title: Distribution of a viscous binder during high shear granulation--sensitivity to the method of delivery and its impact on product properties.
abstract: Binder distribution in the powder mass during high shear granulation is especially critical with the use of viscous liquid binders and with short processing times. A viscous liquid binder was delivered into the powder mass at two flow rates using three methods: pouring, pumping and spraying from a pressure pot. Binder content analyses at the scale of individual granules were conducted to investigate the impact of different delivery conditions on the homogeneity of binder distribution. There was clear evidence of non-uniformity of binder content among individual granules across all delivery conditions, particularly for the fast rates of delivery. Poorer reproducibility values of tablet thickness and disintegration time were observed when binder was poured but this may be overcome by pumping or spraying from the pressure pot. Greater homogeneity of binder distribution occurred with the slow rates of delivery and led to the earlier onset of granule growth and a consequent increase in granule size. Larger granule size and lower proportion of fines were in turn associated with increased granule bulk density and improvement of granule flow. In conclusion, delivery of a viscous binder at a slow rate either by pumping or via a pressure pot was most desirable during granulation.
authors.affiliation: GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Bernice Mei Jin
authors.initials: BM
authors.lastname: Tan
authors.affiliation: GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Zhi Hui
authors.initials: ZH
authors.lastname: Loh
authors.affiliation: Novartis Singapore Pharmaceutical Manufacturing, 10 Tuas Bay Lane, Singapore 437461, Singapore.
authors.forename: Josephine Lay Peng
authors.initials: JL
authors.lastname: Soh
authors.affiliation: GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Celine Valeria
authors.initials: CV
authors.lastname: Liew
authors.affiliation: GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore. Electronic address: phapaulh@nus.edu.sg.
authors.forename: Paul Wan Sia
authors.initials: PW
authors.lastname: Heng
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002744:Chlorpheniramine / Q000737:chemistry; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D006244:Hardness; D011208:Powders; D013213:Starch / Q000737:chemistry; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical; D014783:Viscosity
chemical_list: D005079:Excipients; D011208:Powders; D013607:Tablets; D000082:Acetaminophen; D002744:Chlorpheniramine; D002482:Cellulose; D013213:Starch; C008079:hydroxypropylcellulose; C109691:microcrystalline cellulose
keywords: Binder distribution; Binder flow rate; Granule growth; Granule rheology; High shear granulation; Pressure pot