Controlling granule size by granulation liquid feed pulsing.
The effects of inlet air humidity, granulation liquid feed rate and granulation liquid feed pulsing on the particle-size distribution of final granules were studied in a laboratory scale fluid-bed granulator using a central composite study design. The factors examined were modelled using three different particle-size measurement techniques (sieve analysis, laser light diffraction and the spatial filtering technique). Best goodness of fit (R2=0.94) and goodness of prediction (Q2=0.90) values were obtained using particle-size results of the spatial filtering technique. Increasing inlet air humidity and granulation liquid feed rate resulted in greater median granule size, as expected. When pulsing (interruption of granulation liquid feed in predetermined sequences) was used, the median granule size decreased clearly. This effect was strong, especially with high inlet air humidity and rapid liquid feed rate processes. Granulation liquid feed pulsing is an effective way to modify the particle size of final granules. Pulsing can be used as a controlling tool to compensate for excessive moisture content in the granulation process.
Närvänen
Tero
T
Orion Corporation Orion Pharma, Orionintie 1, P.O. Box 65, FIN-02101 Espoo, Finland. tero.narvanen@orionpharma.com
Lipsanen
Tanja
T
Antikainen
Osmo
O
Räikkönen
Heikki
H
Yliruusi
Jouko
J
D000388:Air / Q000032:analysis; D003627:Data Interpretation, Statistical; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients; D006813:Humidity; D007785:Lactose / Q000737:chemistry; D015233:Models, Statistical; D010316:Particle Size; D011205:Povidone; D011208:Powders; D013806:Theophylline / Q000008:administration & dosage / Q000737:chemistry
D005079:Excipients; D011208:Powders; D013806:Theophylline; D011205:Povidone; D007785:Lactose