Abstract
The solubility behavior of pimozide in individual solvents ranging from nonpolar to highly polar was studied. For understanding the solute-solvent interactions, the partial solubility parameters concept was utilized. Solutions containing excess drug were shaken in a water bath for 72 hours at 25 °C. After the solutions attained equilibrium, they were filtered and analyzed for drug content. A multiple regression method, using extended Hansen’s partial solubility parameters, was applied to verify the solubilities of pimozide in pure polar and nonpolar solvents and to predict its solubility in untested solvents. The three-parameter approach and the Flory-Huggins size correction term ‘B’ give predictions of solubilities with correlations up to 97%. The four-parameter approach involving proton-donor and proton-acceptor parameters was also used in fitting the solubility data. The correlations are appreciable (94%). Further, the ‘B’ term coupled with four-parameter approach was examined in order to improve the data representation, and resulted in a 1% improvement (98%) in the correlation when compared to the Flory-Huggins size-correction method. The solubility parameter obtained by this method is 10.43 H which is closer to the values obtained by theoretical methods, such as Fedors’ and Hoy’s. The resulting partial solubility parameters are δ 2d =8.85 H, δ 2p =2.17 H, δ 2a =3.15 H, and δ 2b =4.08 H, which give insights into the interaction capability of pimozide and are consistent with its chemical structure. Pimozide is a Lewis base as its δ 2b >δ 2a . The total solubility parameter of pimozide is assigned at 10.43 H. This work demonstrates for the first time the validity of the four-parameter approach coupled with the Flory-Huggins size-correction term and therefore the result is interesting.
Similar content being viewed by others
References
Barton, A.F.M.: Handbook of Solubility Parameter and Other Cohesion Parameters. CRC Press, Boca Raton (1991)
Fedors, R.F.: A method of estimating both the solubility parameters and molar volumes of liquids. Polym. Eng. Sci. 14, 147–154 (1974)
Mullins, L.: Some physical mechanisms in narcosis. Chem. Rev. 54, 289–323 (1954)
Khalil, S.A., Abdallah, O.A., Moustafa, M.A.: Absorption of some barbiturates by gambusia fish and its correlation to solubility parameter. Can. J. Pharm. Sci. 11, 26–30 (1976)
Khalil, S.A., Abdullah, O.A., Moustafa, M.A.: The use of the solubility parameter as an index of drug activity. Can. J. Pharm. Sci. 11, 121–126 (1976)
Roy, S.D., Flynn, G.L.: Solubility and related physicochemical properties of narcotic analgesics. Pharm. Res. 15, 1370–1375 (1998)
Martini, L.G., Avontuur, P., George, A., Wilson, R.J., Crowly, P.J.: Solubility parameter and oral absorption. Eur. J. Pharm. Biopharm. 48, 259–263 (1999)
Adjei, A., Newburger, J., Stavchansky, S., Martin, A.: Membrane solubility parameter and in situ release of theophylline. J. Pharm. Sci. 73, 742–745 (1984)
Phuoc, N.H., Tan, L.R.P., Munafo, A., Ruelle, P., Nam-Tran, H., Buchmann, M., Kesselring, U.W.: Determination of partial solubility parameters of lactose by gas-solid chromatography. J. Pharm. Sci. 75, 68–72 (1986)
Javier, F., Lupion, N., Bustamante, P., Escalera, B.: Relationship between swelling of hydroxypropylmethylcellulose and the Hansen and Karger partial solubility parameters. J. Pharm. Sci. 94, 1608–1616 (2005)
Wells, J.I.: Pharmaceutical Preformulation: The Physicochemical Properties of Drug Substances. Ellis Horwood Limited, Chichester (1988)
Bustamante, P., Pena, M.A., Barra, J.: Partial solubility parameters of naproxen and sodium diclofenac. J. Pharm. Pharmacol. 50, 975–982 (1998)
Forster, A., Hempenstall, J., Tucker, I., Rades, T.: Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis. Int. J. Pharm. 226, 147–161 (2001)
Gani, R., Jimenez-Gonzalez, C., Constable, D.J.C.: Method for selection of solvents for promotion of organic reactions. Comput. Chem. Eng. 29, 1661–1676 (2005)
Alazar, N.G., Chandra, V., Mayur, L.: Use of surfactants as plasticizers in preparing solid dispersion of poorly soluble API: Selection of polymer-surfactant combinations using solubility parameters and testing the processability. Int. J. Pharm. 328, 119–129 (2007)
Rowe, R.C.: Adhesion of film coatings to tablet surfaces a theoretical approach based on solubility parameters. Int. J. Pharm. 41, 219–222 (1988)
Rowe, R.C.: Binder-substrate interactions in granulation: a theoretical approach based on surface free energy and polarity. Int. J. Pharm. 52, 149–154 (1989)
Hancock, B.C., York, P., Rowe, R.C.: The use of solubility parameters in pharmaceutical dosage form design. Int. J. Pharm. 148, 1–21 (1997)
Minghetti, P., Cilurzo, F., Casiraghi, A., Montanari, L.: Application of viscometry and solubility parameters in miconazole patches development. Int. J. Pharm. 190, 91–101 (1999)
Wagner, K.G., Dowe, U., Zadnik, J.: Highly loaded interactive mixtures for dry powder inhalers: prediction of the adhesion capacity using surface energy and solubility parameters. Pharmazie 60, 339–344 (2005)
Greenhalgh, D.J., Williams, A.C., Timmins, P., York, P.: Solubility parameters as predictors of miscibility in solid dispersions. J. Pharm. Sci. 88, 1182–1190 (1999)
Martin, A., Mauger, J.: The curious solubility of phenobarbital: how to use solubility parameters. Am. J. Pharm. Educ. 52, 68–75 (1988)
Hansen, C.M.: The three-dimensional solubility parameter—key to paint-component affinities: I. Solvents, plasticizers, polymers, and resins. J. Paint. Technol. 39, 104–117 (1967)
Adjei, A., Newburger, J., Martin, A.: Extended Hildebrand approach: solubility of caffeine in dioxane-water mixtures. J. Pharm. Sci. 69, 659–661 (1980)
Richardson, P.J., McCafferty, D.F., Woolfson, A.D.: Determination of the three-component partial solubility parameters for temazepam and the effects of change in partial molal volume on the thermodynamics of drug solubility. Int. J. Pharm. 78, 189–198 (1992)
Barra, J., Lescure, F., Doelker, E., Bustamante, P.: The expanded Hansen approach to solubility parameters. Paracetamol and citric acid in individual solvents. J. Pharm. Pharmacol. 49, 644–651 (1997)
Martin, A., Wu, P.L., Adjei, A., Beerbower, A., Prausnitz, J.M.: Extended Hansen solubility approach: Naphthalene in individual solvents. J. Pharm. Sci. 70, 1260–1264 (1981)
Beerbower, A., Wu, P.L., Martin, A.: Expanded solubility parameter approach: I. Naphthalene and benzoic acid in individual solvents. J. Pharm. Sci. 73, 179–188 (1984)
Krevelen, D.W.V.: Properties of Polymers. Elsevier, Amsterdam (1990)
Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 12th edn., p. 7593. Merck Research Laboratory, Merck & Co. Inc., White House Station (1996)
Martin, A., Wu, P.L., Beerbower, A.: Expanded solubility parameter approach II: p-hydroxy benzoic acid and methyl p-hydroxy benzoate in individual solvents. J. Pharm. Sci. 73, 188–194 (1984)
Hoy, K.C.: New values of the solubility parameters from vapour pressure data. J. Paint. Technol. 41, 76–118 (1970)
Barton, A.F.M.: Solubility parameters. Chem. Rev. 75, 731–753 (1975)
Ainley, W., Paul, J.W.: Handbook of Pharmaceutical Excipients, 2nd edn. The Pharmaceutical Press, London (1994)
Lawrence, A.T.: Handbook on Injectable Drugs, 10th edn. American Society of Health-System Pharmacists, Bethesda (1998)
Hansen, C.M., Beerbower, A.: Encyclopedia of Chemical Technology, 2nd edn., p. 889. Wiley, New York (1971)
Beckett, A.H., Stenlake, J.B.: Practical Pharmaceutical Chemistry, 3rd edn., pp. 1–5. CBS Publ./Distr., New Delhi (1986)
Bustamante, P., Escalera, B., Martin, A., Selles, E.: Predicting the solubility of sulphamethoxypyridazine in individual solvents. I. Calculating partial solubility parameters. J. Pharm. Sci. 78, 567–573 (1989)
Subrahmanyam, C.V.S., Sarasija, S.: Solubility behaviour of haloperidol in individual solvents determination of partial solubility parameters. Eur. J. Pharm. Biopharm. 47, 289–294 (1999)
Subrahmanyam, C.V.S., Ravi Prakash, K., Gundu Rao, P.: Estimation of the solubility parameter of trimethoprim by current methods. Pharm. Acta Helv. 71, 175–183 (1996)
Bustamante, P., Pena, M.A., Barra, J.: The modified extended Hansen method to determine partial solubility parameters of drugs containing a single hydrogen bonding group and their sodium derivatives: benzoic acid/Na and ibuprofen/Na. Int. J. Pharm. 194, 117–124 (2000)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Thimmasetty, J., Subrahmanyam, C.V.S., Sathesh Babu, P.R. et al. Solubility Behavior of Pimozide in Polar and Nonpolar Solvents: Partial Solubility Parameters Approach. J Solution Chem 37, 1365–1378 (2008). https://doi.org/10.1007/s10953-008-9317-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10953-008-9317-8