Preparation and Dissolution Profiles of the Amorphous, Dihydrated Crystalline, and Anhydrous Crystalline Forms of Paclitaxel

Abstract

The selection of pharmaceutical polymorphisms in the final production step is very important in terms of product recovery, properties, and storage. The amorphous, dihydrated crystalline, and anhydrous crystalline forms of paclitaxel were prepared using precipitation, spray drying, and colloid formation methods. These methods were found to be highly efficient and convenient, giving high recovery, short processing time, and good stability, as compared with conventional methods such as freeze drying, evaporation, recrystallization, and melting. The polymorphic natures of the resulting paclitaxel samples were confirmed by XRPD, IR, TGA, DSC, and SEM. The dissolution rates of the paclitaxel samples were studied in pharmaceutical solvents, which included cotton seed oil, corn oil, tricaprylin, and tributyrin. For each solvent, all of the amorphous paclitaxel samples showed much higher dissolution rates than the dihydrated crystalline, anhydrous crystalline, and commercial forms, and can be used for clinical applications that demand improvements in drug delivery.

Keywords:

• Amorphous paclitaxel
• Anhydrous crystalline paclitaxel
• Dihydrated crystalline paclitaxel
• Dissolution rate
• Morphology

Notes

^a After dissolving in solvent A, the solution was evaporated.

^b After dissolving in solvent A, the solution was added to solvent B to obtain the precipitate, which was filtered.

^c After formation of the colloid in solvent A, the solution was evaporated.

^d After dissolving in solvent A, the solution was loaded onto a spray dryer.

^e Solvent A is the dissolving solvent (DCM, dichloromethane; THF, tetrahydrofuran; EA, ethylacetate).

^f Solvent B is the precipitation solvent.

^a The morphologies of the amorphous, dihydrated (crystalline), and anhydrous (crystalline) forms of paclitaxel were analyzed by XRPD.

^b Samples M and N were purchased from Sigma and Hauser, respectively.