Improvement of Dissolution Rate and Oral Bioavailability of a Sparingly Water-Soluble Drug, (±)-5-[[2-(2-Naphthalenylmethyl)-5-benzoxazolyl]-methyl]-2,4,-thiazolidinedione, in Co-ground Mixture with D-Mannitol

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We investigated the usefulness and efficiency of the co-grinding method with D-mannitol to improve the bioavailability of a sparingly water-soluble drug, (±)-5-[[2-(2-naphthalenylmethyl)-5-benzoxazolyl]methyl]-2,4-thiazolidinedione (174), and compared it with those of the single-grinding method.The co-ground mixtures in drug/carrier weight ratios up to 1 : 5 gave fine particle sizes of less than about 3 μm, which showed a marked increase in the dissolution rate with reduction of particle size, compared with the single-ground powder, even with a similar particle size. The oral bioavailability study of co-ground powders in beagle dose exhibited a dramatic increase, as did the dissolution rate, according to finer particle size. Finally, complete bioavailability was obtained at the finest particle size of 1.2 μm (drug/carrier ratio of 1 : 5,w/w) as was a solution of the drug. Bioavailability had a good linear correlation with the dissolution rate. These findings suggested that the co-grinding method with D-mannitol dramatically increased the available surface area, caused by a reduction of particle size, which not only accelerated the dissolution rate but also resulted in greater enhancement of the bioavailability of 174.
公益社団法人日本薬学会の論文
1997-04-15