THE DISSOLUTION RATE AND ABSORPTION OF NITHIOCYAMINE SOLID DISPERSION

Nithiocyamine is poorly soluble in water, whose GI absorption is rate limited bydissolution. Reduction of the particle size by micronization generally increases the rateof absorption and/or total bioavailability. The large surface area of the particles whichresults from the micronization is associated with surface free energy which makes thesystem thermodynamically unstable. Selecting a physiological inert, easily soluble carriersuch as polyethylene glycol 6,000, solid dispersions are prepared by melting method.The formation of thermodynamically stable interstitial solid solution was demonstratedby X-ray diffraction. The dissolution rate of nithiocyamine-polyethylene glycol 6,000(1:9) was found respectively to be 10.6 and 15 times than that of micronized and purenithiocyamine. In the in vivo studies on mouse, the total areas under the blood concentration curves in 24 hrs for micronized nithiocyamine were found to be approximatly only 59% of those obtained from nithiocyamine-polyethlene glycol 6,000 soliddispersions.