Pellet manufacturing by extrusion-spheronization using process analytical technology
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Pellet manufacturing by extrusion-spheronization using process analytical technology. / Sandler, Niklas; Rantanen, Jukka; Heinämäki, Jyrki; Römer, Meike; Marvola, Martti; Yliruusi, Jouko.
In: AAPS PharmSciTech, Vol. 6, No. 2, 2005, p. E174-83.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Pellet manufacturing by extrusion-spheronization using process analytical technology
AU - Sandler, Niklas
AU - Rantanen, Jukka
AU - Heinämäki, Jyrki
AU - Römer, Meike
AU - Marvola, Martti
AU - Yliruusi, Jouko
PY - 2005
Y1 - 2005
N2 - The aim of this study was to investigate the phase transitions occurring in nitrofurantoin and theophylline formulations during pelletization by extrusion-spheronization. An at-line process analytical technology (PAT) approach was used to increase the understanding of the solid-state behavior of the active pharmaceutical ingredients (APIs) during pelletization. Raman spectroscopy, near-infrared (NIR) spectroscopy, and X-ray powder diffraction (XRPD) were used in the characterization of polymorphic changes during the process. Samples were collected at the end of each processing stage (blending, granulation, extrusion, spheronization, and drying). Batches were dried at 3 temperature levels (60 degrees C, 100 degrees C, and 135 degrees C). Water induced a hydrate formation in both model formulations during processing. NIR spectroscopy gave valuable real-time data about the state of water in the system, but it was not able to detect the hydrate formation in the theophylline and nitrofurantoin formulations during the granulation, extrusion, and spheronization stages because of the saturation of the water signal. Raman and XRPD measurement results confirmed the expected pseudopolymorphic changes of the APIs in the wet process stages. The relatively low level of Raman signal with the theophylline formulation complicated the interpretation. The drying temperature had a significant effect on dehydration. For a channel hydrate (theophylline), dehydration occurred at lower drying temperatures. In the case of isolated site hydrate (nitrofurantoin), dehydration was observed at higher temperatures. To reach an understanding of the process and to find the critical process parameters, the use of complementary analytical techniques are absolutely necessary when signals from APIs and different excipients overlap each other.
AB - The aim of this study was to investigate the phase transitions occurring in nitrofurantoin and theophylline formulations during pelletization by extrusion-spheronization. An at-line process analytical technology (PAT) approach was used to increase the understanding of the solid-state behavior of the active pharmaceutical ingredients (APIs) during pelletization. Raman spectroscopy, near-infrared (NIR) spectroscopy, and X-ray powder diffraction (XRPD) were used in the characterization of polymorphic changes during the process. Samples were collected at the end of each processing stage (blending, granulation, extrusion, spheronization, and drying). Batches were dried at 3 temperature levels (60 degrees C, 100 degrees C, and 135 degrees C). Water induced a hydrate formation in both model formulations during processing. NIR spectroscopy gave valuable real-time data about the state of water in the system, but it was not able to detect the hydrate formation in the theophylline and nitrofurantoin formulations during the granulation, extrusion, and spheronization stages because of the saturation of the water signal. Raman and XRPD measurement results confirmed the expected pseudopolymorphic changes of the APIs in the wet process stages. The relatively low level of Raman signal with the theophylline formulation complicated the interpretation. The drying temperature had a significant effect on dehydration. For a channel hydrate (theophylline), dehydration occurred at lower drying temperatures. In the case of isolated site hydrate (nitrofurantoin), dehydration was observed at higher temperatures. To reach an understanding of the process and to find the critical process parameters, the use of complementary analytical techniques are absolutely necessary when signals from APIs and different excipients overlap each other.
KW - Chemistry, Pharmaceutical
KW - Drug Implants
KW - Freeze Drying
KW - Humidity
KW - Pharmaceutical Preparations
KW - Spectroscopy, Near-Infrared
KW - Technology, Pharmaceutical
U2 - 10.1208/pt060226
DO - 10.1208/pt060226
M3 - Journal article
C2 - 16353975
VL - 6
SP - E174-83
JO - AAPS PharmSciTech
JF - AAPS PharmSciTech
SN - 1530-9932
IS - 2
ER -
ID: 140622369