Effect of hydroxypropyl methylcellulose on beta cyclodextrin complexation of praziquantel in solution and in solid state
- 247 Downloads
The effect of hydroxypropyl methylcellulose (HPMC) on complexation of praziquantel with beta cyclodextrin (PRZ–βCD) in solution and in the solid state was investigated. Phase solubility studies of βCD (0, 3, 6, 9 and 12 mmol L−1) were carried out by adding an excess amount of PRZ (8 mmol L−1) in the absence and presence of the polymer (with and without heating at 120 °C). Equimolar binary and ternary complexes were prepared by kneading and freeze-drying and characterized by DSC, DTA TGA, FTIR, XRPD and SEM patterns. A stoichiometry ratio of 1:1 was indicated by phase-solubility studies both in the presence and absence of 0.5 % HPMC. The molecular modeling confirms the 1:1 stoichiometry rate with Higuchi’s Al type. The presence of HPMC improved the complexation between PRZ and βCD by increases in both the intrinsic solubility of the drug as well as in values of the stability constant, complexation efficiency and Gibb’s free energy of the complex, principally in the presence of heating (up to ninefold relative to aqueous solubility of the drug). The synergic effect of HPMC was also observed in thermal analysis, with lower dehydration enthalpy for ternary complexes. The results of melting enthalpy were according to XRPD results, indicating that the preparation technique and presence of HPMC influenced thermal and crystallographic characteristics of inclusion complexes. The FTIR patterns suggest the complexation mechanism while SEM patterns showed the formation of inclusion complexes. The use of the HPMC and freeze-drying technique suggest more effective formation of PRZ:βCD inclusion complexes.
KeywordsHydroxypropyl methylcellulose Beta cyclodextrin Praziquantel Inclusion complex Kneading Freeze-drying
The authors thank CAPES (Brazil) for the financial support and Gerbrás for purchase praziquantel and hydroxypropyl methylcellulose.
This study was supported by CAPES.
Compliance with ethical standards
Conflict of interest
The author(s) declare(s) that they have no conflicts of interest to disclose.
- 1.United States Pharmacopeial Convention: United States pharmacopeia—USP 31: National Formulary—NF 26. United States Pharmacopeial Convention, Rockville (2008)Google Scholar
- 2.Ali, B.H.: Short review of some pharmacological, therapeutic and toxicological properties of praziquantel in man and animals. Pak. J. Pharm. Sci. 19, 170–175 (2006)Google Scholar
- 8.Petry, M., Borghetti, G.S., Bassani, V.L.: Influência de ciclodextrinas e polímero hidrofílico sobre a hidrossolubilidade de diferentes formas polimórficas de quercetina. Lat. Am. J. Pharm. 26, 831–836 (2007)Google Scholar
- 18.Ammar, H.O., Ghorab, M., El-Nahhas, S.A., Omar, S.M., Ghorab, M.M.: Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation, part 5. Theophylline. Pharm. 54, 42–46 (1996)Google Scholar
- 20.Higuchi, T., Connors, K.A.: Phase-solubility techniques. Adv. Anal. Chem. Instr. 4, 117–122 (1965)Google Scholar
- 22.Soares-Sobrinho, J.L., Santos, F.L.A., Lyra, M.A.M., Alves, L.D.S., Rolim, L.A., Lima, A.A.N., Nunes, L.C.C., Soares, M.F.R., Rolim-Neto, P.J., Torres-Labandeira, J.J.: Benznidazole drug delivery by binary and multicomponent inclusion complexes using cyclodextrins and polymers. Carbohydr. Polym. 89, 323–330 (2012)CrossRefGoogle Scholar
- 25.De Jesus, M.B., Pinto, L.M.A., Fraceto, L.F., Takahata, Y., Lino, A.C.S., Jaime, C., De Paula, E.: Theoretical and experimental study of a praziquantel and—cyclodextrin inclusion complex using molecular mechanic calculations and 1H—nuclear magnetic resonance. J. Pharm. Biomed. Anal. 41, 1428–1432 (2006)CrossRefGoogle Scholar
- 31.Rama, A.C.R., Veiga, F., Figueiredo, I.V., Sousa, A., Caramona, M.: Aspectos biofarmacêuticas da formulação de medicamentos para neonatos. Fundamentos da complexação de indometacina com hidroxipropil-ß-ciclodextrina para tratamento oral do fechamento do canal arterial. Braz. J. Pharm. Sci. 41, 281–299 (2005)Google Scholar
- 35.Loftsson, T.: Cyclodextrins Complexation. United States Patent 5, 472–954 (1995)Google Scholar
- 38.Araújo, M.V.G., Vieira, E.K.B., Lázaro, G.S., Conegerob, L.S., Ferreira, O.P., Almeida, L.E., Barreto, L.S., Costa Jr, N.B., Gimenez, I.F.: Inclusion complexes of pyrimethamine in 2-hydroxypropyl-β-cyclodextrin: characterization, phase solubility and molecular modeling. Bioorg. Med. Chem. 15, 5752–5759 (2007)CrossRefGoogle Scholar
- 45.Veiga, F.J.B., Pecorelli, C.C.M.F., Ribeiro, S.S.L.: As ciclodextrinas em tecnologia farmacêutica. Minerva Coimbra Editora (2006)Google Scholar