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Science (New York, N.Y.) May 2017Hydrotropes are small molecules that solubilize hydrophobic molecules in aqueous solutions. Typically, hydrotropes are amphiphilic molecules and differ from classical...
Hydrotropes are small molecules that solubilize hydrophobic molecules in aqueous solutions. Typically, hydrotropes are amphiphilic molecules and differ from classical surfactants in that they have low cooperativity of aggregation and work at molar concentrations. Here, we show that adenosine triphosphate (ATP) has properties of a biological hydrotrope. It can both prevent the formation of and dissolve previously formed protein aggregates. This chemical property is manifested at physiological concentrations between 5 and 10 millimolar. Therefore, in addition to being an energy source for biological reactions, for which micromolar concentrations are sufficient, we propose that millimolar concentrations of ATP may act to keep proteins soluble. This may in part explain why ATP is maintained in such high concentrations in cells.
Topics: Adenosine Triphosphate; Hydrophobic and Hydrophilic Interactions; Models, Biological; Protein Aggregates; Protein Denaturation; Protein Stability; Solubility; Solutions
PubMed: 28522535
DOI: 10.1126/science.aaf6846 -
International Journal of Pharmaceutics Mar 2020
Topics: Drug Delivery Systems; Humans; Pharmaceutical Preparations; Solubility
PubMed: 31958490
DOI: 10.1016/j.ijpharm.2020.119055 -
Structure (London, England : 1993) Jun 2023Amino acid deletions are high-risk, high-reward mutations, yet structural consequences are poorly understood. In this issue of Structure, Woods et al. (2023)...
Amino acid deletions are high-risk, high-reward mutations, yet structural consequences are poorly understood. In this issue of Structure, Woods et al. (2023) individually deleted 65 residues from a small α-helical protein, structurally assayed the 17 soluble variants, and developed a computational model of deletion solubility combining Rosetta and AlphaFold2.
Topics: Proteins; Amino Acids; Mutation; Solubility
PubMed: 37267922
DOI: 10.1016/j.str.2023.05.005 -
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 -
Drug Development and Industrial Pharmacy Jul 2021The number of active pharmaceutical compounds from the biopharmaceutical classification system (BCS) belonging to Class II and IV have significantly increased in recent... (Review)
Review
The number of active pharmaceutical compounds from the biopharmaceutical classification system (BCS) belonging to Class II and IV have significantly increased in recent years. These compounds have high therapeutic potential but are difficult to formulate as oral dosage forms due to their poor aqueous solubility. The solubility and bioavailability of these poorly water-soluble compounds can be increased by various formulation approaches, such as amorphous solid dispersions (ASD), salt formation, complexations, etc. Out of these techniques, the ASD approach, where compounds are converted into amorphous form and embedded in the hydrophilic matrix, have been successfully used in many marketed preparations. The recent advancement of this ASD approach is the design of ternary solid dispersions (TSD), where an additional component is added to further improve their performance in terms of solubility, stability, and processability. This review discusses the classification, mechanism of performance improvement, preparation techniques, and characterizations for TSD.
Topics: Biological Availability; Pharmaceutical Preparations; Polymers; Solubility; Water
PubMed: 33818224
DOI: 10.1080/03639045.2021.1908342 -
Advanced Drug Delivery Reviews May 2016Amorphisation of poorly water-soluble drugs is one approach that can be applied to improve their solubility and thus their bioavailability. Amorphisation is a process... (Review)
Review
Amorphisation of poorly water-soluble drugs is one approach that can be applied to improve their solubility and thus their bioavailability. Amorphisation is a process that usually requires deliberate external energy input. However, amorphisation can happen both unintentionally, as in process-induced amorphisation during manufacturing, or in situ during dissolution, vaporisation, or lipolysis. The systems in which unintended and in situ amorphisation has been observed normally contain a drug and a carrier. Common carriers include polymers and mesoporous silica particles. However, the precise mechanisms by which in situ amorphisation occurs are often not fully understood. In situ amorphisation can be exploited and performed before administration of the drug or possibly even within the gastrointestinal tract, as can be inferred from in situ amorphisation observed during in vitro lipolysis. The use of in situ amorphisation can thus confer the advantages of the amorphous form, such as higher apparent solubility and faster dissolution rate, without the disadvantage of its physical instability.
Topics: Drug Carriers; Lipolysis; Pharmaceutical Preparations; Polymers; Solubility
PubMed: 26724250
DOI: 10.1016/j.addr.2015.12.014 -
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 -
Critical Reviews in Food Science and... 2022Amorphous solid products have recently gained a lot of attention as key solutions to improve the solubility and bioavailability of poorly soluble nutraceuticals. A pure... (Review)
Review
Amorphous solid products have recently gained a lot of attention as key solutions to improve the solubility and bioavailability of poorly soluble nutraceuticals. A pure amorphous drug is a high-energy form; physically/chemically unstable and so easily gets recrystallized into the less soluble crystalline form limiting solubility and bioavailability issues. Amorphous solid dispersion and co-amorphous are new formulation approach that stabilized unstable amorphous form through different mechanisms such as preventing mobility, high glass transition temperature and molecular interaction. Nutraceuticals have been received the utmost importance due to their health benefits. However, most of these compounds have been associated with poor oral bioavailability due to poor solubility, high lipophilicity, high melting point, poor permeability, degradability and rapid metabolism in the gastrointestinal tract (GIT) which limits its health benefits. This review provides us a systematic application of amorphous systems to the delivery of poorly soluble nutraceuticals, with the aim of overcoming their pharmacokinetic limitations and improved pharmacological potential. In particular, it describes the challenges associated with delivery of oral nutraceuticals, various methods involved in the preparation and characterization of amorphous systems and permeability enhancement of nutraceuticals are in detail.
Topics: Biological Availability; Dietary Supplements; Drug Stability; Pharmaceutical Preparations; Solubility
PubMed: 33103462
DOI: 10.1080/10408398.2020.1836607 -
Drug Development and Industrial Pharmacy Nov 2021Nanocrystal technology is a new way to increase the solubility and bioavailability of poorly soluble drugs. As an intermediate preparation technology, nanocrystals are... (Review)
Review
Nanocrystal technology is a new way to increase the solubility and bioavailability of poorly soluble drugs. As an intermediate preparation technology, nanocrystals are widely used in drug delivery for oral, venous, percutneous and inhalation administration, which exhibits a broad application prospect. By referring to the domestic anforeign literatures, this paper mainly reviews the preparation methods of nanocrystals for poorly soluble natural products and its application in the mucosal delivery for skin, eye, oral cavity and nasal cavity. This can provide the reference for the research and development of nanocrystal technology in natural product preparations.
Topics: Biological Availability; Drug Delivery Systems; Nanoparticles; Pharmaceutical Preparations; Solubility
PubMed: 35287534
DOI: 10.1080/03639045.2022.2053985 -
Future Medicinal Chemistry Feb 2023Prodrug strategy is critical for innovative drug development. Structural modification is the most straightforward and effective method to develop prodrugs. Improving... (Review)
Review
Prodrug strategy is critical for innovative drug development. Structural modification is the most straightforward and effective method to develop prodrugs. Improving drug defects and optimizing the physical and chemical properties of a drug, such as lipophilicity and water solubility, changing the way of administration can be achieved through specific structural modification. Designing prodrugs by linking microenvironment-responsive groups to the prototype drugs is of great help in enhancing drug targeting. In the meantime, making connections between prodrugs and suitable drug delivery systems could realize drug loading increases, greater stability, bioavailability and drug release control. In this paper, lipidic, water-soluble, pH-responsive, redox-sensitive and enzyme-activatable prodrugs are reviewed on the basis of structural modification.
Topics: Prodrugs; Drug Delivery Systems; Solubility; Drug Liberation; Water
PubMed: 36946236
DOI: 10.4155/fmc-2022-0309