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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Interactions of Cyclodextrins and their Hydroxyl Derivatives with Etodolac: Solubility and Dissolution Enhancement

Author(s): Wesam W. Mustafa*, Mouhamad Khoder, Hamdy Abdelkader, Richard Singer and Raid G. Alany

Volume 21, Issue 1, 2024

Published on: 04 April, 2023

Page: [126 - 139] Pages: 14

DOI: 10.2174/1567201820666230320164210

Price: $65

Abstract

Background: Poor solubility and dissolution rate of drugs are largely responsible for erratic drug absorption and limited oral bioavailability. Etodolac (ETO) is a non-steroidal anti-inflammatory drug (NSAID) that is classified as BCS class II (dissolution rate-dependent absorption). ETO has high safety and efficacy in pain relief and control of inflammation. ETO is commercially available as (400- 600 mg) tablets; poor solubility and dissolution rate of ETO could result in variable oral absorption and inconsistent analgesic responses. The aim of this study was to improve solubility and dissolution rates of ETO by complexation with cyclodextrins (CDs).

Methods: Four different CDs namely β-, γ-, HP β-CDs, and HP γ-CDs were prepared using three different methods; solvent evaporation (CO), freeze-drying (FD), and physical mixing (PM). The prepared drug: excipient mixtures were investigated for aqueous solubility, as well as via DSC, XRD, FTIR, SEM, dissolution, and docking.

Results: The results revealed a solubility phase diagram of the AL type, indicating a 1:1 complexation of ETO: CD. These results agreed with our molecular docking calculations. DSC, FTIR, XRD, and SEM results confirmed the formation of an inclusion complex. The complexation efficiency, solubility, and dissolution enhancement were in the order of HPγ-CD > γ -CD > HPβ-CD > β-CD. FD method was superior to both CO and PM.

Conclusion: Superior dissolution enhancements of ETO were recorded for the FD mixture (up to 90% dissolved in less than 10 min). In conclusion, γ- and hydroxypropyl γ-derivative of cyclodextrins can be considered a promising excipient for enhancement of dissolution rates concerned for ETO.

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[1]
Ammar, H.O.; Ghorab, M.; Mostafa, D.M.; Makram, T.S.; Ali, R.M. Host–guest system of etodolac in native and modified β-cyclodextrins: Preparation and physicochemical characterization. J. Incl. Phenom. Macrocycl. Chem., 2013, 77(1-4), 121-134.
[http://dx.doi.org/10.1007/s10847-012-0223-8]
[2]
Ibrahim, M.M.; EL-Nabarawi, M.; El-Setouhy, D.A.; Fadlalla, M.A. Polymeric surfactant based etodolac chewable tablets: Formulation and in vivo evaluation. AAPS PharmSciTech, 2010, 11(4), 1730-1737.
[http://dx.doi.org/10.1208/s12249-010-9548-z] [PMID: 21136309]
[3]
Demerson, C.A.; Humber, L.G.; Abraham, N.A.; Schilling, G.; Martel, R.R.; Pace-Asciak, C. Resolution of etodolac and antiinflammatory and prostaglandin synthetase inhibiting properties of the enantiomers. J. Med. Chem., 1983, 26(12), 1778-1780.
[http://dx.doi.org/10.1021/jm00366a025] [PMID: 6227748]
[4]
Aungst, B.J. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. J. Pharm. Sci., 1993, 82(10), 979-987.
[http://dx.doi.org/10.1002/jps.2600821008] [PMID: 8254497]
[5]
Serajuddin, A.T.M. Solid dispersion of poorly water-soluble drugs: Early promises, subsequent problems, and recent breakthroughs. J. Pharm. Sci., 1999, 88(10), 1058-1066.
[http://dx.doi.org/10.1021/js980403l] [PMID: 10514356]
[6]
Rouchotas, C.; Cassidy, O.E.; Rowley, G. Comparison of surface modification and solid dispersion techniques for drug dissolution. Int. J. Pharm., 2000, 195(1-2), 1-6.
[http://dx.doi.org/10.1016/S0378-5173(99)00350-6] [PMID: 10675674]
[7]
Homdrum, E.M.; Likar, R.; Nell, G. Xefo® rapid: A novel effective tool for pain treatment. Eur. Surg., 2006, 38(5), 342-352.
[http://dx.doi.org/10.1007/s10353-006-0272-6]
[8]
Mustafa, W.; Fletcher, J.; Khoder, M.; Alany, R.G. Solid dispersions of gefitinib prepared by spray drying with improved mucoadhesive and drug dissolution properties. AAPS PharmSciTech, 2021, 23(1), 48.
[http://dx.doi.org/10.1208/s12249-021-02187-4] [PMID: 34984564]
[9]
Rasenack, N.; Müller, B.W. Dissolution rate enhancement by in situ micronization of poorly water-soluble drugs. Pharm. Res., 2002, 19(12), 1894-1900.
[http://dx.doi.org/10.1023/A:1021410028371] [PMID: 12523671]
[10]
Vogt, M.; Kunath, K.; Dressman, J.B. Dissolution enhancement of fenofibrate by micronization, cogrinding and spray-drying: Comparison with commercial preparations. Eur. J. Pharm. Biopharm., 2008, 68(2), 283-288.
[http://dx.doi.org/10.1016/j.ejpb.2007.05.010] [PMID: 17574403]
[11]
Han, H.K.; Choi, H.K. Improved absorption of meloxicam via salt formation with ethanolamines. Eur. J. Pharm. Biopharm., 2007, 65(1), 99-103.
[http://dx.doi.org/10.1016/j.ejpb.2006.07.003] [PMID: 16919925]
[12]
O’Connor, K.M.; Corrigan, O.I. Comparison of the physicochemical properties of the N-(2-hydroxyethyl) pyrrolidine, diethylamine and sodium salt forms of diclofenac. Int. J. Pharm., 2001, 222(2), 281-293.
[http://dx.doi.org/10.1016/S0378-5173(01)00717-7] [PMID: 11427358]
[13]
Viernstein, H.; Weiss-Greiler, P.; Wolschann, P. Solubility enhancement of low soluble biologically active compounds-temperature and cosolvent dependent inclusion complexation. Int. J. Pharm., 2003, 256(1-2), 85-94.
[http://dx.doi.org/10.1016/S0378-5173(03)00065-6] [PMID: 12695014]
[14]
Blagden, N.; de Matas, M.; Gavan, P.T.; York, P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv. Drug Deliv. Rev., 2007, 59(7), 617-630.
[http://dx.doi.org/10.1016/j.addr.2007.05.011] [PMID: 17597252]
[15]
Balakrishnan, A.; Rege, B.D.; Amidon, G.L.; Polli, J.E. Surfactant-mediated dissolution: Contributions of solubility enhancement and relatively low micelle diffusivity. J. Pharm. Sci., 2004, 93(8), 2064-2075.
[http://dx.doi.org/10.1002/jps.20118] [PMID: 15236455]
[16]
Chiou, W.L.; Chen, S.J.; Athanikar, N. Enhancement of dissolution rates of poorly water-soluble drugs by crystallization in aqueous surfactant solutions I: Sulfathiazole, prednisone, and chloramphenicol. J. Pharm. Sci., 1976, 65(11), 1702-1704.
[http://dx.doi.org/10.1002/jps.2600651137] [PMID: 994008]
[17]
Abou-Taleb, H.A.; Fathalla, Z.; Abdelkader, H. Comparative studies of the effects of novel excipients amino acids with cyclodextrins on enhancement of dissolution and oral bioavailability of the non-ionizable drug carbamazepine. Eur. J. Pharm. Sci., 2020, 155, 105562.
[http://dx.doi.org/10.1016/j.ejps.2020.105562] [PMID: 32966851]
[18]
Foster, N.R.; Dehghani, F.; Charoenchaitrakool, K.M.; Warwick, B. Application of dense gas techniques for the production of fine particles. AAPS PharmSci, 2003, 5(2), 32-38.
[http://dx.doi.org/10.1208/ps050211] [PMID: 12866938]
[19]
Jung, J.; Perrut, M. Particle design using supercritical fluids: Literature and patent survey. J. Supercrit. Fluids, 2001, 20(3), 179-219.
[http://dx.doi.org/10.1016/S0896-8446(01)00064-X]
[20]
Del Valle, E.M.M. Cyclodextrins and their uses: A review. Process Biochem., 2004, 39(9), 1033-1046.
[http://dx.doi.org/10.1016/S0032-9592(03)00258-9]
[21]
Eastburn, S.D.; Tao, B.Y. Applications of modified cyclodextrins. Biotechnol. Adv., 1994, 12(2), 325-339.
[http://dx.doi.org/10.1016/0734-9750(94)90015-9] [PMID: 14545896]
[22]
Hedges, A.R. Industrial applications of cyclodextrins. Chem. Rev., 1998, 98(5), 2035-2044.
[http://dx.doi.org/10.1021/cr970014w] [PMID: 11848958]
[23]
Lu, X.; Chen, Y. Chiral separation of amino acids derivatized with fluoresceine-5-isothiocyanate by capillary electrophoresis and laser-induced fluorescence detection using mixed selectors of β-cyclodextrin and sodium taurocholate. J. Chromatogr. A, 2002, 955(1), 133-140.
[http://dx.doi.org/10.1016/S0021-9673(02)00186-3] [PMID: 12061559]
[24]
Baudin, C.; Pean, C.; Perly, B.; Gosselin, P. Inclusion of organic pollutants in cyclodextrins and derivatives. Int. J. Environ. Anal. Chem., 2000, 77(3), 233-242.
[http://dx.doi.org/10.1080/03067310008032685]
[25]
Kumar, R.; Dahiya, J.S.; Singh, D.; Nigam, P. Biotransformation of cholesterol using Lactobacillus bulgaricus in a glucose-controlled bioreactor. Bioresour. Technol., 2001, 78(2), 209-211.
[http://dx.doi.org/10.1016/S0960-8524(00)00174-7] [PMID: 11333043]
[26]
Koukiekolo, R.; Desseaux, V.; Moreau, Y.; Marchis-Mouren, G.; Santimone, M. Mechanism of porcine pancreatic α-amylase. Eur. J. Biochem., 2001, 268(3), 841-848.
[http://dx.doi.org/10.1046/j.1432-1327.2001.01950.x] [PMID: 11168426]
[27]
Selvan, G.T.; Poomalai, S.; Ramasamy, S.; Selvakumar, P.M.; Muthu Vijayan Enoch, I.V.; Lanas, S.G.; Melchior, A. Differential metal ion sensing by an antipyrine derivative in aqueous and β-cyclodextrin media: Selectivity tuning by β-cyclodextrin. Anal. Chem., 2018, 90(22), 13607-13615.
[http://dx.doi.org/10.1021/acs.analchem.8b03810] [PMID: 30412380]
[28]
Chandrasekaran, S.; Sameena, Y.; Enoch, I.V.M.V. Modulation of the interaction of Coumarin 7 with DNA by β-cyclodextrin. J. Incl. Phenom. Macrocycl. Chem., 2015, 81(1-2), 225-236.
[http://dx.doi.org/10.1007/s10847-014-0451-1]
[29]
Sudha, N.; Enoch, I.M.V. Interaction of curculigosides and their β-cyclodextrin complexes with bovine serum albumin: A fluorescence spectroscopic study. J. Solution Chem., 2011, 40(10), 1755-1768.
[http://dx.doi.org/10.1007/s10953-011-9750-y]
[30]
Enoch, I.V.M.V.; Swaminathan, M. Stoichiometrically different inclusion complexes of 2-aminofluorene and 2-amino-9-hydroxyfluorene in β-cyclodextrin: A spectrofluorimetric study. J. Fluoresc., 2006, 16(5), 697-704.
[http://dx.doi.org/10.1007/s10895-006-0112-x] [PMID: 16969690]
[31]
Becket, G.; Schep, L.J.; Tan, M.Y. Improvement of the in vitro dissolution of praziquantel by complexation with α-, β- and γ-cyclodextrins. Int. J. Pharm., 1999, 179(1), 65-71.
[http://dx.doi.org/10.1016/S0378-5173(98)00382-2] [PMID: 10053203]
[32]
Szente, L.; Szejtli, J. Highly soluble cyclodextrin derivatives: chemistry, properties, and trends in development. Adv. Drug Deliv. Rev., 1999, 36(1), 17-28.
[http://dx.doi.org/10.1016/S0169-409X(98)00092-1] [PMID: 10837706]
[33]
Lindberg, B.; Lindberg, J.; Pitha, J.; Rao, C.T.; Harata, K. Synthesis of some 2-O-(2-hydroxyalkyl) and 2-O-(2,3-dihydroxyalkyl) derivatives of cyclomaltoheptaose. Carbohydr. Res., 1991, 222, 113-119.
[http://dx.doi.org/10.1016/0008-6215(91)89010-D] [PMID: 1813102]
[34]
Jambhekar, S.; Casella, R.; Maher, T. The physicochemical characteristics and bioavailability of indomethacin from β-cyclodextrin, hydroxyethyl-β-cyclodextrin, and hydroxypropyl-β-cyclodextrin complexes. Int. J. Pharm., 2004, 270(1-2), 149-166.
[http://dx.doi.org/10.1016/j.ijpharm.2003.10.012] [PMID: 14726131]
[35]
Manosroi, J.; Apriyani, M.G.; Foe, K.; Manosroi, A. Enhancement of the release of azelaic acid through the synthetic membranes by inclusion complex formation with hydroxypropyl-β-cyclodextrin. Int. J. Pharm., 2005, 293(1-2), 235-240.
[http://dx.doi.org/10.1016/j.ijpharm.2005.01.009] [PMID: 15778061]
[36]
Wenz, G.; Höfler, T. Synthesis of highly water-soluble cyclodextrin sulfonates by addition of hydrogen sulfite to cyclodextrin allyl ethers. Carbohydr. Res., 1999, 322(3-4), 153-165.
[http://dx.doi.org/10.1016/S0008-6215(99)00224-4]
[37]
Shuang, S.; Choi, M.M.F. Retention behaviour and fluorimetric detection of procaine hydrochloride using carboxymethyl-β-cyclodextrin as an additive in reversed-phase liquid chromatography. J. Chromatogr. A, 2001, 919(2), 321-329.
[http://dx.doi.org/10.1016/S0021-9673(01)00810-X] [PMID: 11442038]
[38]
Abdelkader, H.; Fatease, A.A.; Fathalla, Z.; Shoman, M.E.; Abou-Taleb, H.A.; Abourehab, M.A.S. Design, preparation and evaluation of supramolecular complexes with curcumin for enhanced cytotoxicity in breast cancer cell lines. Pharmaceutics, 2022, 14(11), 2283.
[http://dx.doi.org/10.3390/pharmaceutics14112283] [PMID: 36365104]
[39]
Muhrer, G.; Meier, U.; Fusaro, F.; Albano, S.; Mazzotti, M. Use of compressed gas precipitation to enhance the dissolution behavior of a poorly water-soluble drug: Generation of drug microparticles and drug–polymer solid dispersions. Int. J. Pharm., 2006, 308(1-2), 69-83.
[http://dx.doi.org/10.1016/j.ijpharm.2005.10.026] [PMID: 16324806]
[40]
Gwak, H.; Choi, J.; Choi, H. Enhanced bioavailability of piroxicam via salt formation with ethanolamines. Int. J. Pharm., 2005, 297(1-2), 156-161.
[http://dx.doi.org/10.1016/j.ijpharm.2005.03.016] [PMID: 15907602]
[41]
Joshi, H.N.; Tejwani, R.W.; Davidovich, M.; Sahasrabudhe, V.P.; Jemal, M.; Bathala, M.S.; Varia, S.A.; Serajuddin, A.T.M. Bioavailability enhancement of a poorly water-soluble drug by solid dispersion in polyethylene glycol–polysorbate 80 mixture. Int. J. Pharm., 2004, 269(1), 251-258.
[http://dx.doi.org/10.1016/j.ijpharm.2003.09.002] [PMID: 14698596]
[42]
Kennedy, M.; Hu, J.; Gao, P.; Li, L.; Ali-Reynolds, A.; Chal, B.; Gupta, V.; Ma, C.; Mahajan, N.; Akrami, A.; Surapaneni, S. Enhanced bioavailability of a poorly soluble VR1 antagonist using an amorphous solid dispersion approach: A case study. Mol. Pharm., 2008, 5(6), 981-993.
[http://dx.doi.org/10.1021/mp800061r] [PMID: 19434920]
[43]
Rincón-López, J.; Almanza-Arjona, Y.C.; Riascos, A.P.; Rojas-Aguirre, Y. Technological evolution of cyclodextrins in the pharmaceutical field. J. Drug Deliv. Sci. Technol., 2021, 61, 102156.
[http://dx.doi.org/10.1016/j.jddst.2020.102156] [PMID: 33078064]
[44]
Mai, N.N.S.; Nakai, R.; Kawano, Y.; Hanawa, T. Enhancing the solubility of curcumin using a solid dispersion system with hydroxypropyl-β-cyclodextrin prepared by grinding, freeze-drying, and common solvent evaporation methods. Pharmacy, 2020, 8(4), 203.
[http://dx.doi.org/10.3390/pharmacy8040203] [PMID: 33147710]
[45]
Miranda, G.M.; Santos, V.O.R.; Bessa, J.R.; Teles, Y.C.F.; Yahouédéhou, S.C.M.A.; Goncalves, M.S.; Ribeiro-Filho, J. Inclusion complexes of non-steroidal anti-inflammatory drugs with cyclodextrins: A systematic review. Biomolecules, 2021, 11(3), 361.
[http://dx.doi.org/10.3390/biom11030361] [PMID: 33673414]
[46]
Zhou, J.; Jia, J.; He, J.; Li, J.; Cai, J. Cyclodextrin inclusion complexes and their application in food safety analysis: Recent developments and future prospects. Foods, 2022, 11(23), 3871.
[http://dx.doi.org/10.3390/foods11233871] [PMID: 36496679]
[47]
Loftsson, T.; Brewster, M.E. Cyclodextrins as functional excipients: Methods to enhance complexation efficiency. J. Pharm. Sci., 2012, 101(9), 3019-3032.
[http://dx.doi.org/10.1002/jps.23077] [PMID: 22334484]
[48]
Trott, O.; Olson, A.J. AutoDock vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576]
[49]
Sherje, A.P.; Kulkarni, V.; Murahari, M.; Nayak, U.Y.; Bhat, P.; Suvarna, V.; Dravyakar, B. Inclusion complexation of etodolac with hydroxypropyl-beta-cyclodextrin and auxiliary agents: Formulation characterization and molecular modeling studies. Mol. Pharm., 2017, 14(4), 1231-1242.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b01115] [PMID: 28248111]
[50]
Magnusdottir, A.; Másson, M.; Loftsson, T. Self association and cyclodextrin solubilization of NSAIDs. J. Incl. Phenom. Macrocycl. Chem., 2002, 44(1/4), 213-218.
[http://dx.doi.org/10.1023/A:1023079322024]
[51]
Salah, S.; Mahmoud, A.A.; Kamel, A.O. Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: ex vivo permeation and in vivo pharmacokinetic studies. Drug Deliv., 2017, 24(1), 846-856.
[http://dx.doi.org/10.1080/10717544.2017.1326539] [PMID: 28535740]
[52]
Veiga, M.D.; Díaz, P.J.; Ahsan, F. Interactions of griseofulvin with cyclodextrins in solid binary systems. J. Pharm. Sci., 1998, 87(7), 891-900.
[http://dx.doi.org/10.1021/js970233x] [PMID: 9649360]
[53]
Neacșu, A. Physicochemical investigation of the complexation between γ-cyclodextrin and doxorubicin in solution and in solid state. Thermochim. Acta, 2018, 661, 51-58.
[http://dx.doi.org/10.1016/j.tca.2018.01.012]
[54]
Pralhad, T.; Rajendrakumar, K. Study of freeze-dried quercetin–cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis. J. Pharm. Biomed. Anal., 2004, 34(2), 333-339.
[http://dx.doi.org/10.1016/S0731-7085(03)00529-6] [PMID: 15013147]

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