Influence of solvent evaporation rate and formulation factors on solid dispersion physical stability

TY - JOUR

T1 - Influence of solvent evaporation rate and formulation factors on solid dispersion physical stability

AU - Wu, Jian-Xiong

AU - Yang, Mingshi

AU - van der Berg, Franciscus Winfried J

AU - Pekka Pajander, Jari

AU - Rades, Thomas

AU - Rantanen, Jukka

PY - 2011/12/18

Y1 - 2011/12/18

N2 - New chemical entities (NCEs) often show poor water solubility necessitating solid dispersion formulation. The aim of the current study is to employ design of experiments in investigating the influence of one critical process factor (solvent evaporation rate) and two formulation factors (PVP:piroxicam ratio (PVP:PRX) and PVP molecular weight (P MW)) on the physical stability of PRX solid dispersion prepared by the solvent evaporation method. The results showed the rank order of an increase in factors contributing to a decrease in the extent of PRX nucleation being evaporation rate > PVP:PRX > P MW. The same rank order was found for the decrease in the extent of PRX crystal growth in PVP matrices from day 0 up to day 12. However, after 12 days the rank became PVP:PRX > evaporation rate > P MW. The effects of an increase in evaporation rate and PVP:PRX ratio in stabilizing PRX were of the same order of magnitude, while the effect from P MW was much smaller. The findings were confirmed by XRPD. FT-IR showed that PRX recrystallization in the PVP matrix followed Ostwald's step rule, and an increase in the three factors all led to increased hydrogen bonding interaction between PRX and PVP. The present study showed the applicability of the Quality by Design approach in solid dispersion research, and highlights the need for multifactorial analysis.

AB - New chemical entities (NCEs) often show poor water solubility necessitating solid dispersion formulation. The aim of the current study is to employ design of experiments in investigating the influence of one critical process factor (solvent evaporation rate) and two formulation factors (PVP:piroxicam ratio (PVP:PRX) and PVP molecular weight (P MW)) on the physical stability of PRX solid dispersion prepared by the solvent evaporation method. The results showed the rank order of an increase in factors contributing to a decrease in the extent of PRX nucleation being evaporation rate > PVP:PRX > P MW. The same rank order was found for the decrease in the extent of PRX crystal growth in PVP matrices from day 0 up to day 12. However, after 12 days the rank became PVP:PRX > evaporation rate > P MW. The effects of an increase in evaporation rate and PVP:PRX ratio in stabilizing PRX were of the same order of magnitude, while the effect from P MW was much smaller. The findings were confirmed by XRPD. FT-IR showed that PRX recrystallization in the PVP matrix followed Ostwald's step rule, and an increase in the three factors all led to increased hydrogen bonding interaction between PRX and PVP. The present study showed the applicability of the Quality by Design approach in solid dispersion research, and highlights the need for multifactorial analysis.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.ejps.2011.10.008

DO - 10.1016/j.ejps.2011.10.008

M3 - Journal article

SN - 0928-0987

VL - 44

SP - 610

EP - 620

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

IS - 5

ER -