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      Polymeric Nanoparticles for Increased Oral Bioavailability and Rapid Absorption Using Celecoxib as a Model of a Low-Solubility, High-Permeability Drug

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          ABSTRACT

          Purpose

          To demonstrate drug/polymer nanoparticles can increase the rate and extent of oral absorption of a low-solubility, high-permeability drug.

          Methods

          Amorphous drug/polymer nanoparticles containing celecoxib were prepared using ethyl cellulose and either sodium caseinate or bile salt. Nanoparticles were characterized using dynamic light scattering, transmission and scanning electron microscopy, and differential scanning calorimetry. Drug release and resuspension studies were performed using high-performance liquid chromatography. Pharmacokinetic studies were performed in dogs and humans.

          Results

          A physical model is presented describing the nanoparticle state of matter and release performance. Nanoparticles dosed orally in aqueous suspensions provided higher systemic exposure and faster attainment of peak plasma concentrations than commercial capsules, with median time to maximum drug concentration (Tmax) of 0.75 h in humans for nanoparticles vs. 3 h for commercial capsules. Nanoparticles released celecoxib rapidly and provided higher dissolved-drug concentrations than micronized crystalline drug. Nanoparticle suspensions are stable for several days and can be spray-dried to form dry powders that resuspend in water.

          Conclusions

          Drug/polymer nanoparticles are well suited for providing rapid oral absorption and increased bioavailability of BCS Class II drugs.

          Related collections

          Most cited references18

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          Drug-like properties and the causes of poor solubility and poor permeability.

          C Lipinski (2001)
          There are currently about 10000 drug-like compounds. These are sparsely, rather than uniformly, distributed through chemistry space. True diversity does not exist in experimental combinatorial chemistry screening libraries. Absorption, distribution, metabolism, and excretion (ADME) and chemical reactivity-related toxicity is low, while biological receptor activity is higher dimensional in chemistry space, and this is partly explainable by evolutionary pressures on ADME to deal with endobiotics and exobiotics. ADME is hard to predict for large data sets because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates. Currently, screening for biological receptor activity precedes or is concurrent with screening for properties related to "drugability." In the future, "drugability" screening may precede biological receptor activity screening. The level of permeability or solubility needed for oral absorption is related to potency. The relative importance of poor solubility and poor permeability towards the problem of poor oral absorption depends on the research approach used for lead generation. A "rational drug design" approach as exemplified by Merck advanced clinical candidates leads to time-dependent higher molecular weight, higher H-bonding properties, unchanged lipophilicity, and, hence, poorer permeability. A high throughput screening (HTS)-based approach as exemplified by unpublished data on Pfizer (Groton, CT) early candidates leads to higher molecular weight, unchanged H-bonding properties, higher lipophilicity, and, hence, poorer aqueous solubility.
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            Improving drug solubility for oral delivery using solid dispersions.

            C Leuner (2000)
            The solubility behaviour of drugs remains one of the most challenging aspects in formulation development. With the advent of combinatorial chemistry and high throughput screening, the number of poorly water soluble compounds has dramatically increased. Although solid solutions have tremendous potential for improving drug solubility, 40 years of research have resulted in only a few marketed products using this approach. With the introduction of new manufacturing technologies such as hot melt extrusion, it should be possible to overcome problems in scale-up and for this reason solid solutions are enjoying a renaissance. This article begins with an overview of the historical background and definitions of the various systems including eutectic mixtures, solid dispersions and solid solutions. The remainder of the article is devoted to the production, the different carriers and the methods used for the characterization of solid dispersions.
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              • Record: found
              • Abstract: not found
              • Article: not found

              Amorphous pharmaceutical solids: preparation, characterization and stabilization.

              Lian Yu (2001)
              The importance of amorphous pharmaceutical solids lies in their useful properties, common occurrence, and physicochemical instability relative to corresponding crystals. Some pharmaceuticals and excipients have a tendency to exist as amorphous solids, while others require deliberate prevention of crystallization to enter and remain in the amorphous state. Amorphous solids can be produced by common pharmaceutical processes, including melt quenching, freeze- and spray-drying, milling, wet granulation, and drying of solvated crystals. The characterization of amorphous solids reveals their structures, thermodynamic properties, and changes (crystallization and structural relaxation) in single- and multi-component systems. Current research in the stabilization of amorphous solids focuses on: (i) the stabilization of labile substances (e.g., proteins and peptides) during processing and storage using additives, (ii) the prevention of crystallization of the excipients that must remain amorphous for their intended functions, and (iii) the selection of appropriate storage conditions under which amorphous solids are stable.
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                Author and article information

                Contributors
                mike.morgen@bendresearch.com
                Journal
                Pharm Res
                Pharmaceutical Research
                Springer US (Boston )
                0724-8741
                1573-904X
                24 August 2011
                24 August 2011
                February 2012
                : 29
                : 2
                : 427-440
                Affiliations
                [1 ]Bend Research Inc., 64550 Research Road, Bend, Oregon 97701 USA
                [2 ]Clinical Pharmacology, Pfizer Oncology, New York, New York 10017 USA
                [3 ]Pharmacokinetics, Dynamics & Metabolism, Pfizer Worldwide Research & Development, Groton, Connecticut 06340 USA
                [4 ]Pharmaceutical Sciences, Pfizer Worldwide Research & Development, Groton, Connecticut 06340 USA
                Article
                558
                10.1007/s11095-011-0558-7
                3264876
                21863477
                07ced027-e364-4e10-a731-e7b8342c0bc9
                © The Author(s) 2011
                History
                : 12 May 2011
                : 2 August 2011
                Categories
                Research Paper
                Custom metadata
                © Springer Science+Business Media, LLC 2012

                Pharmacology & Pharmaceutical medicine
                ethyl cellulose,rapid absorption,nanoparticles,celecoxib,bioavailability

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