Simvastatin dengan Senyawa Turunan Β-Siklodextrin
Abstract
This study aims to determine the profile of the inclusion complex formed between simvastatin and β-cyclodextrin and its derivatives. To determine the level of stability and determine the solubility level of the inclusion complex formed between simvastatin and β-cyclodextrin and its derivatives (2-hydroxypropyl-β-cyclodextrin and 2,6-di-O-methyl-β-cyclodextrin) in water solvent.The method used is qualitative descriptive using the molecular docking method, modeling and anchoring the inclusion complex model.The research results show that the simvastatin/HP-β-CD inclusion complex has a higher level of solubility in water solvents compared to the simvastatin/β-CD and simvastatin/DM-β-CD inclusion complexes, with a ΔGsolvation value of -1032.34 kJ/mol.Conclusion: Simvastatin is able to bind to the cavity of 2-hydroxypropyl-β-cyclodextrin, 2,6-di-O-methyl-β-cyclodextrin, and simvastatin/β-cyclodextrin with the following order of bond strength: simvastatin/2-hydroxypropyl-β -cyclodextrin > simvastatin/2,6-di-O-methyl-β-cyclodextrin > simvastatin/β-cyclodextrin.
Keywords: Inclusion Complex, Molecular Docking, Molecular Dynamics Simulation, Β-Cyclodextrin, Simvastatin.
References
Alshehri, S., Imam, S. S., Hussain, A., Altamimi, M. A., Alruwaili, N. K., Alotaibi, F., ... & Shakeel, F. (2020). Retracted Article: Potential of Solid Dispersions to Enhance Solubility, Bioavailability, and Therapeutic Efficacy of Poorly Water-Soluble Drugs: Newer Formulation Techniques, Current Marketed Scenario and Patents. Drug delivery, 27(1), 1625-1643. https://doi.org/10.1080/10717544.2020.1846638.
Bartkowiak, A., Matyszewska, D., Krzak, A., Zaborowska, M., Broniatowski, M., & Bilewicz, R. (2021). Incorporation of Simvastatin Into Lipid Membranes: Why Deliver A Statin in form of Inclusion Complex with Hydrophilic Cyclodextrin. Colloids and Surfaces B: Biointerfaces, 204, 111784.https://doi.org/10.1016/j.colsurfb.2021.111784.
Chen, S. L., & Chen, K. L. (2023). The Mediating Impact of Innovation Types in the Relationship between Innovation Use Theory and Market Performance. Stats, 7(1), 1-22. https://doi.org/10.3390/stats7010001
Cid-Samamed, A., Rakmai, J., Mejuto, J. C., Simal-Gandara, J., & Astray, G. (2022). Cyclodextrins Inclusion Complex: Preparation Methods, Analytical Techniques and Food Industry Applications. Food Chemistry, 384, 132467. https://doi.org/https://doi.org/10.1016/j.foodchem.2022.132467.
Faris, T. M., Harisa, G. I., Alanazi, F. K., Samy, A. M., & Nasr, F. A. (2020). Developed Simvastatin Chitosan Nanoparticles Co-Crosslinked With Tripolyphosphate and Chondroitin Sulfate for ASGPR-Mediated Targeted HCC Delivery with Enhanced Oral Bioavailability. Saudi Pharmaceutical Journal, 28(12), 1851-1867. https://doi.org/10.1016/j.jsps.2020.11.012.
Gu, F., Ning, J., Fan, H., Wu, C., & Wang, Y. (2018). Preparation and Characterization of Simvastatin/Dmβcd Complex and Its Pharmacokinetics in Rats. Acta pharmaceutica, 68(2), 145-157. https://doi.org/10.2478/acph-2018-0016.
Huang, Y., Quan, P., Wang, Y., Zhang, D., Zhang, M., Li, R., & Jiang, N. (2017). Host-Guest Interaction of Β-Cyclodextrin with Isomeric Ursolic Acid and Oleanolic Acid: Physicochemical Characterization and Molecular Modeling Study. Journal of biomedical research, 31(5), 395.. https://doi.org/10.7555/JBR.31.20160073.
Kaliyadan, F., & Kulkarni, V. (2019). Types of Variables, Descriptive Statistics, and Sample Size. Indian dermatology online journal, 10(1), 82-86. https://doi.org/10.4103/idoj.IDOJ_468_18.
Kumar, R. (2019). Nanotechnology Based Approaches to Enhance Aqueous Solubility And Bioavailability of Griseofulvin: A Literature Survey. Journal of Drug Delivery Science and Technology, 53, 101221. https://doi.org/https://doi.org/10.1016/j.jddst.2019.101221
Lipovetsky, S. (2023). Equation of Finite Change and Structural Analysis of Mean Value. Axioms, 12(10), 962. https://doi.org/10.3390/axioms12100962
Mady, F. M., & Farghaly Aly, U. (2017). Experimental, Molecular Docking Investigations and Bioavailability Study on the Inclusion Complexes of Finasteride and Cyclodextrins. Drug design, development and therapy, 1681-1692.. https://doi.org/10.2147/DDDT.S135084.
Mahboobian, M. M., Dadashzadeh, S., Rezaei, M., Mohammadi, M., & Bolourchian, N. (2022). Simvastatin in Ternary Solid Dispersion Formulations: Improved in Vitro Dissolution and Anti-Hyperlipidemia Efficiency. Journal of Drug Delivery Science and Technology, 74, 103571.. https://doi.org/https://doi.org/10.1016/j.jddst.2022.103571.
Marrink, S. J. (2018). Computational Modeling of Realistic Cell Membranes. Biophysical Journal, 114(3), 367a. https://doi.org/10.1021/acs.chemrev.8b00460.
Meola, T. R., Abuhelwa, A. Y., Joyce, P., Clifton, P., & Prestidge, C. A. (2021). A Safety, Tolerability, and Pharmacokinetic Study of A Novel Simvastatin Silica-Lipid Hybrid Formulation in Healthy Male Participants. Drug delivery and translational research, 11, 1261-1272. https://doi.org/10.1007/s13346-020-00853-x.
Moon, S. J., Lee, S., Jang, K., Yu, K. S., Yim, S. V., & Kim, B. H. (2017). Comparative Pharmacokinetic and Tolerability Evaluation of Two Simvastatin 20 Mg Formulations in Healthy Korean Male Volunteers. Translational and Clinical Pharmacology, 25(1), 10. https://doi.org/10.12793/tcp.2017.25.1.10.
Nurhidayah, E. S., Ivansyah, A. L., Martoprawiro, M. A., & Zulfikar, M. A. (2018, May). A Molecular Docking Study to Predict Enantioseparation of Some Chiral Carboxylic Acid Derivatives by Methyl-Β-Cyclodextrin. In Journal of Physics: Conference Series (Vol. 1013, No. 1, p. 012203). IOP Publishing. Available: https://api.semanticscholar.org/CorpusID:104231823.
Ramyasree, J., Hindustan, A. A., Chinthaguinjala, H., Reshma, T. C., Venkata, H. V. Y., & Bharath, K. (2020). Solubility Enhancement of Drugs with Aid of Surfactants: Research Done Since Last Two Decades. Int J Pharma Bio Sci, 10(5), 11-16. https://doi.org/10.22376/ijpbs/lpr.2020.10.5.p11-16.
Rudrangi, S. R. S., Bhomia, R., Trivedi, V., Vine, G. J., Mitchell, J. C., Alexander, B. D., & Wicks, S. R. (2015). Influence of the Preparation Method on the Physicochemical Properties of Indomethacin and Methyl-Β-Cyclodextrin Complexes. International journal of pharmaceutics, 479(2), 381-390. https://doi.org/10.1016/j.ijpharm.2015.01.010.
Varan, G., Varan, C., Erdoğar, N., Hıncal, A. A., & Bilensoy, E. (2017). Amphiphilic Cyclodextrin Nanoparticles. International journal of pharmaceutics, 531(2), 457-469. https://doi.org/10.1016/j.ijpharm.2017.06.010.
Wüpper, S., Lüersen, K., & Rimbach, G. (2021). Cyclodextrins, Natural Compounds, and Plant Bioactives—A Nutritional Perspective. Biomolecules, 11(3), 401. https://doi.org/10.3390/biom11030401.
Yadav, K. S., Soni, G., Choudhary, D., Khanduri, A., Bhandari, A., & Joshi, G. (2023). Microemulsions for Enhancing Drug Delivery of Hydrophilic Drugs: Exploring Various Routes of Administration. Medicine in Drug Discovery, 100162. https://doi.org/https://doi.org/10.1016/j.medidd.2023.100162.
Bartkowiak, A., Matyszewska, D., Krzak, A., Zaborowska, M., Broniatowski, M., & Bilewicz, R. (2021). Incorporation of Simvastatin Into Lipid Membranes: Why Deliver A Statin in form of Inclusion Complex with Hydrophilic Cyclodextrin. Colloids and Surfaces B: Biointerfaces, 204, 111784.https://doi.org/10.1016/j.colsurfb.2021.111784.
Chen, S. L., & Chen, K. L. (2023). The Mediating Impact of Innovation Types in the Relationship between Innovation Use Theory and Market Performance. Stats, 7(1), 1-22. https://doi.org/10.3390/stats7010001
Cid-Samamed, A., Rakmai, J., Mejuto, J. C., Simal-Gandara, J., & Astray, G. (2022). Cyclodextrins Inclusion Complex: Preparation Methods, Analytical Techniques and Food Industry Applications. Food Chemistry, 384, 132467. https://doi.org/https://doi.org/10.1016/j.foodchem.2022.132467.
Faris, T. M., Harisa, G. I., Alanazi, F. K., Samy, A. M., & Nasr, F. A. (2020). Developed Simvastatin Chitosan Nanoparticles Co-Crosslinked With Tripolyphosphate and Chondroitin Sulfate for ASGPR-Mediated Targeted HCC Delivery with Enhanced Oral Bioavailability. Saudi Pharmaceutical Journal, 28(12), 1851-1867. https://doi.org/10.1016/j.jsps.2020.11.012.
Gu, F., Ning, J., Fan, H., Wu, C., & Wang, Y. (2018). Preparation and Characterization of Simvastatin/Dmβcd Complex and Its Pharmacokinetics in Rats. Acta pharmaceutica, 68(2), 145-157. https://doi.org/10.2478/acph-2018-0016.
Huang, Y., Quan, P., Wang, Y., Zhang, D., Zhang, M., Li, R., & Jiang, N. (2017). Host-Guest Interaction of Β-Cyclodextrin with Isomeric Ursolic Acid and Oleanolic Acid: Physicochemical Characterization and Molecular Modeling Study. Journal of biomedical research, 31(5), 395.. https://doi.org/10.7555/JBR.31.20160073.
Kaliyadan, F., & Kulkarni, V. (2019). Types of Variables, Descriptive Statistics, and Sample Size. Indian dermatology online journal, 10(1), 82-86. https://doi.org/10.4103/idoj.IDOJ_468_18.
Kumar, R. (2019). Nanotechnology Based Approaches to Enhance Aqueous Solubility And Bioavailability of Griseofulvin: A Literature Survey. Journal of Drug Delivery Science and Technology, 53, 101221. https://doi.org/https://doi.org/10.1016/j.jddst.2019.101221
Lipovetsky, S. (2023). Equation of Finite Change and Structural Analysis of Mean Value. Axioms, 12(10), 962. https://doi.org/10.3390/axioms12100962
Mady, F. M., & Farghaly Aly, U. (2017). Experimental, Molecular Docking Investigations and Bioavailability Study on the Inclusion Complexes of Finasteride and Cyclodextrins. Drug design, development and therapy, 1681-1692.. https://doi.org/10.2147/DDDT.S135084.
Mahboobian, M. M., Dadashzadeh, S., Rezaei, M., Mohammadi, M., & Bolourchian, N. (2022). Simvastatin in Ternary Solid Dispersion Formulations: Improved in Vitro Dissolution and Anti-Hyperlipidemia Efficiency. Journal of Drug Delivery Science and Technology, 74, 103571.. https://doi.org/https://doi.org/10.1016/j.jddst.2022.103571.
Marrink, S. J. (2018). Computational Modeling of Realistic Cell Membranes. Biophysical Journal, 114(3), 367a. https://doi.org/10.1021/acs.chemrev.8b00460.
Meola, T. R., Abuhelwa, A. Y., Joyce, P., Clifton, P., & Prestidge, C. A. (2021). A Safety, Tolerability, and Pharmacokinetic Study of A Novel Simvastatin Silica-Lipid Hybrid Formulation in Healthy Male Participants. Drug delivery and translational research, 11, 1261-1272. https://doi.org/10.1007/s13346-020-00853-x.
Moon, S. J., Lee, S., Jang, K., Yu, K. S., Yim, S. V., & Kim, B. H. (2017). Comparative Pharmacokinetic and Tolerability Evaluation of Two Simvastatin 20 Mg Formulations in Healthy Korean Male Volunteers. Translational and Clinical Pharmacology, 25(1), 10. https://doi.org/10.12793/tcp.2017.25.1.10.
Nurhidayah, E. S., Ivansyah, A. L., Martoprawiro, M. A., & Zulfikar, M. A. (2018, May). A Molecular Docking Study to Predict Enantioseparation of Some Chiral Carboxylic Acid Derivatives by Methyl-Β-Cyclodextrin. In Journal of Physics: Conference Series (Vol. 1013, No. 1, p. 012203). IOP Publishing. Available: https://api.semanticscholar.org/CorpusID:104231823.
Ramyasree, J., Hindustan, A. A., Chinthaguinjala, H., Reshma, T. C., Venkata, H. V. Y., & Bharath, K. (2020). Solubility Enhancement of Drugs with Aid of Surfactants: Research Done Since Last Two Decades. Int J Pharma Bio Sci, 10(5), 11-16. https://doi.org/10.22376/ijpbs/lpr.2020.10.5.p11-16.
Rudrangi, S. R. S., Bhomia, R., Trivedi, V., Vine, G. J., Mitchell, J. C., Alexander, B. D., & Wicks, S. R. (2015). Influence of the Preparation Method on the Physicochemical Properties of Indomethacin and Methyl-Β-Cyclodextrin Complexes. International journal of pharmaceutics, 479(2), 381-390. https://doi.org/10.1016/j.ijpharm.2015.01.010.
Varan, G., Varan, C., Erdoğar, N., Hıncal, A. A., & Bilensoy, E. (2017). Amphiphilic Cyclodextrin Nanoparticles. International journal of pharmaceutics, 531(2), 457-469. https://doi.org/10.1016/j.ijpharm.2017.06.010.
Wüpper, S., Lüersen, K., & Rimbach, G. (2021). Cyclodextrins, Natural Compounds, and Plant Bioactives—A Nutritional Perspective. Biomolecules, 11(3), 401. https://doi.org/10.3390/biom11030401.
Yadav, K. S., Soni, G., Choudhary, D., Khanduri, A., Bhandari, A., & Joshi, G. (2023). Microemulsions for Enhancing Drug Delivery of Hydrophilic Drugs: Exploring Various Routes of Administration. Medicine in Drug Discovery, 100162. https://doi.org/https://doi.org/10.1016/j.medidd.2023.100162.
Published
2024-05-19
Section
Articles
Copyright (c) 2024 Devina Wahyu Astaning Cristy, Nuraini Harmastuti, Mardiyono Mardiyono
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