TY - JOUR
T1 - Modelling of molecular phase transitions in pharmaceutical inhalation compounds
T2 - an in silico approach
AU - Abdel-Halim, Heba
AU - Traini, Daniela
AU - Hibbs, David
AU - Gaisford, Simon
AU - Young, Paul
PY - 2011
Y1 - 2011
N2 - Molecular dynamic simulations have been successfully utilised with molecular modelling to estimate the glass transition temperature (Tg) of polymers. In this paper, we use a similar approach to predict the Tg of a small pharmaceutical molecule, beclomethasone dipropionate (BDP). Amorphous beclomethasone dipropionate was prepared by spray-drying. The amorphous nature of the spray-dried material was confirmed with scanning electron microscopy, differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). Molecular models for amorphous BDP were constructed using the amorphous cell module in Discovery studio™. These models were used in a series of molecular dynamic simulations to predict the glass transition temperature. The Tg of BDP was determined by isothermal-isobaric molecular dynamic simulations, and different thermodynamic parameters were obtained in the temperature range of −150 to 400 °C. The discontinuity at a specific temperature in the plot of temperature versus amorphous cell volume (V) and density (ρ) was considered to be the simulated Tg. The predicted Tg from four different simulation runs was 63.8 °C ± 2.7 °C. The thermal properties of amorphous BDP were experimentally determined by DSC and the experimental Tg was found to be ∼65 °C, in good agreement with computational simulations.
AB - Molecular dynamic simulations have been successfully utilised with molecular modelling to estimate the glass transition temperature (Tg) of polymers. In this paper, we use a similar approach to predict the Tg of a small pharmaceutical molecule, beclomethasone dipropionate (BDP). Amorphous beclomethasone dipropionate was prepared by spray-drying. The amorphous nature of the spray-dried material was confirmed with scanning electron microscopy, differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). Molecular models for amorphous BDP were constructed using the amorphous cell module in Discovery studio™. These models were used in a series of molecular dynamic simulations to predict the glass transition temperature. The Tg of BDP was determined by isothermal-isobaric molecular dynamic simulations, and different thermodynamic parameters were obtained in the temperature range of −150 to 400 °C. The discontinuity at a specific temperature in the plot of temperature versus amorphous cell volume (V) and density (ρ) was considered to be the simulated Tg. The predicted Tg from four different simulation runs was 63.8 °C ± 2.7 °C. The thermal properties of amorphous BDP were experimentally determined by DSC and the experimental Tg was found to be ∼65 °C, in good agreement with computational simulations.
KW - Amorphous
KW - Beclomethasone dipropionate
KW - Glass transition temperature
KW - Molecular dynamic simulations
UR - http://www.scopus.com/inward/record.url?scp=79953163397&partnerID=8YFLogxK
U2 - 10.1016/j.ejpb.2010.12.019
DO - 10.1016/j.ejpb.2010.12.019
M3 - Article
C2 - 21172436
SN - 0939-6411
VL - 78
SP - 83
EP - 89
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
IS - 1
ER -