Development of albendazole sulfoxide-loaded Eudragit microparticles: A potential strategy to improve the drug bioavailability

Benzimidazole compounds are especially effective against nematodes found in the gastrointestinal tube in combating adult worms besides their larvae and eggs. They are also highly effective against lung worms. Their mechanism of action is related to several biochemical changes, particularly the inhibition of β-tubulin, leading to the suspension of cellular processes like mitotic division and transport of nutrients, and also the inhibition of the fumarate reductase enzyme in mitochondrial reactions blocking, in this manner, the metabolic route of the parasite.

Albendazole sulfoxide (ABZSO), a broad spectrum antiparasitic drug from the benzimidazole group, is used to control infections by nematodes, cestodes, and trematodes in big and small ruminants, besides companion animals. Apart from their broad spectrum, benzimidazole compounds have the advantage of causing relatively low toxicity to hosts compared to other antiparasitic drugs.

ABZSO is almost insoluble in water and sparingly soluble in water-miscible solvents like ethanol and propylene glycol. Usually, it is administered at a dose of 7.5 mg kg−1 and its bioavailability varies from 36.8% to 40.5%. Besides, this drug is well distributed in the body after intravenous administration, achieving volume of distribution values ranging from 0.67 to 1.2 L kg−1 for cattle and sheep, respectively, due to its low and erratic bioavailability, when administered by other routes, a high dosage is required to achieve plasmatic therapeutic levels.

One of the advantages of micro- and nanoencapsulation processes is their ability to improve bioavailability of poorly water-soluble drugs. According to Devalapally et al., in general, conventional formulations show low and irregular bioavailability of poorly water-soluble drugs. Microencapsulation processes can be used to improve pharmacokinetic properties of these compounds. The reduced size of microparticles (MPs) and the consequent increase in surface area can substantially increase the rate of dissolution, leading to higher maximum plasmatic concentration (Cmax) and area under the curve (AUC).

Marina Claro de Souza and co-workers developed and validated a analytical method in order to quantify ABZSO in a reliable manner. MPs were successfully obtained once they presented a monomodal narrow range of particle size distribution, yield, and entrapment efficiency in accordance with the proposed objectives. The in vitro release profile study showed that MPs were able to increase the rate of dissolution and the mean dissolved percentage of ABZSO in pH 7.4 compared to free drug, once the small size of the MPs promoted an increase in surface area. This could lead to an improvement in bioavailability and, consequently, in antiparasitic action.