Stability and Bioquivalence Studies of Two Marketed Formulations of Coenzyme Q₁₀ in Beagle Dogs

Abstract

Coenzyme Q₁₀ (CoQ₁₀), a highly lipophilic compound present in the inner mitochondrial membrane, is essential for production of celllar energy in the form of ATP. CoQ₁₀ is used as an antioxidant and also in the treatment of various cardiovascular disorders. The relative bioavaliabilities of powder filled capsule (I) and oil-based formulation (II) of CoQ₁₀ were compared in beagle dogs in an open, randomized, multiple dose, cross-over design. Poor and slow absorption characteristics were observer for both the formulations. The AUC, C_max, and T_max for formulation I and II are comparable (p<0.05) where the values for formulation I are 22.84±6.3μg ml^-1h, 0.51±0.11μg/m, and 6.1±2.0h whereas the values for foumulation Ii are 24.32±5.6μg ml^-1h, 0.55±0.16μg/ml, and 6.6±2.3h, respectively. Stability of CoQ₁₀ at various temperature and humidity conditions and its photostability were studied. Various antioxidants were evaluated to determine the type and amount of antioxidant(s) required to improve the stability of CoQ₁₀. Large extent of degradation was observed at 45°Cand 55°C. The effect of humidity conditions on degradation was insignificant. Among the various antioxidants studied, mixture of ascorbic acid (5%) and EDTA (0.1%) offered better protection than phenolic antioxidants such as butylated hydroxy anisole (BHA), butylated hydroxy toluene (BHT), or propyl gallate (PG). Further, increasing concentrations of phenolic antioxidants (from 0.1 to 0.3%) accelerated the degradation.