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Elucidation of the Controlled-Release Behavior of Metoprolol Succinate from Directly Compressed Xanthan Gum/Chitosan Polymers: Computational and Experimental Studies.
ACS Biomater Sci Eng. 2020 01 13; 6(1):21-37.AB

Abstract

The development and evaluation of a controlled-release (CR) pharmaceutical solid dosage form comprising xanthan gum (XG), low molecular weight chitosan (LCS), and metoprolol succinate (MS) are reported. The research is, partly, based upon the utilization of computational tools: in this case, molecular dynamics simulations (MDs) and the response surface method (RSM) in order to underpin the design/prediction and to minimize the experimental work required to achieve the desired pharmaceutical outcomes. The capability of the system to control the release of MS was studied as a function of LCS (% w/w) and total polymer (LCS and xanthan gum (XG)) to drug ratio (P/D) at different tablet tensile strengths. MDs trajectories, obtained by using different ratios of XG/LCS as well as XG and high molecular weight chitosan (HCS), showed that the driving force for the interaction between XG and LCS is electrostatic in nature, the most favorable complex is formed when LCS is used at 15% (w/w) and, importantly, the interaction between XG and LCS is more favorable than that between XG and HCS. RSM outputs revealed that the release of the drug from the LCS/XG matrix is highly dependent on both the % LCS and the P/D ratio and that the required CR effect can be achieved when using weight fractions of LCS ≤ 20% and P/D ratios ≥2.6:1. Results obtained from in vitro drug release and swelling studies on the prepared tablets showed that using LCS at the weight fractions suggested by MDs and RSM data plays a major role in overcoming the high sensitivity of the controlled drug release effect of XG on ionic strength and pH changes of the dissolution media. In addition, it was found that polymer relaxation is the major contributor to the release of MS from LCS/XG tablets. Using Raman spectroscopy, MS was shown to be localized more in the core of the tablets at the initial stages of dissolution due to film formation between LCS and XG on the tablet surface, which prevents excess water penetration into the matrix. In the later stages of the dissolution process, the film starts to dissolve/erode, allowing full tablet hydration and a uniform drug distribution in the swollen tablet.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Dadou SM
Department of Pharmaceutical, Chemical & Environmental Science, Faculty of Engineering & Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, United Kingdom.
El-Barghouthi MI
Department of Chemistry, The Hashemite University, P.O. Box 150459, Zarqa 13115, Jordan. Department of Chemistry, Isra University, Amman 11622, Jordan.
Antonijevic MD
Department of Pharmaceutical, Chemical & Environmental Science, Faculty of Engineering & Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, United Kingdom.
Chowdhry BZ
Department of Pharmaceutical, Chemical & Environmental Science, Faculty of Engineering & Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, United Kingdom.
Badwan AA
Research and Innovation Centre, The Jordanian Pharmaceutical Manufacturing Company (PLC), P.O. Box 94, Naor 11710, Jordan.

MeSH

Chemistry, PharmaceuticalChitosanDelayed-Action PreparationsMetoprololPolymersPolysaccharides, Bacterial

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33463201

Citation

Dadou, Suha M., et al. "Elucidation of the Controlled-Release Behavior of Metoprolol Succinate From Directly Compressed Xanthan Gum/Chitosan Polymers: Computational and Experimental Studies." ACS Biomaterials Science & Engineering, vol. 6, no. 1, 2020, pp. 21-37.
Dadou SM, El-Barghouthi MI, Antonijevic MD, et al. Elucidation of the Controlled-Release Behavior of Metoprolol Succinate from Directly Compressed Xanthan Gum/Chitosan Polymers: Computational and Experimental Studies. ACS Biomater Sci Eng. 2020;6(1):21-37.
Dadou, S. M., El-Barghouthi, M. I., Antonijevic, M. D., Chowdhry, B. Z., & Badwan, A. A. (2020). Elucidation of the Controlled-Release Behavior of Metoprolol Succinate from Directly Compressed Xanthan Gum/Chitosan Polymers: Computational and Experimental Studies. ACS Biomaterials Science & Engineering, 6(1), 21-37. https://doi.org/10.1021/acsbiomaterials.8b01028
Dadou SM, et al. Elucidation of the Controlled-Release Behavior of Metoprolol Succinate From Directly Compressed Xanthan Gum/Chitosan Polymers: Computational and Experimental Studies. ACS Biomater Sci Eng. 2020 01 13;6(1):21-37. PubMed PMID: 33463201.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elucidation of the Controlled-Release Behavior of Metoprolol Succinate from Directly Compressed Xanthan Gum/Chitosan Polymers: Computational and Experimental Studies. AU - Dadou,Suha M, AU - El-Barghouthi,Musa I, AU - Antonijevic,Milan D, AU - Chowdhry,Babur Z, AU - Badwan,Adnan A, Y1 - 2019/03/28/ PY - 2021/1/19/entrez PY - 2021/1/20/pubmed PY - 2021/4/29/medline KW - Raman mapping KW - controlled-release polymeric matrixes KW - low molecular weight chitosan KW - metoprolol succinate KW - molecular dynamics simulations KW - pharmaceutical formulation KW - response surface method KW - tablet swelling KW - xanthan gum SP - 21 EP - 37 JF - ACS biomaterials science & engineering JO - ACS Biomater Sci Eng VL - 6 IS - 1 N2 - The development and evaluation of a controlled-release (CR) pharmaceutical solid dosage form comprising xanthan gum (XG), low molecular weight chitosan (LCS), and metoprolol succinate (MS) are reported. The research is, partly, based upon the utilization of computational tools: in this case, molecular dynamics simulations (MDs) and the response surface method (RSM) in order to underpin the design/prediction and to minimize the experimental work required to achieve the desired pharmaceutical outcomes. The capability of the system to control the release of MS was studied as a function of LCS (% w/w) and total polymer (LCS and xanthan gum (XG)) to drug ratio (P/D) at different tablet tensile strengths. MDs trajectories, obtained by using different ratios of XG/LCS as well as XG and high molecular weight chitosan (HCS), showed that the driving force for the interaction between XG and LCS is electrostatic in nature, the most favorable complex is formed when LCS is used at 15% (w/w) and, importantly, the interaction between XG and LCS is more favorable than that between XG and HCS. RSM outputs revealed that the release of the drug from the LCS/XG matrix is highly dependent on both the % LCS and the P/D ratio and that the required CR effect can be achieved when using weight fractions of LCS ≤ 20% and P/D ratios ≥2.6:1. Results obtained from in vitro drug release and swelling studies on the prepared tablets showed that using LCS at the weight fractions suggested by MDs and RSM data plays a major role in overcoming the high sensitivity of the controlled drug release effect of XG on ionic strength and pH changes of the dissolution media. In addition, it was found that polymer relaxation is the major contributor to the release of MS from LCS/XG tablets. Using Raman spectroscopy, MS was shown to be localized more in the core of the tablets at the initial stages of dissolution due to film formation between LCS and XG on the tablet surface, which prevents excess water penetration into the matrix. In the later stages of the dissolution process, the film starts to dissolve/erode, allowing full tablet hydration and a uniform drug distribution in the swollen tablet. SN - 2373-9878 UR - https://www.unboundmedicine.com/medline/citation/33463201/Elucidation_of_the_Controlled_Release_Behavior_of_Metoprolol_Succinate_from_Directly_Compressed_Xanthan_Gum/Chitosan_Polymers:_Computational_and_Experimental_Studies_ DB - PRIME DP - Unbound Medicine ER -