Abstract
Albendazole (ABZ) and ricobendazole (RBZ) are referred to as class II compounds in the Biopharmaceutical Classification System. These drugs exhibit poor solubility, which profoundly affects their oral bioavailability. Micellar systems are excellent pharmaceutical tools to enhance solubilization and absorption of poorly soluble compounds. Polysorbate 80 (P80), poloxamer 407 (P407), sodium cholate (Na-C), and sodium deoxycholate (Na-DC) have been selected as surfactants to study the solubilization process of these drugs. Fluorescence emission was applied in order to obtain surfactant/fluorophore (S/F) ratio, critical micellar concentration, protection efficiency of micelles, and thermodynamic parameters. Systems were characterized by their size and zeta potential. A blue shift from 350 to 345 nm was observed when ABZ was included in P80, Na-DC, and Na-C micelles, while RBZ showed a slight change in the fluorescence band. P80 showed a significant solubilization capacity: S/F values were 688 for ABZ at pH 4 and 656 for RBZ at pH 6. Additionally, P80 micellar systems presented the smallest size (10 nm) and their size was not affected by pH change. S/F ratio for bile salts was tenfold higher than for the other surfactants. Quenching plots were linear and their constant values (2.17/M for ABZ and 2.29/M for RBZ) decreased with the addition of the surfactants, indicating a protective effect of the micelles. Na-DC showed better protective efficacy for ABZ and RBZ than the other surfactants (constant values 0.54 and 1.57/M, respectively), showing the drug inclusion into the micelles. Entropic parameters were negative in agreement with micelle formation.
References
Uneke C. Soil transmitted helminth infections and schistosomiasis in school age children in sub-Saharan Africa: efficacy of chemotherapeutic intervention since World Health Assembly Resolution 2001. Tanzan J Health Res. 2010;12(1):86–99.
Priotti J, Codina AV, Leonardi D, Vasconi MD, Hinrichsen LI, Lamas MC. Albendazole microcrystal formulations based on chitosan and cellulose derivatives: physicochemical characterization and in vitro parasiticidal activity in Trichinella spiralis adult worms. AAPS PharmSciTech. 2017;18(4):947–56. https://doi.org/10.1208/s12249-016-0659-z.
Mascarini-Serra L. Prevention of soil-transmitted helminth infection. J Glob Infect Dis. 2011;3(2):175–82. https://doi.org/10.4103/0974-777X.81696.
Castro L, Kviecinski MR, Ourique F, Parisotto EB, Grinevicius V, Correia JFG, et al. Albendazole as a promising molecule for tumor control. Redox Biol. 2016;10:90–9. https://doi.org/10.1016/j.redox.2016.09.013.
Pranzo MB, Cruickshank D, Coruzzi M, Caira MR, Bettini R. Enantiotropically related albendazole polymorphs. J Pharm Sci. 2010;99(9):3731–42. https://doi.org/10.1002/jps.22072.
Wu Z, Razzak M, Tucker IG, Medlicott NJ. Physicochemical characterization of ricobendazole: I. Solubility, lipophilicity, and ionization characteristics. J Pharm Sci. 94(5):983–93.
Yadav D, Kumar N. Nanonization of curcumin by antisolvent precipitation: process development, characterization, freeze drying and stability performance. Int J Pharm. 2014;477(1–2):564–77. https://doi.org/10.1016/j.ijpharm.2014.10.070.
García A, Leonardi D, Salazar MO, Lamas MC. Modified β-cyclodextrin inclusion complex to improve the physicochemical properties of albendazole. Complete in vitro evaluation and characterization. PLoS One. 2014;9(2):e88234. https://doi.org/10.1371/journal.pone.0088234.
Castro SG, Bruni SS, Lanusse CE, Allemandi DA, Palma SD. Improved albendazole dissolution rate in pluronic 188 solid dispersions. AAPS PharmSciTech. 2010;11(4):1518–25. https://doi.org/10.1208/s12249-010-9517-6.
Wu Z, Razzak M, Tucker IG, Medlicott NJ. Physicochemical characterization of ricobendazole: I. Solubility, lipophilicity, and ionization characteristics. J Pharm Sci. 2005;94(5):983–93. https://doi.org/10.1002/jps.20282.
Wu Z, Tucker IG, Razzak M, Medlicott NJ. Stability of ricobendazole in aqueous solutions. J Pharm Biomed Anal. 2009;49(5):1282–6. https://doi.org/10.1016/j.jpba.2009.02.032.
Fernández L, Sigal E, Otero L, Silber J, Santo M. Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers. Braz J Chem Eng. 2011;28(4):679–89. https://doi.org/10.1590/S0104-66322011000400013.
Motlagh NSH, Parvin P, Ghasemi F, Atyabi F. Fluorescence properties of several chemotherapy drugs: doxorubicin, paclitaxel and bleomycin. Biomed Opt Express. 2016;7(6):2400–6. https://doi.org/10.1364/BOE.7.002400.
Salahuddin, Shaharyar M, Mazumder A. Benzimidazoles: a biologically active compounds. Arab J Chem. 2017;10(1):S157–S73. https://doi.org/10.1016/j.arabjc.2012.07.017.
Shvadchak VV, Kucherak O, Afitska K, Dziuba D, Yushchenko DA. Environmentally sensitive probes for monitoring protein-membrane interactions at nanomolar concentrations. Biochim Biophys Acta. 2017;1859(5):852–9. https://doi.org/10.1016/j.bbamem.2017.01.021.
Calafato NR, Picó G. Griseofulvin and ketoconazole solubilization by bile salts studied using fluorescence spectroscopy. Colloids Surf B Biointerfaces. 2006;47(2):198–204. https://doi.org/10.1016/j.colsurfb.2005.01.007.
Piñeiro L, Novo M, Al-Soufi W. Fluorescence emission of pyrene in surfactant solutions. Adv Colloid Interface Sci. 2015;215(Supplement C):1–12.
Stępnik KE, Malinowska I. Determination of binding properties of ampicillin in drug-human serum albumin standard solution using N-vinylpyrrolidone copolymer combined with the micellar systems. Talanta. 2017;162:241–8. https://doi.org/10.1016/j.talanta.2016.09.054.
Ashok B, Arleth L, Hjelm RP, Rubinstein I, Önyüksel H. In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization: effects of PEG chain length and PC incorporation. J Pharm Sci. 2004;93(10):2476–87. https://doi.org/10.1002/jps.20150.
Calabrese I, Gelardi G, Merli M, Liveri MLT, Sciascia L. Clay-biosurfactant materials as functional drug delivery systems: slowing down effect in the in vitro release of cinnamic acid. Appl Clay Sci. 2017;135:567–74. https://doi.org/10.1016/j.clay.2016.10.039.
Croy SR, Kwon GS. Polysorbate 80 and cremophor EL micelles deaggregate and solubilize nystatin at the core–corona interface. J Pharm Sci. 2005;94(11):2345–54. https://doi.org/10.1002/jps.20301.
Cheng M, Zeng G, Huang D, Yang C, Lai C, Zhang C, et al. Advantages and challenges of Tween 80 surfactant-enhanced technologies for the remediation of soils contaminated with hydrophobic organic compounds. Chem Eng J. 2017;314:98–113. https://doi.org/10.1016/j.cej.2016.12.135.
Ćirin D, Krstonošić V, Poša M. Properties of poloxamer 407 and polysorbate mixed micelles: influence of polysorbate hydrophobic chain. J Ind Eng Chem. 2017;47:194–201. https://doi.org/10.1016/j.jiec.2016.11.032.
Adams ML, Lavasanifar A, Kwon GS. Amphiphilic block copolymers for drug delivery. J Pharm Sci. 2003;92(7):1343–55. https://doi.org/10.1002/jps.10397.
Pitto-Barry A, Barry NPE. Pluronic[registered sign] block-copolymers in medicine: from chemical and biological versatility to rationalisation and clinical advances. Polym Chem. 2014;5(10):3291–7. https://doi.org/10.1039/C4PY00039K.
Chavda S, Danino D, Aswal VK, Singh K, Marangoni DG, Bahadur P. Microstructure and transitions in mixed micelles of cetyltrimethylammonium tosylate and bile salts. Colloids Surf A Physicochem Eng Asp. 2017;513:223–33. https://doi.org/10.1016/j.colsurfa.2016.10.047.
Holm R, Müllertz A, Mu H. Bile salts and their importance for drug absorption. Int J Pharm. 2013;453(1):44–55. https://doi.org/10.1016/j.ijpharm.2013.04.003.
Hidalgo-Rodríguez M, Fuguet E, Ràfols C, Rosés M. Solute–solvent interactions in micellar electrokinetic chromatography: VII. Characterization of sodium cholate–sodium deoxycholate mixed-micellar systems. J Chromatogr A. 2010;1217(10):1701–8. https://doi.org/10.1016/j.chroma.2010.01.001.
Selvam S, Andrews ME, Mishra AK. A photophysical study on the role of bile salt hydrophobicity in solubilizing amphotericin B aggregates. J Pharm Sci. 2009;98(11):4153–60. https://doi.org/10.1002/jps.21718.
Martin AN, Bustamante P. Physical pharmacy: physical chemical principles in the pharmaceutical sciences. 4th ed. Philadelphia: Lea & Febiger; 1993.
Sepúlveda L, Pérez-Cotapos J. Interactions between alkyl xanthates and cationic micelles. J Colloid Interface Sci. 1986;109(1):21–30. https://doi.org/10.1016/0021-9797(86)90277-8.
Enache M, Volanschi E. Spectral studies on the molecular interaction of anticancer drug mitoxantrone with CTAB micelles. J Pharm Sci. 2011;100(2):558–65. https://doi.org/10.1002/jps.22289.
Jindal N, Mehta SK. Nevirapine loaded Poloxamer 407/Pluronic P123 mixed micelles: optimization of formulation and in vitro evaluation. Colloids Surf B Biointerfaces. 2015;129:100–6. https://doi.org/10.1016/j.colsurfb.2015.03.030.
Lackowicz JR. Principles of fluorescence spectroscopy. 3rd ed. New York: Plenum Press; 1983. https://doi.org/10.1007/978-1-4615-7658-7.
Suksiriworapong J, Rungvimolsin T, Ag-omol A, Junyaprasert VB, Chantasart D. Development and characterization of lyophilized diazepam-loaded polymeric micelles. AAPS PharmSciTech. 2014;15(1):52–64. https://doi.org/10.1208/s12249-013-0032-4.
Balakrishnan A, Rege BD, Amidon GL, Polli JE. Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity. J Pharm Sci. 2004;93(8):2064–75. https://doi.org/10.1002/jps.20118.
Markina A, Ivanov V, Komarov P, Khokhlov A, Tung SH. Self-assembly of micelles in organic solutions of lecithin and bile salt: mesoscale computer simulation. Chem Phys Lett. 2016;664:16–22. https://doi.org/10.1016/j.cplett.2016.09.078.
Kaya A, Yukselen Y. Zeta potential of soils with surfactants and its relevance to electrokinetic remediation. J Hazard Mater. 2005;120(1–3):119–26. https://doi.org/10.1016/j.jhazmat.2004.12.023.
Mallick A, Purkayastha P, Chattopadhyay N. Photoprocesses of excited molecules in confined liquid environments: an overview. J Photochem Photobiol C Photochem Rev. 2007;8(3):109–27. https://doi.org/10.1016/j.jphotochemrev.2007.06.001.
Nayak MK, Dogra SK. Solvatochromism and prototropism in methyl 6-aminonicotinate: failure to observe amine-imine phototautomerism in solvents. J Mol Struct. 2004;702(1–3):85–94. https://doi.org/10.1016/j.molstruc.2004.06.014.
Subuddhi U, Mishra AK. Micellization of bile salts in aqueous medium: a fluorescence study. Colloids Surf B Biointerfaces. 2007;57(1):102–7. https://doi.org/10.1016/j.colsurfb.2007.01.009.
Small DM, Penkett SA, Chapman D. Studies on simple and mixed bile salt micelles by nuclear magnetic resonance spectroscopy. Biochim Biophys Acta. 1969;176(1):178–89. https://doi.org/10.1016/0005-2760(69)90086-1.
Raupp G, Felippe AC, Frizon TEA, Silva L, Paula MMS, Dal-Bó AG. Determination of the stabilization time of the solution-air interface for aggregates formed by NaC in mixtures with SDS and PEO, investigated by dynamic surface tension measurements. Soft. 2014;3:1–10.
Acknowledgements
J.P. is grateful to the CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas) for a Doctoral Fellowship. This work was supported by the Universidad Nacional de Rosario, CONICET (Project No. PIP 112-201001-00194) and Agencia Nacional de Promoción Científica y Tecnológica (Project No. PICT 2006-1126). The authors would like to thank Laura Gutierrez and Antonella Giorello from Facultad de Ingeniería Química, Universidad Nacional del Litoral, for Malvern Zetasizer Nano ZS90. We would like to thank the staff from the English Department (Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario) for the language correction of the manuscript.
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Priotti, J., Leonardi, D., Pico, G. et al. Application of Fluorescence Emission for Characterization of Albendazole and Ricobendazole Micellar Systems: Elucidation of the Molecular Mechanism of Drug Solubilization Process. AAPS PharmSciTech 19, 1152–1159 (2018). https://doi.org/10.1208/s12249-017-0927-6
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DOI: https://doi.org/10.1208/s12249-017-0927-6