title: Enhancing tablet disintegration characteristics of a highly water-soluble high-drug-loading formulation by granulation process.
abstract: The objective of this study was to improve the disintegration and dissolution characteristics of a highly water-soluble tablet matrix by altering the manufacturing process. A high disintegration time along with high dependence of the disintegration time on tablet hardness was observed for a high drug loading (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process. Keeping the formulation composition mostly constant, a fluid-bed granulation (FBG) process was explored as an alternate granulation method using a 2(4-1)fractional factorial design with two center points. FBG batches (10 batches) were manufactured using varying disingtegrant amount, spray rate, inlet temperature (T) and atomization air pressure. The resultant final blend particle size was affected significantly by spray rate (p = .0009), inlet T (p = .0062), atomization air pressure (p = .0134) and the interaction effect between inlet T*spray rate (p = .0241). The compactibility of the final blend was affected significantly by disintegrant amount (p < .0001), atomization air pressure (p = .0013) and spray rate (p = .05). It was observed that the fluid-bed batches gave significantly lower disintegration times than the HSWG batches, and mercury intrusion porosimetry data revealed that this was caused by the higher internal pore structure of tablets manufactured using the FBG batches.
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick , NJ , USA.
authors.forename: Preetanshu
authors.initials: P
authors.lastname: Pandey
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick , NJ , USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Levins
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick , NJ , USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Pafiakis
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick , NJ , USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Zacour
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick , NJ , USA.
authors.forename: Dilbir S
authors.initials: DS
authors.lastname: Bindra
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick , NJ , USA.
authors.forename: Jade
authors.initials: J
authors.lastname: Trinh
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick , NJ , USA.
authors.forename: David
authors.initials: D
authors.lastname: Buckley
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick , NJ , USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Gour
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick , NJ , USA.
authors.forename: Shasad
authors.initials: S
authors.lastname: Sharif
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick , NJ , USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Stamato
mesh_terms: D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D006244:Hardness; D010316:Particle Size; D016062:Porosity; D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D005079:Excipients; D013607:Tablets; D014867:Water
keywords: Disintegration; Fluidized bed; Granulation; High-shear wet granulation; Porosity