A high throughput platform for understanding the influence of excipients on physical and chemical stability
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A high throughput platform for understanding the influence of excipients on physical and chemical stability. / Raijada, Dhara; Cornett, Claus; Rantanen, Jukka; Raijada, Dharaben Kaushikkumar.
In: International Journal of Pharmaceutics, Vol. 453, No. 1, 30.08.2013, p. 285-92.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A high throughput platform for understanding the influence of excipients on physical and chemical stability
AU - Raijada, Dhara
AU - Cornett, Claus
AU - Rantanen, Jukka
AU - Raijada, Dharaben Kaushikkumar
N1 - Copyright © 2012 Elsevier B.V. All rights reserved.
PY - 2013/8/30
Y1 - 2013/8/30
N2 - The present study puts forward a miniaturized high-throughput platform to understand influence of excipient selection and processing on the stability of a given drug compound. Four model drugs (sodium naproxen, theophylline, amlodipine besylate and nitrofurantoin) and ten different excipients were selected. Binary physical mixtures of drug and excipient were transferred to a 96-well plate followed by addition of water to simulate aqueous granulation environment. The plate was subjected for XRPD measurements followed by drying and subsequent XRPD and HPLC measurements of the dried samples. Excipients with different water sorbing potential were found to influence distinctly on the phase transformation behaviour of each drug. Moreover, the amount of water addition was also a critical factor affecting phase transformation behaviour. HPLC analysis revealed one of the drug:excipient pairs with a tendency for chemical degradation. The proposed high-throughput platform can be used during early drug development to simulate typical processing induced stress in a small scale and to understand possible phase transformation behaviour and influence of excipients on this.
AB - The present study puts forward a miniaturized high-throughput platform to understand influence of excipient selection and processing on the stability of a given drug compound. Four model drugs (sodium naproxen, theophylline, amlodipine besylate and nitrofurantoin) and ten different excipients were selected. Binary physical mixtures of drug and excipient were transferred to a 96-well plate followed by addition of water to simulate aqueous granulation environment. The plate was subjected for XRPD measurements followed by drying and subsequent XRPD and HPLC measurements of the dried samples. Excipients with different water sorbing potential were found to influence distinctly on the phase transformation behaviour of each drug. Moreover, the amount of water addition was also a critical factor affecting phase transformation behaviour. HPLC analysis revealed one of the drug:excipient pairs with a tendency for chemical degradation. The proposed high-throughput platform can be used during early drug development to simulate typical processing induced stress in a small scale and to understand possible phase transformation behaviour and influence of excipients on this.
KW - Chemistry, Pharmaceutical
KW - Drug Stability
KW - Excipients
KW - Naproxen
KW - Nitrofurantoin
KW - Powder Diffraction
KW - Theophylline
KW - Water
KW - X-Ray Diffraction
U2 - 10.1016/j.ijpharm.2012.08.025
DO - 10.1016/j.ijpharm.2012.08.025
M3 - Journal article
C2 - 22944300
VL - 453
SP - 285
EP - 292
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1
ER -
ID: 112847783