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      A Statistical Study on the Development of Metronidazole-Chitosan-Alginate Nanocomposite Formulation Using the Full Factorial Design

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          Abstract

          The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (2 1 × 3 1 × 2 1) × 3 = 36 full factorial design (FFD) to investigate the effect of chitosan and alginate polymer concentrations and calcium chloride (CaCl 2) concentration ondrug loading efficiency(LE), particle size and zeta potential. The concentration of CS, Alg and CaCl 2 were taken as independent variables, while drug loading, particle size and zeta potential were taken as dependent variables. The study showed that the loading efficiency and particle size depend on the CS, Alg and CaCl 2 concentrations, whereas zeta potential depends only on the Alg and CaCl 2 concentrations. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and in vitro drug release studies. XRD datashowed that the crystalline properties of MET changed to an amorphous-like pattern when the nanocomposites were formed.The XRD pattern of MET-CS-AlgNPs showed reflections at 2θ = 14.2° and 22.1°, indicating that the formation of the nanocompositesprepared at the optimum conditions havea mean diameter of (165±20) nm, with a MET loading of (46.0 ± 2.1)% and a zeta potential of (−9.2 ± 0.5) mV.The FTIR data of MET-CS-AlgNPs showed some bands of MET, such as 3283, 1585 and 1413 cm −1, confirming the presence of the drug in the MET-CS-AlgNPs nanocomposites. The TGA for the optimized sample of MET-CS-AlgNPs showed a 70.2% weight loss compared to 55.3% for CS-AlgNPs, and the difference is due to the incorporation of MET in the CS-AlgNPs for the formation of MET-CS-AlgNPs nanocomposites. The release of MET from the nanocomposite showed sustained-release properties, indicating the presence of an interaction between MET and the polymer. The nanocomposite shows a smooth surface and spherical shape. The release profile of MET from its MET-CS-AlgNPs nanocomposites was found to be governed by the second kinetic model ( R 2 between 0.956–0.990) with more than 90% release during the first 50 h, which suggests that the release of the MET drug can be extended or prolonged via the nanocomposite formulation.

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          Box-Behnken design: an alternative for the optimization of analytical methods.

          The present paper describes fundamentals, advantages and limitations of the Box-Behnken design (BBD) for the optimization of analytical methods. It establishes also a comparison between this design and composite central, three-level full factorial and Doehlert designs. A detailed study on factors and responses involved during the optimization of analytical systems is also presented. Functions developed for calculation of multiple responses are discussed, including the desirability function, which was proposed by Derringer and Suich in 1980. Concept and evaluation of robustness of analytical methods are also discussed. Finally, descriptions of applications of this technique for optimization of analytical methods are presented.
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            Polymer microspheres for controlled drug release.

            Polymer microspheres can be employed to deliver medication in a rate-controlled and sometimes targeted manner. Medication is released from a microsphere by drug leaching from the polymer or by degradation of the polymer matrix. Since the rate of drug release is controlled by these two factors, it is important to understand the physical and chemical properties of the releasing medium. This review presents the methods used in the preparation of microspheres from monomers or from linear polymers and discusses the physio-chemical properties that affect the formation, structure, and morphology of the spheres. Topics including the effects of molecular weight, blended spheres, crystallinity, drug distribution, porosity, and sphere size are discussed in relation to the characteristics of the release process. Added control over release profiles can be obtained by the employment of core-shell systems and pH-sensitive spheres; the enhancements presented by such systems are discussed through literature examples.
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              Thermal Analysis of Chitosan Based Networks

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                Author and article information

                Journal
                Polymers (Basel)
                Polymers (Basel)
                polymers
                Polymers
                MDPI
                2073-4360
                01 April 2020
                April 2020
                : 12
                : 4
                : 772
                Affiliations
                [1 ]Department of Basic Pharmaceutical Science, Faculty of Pharmacy, Isra University, Amman 11622, Jordan; hazem.sabbagh@ 123456yahoo.com (H.A.K.S.); Zead.abudayeh@ 123456iu.edu.jo (Z.A.); rami.ayoub@ 123456iu.edu.jo (R.A.); abudoleh81@ 123456gmail.com (S.M.A.)
                [2 ]Department of Chemistry, Faculty of Science, Isra University, Amman 11622, Jordan
                [3 ]Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, 43400UPM Serdang, Selangor, Malaysia
                Author notes
                [* ]Correspondence: samer.alali@ 123456iu.edu.jo (S.H.H.-A.-A.); mzobir@ 123456upm.edu.my (M.Z.H.)
                Author information
                https://orcid.org/0000-0002-0741-261X
                Article
                polymers-12-00772
                10.3390/polym12040772
                7240564
                32244671
                5d6aae5f-3471-4cb5-b850-be1572557d5b
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 February 2020
                : 22 March 2020
                Categories
                Article

                full factorial design,optimization,metronidazole,nanocomposites,sodium alginate,chitosan

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