EFFICACY OF HYDROTROPES ON THE SOLUBILITY OF FORSKOLIN IN WATER
Objective: The main purpose of this study is to assess quantitatively, the effect of the addition of hydrotropes, namely urea, sodium salicylate, and sodium benzoate on the solubility of forskolin in water, and to compare the efficacy of hydrotropes in increasing aqueous solubility of forskolin. Hydrotropes were chosen for this study, based on their wavelengths, and physical properties.
Methods: The maximum wavelength of absorption of forskolin was determined spectrophotometrically, using a UV-Vis spectrometer. It was found to be 220 nm and was instrumental in the selection of hydrotropes for this experiment. Physical properties (viscosity, specific gravity and surface tension) of the chosen hydrotropes, namely sodium salicylate, urea, and sodium benzoate, were measured, over a range of concentrations and they indicated the approximate value of the minimum hydrotrope concentration of each hydrotrope. Stock solutions (1M) of the hydrotropes chosen, were prepared, and this was followed by, preparation of standard samples of forskolin, in hydrotropic solutions. These samples were analyzed spectroscopically, to obtain the characteristic calibration curves, for each hydrotrope. Solubility studies were then conducted, and the data obtained, was used to calculate enhancement ratios, which is a measure of the efficacy of a hydrotrope, in increasing aqueous solubility of a solute.
Results: The addition of hydrotropes showed a remarkable increase in aqueous solubility of forskolin. Sodium salicylate proved more effective registering an enhancement ratio of 297.02, compared to sodium benzoate, which recorded a ratio of 296.97 and urea which showed a ratio of 43.35.
Conclusion: Sodium salicylate and sodium benzoate showed very high enhancement ratios when compared to urea. This enhanced performance can be attributed to the large number of carbon atoms and the cyclic structure, which increases the hydrophobic nature of the hydrotrope. Higher efficacy of sodium salicylate can be ascribed to, the presence of hydroxyl group which increases the aqueous solubility of sodium salicylate, leading to better hydrotropic action.
Keywords: Forskolin, Hydrotropy, Solubility, UV Spectrometry, Sodium salicylate, Sodium benzoate, Urea
2. Carl Neuberg. Hydrotropy. Biochem Z; 1916. p. 107-9.
3. Hodgdon TK, Kaler EW. Hydrotropic solutions. Curr Opin Colloid Interface Sci 2007;12:121-8.
4. Lee J, Lee SC, Acharya G, Chang C, Park K. Hydrotropic solubilization of paclitaxel: analysis of chemical structures for the hydrotropic property. Pharm Res 2003;20:1022-30.
5. Laxman M, Sharma MM. Reduction of Isophorone with borohydride: change in regioselectivity with hydrotropes. Synth Commun 1990;20:111-7.
6. Agarwal M, Gaikar VG. Extractive separation using hydrotropes. Sep Technol 1992;2:79-84.
7. Friberg SE, Brancewicz C. O/W Microemulsions, and hydrotropes: the coupling action of a hydrotrope. Langmuir 1994;10:2945-9.
8. Varagunapandiyan N, Nagendra Gandhi N. Enhancement of solubility and mass transfer coefficient through hydrotherapy. Int J Appl Sci Eng 2008;6:97-110.
9. Friberg SE, Lochhead RV, Blute I, Warnheim T. Hydrotropes performance chemicals. J Dispersion Sci Technol 2004;25:243-51.
10. Friberg SE, Yang J, Huang T. Vapor pressure of phenethyl alcohol in an aqueous hydrotrope solution. Colloids Surf A 1997;127:233-9.
11. Roy BK, Moulik SP. Effect of hydrotropes on solution behavior of amphiphiles. Curr Sci 2003;85:1148-56.
12. Srinivas V, Rodley GA, Ravikumar K, Robinson WT, Turbull MM, Balasubramanian D, et al. Molecular organization in hydrotrope assemblies. Langmuir 1997;13:3235-9.
13. Tirucherai GS, Mitra AK. Effect of hydroxypropyl beta-cyclodextrin complexation on aqueous solubility, stability, and corneal permeation of acyl ester prodrugs of ganciclovir. AAPS PharmSciTech 2003;4:45-6.
14. Strickley RG. Solubilizing excipients in oral and injectable formulations. Pharm Res 2004;21:201-30.
15. Nema S, Washkuhn RJ, Brendel RJ. Excipients and their use in injectable products. PDA J Pharm Sci Technol 1997;51:166-71.
16. Rubino JT, Yalkowsky SH. Co-solvency and deviations from linear log solubilization. Pharm Res 1987;4:231-6.
17. Srinivas V, Sundaram CS, Balasubramanian D. Molecular structure as a determinant of hydrotropic action. Int J Chem 1991;30B:147-52.
18. Kumar S, Parveen N, Kabir-ud-Din. Additive-induced association in unconventional systems: A case of the hydrotrope. J Surfactants Deterg 2005;8:109-14.
19. Thenesh Kumar S, Nagendra Gandhi N. A study on the properties of hydrotrope solutions for the enhancement of solubility of p-aminobenzoic acid through Hydrotropy. Int J Pharm Pharm Sci 2012;4:324-30.
20. Ruchi J, Nilesh J, Deepak KJ, Surendra KJ. A novel approach using hydrotropic solubilization technique for quantitative estimation of entacapone in bulk drug and dosage form. Adv Pharm Bull 2013;3:409-13.
21. Thenesh Kumar S, Nagendra Gandhi N. Association model of hydrotropy for the effect of hydrotropes on solubility and mass transfer coefficient of acetylsalicylic acid. Int J Pharm Pharm Sci 2012;4:600-5.
22. Girishpai K, Divya S, Sreenivasa reddy M, Lalit Kumar, Vamshi Krishna T. Solubility enhancement of Norfloxacin by hydrotherapy technique. Int J Pharm Pharm Sci 2014;6:324-30.