title: Enhancement of bioavailability and anthelmintic efficacy of albendazole by solid dispersion and cyclodextrin complexation techniques.
abstract: The objective of this study was to improve the oral bioavailability and therapeutic efficacy of albendazole (ABZ) employing solid dispersion and cyclodextrin complexation techniques. Solid dispersion (dispersion) was prepared using ABZ and polyvinylpyrrolidone (PVP) polymer (1:1 weight ratio). Ternary inclusion complex (ternary complex) was prepared using ABZ, hydroxypropyl beta-cyclodextrin (HPbetaCD) and L-tartaric acid (1:1:1 molar ratio). In rabbits with high gastric acidity (gastric pH approximately 1), ternary complex and solid dispersion showed a bioavailability enhancement of 3.2 and 2.4 fold respectively, compared to a commercial suspension (p < 0.05). The rise in gastric pH (pH > 5) caused a 62% reduction in AUC (area under the plasma level curve) for the commercial suspension, whereas the reduction in case of PVP dispersion and ternary complex was only 43% and 37% respectively. The rapid absorption of the drug from solid dispersion and ternary complex was reflected in improved anthelmintic efficacy against the systemic phases of Trichinella spiralis. The ternary complex was significantly more efficient than solid dispersion and exhibited the highest larvicidal activity (90%) at a dose of 50 mg x kg(-1) (p < 0.05). These results suggest that the bioavailability and therapeutic efficacy of the ternary complex might be high even if there is a great variation in the gastric pH.
authors.affiliation: Department of Pharmacy, Annamalai University, Annamalai Nagar, Tamil Nadu, India. kalaipharmacy@yahoo.com
authors.forename: R
authors.initials: R
authors.lastname: Kalaiselvan
authors.forename: G P
authors.initials: GP
authors.lastname: Mohanta
authors.forename: S
authors.initials: S
authors.lastname: Madhusudan
authors.forename: P K
authors.initials: PK
authors.lastname: Manna
authors.forename: R
authors.initials: R
authors.lastname: Manavalan
mesh_terms: D015766:Albendazole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry; D003627:Data Interpretation, Statistical; D005079:Excipients; D005745:Gastric Acidity Determination; D006863:Hydrogen-Ion Concentration; D011817:Rabbits; D017160:Trichinella spiralis / Q000187:drug effects
chemical_list: D000871:Anthelmintics; D003505:Cyclodextrins; D005079:Excipients; D015766:Albendazole