Indexed on: 20 Oct '04Published on: 20 Oct '04Published in: Drug development and industrial pharmacy
The objective of this study was to produce, by spray freezing into liquid (SFL) technology, high-potency, high glass transition temperature (Tg) danazol/polymer powders that remain amorphous and exhibit high dissolution rates after 6 months. Three polymers were investigated, including polyvinylpyrrolidone (PVP) K-15, poloxamer 407, and PEG 8000. The physicochemical properties of SFL powders were characterized by X-ray diffraction (XRD), scanning electron microscopy, particle size distribution, surface area analysis, moisture content, and dissolution rate. The influence of moisture content, drug potency, and excipient type on Tg of SFL powders was investigated using modulated differential scanning calorimetry (mDSC). XRD results indicated that danazol was amorphous for each added excipient. The surface area of danazol/PVP K-15 powders (89.8 m2/g) was higher than that of danazol/PEG 8000 (12.0 m2/g) and danazol/poloxamer 407 (5.49 m2/g). The SFL powders with the various excipient types exhibited similar and significantly enhanced dissolution rates relative to micronized bulk danazol. As the potency of danazol in the SFL danazol/PVP K-15 powders was increased from 33% to 91%, the Tg decreased from 126 degrees C to 104 degrees C. The SFL powders, which were packaged in sealed 30-mL glass vials with a desiccant, were physically stable when stored at 25 degrees C for 6 months, based on dissolution rates and mDSC and XRD measurements. SFL danazol/PVP K-15 powders with high surface areas and high glass transition temperatures remain amorphous and exhibit rapid dissolution rates after 6 months' storage.