Login Register Cart 0
Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Transdermal Therapeutic Systems for the Treatment of Alzheimer's Disease: A Patent Review

Author(s): Letícia Basso, Silvia Cristina Fagundes, Tatiana Staudt, Karini da Rosa, Elizane Langaro, Hamid Omidian and Charise Dallazem Bertol*

Volume 23, Issue 9, 2024

Published on: 16 November, 2023

Page: [1075 - 1084] Pages: 10

DOI: 10.2174/0118715273275957231102044934

Price: $65

conference banner
Abstract

Background: Two classes of medications are used to treat Alzheimer's disease (AD); donepezil, galantamine, and rivastigmine are acetylcholinesterase inhibitors, and memantine is a non-competitive antagonist of the N-methyl-D-aspartate receptor. Although these are typically taken orally, there are transdermal therapeutic systems (TTSs) commercially available for rivastigmine and donepezil. The transdermal route has been preferable for guardians/caregivers due to ease of use, reduced side effects, and improved adherence to therapy.

Objective: The study aimed to obtain knowledge of the properties of these drugs and to search for patents relating to the TTS for AD using the Espacenet platform.

Methods: The search terms were "rivastigmine AND transdermal AND skin delivery AND Alzheimer’s", changing the drugs "memantine", "donepezil", and "galantamine", between January 2015 and January 2022. Title and abstract were used to choose patents.

Results: TTSs present some limit factors in terms of absorption due to skin physiology and the size of the molecules with established limits of percutaneous penetration (molecular mass of 500 g/mol and log P of 5). We found 1, 4, 4, and 2 patents for galantamine, rivastigmine, donepezil, and memantine, respectively. Galantamine TTS seems to be more challenging due to the molecular mass of 287.35 g/mol and logP of 1.8. The permeator of absorption is necessary. Memantine, rivastigmine, and donepezil present logP of 3.28, 2.3, and 4.27 and molecular weights of 179.30, 250.34, and 415.96 g/mol, respectively.

Conclusion: TTSs are primarily effective for delivering small molecules. The use of absorption enhancers and irritation mitigators can be necessary to enhance the performance. The development of these technologies is essential for the convenience of patients and caregivers.

Keywords: Alzheimer's disease, donepezil, galantamine, memantine, rivastigmine, transdermal therapeutic system.

« Previous Next »
Graphical Abstract

[1]
Joe E, Ringman JM. Cognitive symptoms of Alzheimer’s disease: Clinical management and prevention. BMJ 2019; 367: l6217.
[2]
Porsteinsson AP, Isaacson RS, Knox S, Sabbagh MN, Rubino I. Diagnosis of Early Alzheimer’s Disease: Clinical Practice in 2021. J Prev Alzheimers Dis 2021; 8(3): 371-86.
[PMID: 34101796]
[3]
Rabbito A, Dulewicz M, Kulczyńska-Przybik A, Mroczko B. Biochemical Markers in Alzheimer’s Disease. Int J Mol Sci 2020; 21(6): 1989.
[http://dx.doi.org/10.3390/ijms21061989] [PMID: 32183332]
[4]
Gottesman RT, Stern Y. Behavioral and Psychiatric Symptoms of Dementia and Rate of Decline in Alzheimer’s Disease. Front Pharmacol 2019; 10: 1062.
[http://dx.doi.org/10.3389/fphar.2019.01062]
[5]
Malaiya MK, Jain A, Pooja H, Jain A, Jain D. Controlled delivery of rivastigmine using transdermal patch for effective management of alzheimer’s disease. J Drug Deliv Sci Technol 2018; 45: 408-14.
[http://dx.doi.org/10.1016/j.jddst.2018.03.030]
[6]
Zvěřová M. Clinical aspects of Alzheimer’s disease. Clin Biochem 2019; 72: 3-6.
[http://dx.doi.org/10.1016/j.clinbiochem.2019.04.015] [PMID: 31034802]
[7]
Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers 2015; 1(1): 15056.
[http://dx.doi.org/10.1038/nrdp.2015.56]
[8]
Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology 2021; 190: 108352.
[http://dx.doi.org/10.1016/j.neuropharm.2020.108352] [PMID: 33035532]
[9]
del Río-Sancho S, Serna-Jiménez CE, Sebastián-Morelló M, et al. Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport. Int J Pharm 2017; 517(1-2): 104-11.
[http://dx.doi.org/10.1016/j.ijpharm.2016.11.038] [PMID: 27865983]
[10]
Jeong WY, Kwon M, Choi HE, Kim KS. Recent advances in transdermal drug delivery systems: A review. Biomater Res 2021; 25(1): 24.
[http://dx.doi.org/10.1186/s40824-021-00226-6] [PMID: 33451366]
[11]
Padula C, Nicoli S, Aversa V, et al. Bioadhesive film for dermal and transdermal drug delivery. Eur J Dermatol 2007; 17(4): 309-12.
[PMID: 17540637]
[12]
Kováčik A, Kopečná M, Vávrová K. Permeation enhancers in transdermal drug delivery: Benefits and limitations. Expert Opin Drug Deliv 2020; 17(2): 145-55.
[http://dx.doi.org/10.1080/17425247.2020.1713087] [PMID: 31910342]
[13]
Sabbagh F, Kim BS. Recent advances in polymeric transdermal drug delivery systems. J Control Release 2022; 341: 132-46.
[http://dx.doi.org/10.1016/j.jconrel.2021.11.025] [PMID: 34813879]
[14]
Park J, Lee H, Lim GS, Kim N, Kim D, Kim YC. Enhanced Transdermal Drug Delivery by Sonophoresis and Simultaneous Application of Sonophoresis and Iontophoresis. AAPS PharmSciTech 2019; 20(3): 96.
[http://dx.doi.org/10.1208/s12249-019-1309-z]
[15]
Phatale V, Vaiphei KK, Jha S, Patil D, Agrawal M, Alexander A. Overcoming skin barriers through advanced transdermal drug delivery approaches. J Control Release 2022; 351: 361-80.
[http://dx.doi.org/10.1016/j.jconrel.2022.09.025] [PMID: 36169040]
[16]
Yeung C, Chen S, King B, et al. A 3D-printed microfluidic-enabled hollow microneedle architecture for transdermal drug delivery. Biomicrofluidics 2019; 13(6): 064125.
[http://dx.doi.org/10.1063/1.5127778]
[17]
Jung JH, Jin SG. Microneedle for transdermal drug delivery: Current trends and fabrication. J Pharm Investig 2021; 51(5): 503-17.
[http://dx.doi.org/10.1007/s40005-021-00512-4] [PMID: 33686358]
[18]
Gowda BHJ, Ahmed MG, Sanjana A. Can Microneedles Replace Hypodermic Needles? Resonance 2022; 27(1): 63-85.
[http://dx.doi.org/10.1007/s12045-022-1294-5]
[19]
Gera AK, Burra RK. The rise of polymeric microneedles: Recent developments, advances, challenges, and applications with regard to transdermal drug delivery. J Funct Biomater 2022; 13(2): 1-18.
[http://dx.doi.org/10.3390/jfb13020081] [PMID: 35735936]
[20]
Kim JY, Han MR, Kim YH, Shin SW, Nam SY, Park JH. Tip-loaded dissolving microneedles for transdermal delivery of donepezil hydrochloride for treatment of Alzheimer’s disease. Eur J Pharm Biopharm 2016; 105: 148-55.
[http://dx.doi.org/10.1016/j.ejpb.2016.06.006] [PMID: 27288938]
[21]
Rehman NU, Song C, Kim J, Noh I, Rhee YS, Chung HJ. Pharmacokinetic Evaluation of a Novel Donepezil-Loaded Dissolving Microneedle Patch in Rats. Pharmaceutics 2021; 14(1): 5.
[http://dx.doi.org/10.3390/pharmaceutics14010005] [PMID: 35056902]
[22]
Yan Q, Wang W, Weng J, et al. Dissolving microneedles for transdermal delivery of huperzine A for the treatment of Alzheimer’s disease. Drug Deliv 2020; 27(1): 1147-55.
[http://dx.doi.org/10.1080/10717544.2020.1797240] [PMID: 32729341]
[23]
Kale M, Kipping T, Banga AK. Modulated delivery of donepezil using a combination of skin microporation and iontophoresis. Int J Pharm 2020; 589: 119853.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119853] [PMID: 32898633]
[24]
Lee M, Ryoo JH, Campbell C, Hollen PJ, Williams IC. Exploring the challenges of medical/nursing tasks in home care experienced by caregivers of older adults with dementia: An integrative review. J Clin Nurs 2019; 28(23-24): 4177-89.
[http://dx.doi.org/10.1111/jocn.15007] [PMID: 31323707]
[25]
Choi J, Choi MK, Chong S, Chung SJ, Shim CK, Kim DD. Effect of fatty acids on the transdermal delivery of donepezil: In vitro and in vivo evaluation. Int J Pharm 2012; 422(1-2): 83-90.
[http://dx.doi.org/10.1016/j.ijpharm.2011.10.031] [PMID: 22037444]
[26]
Folch J, Ettcheto M, Petrov D, et al. Una revisión de los avances en la terapéutica de la enfermedad de Alzheimer: Estrategia frente a la proteína β-amiloide. Neurologia 2018; 33(1): 47-58.
[http://dx.doi.org/10.1016/j.nrl.2015.03.012] [PMID: 25825074]
[27]
Ramadon D, McCrudden MTC, Courtenay AJ, Donnelly RF. Enhancement strategies for transdermal drug delivery systems: Current trends and applications. Drug Deliv Transl Res 2022; 12(4): 758-91.
[http://dx.doi.org/10.1007/s13346-021-00909-6] [PMID: 33474709]
[28]
Wokovich A, Prodduturi S, Doub W, Hussain A, Buhse L. Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute. Eur J Pharm Biopharm 2006; 64(1): 1-8.
[http://dx.doi.org/10.1016/j.ejpb.2006.03.009] [PMID: 16797171]
[29]
Hwa C, Bauer EA, Cohen DE. Skin biology. Dermatol Ther 2011; 24(5): 464-70.
[http://dx.doi.org/10.1111/j.1529-8019.2012.01460.x]
[30]
Raphael AP, Garrastazu G, Sonvico F, Prow TW. Formulation design for topical drug and nanoparticle treatment of skin disease. Ther Deliv 2015; 6(2): 197-216.
[http://dx.doi.org/10.4155/tde.14.106] [PMID: 25690087]
[31]
Settimo L, Bellman K, Knegtel RMA. Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds. Pharm Res 2014; 31(4): 1082-95.
[http://dx.doi.org/10.1007/s11095-013-1232-z] [PMID: 24249037]
[32]
de Campos DP, Silva-Barcellos NM, Caldeira TG, Mussel WN, Silveira V, de Souza J. Donepezil Hydrochloride BCS Class Ambiguity: Relevant Aspects to be Considered in Drug Classification. J Pharm Sci 2022; 111(11): 3064-74.
[http://dx.doi.org/10.1016/j.xphs.2022.06.023] [PMID: 35787368]
[33]
Kee K H, Hyung K T, Yong L B, et al. Microneedle percutaneous patch containing donepezil. US2020179272A1 2018.
[34]
Bashyal S, Shin CY, Hyun SM, Jang SW, Lee S. Preparation, Characterization, and In Vivo Pharmacokinetic Evaluation of Polyvinyl Alcohol and Polyvinyl Pyrrolidone Blended Hydrogels for Transdermal Delivery of Donepezil HCl. Pharmaceutics 2020; 12(30): 270.
[35]
Mendes IT, Ruela ALM, Carvalho FC, Freitas JTJ, Bonfilio R, Pereira GR. Development and characterization of nanostructured lipid carrier-based gels for the transdermal delivery of donepezil. Colloids Surf B Biointerfaces 2019; 177: 274-81.
[http://dx.doi.org/10.1016/j.colsurfb.2019.02.007] [PMID: 30763792]
[36]
Soo L E. Donepezil transdermal delivery system. WO2018022817A1 2018.
[37]
Hoo-Kyun C. Transdermal drug delivery system containing donepezil. WO2015127280A1 2015.
[38]
Kweon C Y, Hyun H D, Soo K S. Transdermal composition containing donepezil as active ingredient. US2017290780A1 2017.
[39]
Farlow MR. Clinical pharmacokinetics of galantamine. Clin Pharmacokinet 2003; 42(15): 1383-92.
[http://dx.doi.org/10.2165/00003088-200342150-00005] [PMID: 14674789]
[40]
PubChem Galantamine. 2023. Available From: https://pubchem.ncbi.nlm.nih.gov/compound/Galantamine
[41]
Seltzer B. Galantamine-ER for the treatment of mild-to-moderate Alzheimer’s disease. Clin Interv Aging 2010; 5: 1-6.
[PMID: 20169037]
[42]
Catherine L, Taijung W. Transdermal delivery system containing galantamine or salts thereof. WO2018013452A1 2018.
[43]
PubChem Rivastigmine | C14H22N2O2 | CID 77991. 2023. Available From: https://pubchem.ncbi.nlm.nih.gov/compound/Rivastigmine
[44]
Birks JS, Grimley Evans J. Rivastigmine for Alzheimer’s disease. Cochrane Database of Systematic Reviews (homepage on the Internet) 2015 [cited 2023 Sep 16] 2015; (4): Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001191.pub3/abstract
[45]
Reum N, Mohr P, Laux W, Platt B. Transdermal therapeutic system containing rivastigmine 2019.
[46]
Jann MW. Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer’s disease. Pharmacotherapy 2000; 20(1): 1-12.
[http://dx.doi.org/10.1592/phco.20.1.1.34664] [PMID: 10641971]
[47]
Polinsky RJ. Clinical pharmacology of rivastigmine: A new-generation acetylcholinesterase inhibitor for the treatment of alzheimer’s disease. Clin Ther 1998; 20(4): 634-47.
[http://dx.doi.org/10.1016/S0149-2918(98)80127-6] [PMID: 9737824]
[48]
Sadowsky C, Perez JAD, Bouchard RW, Goodman I, Tekin S. Switching from oral cholinesterase inhibitors to the rivastigmine transdermal patch. CNS Neurosci Ther 2010; 16(1): 51-60.
[http://dx.doi.org/10.1111/j.1755-5949.2009.00119.x] [PMID: 20070789]
[49]
Stevens JR, Justin Coffey M, Fojtik M, Kurtz K, Stern TA. The Use of Transdermal Therapeutic Systems in Psychiatric Care: A Primer on Patches. Psychosomatics 2015; 56(5): 423-44.
[http://dx.doi.org/10.1016/j.psym.2015.03.007] [PMID: 26211981]
[50]
Kurz A, Farlow M, Lefèvre G. Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer’s disease: A review. Int J Clin Pract 2009; 63(5): 799-805.
[http://dx.doi.org/10.1111/j.1742-1241.2009.02052.x] [PMID: 19392927]
[51]
Kensuke M. Rivastigmine transdermal compositions and methods of using the same. US10357463B2 2019.
[52]
Marco E, Nico R, Jessica V, Regine K. Transdermal therapeutic system for the transdermal administration of rivastigmine. WO2019048425A1 2019.
[53]
Katkade B, Tang J, Miller K J, Cai S, Schumacher W. Dispositivo de entrega de fármaco transdérmico. BR112015005944A2 2017.
[54]
del Rio-Sancho S, Serna-Jiménez CE, Calatayud-Pascual MA, et al. Transdermal absorption of memantine – Effect of chemical enhancers, iontophoresis, and role of enhancer lipophilicity. Eur J Pharm Biopharm 2012; 82(1): 164-70.
[http://dx.doi.org/10.1016/j.ejpb.2012.06.005] [PMID: 22732268]
[55]
McShane R, Westby MJ, Roberts E, et al. Cochrane Database Syst Rev 2019; 3: 1-446.
[56]
Johnson J, Kotermanski S. Mechanism of action of memantine. Curr Opin Pharmacol 2006; 6(1): 61-7.
[http://dx.doi.org/10.1016/j.coph.2005.09.007] [PMID: 16368266]
[57]
Liu J, Chang L, Song Y, Li H, Wu Y. The role of NMDA receptors in Alzheimer’s disease. Front Neurosci 2019; 13: 1-22.
[http://dx.doi.org/10.3389/fnins.2019.00043]
[58]
McKeage K. Spotlight on memantine in moderate to severe Alzheimer’s disease. Drugs Aging 2010; 27(2): 177-9.
[http://dx.doi.org/10.2165/11204670-000000000-00000] [PMID: 20104942]
[59]
Soo L E, Parminder S, Appala S. Memantine transdermal delivery systems. WO2018022818A1 2017.
[60]
René E, Michael H, Regine K, et al. Transdermal administration of memantine. US2019298662A1 2019.

Rights & Permissions Print Cite
Article Metrics
35
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy