Effect of Particle Size of Drug on Conversion of Crystals to an Amorphous State in a Solid Dispersion with Crospovidone

Abstract

The effect of particle size on amorphization of drugs in a solid dispersion (SD) was investigated for two drugs, indomethacin (IM) and nifedipine (NP). The SD of drugs were prepared in a mixture with crospovidone by a variety of mechanical methods, and their properties investigated by particle sizing, thermal analysis, and powder X-ray diffraction. IM, which had an initial particle size of 1 m mm and tends to aggregate, was forced through a sieve to break up the particles. NP, which had a large initial particle size, was jet-milled. In both cases, reduction of the particle size of the drugs enabled transition to an amorphous state below the melting point of the drug. The reduction in particle size is considered to enable increased contact between the crospovidone and drug particles, increasing interactions between the two compounds.

Enhanced Oral Bioavailability of Rivaroxaban-Loaded Microspheres by Optimizing the Polymer and Surfactant Based on Molecular Interaction Mechanisms

“…The particle size distribution of the RXB-loaded microspheres prepared by spray drying is shown in Figure G . Particle size and distribution of RXB powder and formulations IV and VIII were investigated.…”

“…Each powder sample was analyzed in triplicate. The particle size distributions were expressed as D10, D50, and D90, which are the 10th, 50th, and 90th percentiles of the cumulative volume distribution, respectively …”

“…The particle size distributions were expressed as D10, D50, and D90, which are the 10th, 50th, and 90th percentiles of the cumulative volume distribution, respectively. 28 2.5.5. Nuclear Magnetic Resonance (NMR).…”

“…41 The particle size distribution of the RXB-loaded microspheres prepared by spray drying is shown in Figure 3G. 28 Particle size and distribution of RXB powder and formulations IV and VIII were investigated. The mean diameter D50 was 5.55 ± 0.20 μm for RXB, and the mean diameters for formulation IV and VIII were 1.70 ± 0.04 and 2.68 ± 0.08 μm, respectively, which were significantly decreased compared to those for RXB powder (p < 0.05).…”

Evaluation of the physicochemical characteristics of crospovidone that influence solid dispersion preparation

“…It was thought that IM content could also be increased when XL10 or INF was used. It was suggested that agglomerates of IM sometimes prevent preparation of amorphous SDs (Sugamura et al, 2011). These results indicated that the immiscibility of the drug and CrosPVP interferes with the determination of the maximum ratio of IM in the SD.…”