The Use of Cyclodextrin Inclusion Complexes to Increase the Solubility and Pharmacokinetic Profile of Albendazole
Abstract
:1. Introduction
2. Results and Discussion
recovery rate | intra-assay coefficient of variation | |
Albendazole | 90.2 ± 6.1% to 109.4 ± 4.8% | 2.2% to 3.62% |
Albendazole sulfoxide | 89.8 ± 3.6% to 117.2 ± 2.2% | 1.81% to 2.24% |
Albendazole sulfone | 93.9 ± 4.1% to 103.2 ± 3.1% | 2.78% to 5.49% |
3. Methods and Materials
3.1. Albendazole’s UV Maximum Absorbance Wavelength Determination
3.2. Establishment of Albendazole HPLC Standard Curve
3.3. Preparation of Citrate-β-cyclodextrin
3.4. Solubility of Albendazole in Different Cyclodextrin Solutions
3.5. Preparation of the Inclusion Complexes of Albendazole with Methyl-β-cyclodextrin
3.6. The Preparation of the Physical Mixture of Albendazole and Methyl-β-cyclodextrin
3.7. Preparation of the Inclusion Complexes with Addition of Trace Amount of Water-Soluble Polymer or Organic Salt
3.8. Fourier-Transform Infrared Spectroscopy Study
3.9. Differential Scanning Calorimetry Study
3.10. Proton NMR Study
3.11. Determination of the Albendazole Content in the Complex
3.12. Determination of Water Solubility of Albendazole in the Complex
3.13. Inclusion Rate and Inclusion Yield Determination
3.14. Dissolution Rate Determination
3.15. In Vivo Pharmacokinetic Studies
3.16. Standard Curves for Albendazole, Albendazole Sulfoxide, and Albendazole Sulfone in Plasma
3.17. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
- Horton, J. Albendazole: A broad spectrum anthelminthic for treatment of individuals and populations. Curr. Opin. Infect. Dis. 2002, 15, 599–608. [Google Scholar] [CrossRef] [PubMed]
- Ehteda, A.; Galettis, P.; Pillai, K.; Morris, D.L. Combination of albendazole and 2-methoxyestradiol significantly improves the survival of HCT-116 tumor-bearing nude mice. BMC Cancer 2013, 13, 86. [Google Scholar] [CrossRef] [PubMed]
- Jung, H.; Medina, L.; Garcia, L.; Fuentes, I.; Esparza, M.R. Absorption studies of albendazole and some physicochemical properties of the drug and its metabolite albendazole sulphoxide. J. Pharm. Pharmacol. 1998, 50, 43–48. [Google Scholar] [CrossRef]
- Chai, J.Y.; Jung, B.K.; Hong, S.J. Albendazole and mebendazole as anti-parasitic and anti-cancer agents: An update. Korean J. Parasitol. 2021, 59, 189–225. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.Y.; Martin, J.H.; Mclachlan, A.J.; Boddy, A.V. Precision dosing of targeted anticancer drugs—Challenges in the real world. Transl. Cancer Res. 2017, 6 (Suppl. S10), S1500–S1511. [Google Scholar] [CrossRef]
- Wang, M.; Xiao, S.; Chai, J.; Liang, B.; Fu, C.; Shen, W.; Peter, H. Albendazole-soybean oil emulsion for the treatment of human cystic echinococcosis: Evaluation of bioavailability and bioequivalence. Acta Tropica 2002, 83, 177–181. [Google Scholar]
- Del Estal, J.L.; Alvarez, A.I.; Villaverde, C.; Coronel, P.; Fabra, S.; Prieto, J.G. Effect of surfactants on Albendazole absorption. J. Pharm. Biomed. Anal. 1991, 9, 1161–1164. [Google Scholar] [CrossRef]
- Maqbool, F.; Moyle, P.M.; Tan, M.S.A.; Thurecht, K.J.; Falconer, J.R. Preparation of albendazole-loaded liposomes by supercritical carbon dioxide processing. Artif. Cells Nanomed. Biotechnol. Int. J. 2018, 46, S1186–S1192. [Google Scholar] [CrossRef]
- Lopez, M.L.; Torrado, S.; Martínez, A.R.; Bolás, F. Improvement of Albendazole Efficacy against Enteral, but Not against Parenteral Stages of Trichinella spiralis by Preparing Solid Dispersions in Polyvinylpyrrolidone. Chemotherapy 1997, 43, 430–435. [Google Scholar] [CrossRef]
- Chen, B.; Zhao, J.; Zhang, H.; Wang, J.; Ma, Y. Determination of Equilibrium solubility of albendazole and its Apparent Oil-Water partition coefficient. China Pharm. 2015, 12, 3092–3095. [Google Scholar]
- Kasetti, Y.; Bharatam, P.V. Tautomerism in drugs with benzimidazole carbamate moiety: An electronic structure analysis. Theor. Chem. Acc. 2012, 131, 1160. [Google Scholar] [CrossRef]
- Pranzo, M.B.; Cruickshank, D.; Coruzzi, M.; Caira, M.R.; Bettini, R. Enantiotropically related albendazole polymorphs. J. Pharm. Sci. 2010, 99, 3731–3742. [Google Scholar] [CrossRef] [PubMed]
- Priotti, J.; García, A.; Leonardi, D.; Ferreira, M.J.; Lamas, M.C.; Nunes, T.G. Succinyl-β-cyclodextrin: Influence of the substitution degree on albendazole inclusion complexes probed by NMR. Mater. Sci. Eng. C 2018, 92, 694–702. [Google Scholar] [CrossRef] [PubMed]
- Brewster, M.E.; Loftsson, T. Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Deliv. Rev. 2007, 59, 645–666. [Google Scholar] [CrossRef]
- Moriwaki, C.; Costa, G.L.; Ferracini, C.N.; de Moraes, F.F.; Zanin, G.M.; Pineda, E.A.G.; Matioli, G. Enhancement of solubility of albendazole by complexation with β-cyclodextrin. Braz. J. Chem. Eng. 2008, 25, 255–267. [Google Scholar] [CrossRef]
- Patel, V.P.; Parikh, R.K.; Gohel, M.C.; Desai, T.R.; Bhimani, D.R.; Tirgar, P.R. In Vitro Dissolution enhancement of albendazole by preparation of inclusion complex with HP-β-Cyclodextrin. Pharma Sci. Monit. Int. J. Pharm. Sci. 2011, 2, 161–173. [Google Scholar]
- Stella, V.J.; Rajewski, R.A. Cyclodextrins: Their future in drug formulation and delivery. Pharm. Res. 1997, 14, 556–557. [Google Scholar] [CrossRef]
- Bassani, V.L.; Krieger, D.; Duchene, D.; Wouessidjewe, D.; Szejtli, J.; Szente, L. Proceedings of the Eighth International Symposium on Cyclodextrons; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1996; pp. 321–324. [Google Scholar]
- Castillo, J.A.; Palomo-Canales, J.; Garcia, J.J.; Lastres, J.L.; Bolas, F. Preparation and characterization of albendazole β-cyclodextrin complexes. Drug Dev. Ind. Pharm. 1999, 25, 1241–1248. [Google Scholar] [CrossRef]
- Anjana, M.N.; Jipnomon, J.; Sreeja, C.N. Solubility and bioavailability enhancement of albendazole by complexing with hydroxy propyl β cyclodextrin. J. Chem. Pharm. Res. 2015, 7, 1131–1141. [Google Scholar]
- Stepniak, A.; Buczkowski, A.; Zavodnik, L.; Belica-Pacha, S.; Palecz, B. Study of the interaction of β-cyclodextrin with albendazole in aqueous solutions. J. Mol. Liq. 2017, 248, 19–23. [Google Scholar] [CrossRef]
- Pourgholami, M.H.; Wangoo, K.T.; Morris, D.L. Albendazole-cyclodextrin complex: Enhanced cytotoxicity in ovarian cancer cells. Anticancer Res. 2008, 28, 2775–2780. [Google Scholar]
- Evrard, B.; Chiap, P.; DeTullio, P.; Ghalmi, F.; Piel, G.; Van Hees, T.; Crommen, J.; Losson, B.; Delattre, L. Oral bioavailability in sheep of albendazole from a suspension and from a solution containing hydroxypropyl-β-cyclodextrin. J. Control. Release 2002, 85, 45–50. [Google Scholar] [CrossRef]
- Ehteda, A.; Galettis, P.; Chu, S.W.L.; Pillai, K.; Morris, D.L. Complexation of albendazole with hydroxypropyl-β-cyclodextrin significantly improves its pharmacokinetic profile, cell cytotoxicity and antitumor efficacy in nude mice. Anticancer Res. 2012, 32, 3659–3666. [Google Scholar]
- Pillai, K.; Akhter, J.; Morris, D.L. Super aqueous solubility of albendazole in β-cyclodextrin for parenteral application in cancer therapy. J. Cancer 2017, 8, 913–923. [Google Scholar] [CrossRef] [PubMed]
- Anjana, M.N. Formulation, in vitro and in vivo analysis of cyclodextrin complexed albendazole composites for enhanced solubility. Der Pharma Chem. 2018, 10, 41–50. [Google Scholar]
- Hedges, A.R. Industrial applications of cyclodextrins. Chem. Rev. 1998, 98, 2035–2044. [Google Scholar] [CrossRef]
- Pradines, B.; Gallard, J.; Iorga, B.I.; Gueutin, C.; Loiseau, P.M.; Ponchel, G.; Bouchemal, K. Investigation of the complexation of albendazole with cyclodextrins for the design of new antiparasitic formulations. Carbohydr. Res. 2014, 398, 50–55. [Google Scholar] [CrossRef]
- Garcı’a, A.; Leonardi, D.; Vasconi, M.D.; Hinrichsen, L.I.; Lamas, M.C. Characterization of albendazole-randomly methylated β-cyclodextrin inclusion complex and in vivo evaluation of its antihelmitic activity in a murine model of trichinellosis. PLoS ONE 2014, 9, e113296. [Google Scholar]
- Ferreira, M.J.G.; García, A.; Leonardi, D.; Salomon, C.J.; Lamas, M.C.; Nunes, T.G. 13C and 15N solid-state NMR studies on albendazole and cyclodextrin albendazole complexes. Carbohydr. Polym. 2015, 123, 130–135. [Google Scholar] [CrossRef]
- Garcı, A.; Leonardi, D.; Salazar, M.O.; Lamas, M.C. Modified β-cyclodextrin inclusion complex to improve the physicochemical properties of albendazole complete in vitro evaluation and characterization. PLoS ONE 2014, 9, 88234. [Google Scholar]
- García, A.; Priotti, J.; Codina, A.V.; Vasconi, M.D.; Quiroga, A.D.; Hinrichsen, L.I.; Leonardi, D.; Lamas, M.C. Synthesis and characterization of a new cyclodextrin derivative with improved properties to design oral dosage forms. Drug Deliv. Transl. Res. 2019, 9, 273–283. [Google Scholar] [CrossRef]
- Rodrigues, L.N.C.; Tavares, A.C.M.; Ferreira, B.T.; Reis, A.K.C.A.; Katiki, L.M. Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles. Braz. J. Pharm. Sci. 2019, 55, 1–11. [Google Scholar] [CrossRef]
- Trandafirescu, C.; Ledeti, I.; Soica, C.; Ledeti, A.; Vlase, G.; Borcan, F.; Dehelean, C.; Coricovac, D.; Racoviceanu, R.; Aigner, Z. Albendazole-cyclodextrins binary systems. J. Therm. Anal. Calorim. 2019, 138, 3039–3054. [Google Scholar] [CrossRef]
- Pacheco, P.A.; Rodrigues, L.N.C.; Ferreira, J.F.S.; Gomes, A.C.P.; Veríssimo, C.J.; Louvandini, H.; Costa, R.L.D.; Katiki, L.M. Inclusion complex and nanoclusters of cyclodextrin to increase the solubility and efficacy of albendazole. Parasitol. Res. 2018, 117, 705–712. [Google Scholar] [CrossRef] [PubMed]
- Rosas, M.D.; Piqueras, C.M.; Piva, G.K.; Veronica, M.; Cardozo, R.L.; Bucalá, F.V. Simultaneous formation of inclusion complex and microparticles containing albendazole and β-cyclodextrin by supercritical antisolvent co-precipitation. J. CO Util. 2021, 47, 101505. [Google Scholar] [CrossRef]
- Eriksen, J.B.; Christensen, S.B.; Bauer-Brandl, A.; Brandl, M. Dissolution/permeation of albendazole in the presence of cyclodextrin and bile salts: A mechanistic in vitro study into factors governing oral bioavailability. J. Pharm. Sci. 2022, 111, 1667–1673. [Google Scholar] [CrossRef]
- Ding, Y.; Prasad, C.V.N.S.V.; Ding, C.; Wang, B. Synthesis of carbohydrate conjugated 6A,6D-bifunctionalized β-cyclodextrin derivatives as potential liver cancer drug carriers. Carbohydr. Poly. 2018, 181, 957–963. [Google Scholar] [CrossRef]
- Ding, Y.; Pang, Y.; Prasad, C.V.N.S.V.; Wang, B. Formation of inclusion complex of enrofloxacin with 2-hydroxypropyl-β-cyclodextrin. Drug Deliv. 2020, 27, 334–343. [Google Scholar] [CrossRef] [PubMed]
- Ding, Y.; Cui, W.; Pang, Y.; Prasad, C.V.N.S.V.; Wang, B. Preparation of inclusion complex of praziquantel with 2-hydroxypropyl-β-cyclodextrin and pharmacokinetic property improvement. Arab. J. Chem. 2021, 14, 103307. [Google Scholar] [CrossRef]
- Ding, Y.; Yu, B.; Zhang, J.; Ding, C.; Zhang, Z.; Xu, S.; Li, L.; Yu, H. Tilmicosin/γ-cyclodextrin complexation through supercritical carbon dioxide assistance and its pharmacokinetic and anti-bacterial study. Euro. J. Pharm. Biopharm. 2022, 181, 104–112. [Google Scholar] [CrossRef]
- Ding, Y.; Yu, B.; Zhou, S.; Ding, C.; Zhang, Z.; Xu, S.; Xu, Z. Improvement of solubility and pharmacokinetic profile of hepatoprotector icariin through complexation with HP-γ-cyclodextrin. Front. Pharmacol. 2023, 14, 1138686. [Google Scholar] [CrossRef]
- De Marco, F.I. Preparation of non-steroidal anti-inflammatory drug/β-cyclodextrin inclusion complexes by supercritical antisolvent process. J. CO2 Util. 2021, 44, 101397. [Google Scholar]
- Wang, C.; Yan, T.; Yan, T.; Wang, Z. Fabrication of hesperetin/hydroxypropyl-β-cyclodextrin complex nanoparticles for enhancement of bioactivity using supercritical antisolvent technology. J. Mol. Struct. 2023, 1279, 134947. [Google Scholar] [CrossRef]
- Donthi, M.R.; Munnangi, S.R.; Krishna, K.V.; Marathe, S.A.; Saha, R.N.; Singhvi, G.; Dubey, S.K. Formulating ternary inclusion complex of sorafenib tosylate using β-cyclodextrin and hydrophilic polymers: Physicochemical characterization and in vitro assessment. AAPS PharmSciTech 2022, 23, 254. [Google Scholar] [CrossRef] [PubMed]
- Mohandoss, S.; Velu, K.S.; Stalin, T.; Ahmad, N.; Alomar, S.Y.; Lee, Y.R. Tenofovir antiviral drug solubility enhancement with β-cyclodextrin inclusion complex and in silico study of potential inhibitor against SARS-CoV-2 main protease (Mpro). J. Mol. Liq. 2023, 377, 121544. [Google Scholar] [CrossRef]
- Huang, Y.; Zu, Y.; Zhao, X.; Wu, M.; Feng, Z.; Deng, Y.; Zu, C.; Wang, L. Preparation of inclusion complex of apigenin-hydroxypropyl-β-cyclodextrin by using supercritical antisolvent process for dissolution and bioavailability enhancement. Int. J. Pharm. 2016, 511, 921–930. [Google Scholar] [CrossRef]
- Higuchi, T.; Connors, K.A. Phase-solubility techniques. Adv. Anal. Chem. Instrum. 1965, 4, 117–212. [Google Scholar]
- Cid-Samamed, A.; Rakmai, J.; Mejuto, J.C.; Simal-Gandara, J.; Astray, G. Cyclodextrins inclusion complex: Preparation methods, analytical techniques and food industry applications. Food Chem. 2022, 384, 132467. [Google Scholar] [CrossRef] [PubMed]
- Politis, S.N.; Colombo, P.; Colombo, G.; Rekkas, D.M. Design of experiments (DoE) in pharmaceutical development. Drug Dev. Ind. Pharm. 2017, 43, 889–901. [Google Scholar] [CrossRef]
- Saokham, P.; Muankaew, C.; Jansook, P.; Loftsson, T. Solubility of cyclodextrins and drug/cyclodextrin complexes. Molecules 2018, 23, 1161. [Google Scholar] [CrossRef]
- Loftsson, T.; Saokham, P.; Couto, A.R.S. Self-association of cyclodextrins and cyclodextrin complexes in aqueous solutions. Int. J. Pharm. 2019, 560, 228–234. [Google Scholar] [CrossRef] [PubMed]
- Dayan, A.D. Albendazole, mebendazole, and praziquantel: Review of nonclinical toxicity and pharmacokinetics. Acta Trop. 2003, 86, 141–159. [Google Scholar] [CrossRef]
- Arroyo, G.; Bustos, J.A.; Lescano, A.G.; Gonzales, I.; Saavedra, H.; Rodriguez, S.; Pretell, D.E.J.; Bonato, P.S.; Lanchote, V.L.; Takayanagui, O.M.; et al. Albendazole sulfoxide plasma levels and efficacy of antiparasitic treatment in patients with parenchymal neurocysticercosis. Clin. Infect. Dis. 2019, 69, 1996–2002. [Google Scholar] [CrossRef] [PubMed]
- Horton, J. Albendazole: A review of anthelmintic efficacy and safety in humans. Parasitology 2000, 121, S113–S312. [Google Scholar] [CrossRef] [PubMed]
- Chaleawlert-umpon, S.; Nuchuchua, O.; Saesoo, S.; Gonil, P.; Ruktanonchai, U.R.; Sajomsang, W.; Pimpha, N. Effect of citrate spacer on mucoadhesive properties of a novel water-soluble cationic β-cyclodextrin-conjugated chitosan. Carbohydr. Poly. 2011, 84, 186–194. [Google Scholar] [CrossRef]
Albendazole | ||||
Parameter | Unit | ABZSO | ABZSO2 | ABZ |
Tmax | h | 3.00 ± 1.15 | 4.00 ± 1.06 | 0.50 ± 0.21 |
Cmax | μg/mL | 2.81 ± 0.67 | 1.63 ± 0.42 | 0.51 ± 0.19 |
T1/2 | h | 18.48 ± 1.13 | 14.66 ± 1.54 | 14.43 ± 2.56 |
AUC0–48 | h⁎μg/mL | 50.72 ± 6.28 | 34.66 ± 4.91 | 9.29 ± 2.53 |
MRT0–48 | h | 24.35 ± 1.42 | 21.55 ± 1.52 | 24.75 ± 4.13 |
Complex | ||||
Parameter | Unit | ABZSO | ABZSO2 | ABZ |
Tmax | h | 6.00 ± 1.29 | 4.00 ± 0.44 | 0.75 ± 0.63 |
Cmax | μg/mL | 10.20 ± 1.91 | 1.16 ± 0.61 | 1.08 ± 0.28 |
T1/2 | h | 3.04 ± 1.07 | 10.18 ± 1.09 | 1.88 ± 0.53 |
AUC0–48 | h⁎μg/mL | 119.95 ± 11.7 | 22.50 ± 3.61 | 3.92 ± 2.06 |
MRT0–48 | h | 7.70 ± 1.16 | 15.53 ± 1.42 | 3.43 ± 1.32 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ding, Y.; Zhang, Z.; Ding, C.; Xu, S.; Xu, Z. The Use of Cyclodextrin Inclusion Complexes to Increase the Solubility and Pharmacokinetic Profile of Albendazole. Molecules 2023, 28, 7295. https://doi.org/10.3390/molecules28217295
Ding Y, Zhang Z, Ding C, Xu S, Xu Z. The Use of Cyclodextrin Inclusion Complexes to Increase the Solubility and Pharmacokinetic Profile of Albendazole. Molecules. 2023; 28(21):7295. https://doi.org/10.3390/molecules28217295
Chicago/Turabian StyleDing, Yili, Zhiyuan Zhang, Charles Ding, Shufeng Xu, and Zhe Xu. 2023. "The Use of Cyclodextrin Inclusion Complexes to Increase the Solubility and Pharmacokinetic Profile of Albendazole" Molecules 28, no. 21: 7295. https://doi.org/10.3390/molecules28217295