the inclusion complex of Nimodipine with Cyclodextrine. FT IR spectroscopy.

Mihaela Toma1, I. Bratu2, O. Cozar1 and Gh. Bora3

1”Babes-Bolyai” University, Faculty of Physics, 1 Kogalniceanu st., Cluj-Napoca

2National Institute for Research and Development of Isotopic and Molecular Technologies, P.O. Box 700, Cluj-Napoca, Romania

3 S.C. ”Terapia”, 126 Fabricii st., Cluj-Napoca

Nimodipine (C21H26N2O7) isfrequently used as antianginal, anti-hypertensive or cerebral vasodilator pharmacon. There are two main disadvantages in its use: it is practically insoluble in water and light sensitive in solution. Cyclodextrin (CD) derivatives may be used as inclusion complex-forming agents to increase the solubility of drugs and different dyes are also available to prevent the photodegradation of these molecules.In order to avoid this inconvenient and to increase the solubility, inclusion complexes (IC) of cyclodextrins with this drug are prepared and investigated. Different procedures, largely recommended in the literature [1], were employed to obtain IC: physical mixtures (pm), coprecipitation (co), kneading (kn) and freeze-drying (fd).The kn and co methods were used [2-4] to prepare IC. A systematic study of the FT IR spectra of the IC complexes obtained was done in order to establish which one of these procedures is more efficient and how the molecule is included in the CD torus. FT IR spectra were obtained with a Bomem DA 3 spectrometer in the 4000 to 400 cm-1 spectral range by using the well-known KBr pellet technique. A detailed analysis of these spectra reveals the following spectral changes:

- the  (O-H) stretching band of -CD is shifted from 3379 cm-1 in pure -CD or pm system to 3388 cm-1 for the complexes obtained by co, fd and kn methods. One can observe that the  (O-H) massif change its intensity distribution on going from pure CD to IC systems specially in the high frequency wing of this profile.

- the  (N-H) stretching band of Nimodipine and pm system is located at 3297 cm-1; this band is shifted to 3276.6 cm-1 for the IC systems obtained by co and kn methods.

In the 1900-1500 cm-1 spectral region the  (C=O) stretching band profile having two components, one at 1699 and other at 1693 cm-1, is located in the spectra of pure Nimodipine and pm system. These components are shifted to 1702 and 1696 cm-1, respectively for the IC systems obtained by co, kn and fd methods. The inversion of the intensities in this band doublet is observed also. One can conclude that the functional groups mainly involved in the inclusion process are the N-H and C=O molecular groups. In both cases, the peak maxima are shifted to higher frequencies for the IC system as compared to the pure Nimodipine and pm complex that means a breaking into the hydrogen bonding assembly. During the complexation process some water molecules are expelled from the inner part of the CD truncated conus, being demonstrated by the intensity decrease in the high frequency wing of the (O-H) profile.

[1] Szejtli, J., Chem. Rev., 98 (1998) 1743-1753.

[2]Chowdary, K. P. R. Kamalakara, Reddy G., Indian Drugs (2001), 38(11), 555-558.

[3] Gyeresi, A., Tokes, B., Regdon, G., Kata, M., Nagy, G.in Szejtli, J.; Szente, L (Editors),

Proc. Intern. Symp Cyclodextrins, 8th, Budapest, Mar. 31-Apr. 2, (1996), 345-348.

[4] Mielcarek, Jadwiga, Acta Poloniae Pharmaceutica, (1995), 52(6), 465-70.