Phase equilibria in the solid disperse system ibuprofen–nicotinamide were studied by differential scanning calorimetry (DSC). It was established that a cocrystal (called ibunicamide) formed at a 1:1 mole ratio of ibuprofen and nicotinamide. Ibunicamide had a melting point of 91°C and underwent a simple eutectic reaction with each of the starting compounds ibuprofen and nicotinamide. The parameters of the invariant equilibrium points were determined for the secondary systems ibuprofen–ibunicamide (E1) and ibunicamide–nicotinamide (E2). Eutectics of these secondary systems appeared at mole ratios 74:26 (±1) with a eutectic melting point of 61°C (E1) and at 82:18 (±1) with melting point 82°C (E2) for the second eutectic composition. Experimental comparison of ibuprofen and the ibuprofen–nicotinamide (ibunicamide) eutectic system showed that the new composition reduced carrageenan-induced exudation by greater than 23 times as compared to the group of animals that were not treated with the NSAID. Also, the exudation after pretreatment with pure ibuprofen at the same dose was only halved. Thus, a new anti-inflammatory and analgesic drug based on the cocrystal of the ibuprofen–nicotinamide eutectic system (ibunicamide) was obtained and tested. The test results demonstrated that the anti-inflammatory activity of ibuprofen in the eutectic composition exceeded its activity in the pure form by greater than 10 times.
Similar content being viewed by others
References
A. I. Tentsova and A. E. Dobrotvorskii, Farmatsiya, XXX(2), 65 – 69 (1981).
G. L. Senov, A. I. Tentsova, and I. S. Azhgikhin, Farmatsiya, XX(2), 3 – 8 (1971).
S. S. Bhupinder, Int. Bull. Drug Res., 1, No. 2, 24 – 39 (2012).
K. Klimova and J. Leitner, Thermochim. Acta, 550, 59 – 64 (2012).
S. Zalac, M. Zahirul, I. Khan, et al., Chem. Pharm. Bull., 47(3), 302 – 307 (1999); https://doi.org/10.1248/cpb.47.302.
M. Bi, S.-J. Hwang, and K. R. Morris, Thermochim. Acta, 404, 213 – 226 (2003).
R. A. Chiarella, R. J. Davey, and M. L. Peterson, Cryst. Growth Des., 7, 1223 – 1226 (2007).
L. E. Zhnyakina, M. L. Tkachenko, Yu. V. Moshchenskii, and I. P. Ivanova, Khim.-farm. Zh., 42(12), 44 – 46 (2008).
Yu. V. Moshchenskii, Prib. Tekh. Eksp., 6, 143 – 144 (2003).
S. V. Fedotov, Interface Software DSC Tool. User’s Guide [in Russian], SamGTU, Samara (2002).
V. Ya. Anosov, M. I. Ozerova, and Yu. Ya. Fialkov, Principles of Physicochemical Analysis [in Russian], Nauka, Moscow (1976), p. 504.
On approval of good laboratory practice rules. RF Ministry of Health and Social Development Order No. 708n of Aug. 23, 2010; Reg. RF Ministry of Justice Oct. 13, 2010, No. 18713, Ros. Gaz, Moscow (2010).
European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (1986); http://conventions.coe.int/Treaty/rus/Treaties/Html/123.htm.
C. Winter, E. Risley, and G. Nuss, Proc. Soc. Exp. Biol. Med., 111, 544 (1962).
A. I. Bondarev, V. A. Davydova, et al., Farmakol. Toksikol., No. 5, 47 – 50 (1991).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 54, No. 9, pp. 43 – 47, September, 2020.
Rights and permissions
About this article
Cite this article
Zhnyakina, L.E., Tkachenko, M.L., Moshchenskii, Y.V. et al. Differential Scanning Calorimetry Study of the Ibuprofen–Nicotinamide Binary Disperse System and the Anti-Inflammatory Activity of One of Its Secondary Eutectics. Pharm Chem J 54, 954–958 (2020). https://doi.org/10.1007/s11094-020-02302-y
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11094-020-02302-y