SOLID-STATE CHARACTERIZATION OF PACLITAXEL

The purpose of this work was to characterize the solid-state propertie s of anhydrous paclitaxel and paclitaxel dihydrate, Paclitaxel I (anhy drous) was suspended in water for 24 h to convert it to paclitaxel 2H( 2)O. Both forms were analyzed by differential scanning calorimetry (DS C) and thermogravimetric analysis (TGA), X-ray powder diffraction (XRP D) patterns were obtained at 25, 100, and 195 degrees. Dissolution pro files of both forms were obtained in water at 37 degrees over 20 h. DS C of paclitaxel 2H(2)O showed two endothermic peaks below 100 degrees, corresponding to dehydration, The resulting solid phase was termed '' dehydrated paclitaxel . 2H(2)O''. at 168 degrees, a solid-solid transi tion was observed in which dehydrated paclitaxel 2H(2)O was converted io a semicrystalline material called ''paclitaxel I/am''. The solid-so lid transition was followed by melting at 220 degrees. TGA of paclitax el . 2H(2)O showed a corresponding biphasic weight loss below 100 degr ees, which was equivalent to the weight of 2 mol of water. DSC of pacl itaxel I showed no transitions before melting at 220 degrees, and no w eight loss was observed by TGA. Quenching of paclitaxel I from the mel t produced amorphous paclitaxel with a glass transition at 152 degrees , XRPD confirmed that paclitaxel I, paclitaxel . 2H(2)O, and dehydrate d paclitaxel . 2H(2)O had different crystal structures. The X-ray patt erns of paclitaxel I and paclitaxel I/am were similar, however the two forms of paclitaxel did not behave identically when analyzed by DSC. The bulk dissolution studies with paclitaxel I showed a rapid increase in concentration to 3 mu g/mL in 4 h, which decreased to 1 mu g/mL af ter 12 h, corresponding to the solubility of paclitaxel . 2H(2)O. The solubility of paclitaxel . 2H(2)O was 1 mu g/mL. The data demonstrate the existence of a dihydrate form of paclitaxel that is the stable for m in equilibrium with water at 37 degrees but which dehydrates at temp eratures > 45 degrees.