TY - JOUR
T1 - Preparation and characterization of beclomethasone dipropionate solvates
AU - Weiss, Cordula
AU - McLoughlin, Peter
AU - Manesiotis, Panagiotis
AU - Redington, Wynette
AU - Cathcart, Helen
N1 - Publisher Copyright:
© 2018 American Chemical Society
PY - 2018/10/3
Y1 - 2018/10/3
N2 - Active pharmaceutical ingredients in dry powder inhaler (DPI) formulations need to have well-defined material properties. These can be influenced by the choice of processing parameters. The impact of methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 1-pentanol, and acetone on the crystallization of beclomethasone dipropionate (BDP), an anti-inflammatory agent, was studied using X-ray powder diffraction, thermal analysis, gas chromatography with mass spectrometry, scanning electron microscopy, and atomic force microscopy. Crystallization from methanol 1-butanol and 1-pentanol resulted in particulate BDP with a predominantly anhydrous character. In contrast, BDP solvates were formed using ethanol, 1-propanol, 2-propanol, or acetone. The solvates had different crystalline structures depending on the solvent used. Distinct thermal properties confirmed the inclusion of ethanol, 1-propanol, 2-propanol, and acetone within the crystalline BDP host. Furthermore, the size, shape, and surface characteristics of the crystalline particles were found to be influenced by the choice of solvent in a reproducible way. These properties were also found to translate to the anhydrous products prepared from the solvates through controlled desolvation. Such information is of value to the pharmaceutical industry, where knowledge of how specific factors affect the crystalline product would potentially allow one to tailor BDP to have specific material properties. Knowledge of how to control these properties by controlling specific processing parameters and to adjust them as desired would be of great benefit to DPI formulations, where surface properties are crucial to the efficacy of the treatment.
AB - Active pharmaceutical ingredients in dry powder inhaler (DPI) formulations need to have well-defined material properties. These can be influenced by the choice of processing parameters. The impact of methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 1-pentanol, and acetone on the crystallization of beclomethasone dipropionate (BDP), an anti-inflammatory agent, was studied using X-ray powder diffraction, thermal analysis, gas chromatography with mass spectrometry, scanning electron microscopy, and atomic force microscopy. Crystallization from methanol 1-butanol and 1-pentanol resulted in particulate BDP with a predominantly anhydrous character. In contrast, BDP solvates were formed using ethanol, 1-propanol, 2-propanol, or acetone. The solvates had different crystalline structures depending on the solvent used. Distinct thermal properties confirmed the inclusion of ethanol, 1-propanol, 2-propanol, and acetone within the crystalline BDP host. Furthermore, the size, shape, and surface characteristics of the crystalline particles were found to be influenced by the choice of solvent in a reproducible way. These properties were also found to translate to the anhydrous products prepared from the solvates through controlled desolvation. Such information is of value to the pharmaceutical industry, where knowledge of how specific factors affect the crystalline product would potentially allow one to tailor BDP to have specific material properties. Knowledge of how to control these properties by controlling specific processing parameters and to adjust them as desired would be of great benefit to DPI formulations, where surface properties are crucial to the efficacy of the treatment.
UR - http://www.scopus.com/inward/record.url?scp=85053184118&partnerID=8YFLogxK
U2 - 10.1021/acs.cgd.8b00465
DO - 10.1021/acs.cgd.8b00465
M3 - Article
AN - SCOPUS:85053184118
SN - 1528-7483
VL - 18
SP - 5832
EP - 5844
JO - Crystal Growth and Design
JF - Crystal Growth and Design
IS - 10
ER -