Perphenazine solid dispersions for orally fast-disintegrating tablets: physical stability and formulation.

摘要

AIM: The aim of this study was to prepare an orally fast-disintegrating tablet (FDT) by direct compression, containing a poorly soluble drug (perphenazine, PPZ) formulated as a stable solid dispersion. METHODS: The stability studies of the fast dissolving 5/1, 1/5, 1/20 (w/w), PPZ/polyvinylpyrrolidone K30 (PVP) or polyethylene glycol 8000 (PEG)) solid dispersions, and amorphous PPZ were conducted with differential scanning calorimetry, X-ray powder diffraction, Fourier-transform infrared spectroscopy, small-angle X-ray scattering, and dissolution rate studies. RESULTS AND DISCUSSION: It was found that 1/5 PPZ/PEG was the most stable dispersion under elevated temperature and/or humidity. FDTs containing 60% of mannitol, 15% of calcium silicate, 15% of crospovidone, and 10% of 1/5 PPZ/PEG solid dispersion exhibited fast disintegration times (37 +/- 3), sufficient hardness (1.28 +/- 0.06 MPa), and fast onset of drug dissolution (34% of PPZ dissolved in 4 minutes), and these properties were found to be retained with storage. Thus, by optimizing the drug/excipient ratio of the solid dispersion and tablet composition, it was possible to produce FDTs that possessed fast disintegration and satisfactory drug dissolution in addition to adequate tensile strength, so that they can be handled and packed normally.