SYNTHESIS AND EVALUATION OF TASTE-MASKED IONIC LIQUID SALTS OF LORATADINE
Objective:- To synthesize & evaluate taste-masked ionic liquid (IL) salts of loratadine.
Methods:-In present work pharmaceutically activeIL saltsof loratadine using selected counter-ions were synthesized. The synthesized IL salts were characterized using melting point, Ultraviolet (UV) Spectroscopy, Fourier Transform Infra-Red (FTIR) Spectroscopy, Differential Scanning Calorimetry (DSC) & X-ray Diffraction (XRD). These salts were also evaluated for solubility, dissolution and palatability studies.
Result:- All synthesized IL salts of loratadine exhibited melting points below 100 °C. UV spectral data and FTIR data confirmed formation of new salt forms with selected counter-ions. Absence of sharp melting point peaks during DSC studies revealed amorphous nature of new salt forms. During XRD studies, loratadine-indomethacin salt yield completely amorphous compound while other counter-ions intensity of the characteristic peaks of loratadine was found to be reduced. Solubility studies revealed decreased solubility of IL salts in water as compared to loratadine due to lipophilic nature of counter-ions i.e., from 35.85 mg/ml to 3.63 mg/ml, 15.39 mg/ml, 5.31 mg/ml & 3.71 mg/ml respectively. Dissolution studies further confirmed it by showing % drug release from 0.5% reduced to in range from 0.5 to 0.1% in 75 minutes considerably. Except for oleate, all of IL salts were found to be palatable by volunteers in range of 2.5 to 2.8 which is standard range for palatability.
Conclusion:- Results obtained in present work indicated that IL salts of loratadine were synthesized successfully using selected counter-ions. They have better taste than pure loratadine & hence can be used in drug products intended for children.
2. Torimoto T, Tsuda T, Okazaki K, Kuwabata S. New Frontier in Material Science opened by Ionic Liquids. Adv Mater 2010;22:1196–221.
3. Rogers RD, Voth GA. Ionic Liquids. Acc ChemRes 2007;40:1077–78.
4. Whitney L, Hough WL, Smiglak M, Rodr?´guez H, Swatloski RP, Spear SK, et al. The Third Evolution of Ionic Liquids: Active Pharmaceutical Ingredients. New J Chem 2007;31:1429–36.
5. Feng R, Zhao D, Guo Y. Revisiting Characteristics of Ionic Liquids: a Review for Further Application Development. Journal of Environmental Protection 2010;1:95-104.
6. Berthod A, Carda-Broach. Uses of ILs in Analytical Chemistry, Laboratories of Analytical Sciences, CNRS, Lyon 1 University, Bat CPE-308, 69622 Villeurbanne, France.
7. Martins MAP, Frizzo CP, Moreira DN, Zanatta, N, Bonacorso HG. Ionic Liquids in Heterocyclic Synthesis. Chem Rev 2008;108:2015-50.
8. Han X, Armstrong DW. Ionic Liquids in Separations. Acc Chem Res 2007;40:1079-86.
9. Arrahman A, Gahayati A, Rizky D, Muslimah S, Mun’im A. Application of imidazole-based ionic liquids in microwave-assisted extraction of Trans-Resveratrol from Gnetum Gnemon L. Seeds. Int J App Pharm 2018;10:39-42.
10. Hough WL, Rogers RD. Ionic liquids then and now: from solvents to materials to active pharmaceutical ingredients. Bull Chem Soc Jpn 2007;80:2262–9.
11. Hapiot P, Lagrost C. Electrochemical reactivity in room-temperature ionic liquids. Chem Rev 2008;108:2238-64.
12. MacFarlane DR, Forsyth M, Howlett PC, Pringle JM, Sun J, Annat G, et al. Ionic liquids in electrochemical devices and processes: Managing interfacial electrochemistry. Acc Chem Res 2007;40:1165?73.
13. Ferraz R, Branzo LC, Prudencio C, Noronha JP, Petrovski Z. Ionic Liquids as Active Pharmaceutical Ingredients. Chem Med Chem 2011:1-12.
14. Stoimenovski J, MacFarlane DR, Bica K, Rogers RD. Crystalline vs. Ionic Liquid Salt Forms of Active Pharmaceutical Ingredients: A Position Paper. Pharmaceutical Research 2010;27(4):521-26.
15. Hough-Troutman WL, Smiglak M, Griffin S, Reichert WM, Mirska I, Jodynis-Liebert J, et al. Ionic Liquids with Dual Biological Function: Sweet & Anti-microbial, Hydrophobic Quaternary Ammonium-based Salts. New J Chem 2009;33:26–33.
16. Claritin (Loratadine) Drug Information. Available at https://www.rxlist.com/claritin-side-effects-drug-center.htm accessed on 12 December 2018.
17. Claritin Product Monograph, Bayer Inc., December 10, 2018. Available at https://www.bayer.ca/omr/online/claritin-pm-en.pdf accessed on 03 January 2019.
18. Loratadine Solution Drug Information. Available at https://www.webmd.com/drugs/2/drug-73-6282/loratadine-oral/loratadine-liquid-oral/details accessed on 12 December 2018.
19. Dagar A, Gudi S, Opawale, Foyeke, inventors, Oral liquid loratadine formulations and methods, PCT/US2007/069360, 13 December 2017.
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