Different types, applications and limits of enabling excipients of pharmaceutical dosage forms
Publication date: Available online 30 April 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Barnabás Palcsó, Romána ZelkóAlong with the development of novel drug delivery systems the material science is also advancing. Conventional and novel synthetic or natural excipients provide opportunities to design dosage forms of the required features including their bioavailability. Emerging trends in the design and development of drug products indicate an increasing need for the functionality-related characterization of excipients. The purpose of this review is to provide an overview of different types of excipients i...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Automated techniques in pKa determination: Low, medium and high-throughput screening methods
Publication date: Available online 10 May 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Christophe DardonvilleDrug discovery programs that generate hundreds of new molecular entities need efficient methodologies for physicochemical profiling. Several high-throughput methods for pKa screening have been developed in the last 15 years to determine this key physicochemical parameter. Separation techniques such as HPLC–MS or capillary electrophoresis are particularly well-suited due to their high throughput and capacity to deal with impure or complex samples. In addition, potentiometric and (mostly) UV-metric-based...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Automated assays for thermodynamic (equilibrium) solubility determination
Publication date: Available online 23 May 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Tomás Sou, Christel A.S. BergströmSolubility is a crucial physicochemical property for drug candidates and is important in both drug discovery and development. Poor solubility is detrimental to absorption after oral administration and can mask compound activity in bioassays in various ways. Hence, solubility liabilities should ideally be identified as early as possible in the drug development process. With the increasing number of compounds as potential drug candidates, automated thermodynamic solubility assays for high thr...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
CRISPR/Cas9 genome surgery for retinal diseases
Publication date: Available online 18 June 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Christine L. Xu, Karen Sophia Park, Stephen H. TsangRetinal diseases that impair vision can impose heavy physical and emotional burdens on patients’ lives. Currently, clustered regularly interspaced short palindromic repeats (CRISPR) is a prevalent gene-editing tool that can be harnessed to generate disease model organisms for specific retinal diseases, which are useful for elucidating pathophysiology and revealing important links between genetic mutations and phenotypic defects. These retinal disease models are fundamenta...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Brief overview of solubility methods: Recent trends in equilibrium solubility measurement and predictive models
Discussion of experimental and computational methods: was based on relevant industrial references. (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
CRISPR/Cas9-mediated genome editing in human stem cell-derived cardiomyocytes: Applications for cardiovascular disease modelling and cardiotoxicity screening
Publication date: Available online 25 June 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Effimia Christidi, Haojun (Margaret) Huang, Liam R. BrunhamCardiovascular diseases (CVDs) are leading causes of death worldwide, and drug-induced cardiotoxicity is among the most common cause of drug withdrawal from the market. Improved models of cardiac tissue are needed to study the mechanisms of CVDs and drug-induced cardiotoxicity. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) have provided a major advance to our ability to study these conditions. Combined with efficient genome editing technologies, such a...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Experimental and pKa prediction aspects of tautomerism of drug-like molecules
Publication date: Available online 27 June 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Yvonne Connolly MartinMolecules that can tautomerize are a challenge to scientists because one must consider the possible tautomers in most tasks involving chemical structures: for example, searching databases, interpreting experimental property measurements, calculating properties, virtual screening, and analyzing structure-bioactivity relationships. The challenge in interpreting property measurements such as pKa values feeds into the general lack of extensive information not only of the relative tautomer stability in water...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Physico-chemical characterization of self-emulsifying drug delivery systems
The objective of this study was to summarize these physicochemical factors characterized SEDDS. Determination of self-emulsification process and ternary phase diagram are the basis of preparations. The position of APIs in SEDDS inclusion can be determined by dye solubilisation test. The end point of self-emulsification was controlled by turbimetric evaluation. Optimisation of droplet size and zeta potential are crucial parameters because they can influence i.e. the dissolution rate of APIs and the stability of SEDDS. Besides the basic methods in the characterization of SEDDS such as dispersibility tests, turbidimetric eval...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Integrating biocatalysis and multicomponent reactions
Publication date: Available online 28 June 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Chiara Lambruschini, Andrea Basso, Luca BanfiWhile often multicomponent reactions (MCR) are used for the diversity-oriented synthesis of racemic (or achiral) molecular entities, this short review describes two alternative approaches for accessing enantiopure products exploiting the power of biocatalysis. Enzymes or microorganisms may be used for preparing enantiopure MCR inputs or for resolving racemic (or achiral) MCR adducts.Graphical abstract (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Multi-component synthesis of fluorophores via catalytic generation of alkynoyl intermediates
Publication date: Available online 2 July 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Thomas J.J. MüllerThis account summarizes recent developments of aggregation-induced emissive and emission solvatochromic fluorophores by multicomponent reactions. Key intermediates are catalytically generated alkynoyl derivatives that are directly transformed into luminophores in a one-pot fashion. The conciseness in combination with ready access to tailored chromophore libraries makes this synthetic methodological concept superior over classical multistep syntheses.Graphical abstract (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Arynes and isocyanides: Two close-knit partners in multicomponent reactions
Publication date: Available online 2 July 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Marta Serafini, Tracey PiraliDespite benzyne has been known since 1940, this fascinating species has received much attention only over the last decades. The renaissance of interest in aryne chemistry is ascribable to the seminal discovery that arynes can be generated in situ from stable and commercially available precursors under mild and neutral conditions. Thanks to their high reactivity, arynes are key intermediates in countless chemical transformations ranging from cycloadditions to insertions and, among all these approac...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Modifying the physicochemical properties of NSAIDs for nasal and pulmonary administration
Publication date: Available online 12 April 2018 Source:Drug Discovery Today: Technologies Author(s): P. Szabó-Révész This review focuses on nasal and pulmonary delivery of NSAIDs (non-steroidal anti-inflammatory drugs) for fast-onset analgesia, for the potential prevention of Alzheimer’s disease (AD), as well as for an add-on treatment in cystic fibrosis (CF) and non-small cell lung cancer (NSCLC). I discuss how the physicochemical properties of NSAIDs can be modified with respect to the biological characteristics of the target site. Innovative technology and/or dosage forms can promote an effective therapy. Graph...
Source: Drug Discovery Today: Technologies - April 13, 2018 Category: Drugs & Pharmacology Source Type: research
Log P as a tool in intramolecular hydrogen bond considerations
Publication date: Available online 30 March 2018 Source:Drug Discovery Today: Technologies Author(s): Giulia Caron, Maura Vallaro, Giuseppe Ermondi Intramolecular hydrogen bonding (IMHB) considerations are gaining relevance in drug discovery and a molecular descriptor which can predict very early the capacity of a compound to form IMHB is needed to speed up the optimization process of drug candidates. Although log Poct is largely used for optimization purposes, in this paper we firstly use the Block Relevance (BR) analysis to theoretically show how log Poct is not a convenient choice to assess IMHB properties of candi...
Source: Drug Discovery Today: Technologies - March 30, 2018 Category: Drugs & Pharmacology Source Type: research
Developing precision medicine using scarless genome editing of human pluripotent stem cells
Publication date: Available online 8 March 2018 Source:Drug Discovery Today: Technologies Author(s): Benjamin Steyer, Evan Cory, Krishanu Saha Many avenues exist for human pluripotent stem cells (hPSCs) to impact medical care, but they may have their greatest impact on the development of precision medicine. Recent advances in genome editing and stem cell technology have enabled construction of clinically-relevant, genotype-specific “disease-in-a-dish” models. In this review, we outline the use of genome-edited hPSCs in precision disease modeling and drug screening as well as describe methodological advances in sca...
Source: Drug Discovery Today: Technologies - March 8, 2018 Category: Drugs & Pharmacology Source Type: research
The multiplexed CRISPR targeting platforms
Publication date: Available online 4 February 2018 Source:Drug Discovery Today: Technologies Author(s): Jian Cao, Qian Xiao, Qin Yan The discovery and engineering of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in the past several years have revolutionized biomedical research. The CRISPR technology showed great potential to advance detection, prevention, and treatment of human diseases in the near future. Compared to previous developed genome editing approaches, such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), the CRISPR-based systems have num...
Source: Drug Discovery Today: Technologies - February 5, 2018 Category: Drugs & Pharmacology Source Type: research
