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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

      105,621 Monthly downloads/views I 7.033 Impact Factor I 10.9 CiteScore I 1.22 Source Normalized Impact per Paper (SNIP) I 1.032 Scimago Journal & Country Rank (SJR)

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      Nanocrystal technology, drug delivery and clinical applications

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          Abstract

          Nanotechnology will affect our lives tremendously over the next decade in very different fields, including medicine and pharmacy. Transfer of materials into the nanodimension changes their physical properties which were used in pharmaceutics to develop a new innovative formulation principle for poorly soluble drugs: the drug nanocrystals. The drug nanocrystals do not belong to the future; the first products are already on the market. The industrially relevant production technologies, pearl milling and high pressure homogenization, are reviewed. The physics behind the drug nanocrystals and changes of their physical properties are discussed. The marketed products are presented and the special physical effects of nanocrystals explained which are utilized in each market product. Examples of products in the development pipelines (clinical phases) are presented and the benefits for in vivo administration of drug nanocrystals are summarized in an overview.

          Most cited references80

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          What is the true solubility advantage for amorphous pharmaceuticals?

          To evaluate the magnitude of the solubility advantage for amorphous pharmaceutical materials when compared to their crystalline counterparts. The thermal properties of several drugs in their amorphous and crystalline states were determined using differential scanning calorimetry. From these properties the solubility advantage for the amorphous form was predicted as a function of temperature using a simple thermodynamic analysis. These predictions were compared to the results of experimental measurements of the aqueous solubilities of the amorphous and crystalline forms of the drugs at several temperatures. By treating each amorphous drug as either an equilibrium supercooled liquid or a pseudo-equilibrium glass, the solubility advantage compared to the most stable crystalline form was predicted to be between 10 and 1,600 fold. The measured solubility advantage was usually considerably less than this, and for one compound studied in detail its temperature dependence was also less than predicted. It was calculated that even for partially amorphous materials the apparent solubility enhancement (theoretical or measured) is likely to influence in-vitro and in-vivo dissolution behavior. Amorphous pharmaceuticals are markedly more soluble than their crystalline counterparts, however, their experimental solubility advantage is typically less than that predicted from simple thermodynamic considerations. This appears to be the result of difficulties in determining the solubility of amorphous materials under true equilibrium conditions. Simple thermodynamic predictions can provide a useful indication of the theoretical maximum solubility advantage for amorphous pharmaceuticals, which directly reflects the driving force for their initial dissolution.
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            Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future.

            An increasing number of newly developed drugs are poorly soluble; in many cases drugs are poorly soluble in both aqueous and organic media excluding the traditional approaches of overcoming such solubility factors and resulting in bioavailability problems. An alternative and promising approach is the production of drug nanoparticles (i.e. nanosuspensions) to overcome these problems. The major advantages of this technology are its general applicability to most drugs and its simplicity. In this article, the production of nanoparticles on a laboratory scale is presented, special features such as increased saturation solubility and dissolution velocity are discussed, and special applications are highlighted, for example, mucoadhesive nanosuspensions for oral delivery and surface-modified drug nanoparticles for site-specific delivery to the brain. The possibilities of large scale production -- the prerequisite for the introduction of a delivery system to the market -- are also discussed.
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              THE RATE OF SOLUTION OF SOLID SUBSTANCES IN THEIR OWN SOLUTIONS.

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                Author and article information

                Journal
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                September 2008
                : 3
                : 3
                : 295-310
                Affiliations
                Department of Pharmaceutical Technology, Biotechnology and Quality Management, Free University of Berlin, Berlin, Germany
                Author notes
                Correspondence: Jens-Uwe A H, Junghanns, Department of Pharmaceutical, Technology, Biotechnology and Quality, Management, Free University of Berlin, Kelchstrasse 31, 12169 Berlin, Germany, Email juj@ 123456junghanns.net
                Article
                ijn-3-295
                10.2147/IJN.S595
                2626933
                18990939
                9d610a56-4042-4628-a4d4-54f5295c6347
                © 2008 Dove Medical Press Limited. All rights reserved
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                Molecular medicine
                dissocubes,pearl milling,high pressure homogenization,nanopure,saturation solubility,dissolution velocity,drug nanocrystals,nanocrystal,bioavailability enhancement

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