Bioavailability and efficacy characteristics of two different oral liquid formulations of albendazole
Introduction
Albendazole (ABZ), methyl [5-(propyl-thio)-1-H-benzimidazole-2yl] carbamate, is a broad spectrum antihelmintic drug with low aqueous solubility, which may limit its oral absorption (Jung et al., 1998). In order to prepare ABZ solutions, different formulation approaches have been experimented in the last years. For instance, since ABZ is basic in nature, its solubility could be increased by ionisation in an acid medium, although this increase in solubility is not enough for the preparation of high ABZ concentration doses. Another way of increasing its solubility is by addition of surfactant agents, such as polysorbate and bile salts, or cosolvent agents, like Transcutol® (Torrado et al., 1996a, Torrado et al., 1997, Redondo et al., 1998). Some of these excipients may also have some absorption enhancer effects, which can be useful on increasing the oral bioavailability of ABZ formulations. Unfortunately, many of these agents can also be irritant to the digestive system linings and so its use must be restricted whenever possible. Alternatively, the ABZ solubility can be improved by elaboration of solid dispersions with polyvinylpyrrolidone (Torrado et al., 1996b, Lopez et al., 1997); although the elaboration method, rotatory evaporator and the use of organic co-solvents, and the high quantity/concentrations of the complexing agent are the application limiting factors for these products. Recently, the use of hydroxypropyl-β-cyclodextrin (HPCD), has facilitated the formulation of high concentration of ABZ solutions (Castillo et al., 1999, Piel et al., 1999).
The aim of this paper, is to compare the bioavailability and anthelmintic activities/characteristics of HPCD–ABZ solution-formulation to a conventional reference ABZ suspension in sodium carboxymethylcellulose. Moreover, the correlation between the bioavailability and anthelmintic efficacy was studied. Thus, different doses of ABZ (50–100 mg/kg) were orally administered to mice and blood samples were taken for analysis of ABZ concentration and its main metabolites by HPLC (Garcia et al., 1999). Furthermore, the anthelmintic activity of ABZ formulations was studied in the Trichinella spiralis model in mice at three different stages (pre-adult, migrating and encysted larvae) of the parasite infection. This in vivo model allows us to study the efficacy at both the enteral stage (pre-adult) and at the parenteral stage (migrating and encysted larvae). Therefore, the model can be used to verify whether a certain formulation might be indicated for various stages of helminthic infections or not (López-Garcı́a et al., 1997, López-Garcı́a et al., 1998).
Section snippets
Chemicals
ABZ and albendazole sulphone (ABZ-SO2) were kindly supplied by Glaxo-Smithkline (England). Albendazole sulphoxide (ABZ-SO) was a gift from Chemo Ibérica (Madrid, Spain). HPCD was supplied by Cerestar Ibérica (Barcelona, Spain). All the products and materials used in this study comply with the pharmaceutical and analytical standards, respectively.
ABZ formulations (8 mg/ml) and determination of dispensing error
- –
ABZ solution was prepared by dissolution of ABZ in a solution of 20% (w/v) HPCD in 0.2 M HCl. The final pH of the solution was 0.92.
- –
ABZ suspension was
Results and discussion
Fig. 1 shows the mean ABZ drug concentrations after the oral administration of the two different liquid formulations at doses of 50 and 100 mg/kg. It is clear from this figure that the cyclodextrin solution improves ABZ oral bioavailability in relation to the conventional oral suspensions. Due to fast ABZ degradation rate, its plasma concentrations are very low. Under our experimental conditions, its apparent elimination constant was 0.33±0.1 per h. For this reason, in our previous studies, the
Acknowledgements
We thank Dr Torrellas (Glaxo-Smithkline), C. Picornell (Chemo Ibérica) and J. Guerrero (Cerestar Ibérica) for kindly supplied us with different materials.
References (21)
- et al.
Chiral behaviour of the metabolite albendazole sulphoxide in sheep, goats and cattle
Res. Vet. Sci.
(1991) - et al.
Quantitative determination of albendazole and its main metabolites in plasma
J. Chromatogr. B
(1999) - et al.
Albendazole versus ricobendazole (albendazole sulphoxide) against enteral and parenteral stages of Trichinella spiralis in mice
Int. J. Parasitol.
(1997) - et al.
Methimazole-mediated enhancement of albendazole oral bioavailability and anthelmintic effects against parenteral stages of Trichinella spiralis in mice: the influence of the dose-regime
Vet. Parasitol.
(1998) - et al.
Formulation parameters of albendazole solution
Int. J. Pharm.
(1996) - et al.
Preparation, dissolution and characterization of albendazole solid dispersions
Int. J. Pharm.
(1996) - et al.
A novel formulation of albendazole solution: oral bioavailability and efficacy evaluation
Int. J. Pharm.
(1997) - et al.
Effect of repeated doses of albendazole on enantiomerism of its sulfoxide metabolite in goats
Am. J. Vet. Res.
(1992) - et al.
Preparation and characterization of albendazole β-cyclodextrin complexes
Drug Dev. Ind. Pharm.
(1999) - et al.
Species differences in the generation of the chiral sulphoxide metabolite of albendazole in sheep and rats
Chirality
(1990)
Cited by (63)
Dissolution/Permeation of Albendazole in the Presence of Cyclodextrin and Bile Salts: A Mechanistic In Vitro Study into Factors Governing Oral Bioavailability
2022, Journal of Pharmaceutical SciencesCitation Excerpt :Furthermore, the oral bioavailability of crystalline albendazole is too low for therapeutic use due to its low solubility. Several in vivo studies have shown that oral bioavailability can be increased when albendazole is formulated together with HP-β-CD.15,17,18,19,20 However, to our knowledge, only the study by Yamashita and co-workers20 may serve as a reference for our mechanistic study, because their formulations were the only ones, which contained no other excipients besides cyclodextrins,; the other studies contained acidic components that may have contributed to the observed higher bioavailability in addition to the effect of the cyclodextrin.
In vitro-in vivo correlation in the effect of cyclodextrin on oral absorption of poorly soluble drugs
2021, International Journal of PharmaceuticsDo albendazole-loaded lipid nanocapsules enhance the bioavailability of albendazole in the brain of healthy mice?
2020, Acta TropicaCitation Excerpt :Several ABZ formulations have been developed, such as complexation with cyclodextrin (Ceballos et al., 2011), solid dispersions (Castro et al., 2010; Martinez-Marcos et al., 2016), microcrystals (Priotti et al., 2017), nanocrystals (Paredes et al., 2018) and solid lipid nanoparticles (Kudtarkar et al., 2017). Available scientific evidence indicates that higher drug bioavailability correlates with improved efficacy of ABZ against systemic parasites such as Echinococcus sp, T. crassiceps, T. solium and Trichinella spiralis (Ceballos et al., 2008, 2011; Garcia et al., 2003, 2013; Osorio et al., 2019; Palomares-Alonso et al., 2010; Pensel et al., 2014, 2015, 2018; Shuhua et al., 2002; Torrado et al., 1997; Ullio Gamboa et al., 2019). Lipid nanocapsules (LNCs) are drug carrier nanosystems prepared by a temperature phase inversion process free of organic solvents.
Albendazole-lipid nanocapsules: Optimization, characterization and chemoprophylactic efficacy in mice infected with Echinococcus granulosus
2019, Experimental ParasitologyCitation Excerpt :Thus, several options are currently being explored in order to overcome these drawbacks. One viable strategy is the choice of a dissolution medium that allow the ionization of this molecule but this solubility enhancement is not enough for preparing formulations containing the required ABZ concentration (Garcia et al., 2003). Another alternative is the use of surfactants, such as polysorbate and bile salts (del Estal et al., 1994; Torrado et al., 1996).
Strategies to Optimize the Efficacy of Anthelmintic Drugs in Ruminants
2018, Trends in ParasitologyConcepts of Hypothesis Testing and Types of Errors
2018, Dosage Form Design Parameters