Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles

Author(s)

Carpentieri Rodrigues, Leticia Norma ^[1] ; Moraes Tavares, Anna Carollina ^[1] ; Ferreira, Beatriz Tavares ^[1] ; Cardoso Amorim Reis, Adriana Karla ^[1] ; Katiki, Luciana Morita ^[2]

Affiliation

^[1] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Rua Sao Nicolau 210, BR-09913030 Diadema, SP - Brazil

^[2] APTA, IZ, Secretaria Agr & Abastecimento Estado Sao Paulo, Nova Odessa, SP - Brazil

• Document type: Journal article
• Source: Brazilian Journal of Pharmaceutical Sciences; v. 55, 2019.
• Web of Science Citations: 0

Abstract

Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, beta-cyclodextrin increased the solubility of albendazole from 0.4188 to similar to 93.47 mu g mL(-1) (223x), and of fenbendazole from 0.1054 to 45.56 mu g mL(-1) (432x); hydroxypropyl-beta-cyclodextrin, on the other hand, increased solubility to similar to 443.06 mu g mL-1 (1058x) for albendazole and similar to 159.36 mu g mL(-1) (1512x) for fenbendazole. The combination of hydroxypropyl-beta-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412x (similar to 591.22 mu g mL-1) for albendazole and 1373x (similar to 144.66 mu g mL(-1)) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-beta-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the H-1 NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates. (AU)

• FAPESP's process: 13/15704-3 - Preparation, characterization and evaluation of biological activity of inclusion complexes and nanoclusters of cyclodextrins self-assembled to increase the solubility of poorly soluble drugs
• Grantee: Leticia Norma Carpentieri Rodrigues
• Support Opportunities: Regular Research Grants