The solvent-shift method was used to identify appropriate polymers that inhibit the growth of felodipine crystals by monitoring particle size in supersaturated drug solutions in the presence of different polymers. We speculated that there would be an intermolecular interaction between the selected polymer (zein) and felodipine by extrapolating the inhibitory effect on crystal growth and then used the selected polymer as a carrier to prepare solid dispersions. The formulations were characterized by crystalline properties, thermodynamics of mixing, dissolution behavior, and physical stability. Powder x-ray diffraction and differential scanning calorimetry experiments indicated that amorphous solid dispersions were formed when the proportion of felodipine was < 30% (w/w). Stability tests showed that a solid dispersion with 20% felodipine remained in an amorphous state and was stable under accelerated storage conditions for 6 months. The dissolution rates of solid dispersions were significantly greater than those of the active pharmaceutical ingredient or physical mixtures. Analysis by Fourier-transform infrared spectroscopy and Raman microspectroscopy indicated the formation of intermolecular interactions between zein and felodipine. The study demonstrates the successful application of the chosen polymer as a carrier in solid dispersions and validates the concept of extrapolating the inhibitory effect on crystal growth to intermolecular interactions.

Bicalutamide-bovine serum albumin (Bic-BSA) complexes were prepared by anti-solvent precipitation. Bovine serum albumin (BSA) was used as a stabilizer for particle growth. The physicochemical properties of Bic-BSA were analyzed by scanning electron microscopy, X-ray powder diffraction and differential scanning calorimetry. The interaction between Bic and BSA was characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, fluorescence spectroscopy and molecular docking. The particle size could be easily reduced to 1-10μm with a good lognormal distribution. The Bic-BSA complexes exhibited nonporous spherical morphology with a uniformly plicated surface. Moreover, the crystal form and thermostability of Bic were altered in the presence of BSA. Bic was found to make hydrogen bonding and hydrophobic interactions with BSA by spectroscopic studies and molecular docking. Results from the Van't Hoff equation and binding free energy calculations indicated that the improvement of physicochemical properties was the consequence of a variety of interactions in the Bic-BSA system. Bic-BSA tablets showed significantly enhanced dissolution. It was concluded that BSA plays an important role in improving the physicochemical properties of Bic due to strong multiple interactions between Bic and BSA.

OBJECTIVE To investigate the influencing mechanism of the particle size of hydroxypropyl methylcellulose (HPMC) on the release behavior of nifedipine from a sustained-release tablet system based on the compaction properties of HPMC.METHODS The compaction properties of HPMC K4M of different particle sizes were determined.Hydrophilic matrix sustained-release tablets were prepared using nifedipine as the active ingredient and HPMC K4M as a hydrophilic matrix former.The effect of compaction properties of HPMC K4M on the porosity,release,and other properties of nifedipine hydrophilic matrix sustained-release tablets were also studied.RESULTS The decrease of the particle size of HPMC K4M resulted in higher bulk density,tap density,compres sibility index,and tensile strength and smaller elastic recovery of HPMC K4M,which all led to the decrease of thickness and porosity and the increase of HPMC concentration per unit volume of nifedipine hydrophilic matrix sustained-release tablets.These factors resulted in faster gelation rate of nifedipine sustained-release tablets and decreased water ingress and polymer swelling,so the release of nifedipine from the delivery system was prolonged.CONCLUSION The obviously different compaction properties of HPMC of differ ent particle sizes influence the porosity and gelation rate and then the release of hydrophilic matrix nifedipine sustained-release tablets.