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      Evaluation of the Release Kinetics of a Pharmacologically Active Substance from Model Intra-Articular Implants Replacing the Cruciate Ligaments of the Knee

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          Abstract

          Implants are readily applied as a convenient method of therapy. There is great interest in the prolonged release of active substances from implants. The objective of this work was to evaluate the dissolution kinetics of steroidal anti-inflammatory preparation (SAP) released from novel implants, and to test the influence of the technology on SAP release kinetics. The proposed long-acting preparations may overcome difficulties resulting from repeated injections and often visits to ambulatory clinic, as the stabilizing function of the artificial ligament would be enriched with pharmacological activity. The potential advantages provided by the new coatings of knee implants include the continuous, sustained, and prolonged release of an active substance. The study was carried out using a modified United States Pharmacopoeia (USP) apparatus 4. The amount of SAP was measured spectroscopically. It was revealed that the transport of the drug was mainly a diffusion process. The drug release kinetics was analyzed using zero-, first-, and second-order kinetics as well as Korsmeyer-Peppas, Higuchi, and Hixon-Crowell models. The highest values of the release rate constants were k 0 = (7.49 ± 0.05) × 10 −5 mg × min −1, k 1 = (6.93 ± 0.05) × 10 −6 min −1, and k 2 = (7.70 ± 0.05) × 10 −7 mg −1 × min −1 as calculated according to zero-, first-, and second-order kinetics equations, respectively. The values of the rate constants obtained for the slowest process were k 0 = (3.63 ± 0.06) × 10 −5 mg × min −1, k 1 = (2.50 ± 0.03) × 10 −6 min −1, and k 2 = (2.80 ± 0.03) × 10 −7 mg −1 × min −1. They may suggest the possibility of sustained release of betamethasone from the system. Due to the statistical analysis, differences were observed between most of the studied implants. Incubation, temperature, time of stabilization of layers, and the method of SAP deposition on the matrix affected the drug release.

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          Mechanisms of solute release from porous hydrophilic polymers

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            Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC).

            The objective of this article is to review the spectrum of mathematical models that have been developed to describe drug release from hydroxypropyl methylcellulose (HPMC)-based pharmaceutical devices. The major advantages of these models are: (i) the elucidation of the underlying mass transport mechanisms; and (ii) the possibility to predict the effect of the device design parameters (e.g., shape, size and composition of HPMC-based matrix tablets) on the resulting drug release rate, thus facilitating the development of new pharmaceutical products. Simple empirical or semi-empirical models such as the classical Higuchi equation and the so-called power law, as well as more complex mechanistic theories that consider diffusion, swelling and dissolution processes simultaneously are presented, and their advantages and limitations are discussed. Various examples of practical applications to experimental drug release data are given. The choice of the appropriate mathematical model when developing new pharmaceutical products or elucidating drug release mechanisms strongly depends on the desired or required predictive ability and accuracy of the model. In many cases, the use of a simple empirical or semi-empirical model is fully sufficient. However, when reliable, detailed information are required, more complex, mechanistic theories must be applied. The present article is a comprehensive review of the current state of the art of mathematical modeling drug release from HPMC-based delivery systems and discusses the crucial points of the most important theories.
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              Synovitis in osteoarthritis: current understanding with therapeutic implications

              Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage, subchondral bone and (increasingly recognized) inflammation of the synovium. The synovium may show significant changes, even before visible cartilage degeneration has occurred, with infiltration of mononuclear cells, thickening of the synovial lining layer and production of inflammatory cytokines. The combination of sensitive imaging modalities and tissue examination has confirmed a high prevalence of synovial inflammation in all stages of OA, with a number of studies demonstrating that synovitis is related to pain, poor function and may even be an independent driver of radiographic OA onset and structural progression. Treating key aspects of synovial inflammation therefore holds great promise for analgesia and also for structure modification. This article will review current knowledge on the prevalence of synovitis in OA and its role in symptoms and structural progression, and explore lessons learnt from targeting synovitis therapeutically.
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                Author and article information

                Journal
                Materials (Basel)
                Materials (Basel)
                materials
                Materials
                MDPI
                1996-1944
                12 April 2019
                April 2019
                : 12
                : 8
                : 1202
                Affiliations
                [1 ]Department of Physical Chemistry, Faculty of Pharmacy, Wroclaw Medical University, ul. Borowska 211A, 55-556 Wroclaw, Poland; dorota.wojcik-pastuszka@ 123456umed.wroc.pl (D.W.-P.); bartosz.macikowski@ 123456gmail.com (B.M.); ryszard.berkowski@ 123456umed.wroc.pl (R.B.)
                [2 ]Department of Mechanics, Materials Science and Engineering, Faculty of Mechanical Engineering, Wroclaw University of Science and Technology, ul. Smoluchowskiego 25, 50-370 Wrocław, Poland; justyna.krzak@ 123456pwr.edu.pl
                [3 ]Department and Clinic of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, pl. Grunwaldzki 51, 50-366 Wroclaw, Poland; vetscidr@ 123456gmail.com
                Author notes
                [* ]Correspondence: witold.musial@ 123456umed.wroc.pl ; Tel.: +48-71-78-40231
                Author information
                https://orcid.org/0000-0002-4834-1125
                https://orcid.org/0000-0002-1525-5589
                https://orcid.org/0000-0002-3025-586X
                https://orcid.org/0000-0002-2970-6205
                https://orcid.org/0000-0001-5695-5998
                Article
                materials-12-01202
                10.3390/ma12081202
                6515312
                31013801
                5bfa4436-45f2-4cd3-ad72-bed5ca722108
                © 2019 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
                : 07 March 2019
                : 09 April 2019
                Categories
                Article

                betamethasone,implants,ligaments,drug release,kinetics
                betamethasone, implants, ligaments, drug release, kinetics

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