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  1. Book ; Online: Recent Progress in Solid Dispersion Technology

    Kawakami, Kohsaku

    2019  

    Abstract: Amorphous solid dispersion (ASD) is a powerful formulation technology to improve oral absorption of poorly soluble drugs. Despite their being in existence for more than half a century, controlling ASD performance is still regarded as difficult because of ...

    Abstract Amorphous solid dispersion (ASD) is a powerful formulation technology to improve oral absorption of poorly soluble drugs. Despite their being in existence for more than half a century, controlling ASD performance is still regarded as difficult because of ASD's natural non-equilibrium. However, recent significant advances in ASD knowledge and technology may enable a much broader use of ASD technology. This Special Issue, which includes 3 reviews and 6 original articles, focuses on recent progresses in ASD technology in hopes of helping to accelerate developmental studies in the pharmaceutical industry. In striving for a deep understanding of ASD non-equilibrium behavior, the Special issue also delves into and makes progress in the theory of soft-matter dynamics
    Keywords Science (General) ; Biology (General)
    Size 1 electronic resource (204 pages)
    Publisher MDPI - Multidisciplinary Digital Publishing Institute
    Document type Book ; Online
    Note eng ; Open Access
    HBZ-ID HT020324001
    ISBN 9783039215010 ; 9783039215027 ; 3039215019 ; 3039215027
    DOI 10.3390/books978-3-03921-502-7
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Rigid Nuclei and Flexible Nuclei: Appearance and Disappearance of Nuclei in Indomethacin Glass Revealed by a Long-Term Annealing Study.

    Kawakami, Kohsaku

    The journal of physical chemistry. B

    2023  Volume 127, Issue 26, Page(s) 5967–5977

    Abstract: In this study, nucleation/crystallization behaviors of indomethacin glass are discussed with emphasis on the fate of nuclei, which is explained using a notion of "rigid" and "flexible" nuclei. The observation was made mainly by thermal analysis of ... ...

    Abstract In this study, nucleation/crystallization behaviors of indomethacin glass are discussed with emphasis on the fate of nuclei, which is explained using a notion of "rigid" and "flexible" nuclei. The observation was made mainly by thermal analysis of indomethacin glass after long-term annealing at various temperatures. Formation of nuclei was evaluated by observing cold crystallization behaviors of the annealed glasses, as they should be dominated by the "nuclei form" produced in the glass. Nuclei of forms α and γ, which have opposite stability trends, were found to appear over a wide temperature range. The nuclei of form α were stable even in the presence of other crystal forms, whereas those of form γ were likely to be easily integrated into other crystals during their growth, which was explained by a notion of rigid and flexible nuclei. Moreover, unconventionally fast crystallization in the glass-transition region and the finding of a new crystal form are also reported.
    Language English
    Publishing date 2023-06-25
    Publishing country United States
    Document type Journal Article
    ISSN 1520-5207
    ISSN (online) 1520-5207
    DOI 10.1021/acs.jpcb.3c02127
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ostwald Ripening of Triacylglycerol Droplets Embedded in Glass-Supported Phospholipid Bilayers.

    Kataoka-Hamai, Chiho / Kawakami, Kohsaku

    Langmuir : the ACS journal of surfaces and colloids

    2023  Volume 39, Issue 29, Page(s) 10001–10010

    Abstract: Lipid droplets are fat storage organelles that consist of a neutral lipid core surrounded by a phospholipid monolayer. Because of their important biological functions, reconstituting model lipid droplets in synthetic phospholipid membranes is of great ... ...

    Abstract Lipid droplets are fat storage organelles that consist of a neutral lipid core surrounded by a phospholipid monolayer. Because of their important biological functions, reconstituting model lipid droplets in synthetic phospholipid membranes is of great interest. In the present study, we investigated the incorporation of triacylglycerol droplets into glass-supported phospholipid bilayers by using fluorescence microscopy. We adsorbed triolein emulsions onto a glass surface that was partially covered with planar bilayers. After adsorption, triolein droplets were found to be immobilized in the bilayer membrane. The volume of each bound droplet varied over time. Large droplets grew, whereas small droplets shrank. Additionally, data on fluorescence recovery after photobleaching obtained for a phospholipid probe indicate that phospholipids on and near triolein droplets were fully mobile. Furthermore, photobleaching data obtained for a triacylglycerol probe indicate that triolein molecules diffused between different droplets along the planar bilayer. These results demonstrate Ostwald ripening, where triolein molecules in a small droplet dissolved in the bilayer, diffused laterally, and eventually bound to the interfaces of larger droplets. We investigated the ripening rate by using the average of the cube root of the fluorescence emission obtained for individual droplets. The ripening slowed after the addition of trilinolein to the triolein phase. Finally, we investigated the time dependence of the size distributions of the triolein droplets. The distribution was initially nearly unimodal and subsequently became bimodal.
    Language English
    Publishing date 2023-07-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2005937-1
    ISSN 1520-5827 ; 0743-7463
    ISSN (online) 1520-5827
    ISSN 0743-7463
    DOI 10.1021/acs.langmuir.3c00835
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Nucleation During Storage Impeded Supersaturation in the Dissolution Process of Amorphous Celecoxib.

    Song, Jingwen / Kawakami, Kohsaku

    Molecular pharmaceutics

    2023  Volume 20, Issue 8, Page(s) 4050–4057

    Abstract: The aqueous solubility of active pharmaceutical ingredients (APIs) is one of the most critical factors in determining the absorption of orally administered drugs. Amorphization of API may offer better drug absorption than the crystalline state owing to ... ...

    Abstract The aqueous solubility of active pharmaceutical ingredients (APIs) is one of the most critical factors in determining the absorption of orally administered drugs. Amorphization of API may offer better drug absorption than the crystalline state owing to enhanced solubility. However, if crystal nuclei are formed during storage, they may develop into crystals upon contact with water, thus limiting the dissolution advantage. In an earlier study, we found that the nuclei of amorphous celecoxib (CEL) could be formed at freezing temperatures (FT) without further crystal growth. Following this finding, we compared the dissolution performances of amorphous CEL annealed at room temperature (RT, 25 °C) or FT (-20 °C). We found that only the RT-annealed CEL could achieve a supersaturated state effectively during the dissolution process, which could be explained by the fast conversion of the FT-annealed amorphous CEL to a crystalline state owing to the presence of nuclei. Investigation of the residual solids revealed that supersaturation could be maintained for a while after the appearance of the crystals, which could be explained by heterogeneous nucleation and competition between the dissolution of amorphous parts and crystallization. In addition, a new crystalline form of CEL was observed during dissolution.
    MeSH term(s) Celecoxib ; Solubility ; Crystallization ; Cold Temperature ; Water/chemistry
    Chemical Substances Celecoxib (JCX84Q7J1L) ; Water (059QF0KO0R)
    Language English
    Publishing date 2023-07-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2138405-8
    ISSN 1543-8392 ; 1543-8384
    ISSN (online) 1543-8392
    ISSN 1543-8384
    DOI 10.1021/acs.molpharmaceut.3c00210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6250: Show issues Location:
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  5. Article: Crystallization Tendency of Pharmaceutical Glasses: Relevance to Compound Properties, Impact of Formulation Process, and Implications for Design of Amorphous Solid Dispersions.

    Kawakami, Kohsaku

    Pharmaceutics

    2019  Volume 11, Issue 5

    Abstract: Amorphous solid dispersions (ASDs) are important formulation strategies for improving the dissolution process and oral bioavailability of poorly soluble drugs. Physical stability of a candidate drug must be clearly understood to design ASDs with superior ...

    Abstract Amorphous solid dispersions (ASDs) are important formulation strategies for improving the dissolution process and oral bioavailability of poorly soluble drugs. Physical stability of a candidate drug must be clearly understood to design ASDs with superior properties. The crystallization tendency of small organics is frequently estimated by applying rapid cooling or a cooling/reheating cycle to their melt using differential scanning calorimetry. The crystallization tendency determined in this way does not directly correlate with the physical stability during isothermal storage, which is of great interest to pharmaceutical researchers. Nevertheless, it provides important insights into strategy for the formulation design and the crystallization mechanism of the drug molecules. The initiation time for isothermal crystallization can be explained using the ratio of the glass transition and storage temperatures (
    Language English
    Publishing date 2019-05-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics11050202
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Layer-by-layer designer nanoarchitectonics for physical and chemical communications in functional materials.

    Ariga, Katsuhiko / Song, Jingwen / Kawakami, Kohsaku

    Chemical communications (Cambridge, England)

    2024  Volume 60, Issue 16, Page(s) 2152–2167

    Abstract: Nanoarchitectonics, as a post-nanotechnology concept, constructs functional materials and structures using nanounits of atoms, molecules, and nanomaterials as materials. With the concept of nanoarchitectonics, asymmetric structures, and hierarchical ... ...

    Abstract Nanoarchitectonics, as a post-nanotechnology concept, constructs functional materials and structures using nanounits of atoms, molecules, and nanomaterials as materials. With the concept of nanoarchitectonics, asymmetric structures, and hierarchical organization, rather than mere assembly and organization of structures, can be produced, where rational physical and chemical communications will lead to the development of more advanced functional materials. Layer-by-layer assembly can be a powerful tool for this purpose, as exemplified in this feature paper. This feature article explores the possibility of constructing advanced functional systems based on recent examples of layer-by-layer assembly. We will illustrate both the development of more basic methods and more advanced nanoarchitectonics systems aiming towards practical applications. Specifically, the following sections will provide examples of (i) advancement in basics and methods, (ii) physico-chemical aspects and applications, (iii) bio-chemical aspects and applications, and (iv) bio-medical applications. It can be concluded that materials nanoarchitectonics based on layer-by-layer assembly is a useful method for assembling asymmetric structures and hierarchical organization, and is a powerful technique for developing functions through physical and chemical communication.
    Language English
    Publishing date 2024-02-20
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/d3cc04952c
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Influence of Nucleation on Relaxation, Molecular Cooperativity, and Physical Stability of Celecoxib Glass.

    Han, Xue / Dai, Kexin / Kawakami, Kohsaku

    Molecular pharmaceutics

    2024  Volume 21, Issue 4, Page(s) 1794–1803

    Abstract: Although nucleation is considered the first step in the crystallization of glass materials, the structure and properties of the nuclei are not understood well. Influence of nucleation on the structure and dynamics of celecoxib glass was evaluated in this ...

    Abstract Although nucleation is considered the first step in the crystallization of glass materials, the structure and properties of the nuclei are not understood well. Influence of nucleation on the structure and dynamics of celecoxib glass was evaluated in this study. The nuclei for Form III were induced by annealing the glass at freezing temperature, and their impact on the relaxation behavior was investigated using thermal analysis and broadband dielectric spectroscopy to find accelerated α relaxation and suppressed β relaxation. In addition, observed after nucleation was a decrease in cooperativity of the molecular motion, presumably because of the appearance of void spaces in the glass structure. During long-term isothermal crystallization studies, crystal growth to Form III was accelerated in the presence of the nuclei, whereas this effect was less remarkable when a different crystal form dominated the crystallization behavior. These observations should provide more detailed insights into the nucleation mechanism and impact of nucleation on molecular dynamics including physical stability of pharmaceutical glasses. In addition, discussed is the remarkable acceleration of the crystallization rate of the celecoxib glass just below its
    MeSH term(s) Celecoxib ; Crystallization/methods ; Cold Temperature ; Molecular Dynamics Simulation ; Glass/chemistry ; Calorimetry, Differential Scanning
    Chemical Substances Celecoxib (JCX84Q7J1L)
    Language English
    Publishing date 2024-02-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2138405-8
    ISSN 1543-8392 ; 1543-8384
    ISSN (online) 1543-8392
    ISSN 1543-8384
    DOI 10.1021/acs.molpharmaceut.3c01116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  8. Article ; Online: Ultraslow Cooling for the Stabilization of Pharmaceutical Glasses.

    Kawakami, Kohsaku

    The journal of physical chemistry. B

    2019  Volume 123, Issue 23, Page(s) 4996–5003

    Abstract: Stabilization technology of glass structures is of great interest in the field of pharmaceutical science, as it may prevent poorly soluble candidate compounds from dropping out of the pipeline. Cooling rate from the melt has been recognized as one ... ...

    Abstract Stabilization technology of glass structures is of great interest in the field of pharmaceutical science, as it may prevent poorly soluble candidate compounds from dropping out of the pipeline. Cooling rate from the melt has been recognized as one parameter to alter the energy state of the glass; however, the relationship between the physicochemical properties of glass and stabilization efficiency of the cooling rate has not been clarified yet. We have investigated the effect of cooling rate on the thermodynamic parameters of 13 pharmaceutical glasses, to find features of the compounds that are closely related to the stabilization efficiency. We have also analyzed the structural differences between slowly cooled and annealed glasses based on Fourier-transform infrared spectra and relaxation enthalpy. Although the degree of stabilization was lower for slowly cooled glasses compared to that for vapor-deposited ones, slow cooling was found to be a prominent method for producing stable glass and is applicable to bulk materials. In this observation, a strong correlation between fragility and the number of rotatable bonds was also found.
    MeSH term(s) Cold Temperature ; Drug Stability ; Glass/chemistry ; Pharmaceutical Preparations/chemistry
    Chemical Substances Pharmaceutical Preparations
    Language English
    Publishing date 2019-06-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1520-5207
    ISSN (online) 1520-5207
    DOI 10.1021/acs.jpcb.9b02122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Molecular machines working at interfaces: physics, chemistry, evolution and nanoarchitectonics.

    Ariga, Katsuhiko / Song, Jingwen / Kawakami, Kohsaku

    Physical chemistry chemical physics : PCCP

    2024  Volume 26, Issue 18, Page(s) 13532–13560

    Abstract: As a post-nanotechnology concept, nanoarchitectonics combines nanotechnology with advanced materials science. Molecular machines made by assembling molecular units and their organizational bodies are also products of nanoarchitectonics. They can be ... ...

    Abstract As a post-nanotechnology concept, nanoarchitectonics combines nanotechnology with advanced materials science. Molecular machines made by assembling molecular units and their organizational bodies are also products of nanoarchitectonics. They can be regarded as the smallest functional materials. Originally, studies on molecular machines analyzed the average properties of objects dispersed in solution by spectroscopic methods. Researchers' playgrounds partially shifted to solid interfaces, because high-resolution observation of molecular machines is usually done on solid interfaces under high vacuum and cryogenic conditions. Additionally, to ensure the practical applicability of molecular machines, operation under ambient conditions is necessary. The latter conditions are met in dynamic interfacial environments such as the surface of water at room temperature. According to these backgrounds, this review summarizes the trends of molecular machines that continue to evolve under the concept of nanoarchitectonics in interfacial environments. Some recent examples of molecular machines in solution are briefly introduced first, which is followed by an overview of studies of molecular machines and similar supramolecular structures in various interfacial environments. The interfacial environments are classified into (i) solid interfaces, (ii) liquid interfaces, and (iii) various material and biological interfaces. Molecular machines are expanding their activities from the static environment of a solid interface to the more dynamic environment of a liquid interface. Molecular machines change their field of activity while maintaining their basic functions and induce the accumulation of individual molecular machines into macroscopic physical properties molecular machines through macroscopic mechanical motions can be employed to control molecular machines. Moreover, research on molecular machines is not limited to solid and liquid interfaces; interfaces with living organisms are also crucial.
    Language English
    Publishing date 2024-05-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1476244-4
    ISSN 1463-9084 ; 1463-9076
    ISSN (online) 1463-9084
    ISSN 1463-9076
    DOI 10.1039/d4cp00724g
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Hydrocarbon Penetration into Phospholipid Monolayers Formed at Hydrocarbon-Water Interfaces.

    Kataoka-Hamai, Chiho / Kawakami, Kohsaku

    Langmuir : the ACS journal of surfaces and colloids

    2022  Volume 38, Issue 12, Page(s) 3720–3728

    Abstract: Phospholipid monolayers formed at oil-water interfaces are used for various biological applications. However, monolayer structures are not well understood. Herein, we investigated hydrocarbon partitioning in 1-palmitoyl-2-oleoyl- ...

    Abstract Phospholipid monolayers formed at oil-water interfaces are used for various biological applications. However, monolayer structures are not well understood. Herein, we investigated hydrocarbon partitioning in 1-palmitoyl-2-oleoyl-
    MeSH term(s) Hydrocarbons ; Phosphatidylcholines/chemistry ; Phospholipids/chemistry ; Surface Properties ; Water/chemistry
    Chemical Substances Hydrocarbons ; Phosphatidylcholines ; Phospholipids ; Water (059QF0KO0R)
    Language English
    Publishing date 2022-03-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2005937-1
    ISSN 1520-5827 ; 0743-7463
    ISSN (online) 1520-5827
    ISSN 0743-7463
    DOI 10.1021/acs.langmuir.1c03269
    Database MEDical Literature Analysis and Retrieval System OnLINE

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