EFFECTS OF MICRONIZATION ON DIGESTIVE ABSORPTION OF DIOSMIN

Objective: To investigate the effect of diosmin particle size on the r ate and extent of absorption and excretion of total radioactivity, fol lowing oral administration of micronized and non-micronized [C-14]-dio smin 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 microni zed formulation was prepared using a Microdismembrator II, and all pre pared doses were suspended in 0.5% w/v aqueous methylcellulose at a ta rget concentration of 5 mg/ml. Particle size analysis indicated that i n the micronized formulation, 90% of particles were not less than or e qual to 2 mu m, and in the non-micronized formulation, more than 75% o f particles were greater than or equal to 3 mu m. Results: Analysis of percentage dose excreted via urine post-dose indicated a higher urina ry 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 fo rmulation. Statistical analysis showed these differences to be highly significant (p < 0.0001), with no evidence of sequence or phase effect s. Conclusion: Reduction of particle size of [C-14]-diosmin when admin istered orally as a suspension to rabbits resulted in a marked increas e in the proportion of the dose excreted in urine. This increase was c onsidered to reflect an increased absorption of radiolabelled componen ts from the micronized dose.