title: Impact of moisture and magnesium stearate functionality on manufacturability of wet granulated metformin tablets.
abstract: During the development of a wet granulated 850 mg metformin hydrochloride tablet formulation, the tablets exhibited high friability (>3% w/w) irrespective of the source of extra-granular magnesium stearate (MgSt). High friability values indicated that an anti-bonding effect of MgSt was too high to be overcome by 3.3% w/w povidone as a binder in the formulation with 1.5% w/w residual granule moisture. Increasing the povidone concentration up to 7% w/w showed limited improvement in friability, with tablets showing variable friability depending on MgSt source. Characterization of MgSt indicated differences in crystallinity, surface area and particle morphology between different vendors. In addition, a new bulk yield strength test, which determines the MgSt fragmentation tendency, was found to be indicative of the MgSt performance in the tablet formulation. To improve bonding properties of granules, residual granule moisture was increased to 2% w/w at different povidone concentrations. At 2% w/w residual granule moisture content, regardless of MgSt source, the tablets showed significant improvement in friability (∼0.6% w/w) even at the lowest povidone concentration (3.3% w/w). The bonding power of higher residual granule moisture had a greater impact than higher povidone concentration in overcoming the anti-bonding effects of magnesium stearate.
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb Co , New Brunswick , NJ , USA.
authors.forename: Umesh
authors.initials: U
authors.lastname: Kestur
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb Co , New Brunswick , NJ , USA.
authors.forename: Divyakant
authors.initials: D
authors.lastname: Desai
authors.affiliation: b Analytical & Bioanalytical Development, Bristol-Myers Squibb Co , New Brunswick , NJ , USA.
authors.forename: Shasad
authors.initials: S
authors.lastname: Sharif
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb Co , New Brunswick , NJ , USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wong
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb Co , New Brunswick , NJ , USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Guo
authors.affiliation: b Analytical & Bioanalytical Development, Bristol-Myers Squibb Co , New Brunswick , NJ , USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Tang
authors.affiliation: a Drug Product Science and Technology, Bristol-Myers Squibb Co , New Brunswick , NJ , USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Chan
mesh_terms: D005079:Excipients; D008687:Metformin; D013607:Tablets
chemical_list: D005079:Excipients; D013607:Tablets; D008687:Metformin
keywords: Bulk yield strength; friability; magnesium stearate; metformin; residual moisture