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International Journal of Pharmaceutics Mar 2020
Topics: Drug Delivery Systems; Humans; Pharmaceutical Preparations; Solubility
PubMed: 31958490
DOI: 10.1016/j.ijpharm.2020.119055 -
Molecules (Basel, Switzerland) May 2018Cyclodextrins (CDs), a group of oligosaccharides formed by glucose units bound together in a ring, show a promising ability to form complexes with drug molecules and... (Review)
Review
Cyclodextrins (CDs), a group of oligosaccharides formed by glucose units bound together in a ring, show a promising ability to form complexes with drug molecules and improve their physicochemical properties without molecular modifications. The stoichiometry of drug/CD complexes is most frequently 1:1. However, natural CDs have a tendency to self-assemble and form aggregates in aqueous media. CD aggregation can limit their solubility. Through derivative formation, it is possible to enhance their solubility and complexation capacity, but this depends on the type of substituent and degree of substitution. Formation of water-soluble drug/CD complexes can increase drug permeation through biological membranes. To maximize drug permeation the amount of added CD into pharmaceutical preparation has to be optimized. However, solubility of CDs, especially that of natural CDs, is affected by the complex formation. The presence of pharmaceutical excipients, such as water-soluble polymers, preservatives, and surfactants, can influence the solubilizing abilities of CDs, but this depends on the excipients' physicochemical properties. The competitive CD complexation of drugs and excipients has to be considered during formulation studies.
Topics: Chemical Phenomena; Chemistry, Pharmaceutical; Cyclodextrins; Solubility; Solvents
PubMed: 29751694
DOI: 10.3390/molecules23051161 -
Molecules (Basel, Switzerland) Aug 2020Lipid-soluble bioactives are important nutrients in foods. However, their addition in food formulations, is often limited by limited solubility and high tendency for... (Review)
Review
Lipid-soluble bioactives are important nutrients in foods. However, their addition in food formulations, is often limited by limited solubility and high tendency for oxidation. Lipid-soluble bioactives, such as vitamins A, E, D and K, carotenoids, polyunsaturated fatty acids (PUFA) and essential oils are generally dispersed in water-based solutions by homogenization. Among the different homogenization technologies available, nanoemulsions are one of the most promising. Accordingly, this review aims to summarize the most recent advances in nanoemulsion technology for the encapsulation of lipid-soluble bioactives. Modern approaches for producing nanoemulsion systems will be discussed. In addition, the challenges on the encapsulation of common food ingredients, including the physical and chemical stability of the nanoemulsion systems, will be also critically examined.
Topics: Algorithms; Drug Compounding; Drug Stability; Emulsions; Lipids; Models, Theoretical; Molecular Structure; Nanoparticles; Nanotechnology; Solubility
PubMed: 32878137
DOI: 10.3390/molecules25173966 -
Drug Discovery Today Feb 2024Poor solubility of drugs and therapeutic candidates poses a significant challenge in drug research and development. Biopharmaceutical class II drugs exhibit limited... (Review)
Review
Poor solubility of drugs and therapeutic candidates poses a significant challenge in drug research and development. Biopharmaceutical class II drugs exhibit limited absorption because of their weak solubility and high permeability. Co-amorphous systems (CAMs) have been studied widely as a way to improve the solubility of drugs. This review summarizes recent advancements in dual-drug CAMs, including improvements in formulation, manufacturing, and solid-state characterization, and highlights the importance of enhancing solubility and stability. It emphasizes the potential synergistic effects of two drugs in CAMs and explores formulation strategies and challenges related to maintaining the amorphous state. Case studies demonstrate the successful application of CAMs in combination therapies that offer improved therapeutic efficacy.
Topics: Polymers; Solubility; Drug Stability
PubMed: 38141778
DOI: 10.1016/j.drudis.2023.103863 -
The Journal of Physical Chemistry. B Nov 2015It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not...
It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not clear. Here we use a simple protein model and perform Monte Carlo simulations to directly measure the solubility of amyloid fibrils as a function of the interaction between the fibril building blocks. Our simulations confirms that the fibril solubility depends on the fibril thickness and that the relationship between the interactions and the solubility can be described by a simple analytical formula. The results presented in this study reveal general rules how side-chain-side-chain interactions, backbone hydrogen bonding, and temperature affect amyloid fibril solubility, which might prove to be a powerful tool to design protein fibrils with desired solubility and aggregation properties in general.
Topics: Amyloid; Hydrogen Bonding; Solubility
PubMed: 26496385
DOI: 10.1021/acs.jpcb.5b09210 -
Biochemical Society Transactions Jun 2016Membrane proteins play crucial roles in cellular processes and are often important pharmacological drug targets. The hydrophobic properties of these proteins make full... (Review)
Review
Membrane proteins play crucial roles in cellular processes and are often important pharmacological drug targets. The hydrophobic properties of these proteins make full structural and functional characterization challenging because of the need to use detergents or other solubilizing agents when extracting them from their native lipid membranes. To aid membrane protein research, new methodologies are required to allow these proteins to be expressed and purified cheaply, easily, in high yield and to provide water soluble proteins for subsequent study. This mini review focuses on the relatively new area of water soluble membrane proteins and in particular two innovative approaches: the redesign of membrane proteins to yield water soluble variants and how adding solubilizing fusion proteins can help to overcome these challenges. This review also looks at naturally occurring membrane proteins, which are able to exist as stable, functional, water soluble assemblies with no alteration to their native sequence.
Topics: Bacteria; Bacterial Proteins; Hydrophobic and Hydrophilic Interactions; Membrane Proteins; Solubility; Water
PubMed: 27284043
DOI: 10.1042/BST20160025 -
Angewandte Chemie (International Ed. in... Dec 2022Poor water solubility and low bioavailability of active pharmaceutical ingredients (APIs) are major causes of friction in the pharmaceutical industry and represent a... (Review)
Review
Poor water solubility and low bioavailability of active pharmaceutical ingredients (APIs) are major causes of friction in the pharmaceutical industry and represent a formidable hurdle for pharmaceutical drug development. Drug delivery remains the major challenge for the application of new small-molecule drugs as well as biopharmaceuticals. The three challenges for synthetic delivery systems are: (i) controlling drug distribution and clearance in the blood; (ii) solubilizing poorly water-soluble agents, and (iii) selectively targeting specific tissues. Although several polymer-based systems have addressed the first two demands and have been translated into clinical practice, no targeted synthetic drug delivery system has reached the market. This Review is designed to provide a background on the challenges and requirements for the design and translation of new polymer-based delivery systems. This report will focus on chemical approaches to drug delivery for systemic applications.
Topics: Drug Delivery Systems; Solubility; Pharmaceutical Preparations; Polymers; Water
PubMed: 35575255
DOI: 10.1002/anie.202203942 -
Bioinformatics (Oxford, England) Sep 2020Recombinant protein production is a widely used technique in the biotechnology and biomedical industries, yet only a quarter of target proteins are soluble and can...
MOTIVATION
Recombinant protein production is a widely used technique in the biotechnology and biomedical industries, yet only a quarter of target proteins are soluble and can therefore be purified.
RESULTS
We have discovered that global structural flexibility, which can be modeled by normalized B-factors, accurately predicts the solubility of 12 216 recombinant proteins expressed in Escherichia coli. We have optimized these B-factors, and derived a new set of values for solubility scoring that further improves prediction accuracy. We call this new predictor the 'Solubility-Weighted Index' (SWI). Importantly, SWI outperforms many existing protein solubility prediction tools. Furthermore, we have developed 'SoDoPE' (Soluble Domain for Protein Expression), a web interface that allows users to choose a protein region of interest for predicting and maximizing both protein expression and solubility.
AVAILABILITY AND IMPLEMENTATION
The SoDoPE web server and source code are freely available at https://tisigner.com/sodope and https://github.com/Gardner-BinfLab/TISIGNER-ReactJS, respectively. The code and data for reproducing our analysis can be found at https://github.com/Gardner-BinfLab/SoDoPE_paper_2020.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
Topics: Computers; Escherichia coli; Proteins; Software; Solubility
PubMed: 32559287
DOI: 10.1093/bioinformatics/btaa578 -
International Journal of Pharmaceutics Jun 2021Nanosizing of pharmaceutical drug particles is one of the most important drug delivery platforms approaches for the commercial development of poorly water-soluble drug... (Review)
Review
Nanosizing of pharmaceutical drug particles is one of the most important drug delivery platforms approaches for the commercial development of poorly water-soluble drug molecules. Though nanosizing of drug particles has been proven to greatly enhance drugs dissolution rate and apparent solubility, nanosized materials have presented significant challenges for their formulation as solid dosage forms (e.g. tablets, capsules). This is due to the strong Van der Waals attraction forces between dry nanoparticles leading to aggregation, cohesion, and consequently poor flowability. In this review, the broad area of nanomedicines is overviewed with the primary focus on drug nanocrystals and the top-down and bottom-up methods used in their fabrication. The review also looks at how nanosuspensions of pharmaceutical drugs are generated and stabilised, followed by subsequent strategies for isolation of the nanoparticles. A perspective on the future outlook for drug nanocrystals is also presented.
Topics: Chemistry, Pharmaceutical; Drug Delivery Systems; Nanoparticles; Pharmaceutical Preparations; Solubility; Tablets; Technology, Pharmaceutical
PubMed: 33992712
DOI: 10.1016/j.ijpharm.2021.120708 -
Polimery W Medycynie 2018Polymorphism of pharmaceutical substances has a significant impact on their physicochemical properties, durability, bioavailability and consequently on their... (Review)
Review
Polymorphism of pharmaceutical substances has a significant impact on their physicochemical properties, durability, bioavailability and consequently on their pharmacological activity. Solid dosage forms may exist in both crystalline and amorphous forms. Amorphous varieties are characterized by higher solubility and dissolution rates, while crystalline forms show greater purity and storage stability. The choice between the crystalline or amorphous form of a drug is extremely important to ensure effective and safe pharmacotherapy. Statins - the most commonly used group of drugs in the treatment of lipid disorders - are an example of drugs that occur in many crystalline and amorphous forms. Statins belong to class II in the biopharmaceutical classification system (BCS), which means that they are poorly soluble, but permeate biological membranes well. The bioavailability of statins shows considerable variation, which is associated with the first-pass effect in the liver and the accumulation of the drug in the hepatocytes. The improvement of bioavailability after oral administration of poorly soluble medicinal substances remains one of the most challenging aspects of the drug development process. A specific polymorphic form is obtained by applying appropriate conditions during the process of its preparation under industrial conditions, including the use of a suitable solvent, a specific temperature or rate of crystallization. The article provides a comprehensive update on the current knowledge of the influence of polymorphic form on statin solubility and bioavailability. Research is still being carried out to obtain new polymorphic varieties of statins that are characterized by better physicochemical and pharmacokinetic parameters.
Topics: Biological Availability; Chemistry, Pharmaceutical; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmaceutical Preparations; Solubility
PubMed: 30916495
DOI: 10.17219/pim/102978