Surface modification and improvement of dissolution property of poorly water-soluble drug by jet mill pulverization

摘要

To improve the dissolution property of poorly water-soluble drug, flurbiprofen, we have conducted the following three methods; (i) pulverization of drug by a jet mill, (ii) mixing of light anhydrous silicic acid to the fine drug, and (iii) surface modification of the fine drug with light anhydrous silicic acid by jet mill pulverization. First of all, flurbiprofen was pulverized by a jet mill and dissolution property of the pulverized fine flurbiprofen was investigated. The fine flurbiprofen prepared by jet mill pulverization could not improve the dissolution property, since surface area of the fine flurbiprofen decreased by self-agglomeration due to its adhesive-agglomeration property. In order to prevent the self-agglomeration of the fine flurbiprofen, light anhydrous silicic acid was added to the fine flurbiprofen by a high shear mixing. However, the dissolution property of the mixture was improved slightly due to the slight improvement of its wettability and dispersibility. The surface modification was then conducted by pulverizing the mixture of original flurbiprofen and light anhydrous silicic acid. The results indicated the drastic improvement of the dissolution property. In addition, pulverization of the surface modified fine flurbiprofen together with sugar alcohol achieved greater improvement of the dissolution property. As a result, it was concluded that the surface modification of poorly water-soluble drug with light anhydrous silicic acid by using jet mill pulverization was very effective to improve the dissolution property.