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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

In vitro Modified Release Studies on Melatoninergic Fluorinated Phenylalkylamides: Circumventing their Lipophilicity for Oral Administration

Author(s): Marilena Vlachou*, Angeliki Siamidi, Chrystalla Protopapa, Michalis Vlachos, Sophia Kloutsou, Chrysoula-Christina Dreliozi and Ioannis P. Papanastasiou

Volume 30, Issue 18, 2024

Published on: 09 April, 2024

Page: [1433 - 1441] Pages: 9

DOI: 10.2174/0113816128304967240328065809

Abstract

Introduction: In an attempt to circumvent the lipophilicity burden for the oral administration of new potent synthetic melatoninergic fluorine-substituted methoxyphenylalkyl amides, we conducted in vitro modified release studies using carefully selected matrix tablets’ biopolymeric materials in different ratios.

Methods: In particular, we sought to attain release profiles of these analogues similar to that of the parent compound, the chronobiotic hormone Melatonin (MLT), and also of the commercially available drug, Circadin®.

Results: It was found that some of these systems, albeit being more lipophilic than MLT, mimic the in vitro release patterns of melatonin and Circadin®.

Conclusion: Moreover, a number of these derivatives were proven suitable for dealing with sleep onset problems, whilst others for dealing with combined sleep onset/sleep maintenance dysfunctions.

Keywords: Melatonin, synthetic melatoninergic analogues, lipophilicity, matrix tablets, in vitro dissolution studies, oral administration.

« Previous Next »
[1]
Reppart SM, Weaver DR, Godson C. Melatonin receptors step into the light: Cloning and classification of subtypes. Trends Pharmacol Sci 1996; 17(3): 100-2.
[http://dx.doi.org/10.1016/0165-6147(96)10005-5 ] [PMID: 8936344]
[2]
Tarocco A, Caroccia N, Morciano G, et al. Melatonin as a master regulator of cell death and inflammation: Molecular mechanisms and clinical implications for newborn care. Cell Death Dis 2019; 10(4): 317.
[http://dx.doi.org/10.1038/s41419-019-1556-7] [PMID: 30962427]
[3]
Jaworek AK, Szepietowski JC, Hałubiec P, Wojas-Pelc A, Jaworek J. Melatonin as an antioxidant and immunomodulator in atopic dermatitis A new look on an old story: A review. Antioxidants 2021; 10(8): 1179.
[http://dx.doi.org/10.3390/antiox10081179] [PMID: 34439427]
[4]
Morgan PJ, Barrett P, Howell HE, Helliwell R. Melatonin receptors: Localization, molecular pharmacology and physiological significance. Neurochem Int 1994; 24(2): 101-46.
[http://dx.doi.org/10.1016/0197-0186(94)90100-7 ] [PMID: 8161940]
[5]
Tsotinis A, Afroudakis PA, Davidson K, Prashar A, Sugden D. Design, synthesis, and melatoninergic activity of new azido and isothiocyanato-substituted indoles. J Med Chem 2007; 50(25): 6436-40.
[http://dx.doi.org/10.1021/jm7010723] [PMID: 17988084]
[6]
Tsotinis A, Afroudakis PA, Papanastasiou IP, et al. Mapping the melatonin receptor 8. Selective MT2 agonists derived from 5,6‐Dihydroindolo[2,1‐a]isoquinolines and related systems. ChemMedChem 2022; 17(12): e202200129.
[http://dx.doi.org/10.1002/cmdc.202200129] [PMID: 35478275]
[7]
Vlachou M, Siamidi A, Dedeloudi A, Konstantinidou S, Papanastasiou I. Pineal hormone melatonin as an adjuvant treatment for COVID-19 (Review). Int J Mol Med 2021; 47(4): 47.
[http://dx.doi.org/10.3892/ijmm.2021.4880] [PMID: 33576451]
[8]
Vlachou M, Siamidi A, Anagnostopoulou D, Christodoulou E, Bikiaris ND. Modified release of the pineal hormone melatonin from matrix tablets containing poly(L-lactic acid) and its PLA-co-PEAd and PLA-co-PBAd copolymers. Polymersfpage 2022; 14(8): 1504.
[http://dx.doi.org/10.3390/polym14081504] [PMID: 35458252]
[9]
Kumar A, Agarwal SP, Khanna R. Modified release bi-layered tablet of melatonin using beta-cyclodextrin. Pharmazie 2003; 58(9): 642-4.
[PMID: 14531461]
[10]
Vlachou M, Siamidi A, Anagnostopoulou D, et al. Potent lipophilic Melatoninergic x-fluoro-y-methoxy substituted phenylalkylamides: Molecular dynamics calculations and in vitro modified release in aqueous media from tablet formulations. Curr Pharm Des 2023; 29(17): 1370-8.
[http://dx.doi.org/10.2174/1381612829666230607093311] [PMID: 37287297]
[11]
Srinivasan V, Pandi-Perumal SR, Trahkt I, et al. Melatonin and melatonergic drugs on sleep: Possible mechanisms of action. Int J Neurosci 2009; 119(6): 821-46.
[http://dx.doi.org/10.1080/00207450802328607] [PMID: 19326288]
[12]
Tsotinis A, Kompogennitaki R, Papanastasiou I, Garratt PJ, Bocianowska A, Sugden D. Fluorine substituted methoxyphenylalkyl amides as potent melatonin receptor agonists. MedChemComm 2019; 10(3): 460-4.
[http://dx.doi.org/10.1039/C8MD00604K] [PMID: 31191854]
[13]
Garratt PJ, Travard S, Vonhoff S, Tsotinis A, Sugden D. Mapping the melatonin receptor 4. Comparison of the binding affinities of a series of substituted phenylalkyl amides. J Med Chem 1996; 39(9): 1797-805.
[http://dx.doi.org/10.1021/jm9508189] [PMID: 8627603]
[14]
Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 2010; 67(3): 217-23.
[PMID: 20524422]
[15]
Siamidi A, Konstantinou A, Pavlou P, Siamidis I, Vlachou M. Modified release of acetaminophen from matrix tablet formulations: Influence of tablet geometry. Lett Drug Des Discov 2024; 21(3): 568-74.
[http://dx.doi.org/10.2174/1570180820666221017162352]
[16]
Vlachou M, Siamidi A. Biopolymers, liposomes, and nanofibers as modified peroral drug release formulants in. Nanomat Clin Appl 2020; pp. 249-70.
[http://dx.doi.org/10.1016/B978-0-12-816705-2.00008-4]
[17]
Siepmann J, Peppas NA. Higuchi equation: Derivation, applications, use and misuse. Int J Pharm 2011; 418(1): 6-12.
[http://dx.doi.org/10.1016/j.ijpharm.2011.03.051] [PMID: 21458553]
[18]
Pharmacopeia US. USP 39-NF34. In the USP Convention. Rockville 2016, pp. 308-309.
[19]
Greenspan L. Humidity fixed points of binary saturated aqueous solutions. J Res Natl Bur Stand, A Phys Chem 1977; 81A(1): 89.
[http://dx.doi.org/10.6028/jres.081A.011]
[20]
Khaled A, Abdel-Hamid S, Nasr M, Sammour OA. Fabrication of extended-dissolution divalproex tablets: A green solvent-free granulation technique. Drug Dev Ind Pharm 2020; 46(6): 975-87.
[http://dx.doi.org/10.1080/03639045.2020.1764023] [PMID: 32362159]
[21]
Maclean N, Khadra I, Mann J, et al. Investigating the role of excipients on the physical stability of directly compressed tablets. Int J Pharm X 2022; 4(4): 100106.
[http://dx.doi.org/10.1016/j.ijpx.2021.100106] [PMID: 34977560]
[22]
Siamidi A, Dedeloudi A, Vlachou M. Probing the release of bupropion and naltrexone hydrochloride salts from biopolymeric matrices of diverse chemical structures. Polymersfpage 2021; 13(9): 1456.
[http://dx.doi.org/10.3390/polym13091456] [PMID: 33946250]
[23]
Kalogeropoulou F, Papailiou D, Protopapa C, et al. Design and development of low- and medium-viscosity alginate beads loaded with Pluronic® F-127 nanomicelles. Materialsfpage 2023; 16(13): 4715.
[http://dx.doi.org/10.3390/ma16134715] [PMID: 37445029]
[24]
Suzuki S, Green PG, Bumgarner RE, Dasgupta S, Goddard WA III, Blake GA. Benzene forms hydrogen bonds with water. Science 1992; 257(5072): 942-5.
[http://dx.doi.org/10.1126/science.257.5072.942] [PMID: 17789637]
[25]
Laracuente ML, Yu MH, McHugh KJ. Zero-order drug delivery: State of the art and future prospects. J Control Release 2020; 327: 834-56.
[http://dx.doi.org/10.1016/j.jconrel.2020.09.020] [PMID: 32931897]
[26]
Saurí J, Millán D, Suñé-Negre JM, et al. Quality by Design approach to understand the physicochemical phenomena involved in controlled release of captopril SR matrix tablets. Int J Pharm 2014; 477(1-2): 431-41.
[http://dx.doi.org/10.1016/j.ijpharm.2014.10.050] [PMID: 25445523]

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