CaAl-layered double hydroxide as a drug delivery system: effects on solubility and toxicity of the antiretroviral efavirenz
- 266 Downloads
The use of layered double hydroxides associated with biologically active molecules is becoming a promising alternative in the development of drug delivery systems that may be applied to drug therapies for different diseases. Efavirenz is an antiretroviral belonging to class II of the biopharmaceutical classification system (low solubility, high permeability). Due to its low aqueous solubility, absorption problems occur in the gastrointestinal tract and, consequently, inadequate oral bioavailability. In this paper, the association between efavirenz and CaAl-layered double hydroxide was obtained by stirring in an acetonic solution until complete evaporation of the solvent. The hybrid material obtained was characterized by X-ray diffraction, differential scanning calorimetry and fourier transform infrared spectroscopy. It was observed that in systems containing up to 30 % of efavirenz, the drug became a molecule with amorphous characteristics and lost its crystalline character. This phenomenon can be demonstrateby the absence of the drug in crystalline plane diffractograms, as well as the absence of its melting point in thermal analysis. In the release test, these systems have been successful in increasing solubility. The system carrier-drug with 30 % of efavirenz was more promising with an increase of 558 % of soluble drug, compared to the drug alone. In antiproliferative activity on human macrophage cell lines, it was observed that the isolate efavirenz presented an IC50 value of 15.71 mg ml−1, while the system carrierdrug with 30 % of efavirenz showed an IC50 value of 20.83 mg ml−1, demonstrating that efavirenz in association with a CaAl-layered double hydroxide provided a reduction in drug toxicity.
KeywordsLayered double hydroxide Efavirenz Improvement of solubility Toxicity
The authors wish to express their gratitude to Laboratory for Pharmaceutical Technology, Federal University of Pernambuco—UFPE/Brazil; Laboratory Biofarmatox, UFPE/Brazil; Laboratory Rare Earths BSTR, UFPE/Brazil; Ping I. Lee Research Group, University of Toronto, Canada, for providing the necessary facilities to develop the present research. This research was supported by Technology Support Foundation of Pernambuco—FACEPE.
Compliance with Ethical Standards
Conflict of interest
The authors declare that there is no conflict of interests that could affect the impartiality of the research reported.
- 8.Sahbaz, Y., Williams, H.D., Nguyen, T., Saunders, T., Ford, L., Charman, S.A., Scammells, P.J., Porter, C.J.H.: Transformation of poorly water-soluble drugs into lipophilic ionic liquids enhances oral drug exposure from lipid based formulations. Mol. Pharm. (2015). doi: 10.1021/mp500790t Google Scholar
- 9.Vieira, A.C.C., Fontes, D.A.F., Chaves, L.L., Alves, L.D.S., Freitas-neto, J.L., Soares, M.F.R., Soares-sobrinho, J.L., Rolim, L.A., Rolim-neto, P.J.: Multicomponent systems with cyclodextrins and hydrophilic polymers for the delivery of Efavirenz. Carbohyd. Polym. (2015). doi: 10.1016/j.carbpol.2015.04.050 Google Scholar
- 11.Schönherr, D., Wollatz, U., Haznar-Garbacz, D., Hanke, U., Box, K.J., Taylor, R., Ruiz, R., Beato, S., Becker, D., Weitschies, W.: Characterisation of selected active agents regarding pKavalues, solubility concentrations and pH profiles by SiriusT3. Eur. J. Pharm. Biopharm. (2015). doi: 10.1016/j.ejpb.2015.02.028 Google Scholar
- 13.Alves, L.D.S., Soares, M.F.L.R., Albuquerque, C.T., Silva, E.R., Vieira, A.C.C., Fontes, D.A.F., Figueirêdo, C.B.M., Soares-Sobrinho, J.L., Rolim-Neto, P.J.: Solid dispersion of efavirenz in PVP K-30 by conventional solvent and kneading methods. Carbohyd. Polym. (2014). doi: 10.1016/j.carbpol.2014.01.027 Google Scholar
- 18.Ganesan, P., Soundararajan, R., Shanmugam, U., Ramu, V.: Development, characterization and solubility enhancement of comparative dissolution study of second generation of solid dispersions and microspheres for poorly water soluble drug. Asian J. Pharm. Sci. (2015). doi: 10.1016/j.ajps.2015.05.001 Google Scholar
- 21.Vieira, A.C.C., Fontes, D.A.F., Chaves, L.L., Freitas-Neto, J.L., Soares, M.F.L.R., Soares-Sobrinho, J.L., Rolim, L.A., Rolim-Neto, P.J.: Multicomponent systems with cyclodextrins and hydrophilic polymers for the delivery of Efavirenz. Carbohydr. Polym. (2015). doi: 10.1016/j.carbpol.2015.04.050 Google Scholar