ORAL ABSORPTION IMPROVEMENT OF POORLY SOLUBLE DRUG USING SOLID DISPERSION TECHNIQUE

A new triazol antifungal agent, H-1,2,4-triazol-1-yl)pyridazin-3-ylthi o]butan-2-ol (MFB-1041), shows poor oral absorption and is practically insoluble in water (1.2 mu g/ml). Solid dispersion systems with an en teric polymer such as hydroxypropylmethylcellulose phthalate (HP-55(R) ) and carboxymethylethylcellulose (CMEC(R)), and a nonenteric polymer, hydroxypropylmethylcellulose (Metolose(R)) were evaluated to improve drug absorption and solubility. The oral bioavailabilities of these so lid dispersions in beagle dogs were over 6 times higher than that of a suspension system with increasing drug solubility in an alkaline medi um, X-Ray powder diffraction measurement of the solid dispersion showe d a complete drug phase change from a crystal to an amorphous state, F urther, from the results of a stability test, the preparations were st able in a desiccated condition and the absorption profiles also showed no change, From the results, it was suggested that the oral administr ative preparation of MFB-1041 having a superior absorption profile and a high stability could be obtained by a drug phase change from a crys tal to an amorphous state, especially in the spray-drying method using enteric polymers.