Relative Bioavailability of Three Newly Developed Albendazole Formulations: a Randomized Crossover Study with Healthy Volunteers

Abstract

This study of healthy volunteers shows that the relative bioavailability of albendazole formulations that use arachis oil-polysorbate 80 or hydroxypropyl-␤-cyclodextrin as an excipient was enhanced 4.3-and 9.7-fold compared to the results seen with commercial tablets. Administration of macrogol suppositories did not result in measurable plasma concentrations of albendazole sulfoxide.The therapeutic response of albendazole (20 to 50%) in cases of echinococcosis is variable and difficult to predict (2, 8). Albendazole's poor intestinal absorption (Ͻ5%) (due to its low aqueous solubility) is probably a major determinant of the variable response rate (9). In animal studies, the main strategy to enhance albendazole bioavailability was by that of increasing water and lipid solubility by the use of cosolvents or surfactants or of incorporating albendazole into particles. The relative bioavailability of albendazole in mice increased 1.8-fold by combining it with the cosolvent Transcutol (diethylene glycol monoethylether) (18). A formulation of a solid dispersion enhanced the relative bioavailability in rabbits threefold (11). Albendazole coadministered with the surfactant sodium taurocholate or polysorbate enhanced the area under the concentration curve (AUC) value for rats by 55 or 88%, respectively (3, 4, 5), whereas incorporation into liposomes increased the uptake in rats by more than twofold (19) and incorporation into a cyclodextrin increased the AUC for sheep by 37% (6, 16).For humans, several strategies were studied to enhance albendazole bioavailability. When combined with a fatty meal, administration of albendazole sulfoxide (ABZSX) increased the maximum concentration of drug in serum (C max ) 4.5-to 9-fold (1,7,12,15). To inhibit CYP3A4 isozyme-related ABZSX degradation, albendazole was coadministered with cimetidine. However, this caused a 52% decrease in ABZSX C max values (probably due to inhibition of gastric acid secretion) (15,17), suggesting that absorption is pH dependent. When coadministered with grapefruit juice, the ABZSX C max was enhanced 3.2-fold, probably due to inhibition of the intraluminal degradation of albendazole by CYP3A4 enzymes (15). In one human study, a soybean oil emulsion was used to enhance albendazole solubility and showed a 1.6-fold enhancement of relative bioavailability compared with tablets (14).The present report presents findings for a human study comparing the relative levels of bioavailability of three new pharmaceutical albendazole formulations with that of the commercially available tablet. These three new formulations include an oral suspension with arachis oil and the surfactant polysorbate 80 (aimed at increasing lipid solubility), an oral solution of albendazole incorporated into hydroxypropyl-␤-cyclodextrin (aimed at increasing water solubility), and a macrogol suppository (aimed at avoiding the intestinal degradation of albendazole).The suspension was prepared by mixing 9.0 g of albendazole (Duchefa, Haarlem, The Netherlands) with 36.0 g of arachis oil, 2.0 g of a...

Improvement of Albendazole Dissolution by Preparing Microparticles Using Spray-Drying Technique

“…Consequently, it is poorly absorbed from the gastrointestinal tract (< 5%) [4] and it has low oral bioavailability [5]. This property is a major disadvantage for the use of ABZ in the treatment of systemic helminthiasis [6]. Furthermore, the lack of water solubility reduces flexibility for ABZ formulation and administration.…”

Formulation development of an albendazole self-emulsifying drug delivery system (SEDDS) with enhanced systemic exposure / Razvoj samoemulzifirajućeg sustava za isporuku albendazola (SEDDS) s pojačanom sistemskom apsorpcijom

“…ABZ falls into the BCS class II category as has high permeability and low solubility. Because of its low aqueous solubility, it is poorly and erratically absorbed following oral administration (15). Following oral administration to rats, it was found to absorb 20-30 %, whereas in humans the percent absorbed is 1-5 (16).…”

Bioavailability and Bioequivalence

“…For example, the anthelmintic agent albendazole undergoes rapid and essentially complete first-pass metabolism to a sulfoxide metabolite. Suspension and solution formulations were found to provide 4.3-and 9.7-fold improvements in oral bioavailability relative to tablets, respectively, as demonstrated by comparing AUC exposures of the sulfoxide metabolite [36]. Similarly, the potent desmethyl metabolite of tramadol, a centrally acting analgesic, was monitored to compare the PK of an extended-release tablet relative to an immediate-release reference product [37].…”