Understanding processing-induced phase transformations in erythromycin-PEG 6000 solid dispersions
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Understanding processing-induced phase transformations in erythromycin-PEG 6000 solid dispersions. / Mirza, Sabiruddin; Heinämäki, Jyrki; Miroshnyk, Inna; Rantanen, Jukka; Christiansen, Leena; Karjalainen, Milja; Yliruusi, Jouko.
In: Journal of Pharmaceutical Sciences, Vol. 95, No. 8, 08.2006, p. 1723-32.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Understanding processing-induced phase transformations in erythromycin-PEG 6000 solid dispersions
AU - Mirza, Sabiruddin
AU - Heinämäki, Jyrki
AU - Miroshnyk, Inna
AU - Rantanen, Jukka
AU - Christiansen, Leena
AU - Karjalainen, Milja
AU - Yliruusi, Jouko
N1 - Copyright 2006 Wiley-Liss, Inc.
PY - 2006/8
Y1 - 2006/8
N2 - Since the quality and performance of a pharmaceutical solid formulation depend on solid state of the drug and excipients, a thorough investigation of potential processing-induced transformations (PITs) of the ingredients is required. In this study, the physical phenomena taking place during formulation of erythromycin (EM) dihydrate solid dispersions with polyethylene glycol (PEG) 6000 by melting were investigated. PITs were monitored in situ using variable temperature X-ray powder diffraction (VT-XRPD), differential scanning calorimetry (DSC), and hot-stage microscopy (HSM). Possible intermolecular interactions between the drug and polymer in the solid state were further studied by Fourier transform infrared (FTIR) spectroscopy. While in the absence of PEG the dehydration was the only transformation observed, hot-melt processing with the polymer caused the drug to undergo multiple phase transformations (EM dihydrate --> EM dehydrate --> EM anhydrate). This alteration in phase behavior of EM was attributed to the ability of PEG in promoting nucleation and crystal growth of the EM anhydrate through a solvent-mediated route. In situ monitoring of solid dispersion formation, especially by VT-XRPD and HSM, enabled both early-stage detection of phase transformations during the hot-melt processing and better process understanding.
AB - Since the quality and performance of a pharmaceutical solid formulation depend on solid state of the drug and excipients, a thorough investigation of potential processing-induced transformations (PITs) of the ingredients is required. In this study, the physical phenomena taking place during formulation of erythromycin (EM) dihydrate solid dispersions with polyethylene glycol (PEG) 6000 by melting were investigated. PITs were monitored in situ using variable temperature X-ray powder diffraction (VT-XRPD), differential scanning calorimetry (DSC), and hot-stage microscopy (HSM). Possible intermolecular interactions between the drug and polymer in the solid state were further studied by Fourier transform infrared (FTIR) spectroscopy. While in the absence of PEG the dehydration was the only transformation observed, hot-melt processing with the polymer caused the drug to undergo multiple phase transformations (EM dihydrate --> EM dehydrate --> EM anhydrate). This alteration in phase behavior of EM was attributed to the ability of PEG in promoting nucleation and crystal growth of the EM anhydrate through a solvent-mediated route. In situ monitoring of solid dispersion formation, especially by VT-XRPD and HSM, enabled both early-stage detection of phase transformations during the hot-melt processing and better process understanding.
KW - Chemistry, Pharmaceutical
KW - Erythromycin
KW - Polyethylene Glycols
KW - Spectroscopy, Fourier Transform Infrared
KW - X-Ray Diffraction
U2 - 10.1002/jps.20640
DO - 10.1002/jps.20640
M3 - Journal article
C2 - 16795009
VL - 95
SP - 1723
EP - 1732
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 8
ER -
ID: 140618681