Drug particles with spherical morphology possess amazing advantages in terms of particle flowability,mechanical properties,drug solubility,and bioavailability.The growth mechanism of drug spherulite is of great importance for the preparation and regulation of spherulites.Herein,ceftriaxone sodium spherulites were fabricated by the antisolvent crystallization method using dropwise addition of ceftriaxone sodium solution to acetone.Online observation of the whole crystallization process combined with electron microscopy technique revealed the spherical growth process from amorphous form to spherulites.As the supersaturation of the crystallization system was adjusted,the ceftriaxone sodium crystals transformed from amorphous form to spherulites.In the process of antisolvent crystallization with acetone as antisolvent,when the theoretical supersaturation degree S was higher than 2.62,the crystallization system tended to appear amorphous form;when S was between 2.57 and 2.62,the amorphous form transformed into clustered spherulites;when S was less than 2.57,the surface of spherulites will be covered with flaky crystal,which transformed into urchin-like type.With the understanding of the spherical growth mechanism,the ceftriaxone sodium spherulites prepared in this research with modified supersaturation control had a low residue of antisolvent acetone,and the flowability was significantly improved.
Swift cooling crystallization of vanillin was investigated in water,ethanol,isopropanol and ethyl acetate.Morphology and polymorph evolution of vanillin were discussed in terms of solvent,supersaturation ratio and silica template.PXRD,DSC,FTIR and microscope were used to identify polymorphs of vanillin.Results showed that the nucleated polymorphs of vanillin depended largely on the solvent,supersaturation ratio and silica template.Low supersaturation ratios favor the nucleation of stable form I in water,and high supersaturation ratio exceeds 7 generating 100%metastable form II.However,if the supersaturation ratio is too high(S>8),liquid-liquid phase separation will occur,and no crystals could be obtained.In other solvents such as ethanol,isopropanol and ethyl acetate,only form I was obtained.However,it should be noted that the morphology of form I prepared in ethanol,isopropanol and ethyl acetate is distinct from that obtained in water,the former is flake-like and the latter is rod-like.The nucleation of vanillin from different solution was also studied with the presence of SiO_(2),SiO_(2)-NH_(2)and SiO_(2)−COOH templates,which did not change the nucleated polymorph of vanillin,but changed the nucleation and growth rate of stable form I.
Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs.However,how stabilizers affect the bioavailability of NCs remains unknown.In this study,F68,F127,HPMC,and PVP were each used as a stabilizer to formulate naringenin NCs.The NCs formulated with PVP exhibited excellent release behaviors,cellular uptake,permeability,oral bioavailability,and anti-inflammatory effects.The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer,which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved.This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.
