Improving Properties of Albendazole Desmotropes by Supramolecular Systems with Maltodextrin and Glutamic Acid
- 93 Downloads
Albendazole, an effective broad-spectrum anthelmintic agent, showed unpredictable therapeutic response caused by poor water solubility and slow dissolution rate. Then, novel binary and multicomponent supramolecular systems of two different solid forms of albendazole (I and II) with maltodextrin alone or with glutamic acid were studied as an alternative to improve the oral bioavailability of albendazole. The interactions and effects on the properties of albendazole were studied in solution and solid state. The solid systems were characterized using Raman and Fourier transform-infrared spectroscopy, thermal analysis, powder X-ray diffraction, and scanning electron microscopy. The solubility measurements, performed in aqueous and simulated gastric fluid, showed that albendazole (form II) was the most soluble form, while its supramolecular systems showed the highest solubility in simulated gastric fluid. On the other hand, the dissolution profiles of binary and multicomponent systems in simulated gastric fluid displayed pronounced increments of the dissolved drug and a faster dissolution rate compared to those of free albendazole forms. Thus, these supramolecular structures constitute an interesting alternative to improve the physicochemical properties of albendazole, with potential application for the preparation of pharmaceutical oral formulations.
KEY WORDSalbendazole desmotrope maltodextrin glutamic acid solubility dissolution
Authors wish to acknowledge the assistance of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and the Universidad Nacional de Córdoba, both of which provided support and facilities for this investigation. Also, project MinCyT-CONICET-CAPES is gratefully acknowledged.
The authors thank the Fondo para la Investigación Científica y Tecnológica (FONCYT) [Préstamo BID PICT 2013-0504], the Secretaría de Ciencia y Técnica de la Universidad Nacional de Córdoba (SECyT), and the Brazilian National Council for Scientific and Technological Development (CNPQ) for financial support.
- 1.Bauer JF. Polymorphism: a critical consideration in pharmaceutical development, manufacturing and stability. J Technol. 2008;15–23.Google Scholar
- 3.Flórez J. Fármacos antiparasitarios. II. Helmintos y artrópodos. In: Farmacología Humana. Barcelona: Masson S.A.; 1998. p. 1239–47.Google Scholar
- 5.García A, Barrera MG, Piccirilli G, Vasconi MD, Di Masso RJ, Leonardi D, et al. Novel albendazole formulations given during the intestinal phase of Trichinella spiralis infection reduce effectively parasitic muscle burden in mice. Parasitol Int. 2013;62(6):568–70. https://doi.org/10.1016/j.parint.2013.08.009.CrossRefPubMedGoogle Scholar
- 10.Priotti J, Codina AV, Leonardi D, Vasconi MD, Hinrichsen LI, Lamas MC. Albendazole microcrystal formulations based on chitosan and cellulose derivatives: physicochemical characterization and in vitro parasiticidal activity in Trichinella spiralis adult worms. AAPS PharmSciTech. 2017;18(4):947–56. https://doi.org/10.1208/s12249-016-0659-z.CrossRefPubMedGoogle Scholar
- 20.Higuchi T, Connors KA. Phase-solubility techniques in advances. In: Analytical chemistry and instrumentation, vol. 4. New York: Interscience; 1965. p. 117–212.Google Scholar
- 21.Moore WJ, Flanner HH. Mathematical comparison of dissolution profiles. Pharm Technol. 1996;20:64–74.Google Scholar
- 24.Lindenberg M, Kopp S, Dressman JB. Classification of orally administered drugs on the World Health Organization model list of essential medicines according to the biopharmaceutics classification system. Eur J Pharm Biopharm. 2004;58(2):265–78. https://doi.org/10.1016/j.ejpb.2004.03.001.CrossRefPubMedGoogle Scholar