Tablets of amorphous sucrose and sucrose-polyvinylpyrrolidone (PVP) amorphous solid dispersions were compressed at 25, 75, or 150 MPa at dwell times ranging from 5 to 900 s. Compression-induced physical destabilization was evident from differential scanning calorimetry. Crystallization kinetics was monitored using a laboratory source X-ray diffractometer, while crystallization was detected using highly sensitive synchrotron radiation. At the highest compression pressure, sucrose crystallization was evident immediately after compression. However, the addition of PVP, even at a low concentration of 1% w/w, inhibited crystallization. Furthermore, nucleation itself was completely prevented at higher PVP concentrations (≥15% w/w) under a compression pressure of practical interest (150 MPa with 5 s dwell time). However, an increase in dwell time (e.g., to 60 s) facilitated nucleation, and there was an increase in nucleation density as a function of dwell time. Both polymer content and sample history were pivotal factors limiting compression-induced crystallization in plasticized amorphous systems. Generally, plasticization was found to amplify compression-induced destabilization. PVP, in a concentration dependent manner, attenuated this effect.
Bibliographical noteFunding Information:
K.B. was supported by the Baltic-American Freedom Foundation (BAFF) fellowship. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. Parts of this work were carried out in Characterization Facility, University of Minnesota, which receives partial support from NSF through the MSRC program. We thank Dr. Wenqian Xu at Argonne National Laboratory for his help during the synchrotron data collection. Dr. Naveen Thakral, Dr. Seema Thakral, Dr. Mehak Mehta, Dr. Pinal Mistry, Michelle Fung, and Sampada Koranne are thanked for their useful comments.