Effects of Micronization on Digestive Absorption of Diosmin

Objective: To investigate the effect of diosmin particle size on the rate and extent of absorption and excretion of total radioactivity, following oral administration of micronized and non-micronized [ 14 C]-diosmin to New Zealand White rabbits. Design: This study was conducted in a 2 x 12 cross-over design at a uniform target dose level of 10 mg/kg, and was conducted according to Good Laboratory Practice. The micronized formulation was prepared using a Microdismembrator II, and all prepared doses were suspended in 0.5% w/v aqueous methylcellulose at a target concentration of 5 mg/ml. Particle size analysis indicated that in the micronized formulation, 90% of particles were ≤2 <m, and in the non-micronized formulation, more than 75% of particles were ≥3 <m. Results: Analysis of percentage dose excreted via urine post-dose indicated a higher urinary output in the animals that received micronized diosmin (mean of 72% dose in both 0–48 h and 0–168 h) compared with means of 16% dose and 17% dose, respectively, in animals that received the non-micronized formulation. Statistical analysis showed these differences to be highly significant ( p < 0.0001), with no evidence of sequence or phase effects. Conclusion: Reduction of particle size of [ 14 C]-diosmin when administered orally as a suspension to rabbits resulted in a marked increase in the proportion of the dose excreted in urine. This increase was considered to reflect an increased absorption of radiolabelled components from the micronized dose.