Solid dispersion of spironolactone with porous silica prepared by the solvent method.
Solid dispersions of spironolactone (SPI) with porous silica (Sylysia 730 and Sylysia 350) were prepared by the solvent method. The physicochemical properties of the prepared solid dispersions were evaluated by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and atomic force microscopy (AFM). In the SEM study, no differences in the surface condition between Sylysia 350 and the solid dispersion of a Sylysia 350:SPI system in a weight ratio of 1:1 were observed. However, AFM phase images showed that the surface of the solid dispersion of the Sylysia 350:SPI system (weight ratio of 1:1) was rather smooth due to the adsorption of SPI as compared with that of a Sylysia 350 intact. The results of PXRD and DSC data in the solid dispersion of the Sylysia 350:SPI system (weight ratio of 1:1) indicated that the molecular state of the adsorbed SPI changed from crystalline to amorphous. Although the decrease in the SPI concentration increased with the amorphous fraction in the solid dispersion, the diffraction peaks due to SPI crystals still remained in the solid dispersion of a Sylysia 730:SPI system (weight ratio of 1:1), indicating that the mean pore diameter and specific surface area of an additive are some of the important factors for the amorphization of SPI crystals. The dissolution property of the SPI from the solid dispersions was remarkably improved in comparison with that of SPI crystals. The dissolution rate of the SPI from the solid dispersions with Sylysia 350 was faster than that of the SPI from the solid dispersions with Sylysia 730. The difference in the dissolution properties of SPI from both the solid dispersions was attributed to the difference in the molecular state of the SPI in both the solid dispersions. In the stability test, the amorphous state of the SPI in the solid dispersion of the Sylysia 350:SPI system (weight ratio of 1:1) was maintained for 2 weeks at 25 degrees C and 0% RH, while the amorphous SPI without Sylysia 350 crystallized under the same conditions.
Uchino
T
T
Department of Pharmacy, Faculty of Medicine, The University of Tokyo Hospital, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. uchinot-tky@umin.ac.jp
Yasuno
N
N
Yanagihara
Y
Y
Suzuki
H
H
D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding; D005079:Excipients; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000737:chemistry*; D012822:Silicon Dioxide; D012997:Solvents; D013148:Spironolactone / Q000008:administration & dosage / Q000737:chemistry*; D014961:X-Ray Diffraction
D005079:Excipients; D000451:Mineralocorticoid Receptor Antagonists; D012997:Solvents; D013148:Spironolactone; D012822:Silicon Dioxide