Abstract
Paclitaxel (PTX) is a poor water-soluble antineoplastic drug with significant antitumor activity. However, its low bioavailability is a major obstacle for its biomedical applications. Thus, this experiment is designed to prepare PTX crystal powders through an antisolvent precipitation process using 1-hexyl-3-methylimidazolium bromide (HMImBr) as solvent and water as an antisolvent. The factors influencing saturation solubility of PTX crystal powders in water in water were optimized using a single-factor design. The optimum conditions for the antisolvent precipitation process were as follows: 50 mg/mL concentration of the PTX solution, 25 °C temperature, and 1:7 solvent-to-antisolvent ratio. The PTX crystal powders were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, high-performance liquid chromatography–mass spectrometry, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Raman spectroscopy, solid-state nuclear magnetic resonance, and dissolution and oral bioavailability studies. Results showed that the chemical structure of PTX crystal powders were unchanged; however, precipitation of the crystalline structure changed. The dissolution test showed that the dissolution rate and solubility of PTX crystal powders were nearly 3.21-folds higher compared to raw PTX in water, and 1.27 times higher in artificial gastric juice. Meanwhile, the bioavailability of PTX crystal increased 10.88 times than raw PTX. These results suggested that PTX crystal powders might have potential value to become a new oral PTX formulation with high bioavailability.
Highlights
Polymorphisms refer to the variety of crystal structures created by different interactions between the same molecules in a solid state, which decides the physiochemical properties of crystals
The factors influencing the water saturation solubility of the PTX crystal powders were optimized through a single-factor design, and the optimum conditions were determined as follows—50 mg/mL concentration of PTX–hexyl-3-methylimidazolium bromide (HMImBr) solution, 1:7 solvent-to-antisolvent volume ratio, and 25 ◦C reaction temperature
The PTX crystal powder were obtained with the saturation solubility of 6.05 μg/mL, which was six times higher than that of the raw PTX
Summary
Polymorphisms refer to the variety of crystal structures created by different interactions between the same molecules in a solid state, which decides the physiochemical properties of crystals. Determination of distinct crystal habits is significantly influenced by solvent recrystallization because the morphology depends on the solute–solvent interaction on various crystal faces [2,3,4]. Drug crystallization methods include solution crystallization from single or mixed solvents [5,6,7], supercritical fluids crystallization [8], seeding strategies [9], capillary crystallization [10], polymer-induced heteronucleation [11], heteronucleation on substrates [12], and laser-induced nucleation [13]. Solution crystallization is one of the most popular methods in drug crystallization. Crystallization conditions include solvent/antisolvent species, temperature, additive, supersaturation, agitation etc. In these conditions, solvent/antisolvent species is often considered the most important factor that determines the polymorphs in crystallization
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