Hemicelluloses for fuel ethanol: A review.

Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.

Strategies to Address Low Drug Solubility in Discovery and Development

Solubility, the phenomenon of dissolution of solute in solvent to give a homogenous system, is one of the important parameters to achieve desired concentration of drug in systemic circulation for desired (anticipated) pharmacological response. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as for the generic development. More than 40% NCEs (new chemical entities) developed in pharmaceutical industry are practically insoluble in water. Solubility is a major challenge for formulation scientist. Any drug to be absorbed must be present in the form of solution at the site of absorption. Various techniques are used for the enhancement of the solubility of poorly soluble drugs which include physical and chemical modifications of drug and other methods like particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant, complexation, and so forth. Selection of solubility improving method depends on drug property, site of absorption, and required dosage form characteristics.

/pdf/drug-solubility-importance-and-enhancement-techniques-qt85p6nf0s.pdf

Drug Solubility: Importance and Enhancement Techniques

The fact that a new text book introducing the essentials of computational chemistry contains more than 500 pages shows impressively the grown and still growing size and importance of this field of chemistry. The author’s objectives of the book, using his own words, are “to provide a survey of computational chemistry its underpinnings, its jargon, its strengths and weaknesses that will be accessible to both the experimental and theoretical communities”. This design as a general introduction into computational chemistry makes it an alternative to Andrew R. Leach’s well-established “Molecular Modeling” (Prentice Hall) and Frank Jensen’s “Introduction to Computational Chemistry” (Wiley), although the latter focuses on the theory of electronic structure methods. Cramer’s “Essentials” covers force field and molecular orbital theory, Monte Carlo and Molecular Dynamics simulations, thermodynamic and electronic (spectroscopic) property calculation, condensed phase treatment and a few more topics. Moreover, the book contains thirteen selected case studies sexamples taken from the literature sto illustrate the application of the just presented theoretical and computational models. This especially makes the text book well suited for both classroom discussion and self-study. Each chapter of “Essentials” covers a main topic of computational chemistry and will be briefly described here; all chapters are ended by a bibliography and suggested additional readings as well as the literature references cited in the text. In chapter 1 the author defines basic terms such as “theory”, “model”, and “computation”, introduces the concept of the potential energy surface and provides some general considerations about hardware and software. Interestingly, the first equation occurring in the text is not Schro ̈dinger’s equation, as is the case for most computational chemistry introductions, but the famous Einstein relation. The second chapter deals with molecular mechanics. It explains the different potential energy contributions, introduces the field of structure optimization, and provides an overview of the variety of modern force fields. Chapter 3 covers the simulation of molecular ensembles. It defines phase space and trajectories and shows the formalism of, and problems and difference between, Monte Carlo and molecular dynamics. In chapter 4 the author introduces the foundations of molecular orbital theory. Basic concepts such as Hamilton operator, LCAO basis set approach, many-electron wave functions, etc. are explained. To illuminate the LCAO variational process, the Hu ̈ckel theory is presented with an example. Chapter 5 deals with semiempirical molecular orbital (MO) theory. Besides the classical approaches (extended Hu ̈ckel, CNDO, INDO, NDDO) and methods (e.g., MNDO, AM1, PM3) and their performance, examples are provided from the ongoing development in that still fascinating area. Ab initio MO theory is presented in chapter 6; the basis set concept is discussed in detail, and, after some considerations from an user’s point of view, the general performance of ab initio methods is explicated. The next chapter covers the problem of electron correlation and gives the most prominent solutions for its treatment: configuration interaction, theory of the multiconfiguration self-consistent field, perturbation, and coupled cluster. Practical issues are also discussed. Chapter 8’s topic is density functional theory (DFT). Its theoretical foundation, methodology, and some functionals as well as its pros and cons compared to MO theory are presented together with a general performance overview. The next two chapters deal with charge distribution, derived and spectroscopic properties (e.g., atomic charges, polarizability, rotational, vibrational, and NMR spectra), and thermodynamic properties (e.g., zero-point vibrational energy, free energy of formation, and reaction). The modeling of condensed phases is addressed in chapters 11 (implicit models) and 12 (explicit models), which closes with a comparison between the two approaches. Chapter 13 familiarizes the reader with hybrid quantum mechanical/molecular mechanical (QM/MM) models. Polarization as well as the problematic implications of unsaturated QM and MM components are discussed, and empirical valence bond methods are also presented. The treatment of excited states is the topic of chapter 14; besides CI and MCSCF as computational methods, transition probabilities and solvatochromism are discussed. The last chapter deals with reaction dynamics, mostly adiabaticskinetics, rate constants, reaction paths, and transition state theory are section topics here sbut also nonadiabatic, introducing curve crossing and Marcus theory in brief. The appendix is divided into four parts: an acronym glossary (which is very helpful), an overview of symmetry and group theory, an introduction to spin algebra, and finally a section about orbital localization. A rather detailed index ends the book. The “Essentials” writing style fits the fascinating topic: one reads on and on andssurprise! sanother chapter has been absorbed. The text is complemented by a large number of black and white figures and clear tables, mostly self-explanatory with descriptive captions. The use of equations and mathematical formulas in general is well-balanced, and the level of math should be understandable for every natural scientist with some basic knowledge of physics. There are only a few minor shortcomings: for example, a literature reference cited in the text (“Beck et al.”, p 142) is missing in the bibliography; “Kronecker” is mistyped with o ̈; and the author completely forgot to reference Leach’s text book when referring to other computational chemistry introductions. However, the author has established a specific errata web page (http://pollux.chem.umn.edu/ ∼cramer/Errors.html) with all known errors. These will be corrected in the next printing or next revised edition, respectively. With its emphasis, on one hand, on the basic concepts and applications rather than pure theory and mathematics, and on the other hand, coverage of quantum mechanical and classical mechanical models including examples from inorganic, organic, and biological chemistry, “Essentials” is a useful tool not only for teaching and learning but also as a quick reference, and thus will most probably become one of the standard text books for computational chemistry.

Essentials Of Computational Chemistry Theories And Models

The use of supercritical carbon dioxide as a processing solvent for the physical processing of polymeric materials is reviewed. Fundamental properties of CO2/polymer systems are discussed with an emphasis on available data and measurement techniques, the development of theory or models for a particular property, and an evaluation of the current state of understanding for that property. Applications such as impregnation, particle formation, foaming, blending, and injection molding are described in detail including practical operating information for selected topics. The review concludes with some forward-looking discussion on the future of CO2 in polymer processing.

A Review of CO2 Applications in the Processing of Polymers

Supercritical fluid dyeing is an interesting alternative to the conventional aqueous process because of its environmental benefits. The aim of the paper is to provide the reader with an up-to-date overview of this subject, covering various aspects, such as the solubility and equilibrium partitioning of the dyes, mass transfer phenomena and solvent–polymer interactions occurring during coloration, up to the most recent reports on the technology of the dyeing process. Even though the best results have been obtained in the coloration of synthetic textiles, particular attention is given to the dyeing of natural textiles, which is, at the moment, the limiting step of this technology.

Supercritical fluid dyeing of synthetic and natural textiles – a review

Synthesis of biodiesel from edible, non-edible and waste cooking oils via supercritical methyl acetate transesterification

The aim of the work is to enhance the oral bioavailability of ketoprofen by inserting it into a water-soluble polymer, poly(vinylpyrrolidone) (PVP) K30, using supercritical carbon dioxide as the impregnating solvent. Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) characterized by low solubility and a low dissolution rate in the gastrointestinal tract, PVP is a biocompatible water-soluble polymer with a fast dissolution rate and supercritical CO2 is a clean non-toxic solvent that is able to plasticize amorphous polymers. The physical state of the drug in the polymer has been investigated through Fourier Transform Infrared (FTIR) spectroscopy and powder X-ray diffraction (PXRD) and it has been compared with that of the PVP-ketoprofen physical mixtures. The results of the analyses show that an amorphous solid dispersion of the drug in the polymer can be obtained even at high concentrations. Impregnated polymer powders were compressed into tablets and the release kinetics was evaluated to study the drug dissolution rate. The release curves of the physical mixtures, with the same drug content, were also measured and compared with those of the impregnated polymer tablets. The results show that the release mechanism depends on the tablet composition and that it is necessary to work with not too high a drug content to obtain a large enhancement of the dissolution kinetics.

Impregnation of PVP microparticles with ketoprofen in the presence of supercritical CO2

Studying mass transfer phenomena in polymeric films subjected to impregnation with a supercritical fluid can give interesting information for textile dyeing performances and for applications in the pharmaceutical field. The aim of this work is to propose an experimental technique to evaluate diffusion coefficients of disperse dyes in a PET film. The ‘film roll method’ was used by other researchers in water impregnating systems to evaluate diffusion coefficients of non-ionic dyes in synthetic polymers. It has been extended and adapted to a supercritical impregnating system. Diffusion coefficients of two disperse dyes at different temperature (90 and 110°C) and pressure values (22 and 25 MPa) have been measured and their dependence on working conditions gives a first explanation of mass transfer phenomena of disperse dyes in a PET film: experimental data can also be used to evaluate diffusion-concentration dependence.

Diffusion of disperse dyes in PET films during impregnation with a supercritical fluid

Triglycerides and/or polyphenols have been extracted through supercritical CO2 from waste hazelnuts (bug-damaged nuts, rotten nuts and damaged roasted nuts), spent ground coffee, grape skins and grape seeds to achieve the valorization of food wastes with a clean and property-preserving-of-extracts technique. With respect to soxhlet extractions satisfactory yields (55–100%) were obtained for triglycerides. Grape seeds and spent ground coffee provided the highest yields (85–100%) while hazelnut wastes provided the highest amounts of triglycerides (0.3–0.4 goil/gwaste). Polyphenols were extracted from grape skins and seeds after adding a cosolvent (ethanol). Results showed that phenolic recovery was less efficient (11–25%) and that cosolvent amounts greater than 5% do not significantly affect the extraction yield. Preliminary tests on grape seeds pointed out that a single supercritical treatment can be used for the fractionated recovery of triglycerides and polyhenols by changing the polarity of the solvent during the extraction process through the addition of a cosolvent.

Mauro Banchero

Papers

Supercritical fluid dyeing of synthetic and natural textiles – a review

Synthesis of biodiesel from edible, non-edible and waste cooking oils via supercritical methyl acetate transesterification

Impregnation of PVP microparticles with ketoprofen in the presence of supercritical CO2

Diffusion of disperse dyes in PET films during impregnation with a supercritical fluid

Valorization of hazelnut, coffee and grape wastes through supercritical fluid extraction of triglycerides and polyphenols