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Pharmaceutical Nanotechnology

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ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Research Article

Curcumin- β-Cyclodextrin Molecular Inclusion Complex: A Water- Soluble Complex in Fast-dissolving Tablets for the Treatment of Neurodegenerative Disorders

Author(s): Sruthi Laakshmi Mugundhan, Purushothaman Balasubramaniyan, Damodharan Narayanasamy and Mothilal Mohan*

Volume 12, Issue 4, 2024

Published on: 08 January, 2024

Page: [365 - 377] Pages: 13

DOI: 10.2174/0122117385273171231120051021

Price: $65

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Abstract

Background: Orally disintegrating tablets (ODTs) have become an excellent choice for delivering drugs as their palatability is greatly improved. In this work, β-cyclodextrin has been used to improve the solubility of curcumin by encapsulating it into the hydrophobic cavity for the treatment of neurodegenerative disorders.

Objectives: The current study aimed to present the design, formulation, and optimisation of fastdissolving oral tablets of curcumin- β-cyclodextrin molecular inclusion complex using a 32-factorial design.

Methods: The drug-excipient compatibility was studied by FTIR spectroscopy. The inclusion complex of curcumin-β-cyclodextrin was prepared using solvent casting and confirmed using XRD studies. Powder blends were evaluated for flow properties. Tablets prepared by direct compression were evaluated for post-compression parameters. Further, the effect of formulation variables, such as sodium starch glycolate (X1) and Neusilin® ULF2 (X2), on various responses, including disintegration time and dissolution at 2 hours, was studied using statistical models.

Results: Post-compression parameters, i.e., hardness (4.4-5 kg/cm2), thickness (3.82-3.93 mm), weight variation (±7.5%), friability (< 1%), wetting time (51-85 seconds) and drug content (96.28- 99.32%) were all found to be within the permissible limits and the disintegration time of tablets with super-disintegrants ranged between 45-58 seconds. The in-vitro dissolution profile of tablets showed that higher SSG and Neuslin® ULF2 levels promoted drug release. For statistical analysis, the 2FI model was chosen. Optimised variables for formulation have been determined and validated with the experimental findings based on the significant desirability factor.

Conclusion: The current study reveals the validated curcumin-β-cyclodextrin inclusion complex fastdissolving tablets with SSG and Neusilin® ULF2 to be an ideal choice for effectively treating neurodegenerative disorders.

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[1]
Kumar R, Aadil KR, Mondal K, et al. Neurodegenerative disorders management: State-of-art and prospects of nano-biotechnology. Crit Rev Biotechnol 2022; 42(8): 1180-212.
[http://dx.doi.org/10.1080/07388551.2021.1993126] [PMID: 34823433]
[2]
Błaszczyk JW. Energy metabolism decline in the aging brain—Pathogenesis of neurodegenerative disorders. Metabolites 2020; 10(11): 450.
[http://dx.doi.org/10.3390/metabo10110450] [PMID: 33171879]
[3]
Mortada I, Farah R, Nabha S, et al. Immunotherapies for neurodegenerative diseases. Front Neurol 2021; 12: 654739.
[http://dx.doi.org/10.3389/fneur.2021.654739] [PMID: 34163421]
[4]
Poddar MK, Chakraborty A, Banerjee S. Neurodegeneration: Diagnosis, prevention, and therapy. In: Oxidoreductase. London, UK: IntechOpen 2021.
[5]
Müller T, Mueller BK, Riederer P. Perspective: Treatment for disease modification in chronic neurodegeneration. Cells 2021; 10(4): 873.
[http://dx.doi.org/10.3390/cells10040873] [PMID: 33921342]
[6]
Wright DJ, Smithard DG, Griffith R. Optimising medicines administration for patients with Dysphagia in Hospital: Medical or nursing responsibility? Geriatrics 2020; 5(1): 9.
[http://dx.doi.org/10.3390/geriatrics5010009] [PMID: 32092854]
[7]
Topal F, Ertas B, Guler E, et al. A novel multi-target strategy for Alzheimer’s disease treatment via sublingual route: Donepezil/memantine/curcumin-loaded nanofibers. Biomaterials Advances 2022; 138: 212870.
[http://dx.doi.org/10.1016/j.bioadv.2022.212870] [PMID: 35913251]
[8]
Darvesh AS, Carroll RT, Bishayee A, Novotny NA, Geldenhuys WJ, Van der Schyf CJ. Curcumin and neurodegenerative diseases: A perspective. Expert Opin Investig Drugs 2012; 21(8): 1123-40.
[http://dx.doi.org/10.1517/13543784.2012.693479] [PMID: 22668065]
[9]
Laurindo LF, de Carvalho GM, de Oliveira Zanuso B, et al. Curcumin-based nanomedicines in the treatment of inflammatory and immunomodulated diseases: An evidence-based comprehensive review. Pharmaceutics 2023; 15(1): 229.
[http://dx.doi.org/10.3390/pharmaceutics15010229] [PMID: 36678859]
[10]
Mohseni M, Sahebkar A, Askari G, Johnston TP, Alikiaii B, Bagherniya M. The clinical use of curcumin on neurological disorders: An updated systematic review of clinical trials. Phytother Res 2021; 35(12): 6862-82.
[http://dx.doi.org/10.1002/ptr.7273] [PMID: 34528307]
[11]
Sotoyama M, Uchida S, Kamiya C, et al. Ease of taking and palatability of fixed-dose orally disintegrating mitiglinide/voglibose tablets. Chem Pharm Bull 2019; 67(6): 540-5.
[http://dx.doi.org/10.1248/cpb.c18-00902] [PMID: 31155559]
[12]
Dei Cas M, Ghidoni R. Dietary curcumin: correlation between bioavailability and health potential. Nutrients 2019; 11(9): 2147.
[http://dx.doi.org/10.3390/nu11092147] [PMID: 31500361]
[13]
Hussain A, Mahmood F, Arshad MS, et al. Personalised 3D printed fast-dissolving tablets for managing hypertensive crisis: In-vitro/in-vivo studies. Polymers 2020; 12(12): 3057.
[http://dx.doi.org/10.3390/polym12123057] [PMID: 33419348]
[14]
Benameur T, Giacomucci G, Panaro MA, et al. New promising therapeutic avenues of curcumin in brain diseases. Molecules 2021; 27(1): 236.
[http://dx.doi.org/10.3390/molecules27010236] [PMID: 35011468]
[15]
Oliveira AP, Silva ALN, viana LGFC, et al. β-Cyclodextrin complex improves the bioavailability and antitumor potential of cirsiliol, a flavone isolated from Leonotis nepetifolia (Lamiaceae). Heliyon 2019; 5(10): e01692.
[http://dx.doi.org/10.1016/j.heliyon.2019.e01692] [PMID: 31720439]
[16]
Maji TK, Bagchi D, Pan N, et al. A combined spectroscopic and ab initio study of the transmetalation of a polyphenol as a potential purification strategy for food additives. RSC Advances 2020; 10(10): 5636-47.
[http://dx.doi.org/10.1039/C9RA10596D] [PMID: 35497419]
[17]
Li J, Xu F, Dai Y, et al. A review of cyclodextrin encapsulation and intelligent response for the release of curcumin. Polymers 2022; 14(24): 5421.
[http://dx.doi.org/10.3390/polym14245421] [PMID: 36559788]
[18]
Huang W, Yong J, Wang D, She Y, Zhou J, Gao H. Curcumin inhibits memory retrieval dysfunction in adult mice induced by sevoflurane via activation of autophagy in hippocampal neurons. Chinese J Integ Trad Western Med 2019; 39(7): 838-41.
[19]
Ghourichay MP, Kiaie SH, Nokhodchi A, Javadzadeh Y. Formulation and quality control of orally disintegrating tablets (ODTs): recent advances and perspectives. BioMed Res Int 2021; 2021: 1-12.
[http://dx.doi.org/10.1155/2021/6618934] [PMID: 34977245]
[20]
Bhargav E, Chaithanya Barghav G, Padmanabha Reddy Y, Pavan kumar C, Ramalingam P, Haranath C. A Design of Experiment (DoE) based approach for development and optimization of nanosuspensions of telmisartan, a BCS class II antihypertensive drug. Future J Pharmaceut Sci 2020; 6(1): 14.
[http://dx.doi.org/10.1186/s43094-020-00032-2]
[21]
Nikolić L, Urošević M, Nikolić V, et al. The formulation of curcumin: 2-hydroxypropyl-β-cyclodextrin complex with smart hydrogel for prolonged release of curcumin. Pharmaceutics 2023; 15(2): 382.
[http://dx.doi.org/10.3390/pharmaceutics15020382] [PMID: 36839703]
[22]
Mashaqbeh H, Obaidat R, Al-Shar’i N. Evaluation and characterization of curcumin-β-cyclodextrin and cyclodextrin-based nanosponge inclusion complexation. Polymers 2021; 13(23): 4073.
[http://dx.doi.org/10.3390/polym13234073] [PMID: 34883577]
[23]
Mihály ÁL. Biological activity of curcumin-loaded cyclodextrin-decorated superparamagnetic iron oxide nanoparticles. Diploma Thesis, Technische Universität Wien 2022.
[24]
Kotha RR, Luthria DL. Curcumin: biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules 2019; 24(16): 2930.
[http://dx.doi.org/10.3390/molecules24162930] [PMID: 31412624]
[25]
Farooqui T, Farooqui AA, Eds. Curcumin for neurological and psychiatric disorders: neurochemical and pharmacological properties. Academic Press 2019.
[26]
Cunha FVM, do Nascimento Caldas Trindade G, da Silva Azevedo PS, et al. Ethyl ferulate/β-cyclodextrin inclusion complex inhibits edema formation. Mater Sci Eng C 2020; 115: 111057.
[http://dx.doi.org/10.1016/j.msec.2020.111057] [PMID: 32600687]
[27]
Obeid MA, Alsaadi M, Aljabali AA. Recent updates in curcumin delivery. J Liposome Res 2023; 33(1): 53-64.
[http://dx.doi.org/10.1080/08982104.2022.2086567] [PMID: 35699160]
[28]
Abdulmalek S, Nasef M, Awad D, Balbaa M. Protective effect of natural antioxidant, curcumin nanoparticles, and zinc oxide nanoparticles against type 2 diabetes-promoted hippocampal neurotoxicity in rats. Pharmaceutics 2021; 13(11): 1937.
[http://dx.doi.org/10.3390/pharmaceutics13111937] [PMID: 34834352]
[29]
Hegde M, Girisa S, BharathwajChetty B, Vishwa R, Kunnumakkara AB. Curcumin formulations for better bioavailability: What we learned from clinical trials thus far? ACS Omega 2023; 8(12): 10713-46.
[http://dx.doi.org/10.1021/acsomega.2c07326] [PMID: 37008131]
[30]
Stasiłowicz-Krzemień A, Rosiak N, Płazińska A, et al. Cyclodextrin derivatives as promising solubilizers to enhance the biological activity of rosmarinic acid. Pharmaceutics 2022; 14(10): 2098.
[http://dx.doi.org/10.3390/pharmaceutics14102098] [PMID: 36297533]
[31]
Monroy A, Lithgow GJ, Alavez S. Curcumin and neurodegenerative diseases. Biofactors 2013; 39(1): 122-32.
[http://dx.doi.org/10.1002/biof.1063] [PMID: 23303664]
[32]
Hu S, Maiti P, Ma Q, et al. Clinical development of curcumin in neurodegenerative disease. Expert Rev Neurother 2015; 15(6): 629-37.
[http://dx.doi.org/10.1586/14737175.2015.1044981] [PMID: 26035622]
[33]
Silvestro S, Sindona C, Bramanti P, Mazzon E. A state of the art of antioxidant properties of curcuminoids in neurodegenerative diseases. Int J Mol Sci 2021; 22(6): 3168.
[http://dx.doi.org/10.3390/ijms22063168] [PMID: 33804658]
[34]
Eghbaliferiz S, Farhadi F, Barreto GE, Majeed M, Sahebkar A. Effects of curcumin on neurological diseases: focus on astrocytes. Pharmacol Rep 2020; 72(4): 769-82.
[http://dx.doi.org/10.1007/s43440-020-00112-3] [PMID: 32458309]
[35]
Fuji Chemicals Industry Co., Ltd.,News Letter. Available from: https://www.fujichemical.co.jp/english/newsletter/newsletter_pharma_0710.html
[36]
Sabouni N, Marzouni HZ, Palizban S, et al. Role of curcumin and its nanoformulations in the treatment of neurological diseases through the effects on stem cells. J Drug Target 2023; 31(3): 243-60.
[http://dx.doi.org/10.1080/1061186X.2022.2141755] [PMID: 36305097]
[37]
Sekhar Naik DC, Bharathi A. Design and Evaluation of Fast Dissolving Tablets a Novel Natural Superdisintegrant is used in the Development of a BCS Class -II Drug. Res J Pharma Technol 2023; 16(4): 1861-8.
[http://dx.doi.org/10.52711/0974-360X.2023.00305]
[38]
Elsegaie D, El-Nabarawi MA, Mahmoud HA, Teaima M, Louis D. A comparative study on cyclodextrin derivatives in improving oral bioavailability of etoricoxib as a model drug: Formulation and evaluation of solid dispersion-based fast-dissolving tablets. Biomedicines 2023; 11(9): 2440.
[http://dx.doi.org/10.3390/biomedicines11092440]
[39]
Komínová P, Kulaviak L, Zámostný P. Stress-dependent particle interactions of magnesium aluminometasilicates as their performance factor in powder flow and compaction applications. Materials 2021; 14(4): 900.
[http://dx.doi.org/10.3390/ma14040900] [PMID: 33672812]
[40]
Yousaf A, Naheed F, Shahzad Y, Hussain T, Mahmood T. Influence of sodium starch glycolate, croscarmellose sodium and crospovidone on disintegration and dissolution of stevia-loaded tablets. Polim Med 2019; 49(1): 19-26.
[http://dx.doi.org/10.17219/pim/111516] [PMID: 31756060]
[41]
Dhere MD, Bhavya E. Design And Characterization Of Barberine Liquisolid Compacts For Escalating Bioavailability And Antidiabetic Potential: In vitro, in vivo and in silico approach. J Pharmaceut Negative Result 2022; 9394-414.
[42]
United States Pharmacopeia. Uniformity of dosage units. 2011. Available from:https://www.usp.org/sites/default/files/usp/document/harmonization/gen-method/q0304_stage_6_monograph_25_feb_2011.pdf
[44]
Hasan A, Abd Elghany M, Sabry S. Design and characterization of intra-oral fast dissolving tablets containing diacerein-solid dispersion. J Appl Pharmaceut Sci 2020; 10(6): 044-53.
[45]
Mustafa WW, Khoder M, Abdelkader H, Singer R, Alany R. Interactions of cyclodextrins and their hydroxyl derivatives with etodolac: Solubility and dissolution enhancement. Curr Drug Deliv 2023.
[PMID: 36959150]
[48]
[49]
Sharifi-Rad J, Rapposelli S, Sestito S, et al. Multi-target mechanisms of phytochemicals in Alzheimer’s disease: Effects on oxidative stress, neuroinflammation and protein aggregation. J Pers Med 2022; 12(9): 1515.
[http://dx.doi.org/10.3390/jpm12091515] [PMID: 36143299]
[50]
Garodia P, Hegde M, Kunnumakkara AB, Aggarwal BB. Curcumin, inflammation, and neurological disorders: How are they linked? Integr Med Res 2023; 12(3): 100968.
[http://dx.doi.org/10.1016/j.imr.2023.100968] [PMID: 37664456]
[51]
Sharifi-Rad J, Rayess YE, Rizk AA, et al. Turmeric and its major compound curcumin on health: Bioactive effects and safety profiles for food, pharmaceutical, biotechnological and medicinal applications. Front Pharmacol 2020; 11: 01021.
[http://dx.doi.org/10.3389/fphar.2020.01021] [PMID: 33041781]
[52]
Maiti P, Dunbar G. Use of curcumin, a natural polyphenol for targeting molecular pathways in treating age-related neurodegenerative diseases. Int J Mol Sci 2018; 19(6): 1637.
[http://dx.doi.org/10.3390/ijms19061637] [PMID: 29857538]
[53]
Malviya V, Thakur Y, Shrikhande S, Gudadhe K, Tawar M. Formulation and evaluation of natural gum based fast dissolving tablet of Meclizine hydrochloride by using 32 factorial design. Asian J Pharm Pharmacol 2020; 6(2): 94-100.
[http://dx.doi.org/10.31024/ajpp.2020.6.2.7]
[54]
Shah KA, Gao B, Kamal R, et al. Development and characterizations of pullulan and maltodextrin-based oral fast-dissolving films employing a box–behnken experimental design. Materials 2022; 15(10): 3591.
[http://dx.doi.org/10.3390/ma15103591] [PMID: 35629620]
[55]
Li W, Zhang Y, Huang P, et al. Application of NMP and Neusilin US2-integrated liquisolid technique in mini-tablets for improving the physical performances and oral bioavailability of liposoluble supercritical fluid extracts. J Drug Deliv Sci Technol 2023; 81: 104205.
[http://dx.doi.org/10.1016/j.jddst.2023.104205]
[56]
Lin Z, Zheng K, Azad MA, Davé RN. Preparation of free-flowing spray-dried amorphous composites using neusilin®. AAPS PharmSciTech 2023; 24(1): 51.
[http://dx.doi.org/10.1208/s12249-023-02511-0] [PMID: 36703032]
[57]
Elbl J, Veselý M, Blaháčková D, et al. Development of 3D printed multi-layered orodispersible films with porous structure applicable as a substrate for inkjet printing. Pharmaceutics 2023; 15(2): 714.
[http://dx.doi.org/10.3390/pharmaceutics15020714] [PMID: 36840036]
[58]
European Patent Specification. W.O. Patent 2011/019045, 2011.
[59]
Patel H, Gupta N, Pandey S, Ranch K. Development of liquisolid tablets of chlorpromazine using 32 full factorial design. Indian J Pharm Sci 2019; 81(6)
[60]
Thummala UK, Maddi EG, Avula PR. Optimization of fast-dissolving tablets of ledipasvirsofosbuvir inclusion complexes by design of experiments. Indian J Pharmaceut Educ Res 2023; 57(1): 33-44.
[http://dx.doi.org/10.5530/001954641530]
[61]
Lo Cascio F, Marzullo P, Kayed R, Palumbo Piccionello A. Curcumin as scaffold for drug discovery against neurodegenerative diseases. Biomedicines 2021; 9(2): 173.
[http://dx.doi.org/10.3390/biomedicines9020173] [PMID: 33572457]
[62]
Giri BR, Lee J, Lim DY, Kim DW. Docetaxel/dimethyl-β-cyclodextrin inclusion complexes: Preparation, In Vitro evaluation and physicochemical characterization. Drug Dev Ind Pharm 2021; 47(2): 319-28.
[http://dx.doi.org/10.1080/03639045.2021.1879840] [PMID: 33576707]
[63]
Kamali H, Farzadnia P, Movaffagh J, Abbaspour M. Optimization of curcumin nanofibers as fast dissolving oral films prepared by emulsion electrospinning via central composite design. J Drug Deliv Sci Technol 2022; 75: 103714.
[http://dx.doi.org/10.1016/j.jddst.2022.103714]
[64]
Deng C, Cao C, Zhang Y, et al. Formation and stabilization mechanism of β-cyclodextrin inclusion complex with C10 aroma molecules. Food Hydrocoll 2022; 123: 107013.
[http://dx.doi.org/10.1016/j.foodhyd.2021.107013]
[65]
Dangre PV, Gurram NJ, Surana SJ, Chalikwar SS. Development and optimization of vitamin D3 solid self-microemulsifying drug delivery system: Investigation of flowability and shelf life. AAPS PharmSciTech 2022; 23(4): 110.
[http://dx.doi.org/10.1208/s12249-022-02267-z] [PMID: 35411421]
[66]
Yilmaz Usta D, Olgac S, Timur B, Teksin ZS. Development and pharmacokinetic evaluation of Neusilin® US2-based S-SNEDDS tablets for bosentan: Fasted and fed states bioavailability, IVIS® real-time biodistribution, and ex-vivo imaging. Int J Pharm 2023; 643: 123219.
[http://dx.doi.org/10.1016/j.ijpharm.2023.123219] [PMID: 37433349]
[67]
Novel poorly water-soluble curcumin-loaded modified drug delivery systems with enhanced solubility and oral bioavailability. Graduate School, Pharmacy Department, Thesis (Master)
[68]
Khan A, Prasad S, Dubey G. Formulation and evaluation of bi-layered tablet of divalproex sodium. J Pharmacogn Phytochem 2023; 12(2): 16-22.
[http://dx.doi.org/10.22271/phyto.2023.v12.i2a.14621]
[69]
Abdelkader A, Preis E, Keck CM. smartFilm tablets for improved oral delivery of poorly soluble drugs. Pharmaceutics 2022; 14(9): 1918.
[http://dx.doi.org/10.3390/pharmaceutics14091918] [PMID: 36145666]
[70]
Ornik J, Knoth D, Koch M, Keck CM. Terahertz-spectroscopy for non-destructive determination of crystallinity of L-tartaric acid in smartFilms® and tablets made from paper. Int J Pharm 2020; 581: 119253.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119253] [PMID: 32217156]
[71]
Som S, Singh SK, Khatik GL, et al. Quality by design-based crystallization of curcumin using liquid antisolvent precipitation: Micromeritic, biopharmaceutical, and stability aspects. Assay Drug Dev Technol 2020; 18(1): 11-33.
[http://dx.doi.org/10.1089/adt.2018.913] [PMID: 31268345]
[72]
Arya P, Raghav N. In-vitro studies of Curcumin-β-cyclodextrin inclusion complex as sustained release system. J Mol Struct 2021; 1228: 129774.
[http://dx.doi.org/10.1016/j.molstruc.2020.129774]
[73]
Jafar M, Khalid MS, Aldossari MFE, et al. Formulation of Curcumin-β-cyclodextrin-polyvinylpyrrolidone supramolecular inclusion complex: Experimental, molecular docking, and preclinical anti-inflammatory assessment. Drug Dev Ind Pharm 2020; 46(9): 1524-34.
[http://dx.doi.org/10.1080/03639045.2020.1810268] [PMID: 32808552]
[74]
van der Merwe J, Steenekamp J, Steyn D, Hamman J. The role of functional excipients in solid oral dosage forms to overcome poor drug dissolution and bioavailability. Pharmaceutics 2020; 12(5): 393.
[http://dx.doi.org/10.3390/pharmaceutics12050393] [PMID: 32344802]
[75]
Celebioglu A, Uyar T. Fast-dissolving antioxidant curcumin/cyclodextrin inclusion complex electrospun nanofibrous webs. Food Chem 2020; 317: 126397.
[http://dx.doi.org/10.1016/j.foodchem.2020.126397] [PMID: 32078994]
[76]
Jiang L, Xia N, Wang F, et al. Preparation and characterization of curcumin/β-cyclodextrin nanoparticles by nanoprecipitation to improve the stability and bioavailability of curcumin. Lebensm Wiss Technol 2022; 171: 114149.
[http://dx.doi.org/10.1016/j.lwt.2022.114149]

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