In vitro anthelmintic activity of albendazole microcrystal formulations based on chitosan and cellulose derivatives

VASCONI, MD.; HINRICHSEN, LI.; PRIOTTI, J.; MICHELETTI, L.; LAMAS, MC.; CODINA, AV.; LEONARDI, D.

Rosario

Congreso; 4ta. Reunión Internacional de Ciencias Farmacéuticas; 2016

Oral administration of dosage forms offers remarkable advantages over other routes. Notwithstanding, one of the most important questions to be solved is the poor solubility of most drugs which produces low bioavailability and delivery problems. Albendazole (ABZ), a benzimidazole carbamate, is commonly used in oral chemotherapy against intestinal parasites, because of its extended spectrum activity and low cost; its main disadvantage is poor bioavailability due to low solubility in water. Twenty novel ABZ microcrystal structures were produced using bottom-up methodology to optimize oral absorption of the ABZ. Five different polymers were employed at concentrations 0.1 and 0.5% w/v: hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), carboxymethylcellulose (CMC), methylcellulose (MC) and chitosan (CH) with or without poloxamer 338. The main objective of this study was to evaluate the in vitro biological activity of these microcrystal systems. Their effect on in vitro ability of ABZ to kill adult T. spiralis worms was assessed by the survival curves of the female parasite cultured for 48 h in medium RPMI 1640 containing the ABZ microcrystals. The survival curves in the in vitro studies showed that exposure to the formulations affected the viability of the adult forms of the parasite in a time and polymer dependent manner; addition of the surfactant P338 had little or no impact on improving ABZ effectiveness. In general, low killing efficiencies were associated with high median survival times. All these microcrystal formulations had a significantly better activity than the ABZ (pure drug) (P