrystals have obtained regulatory approval and they successfully made into the market place followed by a fair number of cocrystals that are currently in the clinical phases. Considering all these facts about cocrystals, the formulation scientists have been inspired to undertake more relevant research to extract out maximum benefits. Here in this review cocrystallization technique will be discussed in detail with respect to its background, different synthesis approaches, synthesis mechanism, application and improvements in drug delivery systems and its regulatory perspective.
Topics: Biological Availability; Crystallization; Permeability; Pharmaceutical Preparations; Solubility
PubMed: 32691702
DOI: 10.2174/1381612826666200720114638 -
Research in Social & Administrative... Sep 2021Drug shortages have a negative impact on individual health outcomes for patients and health care systems more broadly. In recent years, regulatory bodies, such as the...
BACKGROUND
Drug shortages have a negative impact on individual health outcomes for patients and health care systems more broadly. In recent years, regulatory bodies, such as the Therapeutic Good Administration in Australia, have provided information about an increasing number of drug shortages. It is reported that 90% of medicines in Australia are imported; this leaves Australia vulnerable to international drug shortages. It has been suggested that Australia is heavily reliant on the US as its primary source of medicines.
OBJECTIVE(S)
To determine whether there are significant trends in the quantity, frequency, and nature of drug shortages between the US and Australia in a pre-pandemic and pandemic climate.
METHODS
This study mapped and analyzed drug shortages reported by both the United States Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA) in 2019 and 2020.
RESULTS
In 2019 (pre-COVID19), only 4% of US drug shortages were reported in Australia; this rose to 7% in 2020. Between 2019 and 2020, the number of US drug shortages increased by 37%, whilst the number of Australian drug shortages increased by 300%.
CONCLUSIONS
The Australian pharmaceuticals market is indeed more vulnerable to drug shortages, particularly in the event of a global pandemic such as COVID-19. However, these shortages are not significantly influenced by the US drug market.
Topics: Australia; COVID-19; Humans; Pandemics; Pharmaceutical Preparations; SARS-CoV-2; United States
PubMed: 33323334
DOI: 10.1016/j.sapharm.2020.12.001 -
Physical Review. E Sep 2021Determination of the spin echo signal evolution and of transverse relaxation rates is of high importance for microstructural modeling of muscle tissue in magnetic...
Determination of the spin echo signal evolution and of transverse relaxation rates is of high importance for microstructural modeling of muscle tissue in magnetic resonance imaging. So far, numerically exact solutions for the NMR signal dynamics in muscle tissue models have been reported only for the gradient echo free induction decay, with spin echo problems usually solved by approximate methods. In this work, we modeled the spin echo signal numerically exact by discretizing the radial dimension of the Bloch-Torrey equation and expanding the angular dependency in terms of even Chebyshev polynomials. This allows us to express the time dependence of the local magnetization as a closed-form matrix expression. Using this method, we were able to accurately capture the spin echo local and total magnetization dynamics. The obtained transverse relaxation rates showed a high concordance with random walker and finite-element simulations. We could demonstrate that in cases of smaller diffusion coefficients, the commonly used strong collision approximation significantly underestimates the true value considerably. Instead, the limiting behavior in this regime is correctly described either by the full solution or by the slow diffusion approximation. Experimentally measured transverse relaxation rates of a mouse limb muscle showed an angular dependence in accordance with the theoretical prediction.
PubMed: 34654209
DOI: 10.1103/PhysRevE.104.034419 -
Biochimie Aug 2020Proteins are supposed to bind to their substrates/ligands in a specific manner via their pre-formed binding sites, according to classical biochemistry. In recent years,... (Review)
Review
Proteins are supposed to bind to their substrates/ligands in a specific manner via their pre-formed binding sites, according to classical biochemistry. In recent years, several types of deviations from this norm have been observed and called promiscuous behavior. Enzymatic promiscuities allow several biochemical functions to be carried out by the same enzyme. The promiscuous activity can also be the origin of "new proteins" via gene duplication. In more recent years, proteins from prokaryotes, eukaryotes and viruses have been found to have intrinsic disorder and lack a preformed binding site. Intrinsic disorder is exploited in regulatory proteins such as those that are involved in transcription and signal transduction. Such proteins function by folding locally while binding to their ligands or interacting with other proteins. These phenomena have also been classified as examples of protein promiscuity and encompass diverse kinds of ligands that can bind to a protein. Given the significant extent of structural homology in many protein families, it is not surprising that ligands also have been found to display promiscuity. Promiscuous behavior of proteins offers both challenges and opportunities to the drug discovery programs such as drug repurposing. Pathogens when exposed to antibiotics exploit protein promiscuity in several ways to develop resistance to the drug. There is increasing evidence now to support that the disorder in proteins is a major tool used by pathogens for virulence and evade drug action by exploiting protein promiscuity. This review provides a holistic view of this multi-faceted phenomenon called protein promiscuity.
Topics: Bacterial Proteins; Drug Discovery; Drug Repositioning; Drug Resistance, Microbial; Fungal Proteins; Humans; Pharmaceutical Preparations; Viral Proteins
PubMed: 32416199
DOI: 10.1016/j.biochi.2020.05.004 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Nov 2022There are many kinds of pharmaceutical preparations for children in China, which are generally divided into oral solid preparations and oral liquid preparations. Solid... (Review)
Review
There are many kinds of pharmaceutical preparations for children in China, which are generally divided into oral solid preparations and oral liquid preparations. Solid preparations, such as microtablets, pellets, dispersible tablets, and fine granules, have become the development trend of pediatric drugs. Liquid preparations mainly include syrup, suspension, oral solution, and drops. The poor taste and the treatment of drugs in children of different ages are the key factors affecting the efficacy, safety, and compliance of pediatric drugs. To reduce the risk caused by the fluctuation of blood concentration and improve the oral compliance of pediatric drugs, it is urgent to develop new techniques for granulation and flavor maskingto improve the poor taste of solid preparations. For liquid pre-parations with poor taste, the flavor correction technique should be used. This paper summarized the new pharmaceutical techniques for granulation and flavor masking, and it was found that sustained/controlled-releasegranules, fine granules, and chewing solid mini-tablets became the mainstream of oral solid preparations for children. Generally, multiparticle preparation, coating, microencapsulation, and other granulating techniques were involved in these preparations. Granulation and flavor masking are closely related and synergetic. Flavor masking techniques mask the bitter taste of Chinese medicine from four aspects, including confusing the brain taste, changing the compounds, reducing the exposure of bitter molecules to bitter receptors in the mouth, and numbing the taste cells to increase the threshold of bitter perception. At present, the main drugs for children on the market mainly inhibit the oral release of bitter drugs.
Topics: Child; Humans; Chemistry, Pharmaceutical; Administration, Oral; Tablets; Taste; China
PubMed: 36471989
DOI: 10.19540/j.cnki.cjcmm.20220610.602 -
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 -
BMJ Health & Care Informatics Feb 2023Computerised provider order entry (CPOE) systems have been implemented around the world as a solution to reduce ordering and transcription errors. However, previous... (Observational Study)
Observational Study
OBJECTIVES
Computerised provider order entry (CPOE) systems have been implemented around the world as a solution to reduce ordering and transcription errors. However, previous literature documented many challenges to attain this goal, especially in paediatric settings. The objectives of this study were to (1) analyse the impact of a paediatric CPOE system on medication safety and (2) suggest potential error prevention strategies.
METHODS
A pre-post observational study was conducted at the pilot ward (n=60 beds) of a paediatric academic health centre through mixed methods. The implementation project and medication management workflows were described through active participation to the project management team, observation, discussions and analysis of related documents. Furthermore, using incident reports, the nature of each error and error rate was compared between the preperiod and postperiod.
RESULTS
The global error rate was lower, but non-statistically significant, in the post implementation phase, which was mostly driven by a significant reduction in errors during order acknowledgement, transmission and transcription. Few errors occurred at the prescription step, and most errors occurred during medication administration. Furthermore, some errors could have been prevented using a CPOE in the pre-implementation period, and the CPOE led to few technology-related errors.
DISCUSSION AND CONCLUSION
This study identified both intended and unintended effects of CPOE adoption through the entire medication management workflow. This study revealed the importance of simplifying the acknowledgement, transmission and transcribing steps through the implementation of a CPOE to reduce medication errors. Improving the usability of the electronic medication administration record could help further improve medication safety.
Topics: Humans; Child; Medical Order Entry Systems; Hospitals, Pediatric; Medication Errors; Pharmaceutical Preparations; Risk Management
PubMed: 36787953
DOI: 10.1136/bmjhci-2022-100622 -
Physical Review. E May 2021We show an amazing complexity of the chimeras in small networks of coupled phase oscillators with inertia. The network behavior is characterized by heteroclinic...
We show an amazing complexity of the chimeras in small networks of coupled phase oscillators with inertia. The network behavior is characterized by heteroclinic switching between multiple saddle chimera states and riddling basins of attractions, causing an extreme sensitivity to initial conditions and parameters. Additional uncertainty is induced by the presumable coexistence of stable phase-locked states or other stable chimeras as the switching trajectories can eventually tend to them. The system dynamics becomes hardly predictable, while its complexity represents a challenge in the network sciences.
PubMed: 34134258
DOI: 10.1103/PhysRevE.103.L050204 -
Journal of Pharmaceutical Sciences Oct 2022The term "Medical devices" includes technology-based devices or articles, both basic and complex. Due to these types of variations, a strict, robust, transparent, and... (Review)
Review
The term "Medical devices" includes technology-based devices or articles, both basic and complex. Due to these types of variations, a strict, robust, transparent, and sustainable regulatory framework is required. In recent clinical practice, incidents including the breast implant and the hip replacement crisis have made it necessary to improve the regulatory and compliance approaches for the industry to ensure the manufacturing and distribution of safe and innovative MDs within the EU. In response to this, the EU revised the laws governing medical devices and in vitro diagnostics to align with the developments of the sector, address critical safety issues and support innovation. The new regulation (EU) 2017/745 on Medical Devices (MDR) is now applicable from May 26 2021 and the In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746 will take effect from May 2022.In this review, we aim to provide an update on the new Medical Device Regulations in the context of the current medical needs of the world, and also to give a glimpse at the non-EU regulatory landscape. Finally, we take a look at the closed-system transfer devices (CSTD) and COVID facilitated changes promoting demand for continuous improvement and trends in the pharmaceutical and medical industry related areas.
Topics: COVID-19; Commerce; Humans; Medical Device Legislation; Pharmaceutical Preparations; Reagent Kits, Diagnostic
PubMed: 35872025
DOI: 10.1016/j.xphs.2022.07.011 -
The International Journal of Risk &... 2021Off-label drug (OLD) use is common in neonates.
BACKGROUND
Off-label drug (OLD) use is common in neonates.
OBJECTIVE
There is a dearth of information associating the OLD use and the risk of medication errors in critically ill neonates. Hence, the present study was carried out.
METHODS
Drug prescriptions in neonates admitted to the intensive care unit of a tertiary care hospital between September 2018 and June 2019 were evaluated. Details on their demographics, reason for admission in intensive care unit, drug-related information and serum creatinine were extracted. United States Food and Drug Administration approved drug labels were compared. World Health Organization (WHO) anatomy, therapeutic and chemical (ATC) classification was used for drug categorization. We assessed the risk of medication errors in the adult population using a validated tool: medication risk score (MERIS).
RESULTS
One hundred and seventy-one neonates with 2394 prescriptions were included in this study. Seventy one percent of the neonates in the present study received at least one OLD/unlicensed prescription item. A trend in increased numbers of OLD/unlicensed drug use in more premature and lower birth weight neonates were observed. Medication risk score was significantly higher in neonates receiving OLD/unlicensed drugs compared to those with only labelled drugs. Very and extreme pre-term (along with very low and extremely low birth weight) neonates were at higher risk of medication errors compared to others. Presence of OLD/unlicensed prescribed items is associated with a potentially increased risk of medication errors by an odds ratio of 20.4 compared to labelled drugs.
CONCLUSION
Significant proportions of critically ill neonates received at least one OLD/unlicensed drug and such use was associated with potentially increased risk of medication errors.
Topics: Critical Illness; Humans; Infant, Newborn; Medication Errors; Off-Label Use; Pharmaceutical Preparations; Pilot Projects; United States
PubMed: 33646182
DOI: 10.3233/JRS-200058