Physicochemical characterization of Albendazole-b-cyclodextrin derivative complexes. Evaluation in the parenteral stage of Trichinellosis in mice

GARCIA, A.; CODINA, A.V.; LEONARDI, D.; VASCONI, M.D.; DI MASSO, R.J.; HINRICHSEN, L.; LAMAS, M. C.

Lisboa

Congreso; 9TH WORLD MEETING on Pharmaceutics, Biopharmaceuticsand Pharmaceutical Technology; 2014

Trichinellosis, is a foodborne parasitic zoonosis widely distributed all over the world in most climates, except for deserts, carrying a burden of approximately 10,000 people per year and a 0.2% mortality rate. Human population acquires the infection by ingestion of improperly cooked meat contaminated with Trichinella sp. The administration of anthelmintic drugs at the stage of the intestinal invasion is remarkably important to obtain an effective therapy. Albendazole (ABZ) is a benzimidazole carbamate widely used for the treatment of trichinellosis. It is a poorly water soluble and highly lipophilic (log P of 2.55) drug, belongs to the Class II in the Biopharmaceutics Classification System (BCS) and, as a consequence; it can exhibit unfavorable bioavailability after oral administration, leading to a variable oral absorption. In this context, several formulation techniques have been investigated previously to increase ABZ dissolution rate, including complexation with cyclodextrins (CDs) and microencapsulation by means of a wide variety of polymeric carriers. The main interest in CDs could be found in the pharmaceutical field to increase the apparent solubility of poorly water soluble compounds, the dissolution rate, the chemical and physical stability, and,as consequence, their bioavailability. Due to the fact â-CD, has attained pharmaceutical relevance, and this natural CD has an anomalously low solubility in water, a chemical modification may produce an increase in solubility. The random substitution, produce very heterogeneous and non cristallizable products. CDs derivatives presenting acidic groups in their structure may interact strongly with basic drugs generating extremely stable inclusion complexes. Therefore, the aim of this work was focused in the synthesis of a b-CD-citrate (C-b-CD) to improve the solubility and dissolution rate of ABZ and the design of new oral delivery systems to improve the drug efficacy in a murine model.