Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter April 5, 2013

Effect of Non-electrolytes on the Cloud Point and Dye Solubilization of Antidepressant Drug, Clomipramine Hydrochloride

Effekt von Nicht-Elektrolyten auf den Cloud-Point und die Farbstofflöslichkeit des antidepressiven Wirkstoffs Clomipraminhydrochlorid
  • A. Z. Naqvi , M. D. A. Al-Ahmadi , M. Akram and Kabir-ud-Din


Clomipramine hydrochloride (CLP, an amphiphilic drug) solutions, prepared in sodium phosphate buffer, show temperature dependent phase separation (commonly known as Cloud Point, CP). CP can be varied with the help of additives. Hence, in this paper we are reporting the effect of various additives on the CP of CLP. Alcohols affect in two ways: CP either remains constant (or increases slightly) or decreases. Short chain alcohols remain soluble in aqueous phase and CP remains nearly constant in their presence as alcohol-water mixed system proves better solvent for the drug. Long chain alcohols, due to their hydrophobic nature, partition into the drug micelles and cause micellar growth which, in turn, decreases the CP. Sugars enhance the hydrophobic forces and decrease the CP. CP with amino acids is found to be nature dependent: acidic amino acids and hydrochloride salts of basic amino acids increase the CP (due to the interaction of their negatively charged side chains with the drug molecules). Basic amino acids decrease the CP. With polar and uncharged polar amino acids, CP remains constant. This last class of amino acids either remains in the bulk phase or solubilizes inside the micelle, and in either case, the hydration of micelles, and the CP, remain unaffected.


Lösungen aus Clomipraminhydrochlorid (CLP, ein amphiphiler Wirkstoff), die in Phosphatpuffer hergestellt wurden, zeigen eine temperaturabhängige Phasentrennung (bekannt als Cloud-Point, CP). Die Lage des CP kann mit Hilfe von Additiven variiert werden. Wir berichten hier über den Einfluss verschiedener Additive auf den CP von CLP. Alkohole wirken auf zwei Wegen: Der CP bleibt entweder konstant (oder nimmt geringfügig zu) oder er nimmt ab. Kurzkettige Alkohole verbleiben in der wässrigen Phase und der CP bleibt in ihrer Anwesenheit nahezu konstant, da sich das Alkohol-Wasser-Mischsystem als das besseres Lösemedium für den Wirkstoff erweist. Wegen ihrer hydrophoben Natur partizipieren die langkettigen Alkohole an den Wirkstoffmizellen und verursachen Mizellenwachstum, wodurch als Folge der CP abnimmt. Zucker steigern die hydrophoben Kräfte und der CP nimmt ab. Bei Anwesenheit von Aminosäureadditiven hängt der CP von der Art der Aminosäure ab: Saure Aminosäuren und salzsaure Aminosäuresalze steigern den CP (wegen der Wechselwirkung ihrer negative geladenen Seitenketten mit den Wirkstoffmolekülen). Basische Aminosäuren verringern den CP. Der CP bleibt konstant in Anwesenheit von polaren und ungeladenen Aminosäuren. Diese Aminosäuren verbleiben entweder in der Bulkphase oder lösen sich im Inneren der Mizellen; in jedem Fall bleiben die Hydratation der Mizellen und der CP unbeeinflusst.

Prof. Kabir-ud-Din, Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India, Tel.: 0571-2703515. E-Mail: ,

Dr. Andleeb Z. Naqvi received her M.Sc. and Ph.D. degrees from Aligarh Muslim University. Her research interest is in the solution behavior of amphiphiles. Currently she is working in DST SERC Scheme (SR/FTP/CS-49/2007).

Dr. Mohammed D. A. Al-Ahmadi has completed his Ph.D. from Department of Chemistry, Aligarh Muslim University. Now he is a faculty member of Aden University, Yemen.

Dr. Mohd. Akram is a Sr. lecturer in Department of Chemistry at Aligarh Muslim University. He received his M.Sc. and Ph.D. degrees from Aligarh Muslim University. His research interests include micellar catalysis, kinetics and solution behavior of amphiphiles.

Prof. Kabir-ud-Din received his M.Sc. and Ph.D. degrees in Chemistry from Aligarh Muslim University, Aligarh, India in 1965 and 1969, respectively. In 1969 he joined the same university as a Lecturer. He held several post-doctoral positions (at Prague: 1973–1974, Keele, UK: 1975–1977 and Austin, USA: 1977–1978) and also worked as an Associate Professor in Libya (1985–1990). Currently he is a Professor of Physical Chemistry. He has guided 26 Ph.D. and 09 M.Phil. students. He has more than 240 research publications to his credit. His research encompasses the areas of electrochemistry, micellar catalysis, and catalysis through colloidal particles, micellar growth and clouding phenomena in amphiphilic compounds (surfactants and drugs).


1. Schreier, S., Malheiros, S. V. P. and de Paula, E.: Biochim. Biophys. Acta1508 (2000) 210. 10.1016/S0304-4157(00)00012-5Search in Google Scholar

2. Attwood, D. and Florence, A. T.: Surfactant Systems, Their Chemistry, Pharmacy and Biology, Chapman and Hall, New York, (1983).10.1007/978-94-009-5775-6Search in Google Scholar

3. Atherton, A. D. and Barry, B. W.: J. Colloid Interface Sci.106 (1985) 479. 10.1016/S0021-9797(85)80023-0Search in Google Scholar

4. Taboada, P., Attwood, D., Ruso, J. M., Garcia, M. and Mosquera, V.: Phys. Chem. Chem. Phys.2 (2000) 5175. 10.1039/b006400iSearch in Google Scholar

5. Gutierrez-Pichel, M., Attwood, D., Taboada, P. and Mosquera, V.: Mol. Phys.101 (2003) 3455. 10.1080/0026897032000174254Search in Google Scholar

6. Taboada, P., Gutierrez-Pichel, M. and Mosquera, V.: Chem. Phys.298 (2004) 65. 10.1016/j.chemphys.2003.11.004Search in Google Scholar

7. Attwood, D. and Natarajan, R.: J. Pharma. Pharmacol.33 (1981) 136. 10.1111/j.2042-7158.1981.tb13735.xSearch in Google Scholar

8. Katzung, B. G.: Basic and Clinical Pharmacology, 9th ed., McGraw Hill, New York (2004).Search in Google Scholar

9. Hansch, C.: Comprehensive Medicinal Chemistry: The Rational Design, Mechanistic Study & Therapeutic Application of Chemical Compounds, Pergamon Press, New York, (1990).Search in Google Scholar

10. Davis, H. T.: Statistical Mechanics of Phases, Interfaces, and Their Films, Wiley-VCH, New York, (1996).Search in Google Scholar

11. Schick, M. J.: J. Colloid Sci.17 (1962) 801. 10.1016/0095-8522(62)90060-0Search in Google Scholar

12. Tasaki, K.: J. Am. Chem. Soc.118 (1996) 8459. 10.1021/ja951005cSearch in Google Scholar

13. Goldfrab, J. and Sepulveda, L.: J. Colloid Interface Sci.31 (1969) 454. 10.1016/0021-9797(69)90046-0Search in Google Scholar

14. Rupert, L. A. M.: J. Colloid Interface Sci.153 (1992) 92. 10.1016/0021-9797(92)90300-BSearch in Google Scholar

15. Gu, T. and Galera-Gomez, P. A.: Colloids Surf. A147 (1999) 365. 10.1016/S0927-7757(98)00710-9Search in Google Scholar

16. Kim, E. J. and Shah, D. O.: Langmuir18 (2000) 10105. 10.1021/la0262102Search in Google Scholar

17. Marszall, L.: Langmuir6 (1990) 347. 10.1021/la00092a010Search in Google Scholar

18. Kabir-ud-Din, Khatoon S., and Naqvi, A. Z.: J. Dispersion Sci. Tech.29 (2008) 485. 10.1080/01932690701727140Search in Google Scholar

19. Alam, M. S., Naqvi, A. Z. and Kabir-ud-Din: Colloid Polym. Sci.285 (2007) 1573. 10.1007/s00396-007-1727-4Search in Google Scholar

20. Kabir-ud-Din, Al-Ahmadi M. D. A., Naqvi, A. Z., and Akram, M.: J. Surf. Deterg.10 (2007) 231. 10.1007/s11743-007-1037-3Search in Google Scholar

21. Roy, B. K. and Moulik, S. P.: Colloids Surf. A203 (2002) 155. 10.1016/S0927-7757(01)01099-8Search in Google Scholar

22. Majhi, P. R., Mukherjee, K., Moulik, S. P., SenS. and Sahu, N. P.: Langmuir15 (1999) 6624. 10.1021/la980334qSearch in Google Scholar

23. Chatterjee, A., Roy, B. K., Moulik, S. P., SahuN.P. and Mondal, N. B.: J. Dispersion Sci. Technol.23 (2002) 747. 10.1081/DIS-120015972Search in Google Scholar

24. Prasad, M., Moulik, S. P., Chisholm, D. and Palepu, R.: J. Oleo Sci.52 (2003) 523. 10.5650/jos.52.523Search in Google Scholar

25. Dan, A., GhoshS. and Moulik, S. P.: J. Phys. Chem. B112 (2008) 3617. 10.1021/jp077733rSearch in Google Scholar PubMed

26. Caponetti, E., Chillura Martino, D., Floriano, M. A. and Triolo, R.: Langmuir13 (1997) 3277. 10.1021/la961013mSearch in Google Scholar

27. Suzuki, H.: Bull. Chem. Soc. Jpn.49 (1976) 1470. 10.1246/bcsj.49.1470Search in Google Scholar

28. Mitchell, D. J. and Ninham, B. W.: J. Chem. Soc., Faraday Trans II77 (1981) 601. 10.1039/f29817700601Search in Google Scholar

29. Kabir-ud-Din, Kumar S., and Goyal, P. S.: Langmuir12 (1996) 1490. 10.1021/la950677dSearch in Google Scholar

30. Lakshmi, T. S. and Nandi, P. K.: J. Phys. Chem.80 (1976) 249. 10.1021/j100544a008Search in Google Scholar

Received: 2010-01-22
Published Online: 2013-04-05
Published in Print: 2010-11-01

© 2010, Carl Hanser Publisher, Munich

Downloaded on 2.12.2023 from
Scroll to top button