Inclusion complex and nanoclusters of cyclodextrin to increase the solubility and efficacy of albendazole
- 92 Downloads
Albendazole (ABZ), a benzimidazole widely used to control gastrointestinal parasites, is poorly soluble in water, resulting in variable and incomplete bioavailability. This has favored the appearance ABZ-resistant nematodes and, consequently, an increase in its clinical ineffectiveness. Among the pharmaceutical techniques developed to increase drug efficacy, cyclodextrins (CDs) and other polymers have been extensively used with water-insoluble pharmaceutical drugs to increase their solubility and availability. Our objective was to prepare ABZ formulations, including β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD), associated or not to the water-soluble polymer polyvinylpyrrolidone (PVP). These formulations had their solubility and anthelmintic effect both evaluated in vitro. Also, their anthelmintic efficacy was evaluated in lambs naturally infected with gastrointestinal nematodes (GIN) through the fecal egg count (FEC) reduction test. In vitro, the complex ABZ/HPβCD had higher solubility than ABZ/βCD. The addition of PVP to the complexes increased solubility and dissolution rates more effectively for ABZ/HPβCD than for ABZ/βCD. In vivo, 48 lambs naturally infected with GIN were divided into six experimental groups: control, ABZ, ABZ/βCD, ABZ/βCD-PVP, ABZ/HPβCD, and ABZ/HPβCD-PVP. Each treated animal received 10 mg/kg of body weight (based on the ABZ dose) for three consecutive days. After 10 days of the last administered dose, treatment efficacy was calculated. The efficacy values were as follows: ABZ (70.33%), ABZ/βCD (85.33%), ABZ/βCD-PVP (82.86%), ABZ/HPβCD (78.37%), and ABZ/HPβCD-PVP (43.79%). In vitro, ABZ/HPβCD and ABZ/HPβCD-PVP had high solubility and dissolution rates. In vivo, although the efficacies of ABZ/βCD, ABZ/βCD-PVP, and ABZ/HPβCD increased slightly when compared to pure ABZ, this increase was not significant (P > 0.05).
KeywordsAlbendazole Inclusion complex Cyclodextrin Solubility Anthelmintic Sheep
Compliance with ethical standards
Animal procedures and management protocols were approved by the Ethics Committee on Animal Use (CEUA) of the Instituto de Zootecnia (IZ/APTA/SAA) and received protocol number IZ/229-16.
Conflict of interest
The authors declare that they have no conflict of interest.
- Carvalho WF (1999) Técnicas Médicas de Hematologia e Imuno-Hematologia, 6th edn. Cooperativa Editora e de Cultura Médica, Belo Horizonte, pp 66–175Google Scholar
- Charkoftaki G, Dokoumetzidis A, Valsami G, Macheras P (2009) Biopharmaceutical classification based on solubility and dissolution: a reappraisal of criteria for hypothesis models in the light of the experimental observations. Basic Clin Pharmacol 106(3):168–172. https://doi.org/10.1111/j.1742-7843.2009.00506.xCrossRefGoogle Scholar
- Coles GC, Bauer C, Borgsteede FHM, Geerts S, Klei TR, Taylor MA, Waller PJ (1992) World Association for the Advancement of Veterinary Parasitology (WAAVP) methods for the detection of anthelmintic resistance in nematodes of veterinary importance. Vet Parasitol 44(1-2):35–44. https://doi.org/10.1016/0304-4017(92)90141-UCrossRefPubMedGoogle Scholar
- Dezani AB (2010) Avaliação in vitro da solubilidade e da permeabilidade da lamivudina e da zidovudina. Aplicações na classificação biofarmacêutica. Dissertation, University of São PauloGoogle Scholar
- Evrard B, Chiap P, De Tullio P, Ghalmi F, Piel G, Van Hees T, Crommen J, Losson B, Delattre L (2002) Oral bioavailability in sheep of albendazole from a suspension and from a solution containing hydroxypropyl-β-cyclodextrin. J Control Release 85(1-3):45–50. https://doi.org/10.1016/S0168-3659(02)00270-5CrossRefPubMedGoogle Scholar
- García A, Leonardi D, Salazar MO, Lamas MC (2014) Modified β-cyclodextrin inclusion complex to improve the physicochemical properties of albendazole. Complete in vitro evaluation and characterization. PLoS One 9(2):e88234.Google Scholar
- Higuchi T, Connors KA (1965) Phase-solubility techniques. Adv Anal Chem Instrum 4:117–122Google Scholar
- Molento MB (2004) Resistência de helmintos em ovinos e caprinos. Revista Brasileira de ParasitologiaVeterinária 13:82–87Google Scholar
- Moreno L, Echevarria F, Muñoz F, Alvrez L, Bruni SS, Lanusse C (2004) Dose-dependent activity of albendazole against benzimidazole-resistant nematodes in sheep: relationship between pharmacokinetics and efficacy. Exp Parasitol 106(3-4):150–157. https://doi.org/10.1016/j.exppara.2004.03.003CrossRefPubMedGoogle Scholar
- Palomares-Alonso F, González CR, Bernad-Bernad MJ, Montie MD, Hernández GP, González-Hernández I, Castro-Torres N, Estrada EP, Jung-Cook H (2010) Two novel ternary albendazole-cyclodextrin-polymer systems: dissolution, bioavailability and efficacy against Taenia crassiceps cysts. Acta Trop 113(1):56–60. https://doi.org/10.1016/j.actatropica.2009.09.006CrossRefPubMedGoogle Scholar
- Pensel PE, Castro S, Allemandi D, Bruni SS, Palma SD, Elissondo MC (2014) Enhanced chemoprophylatic and clinical efficacy of albendazole formulated as solid dispersions in experimental cystic echinococcosis. Vet Parasitol 203(1-2):80–86. https://doi.org/10.1016/j.vetpar.2014.01.027CrossRefPubMedGoogle Scholar
- Schwarz W (1990) PVP: a critical review of the kinetics and toxicology of polyvinylpyrrolidone (povidone). CRC Press, Boca RatonGoogle Scholar
- Soares-Sobrinho JL, Santos FLA, Lyra MAM, Alves LDS, Rolim LA, Lima AAN, Nunes LCC, Soares MFR, Rolim-Neto PJ, Torres-Labandeira JJ (2012) Benznidazole drug delivery by binary and multicomponent inclusion complexes using cyclodextrins and polymers. Carbohydr Polym 89(2):323–330. https://doi.org/10.1016/j.carbpol.2012.02.042CrossRefPubMedGoogle Scholar
- Ueno H, Gonçalves PC (1998) Manual para diagnóstico das helmintoses de ruminantes, 4th edn. Japan International Cooperation Agency, TokyoGoogle Scholar
- Villanova JCO, Sá VR (2009) Excipientes: guia prático para padronização. Pharmabooks, São PauloGoogle Scholar
- Woodgate RG, Cornell AJ, Sangster NC (2017) Occurrence, measurement and clinical perspectives of drug resistance in important parasitic helminths of livestock. In: Mayers DL, Sobel JD, Ouellette M, Kaye KS, Marchaim D (eds) Antimicrobial drug resistance: clinical and epidemiological aspects. Springer International Publishing, Cham, pp 1305–1326. https://doi.org/10.1007/978-3-319-47266-9_30CrossRefGoogle Scholar