title: Effect of spray-dried mannitol on the performance of microcrystalline cellulose-based wet granulated tablet formulation.
abstract: The purpose of this study was to evaluate mannitol as filler along with microcrystalline cellulose (MCC) in wet granulated tablet formulation, in situations where lactose cannot be included in the formulation due to chemical incompatibility with the active drug. A two-level full factorial design with two center points was used to study the effect of three variables: mannitol: MCC ratio (mannitol weight fraction of the filler; low 0 (no mannitol) and high 0.5), water to intragranular solids ratio (low 0.25 and high 0.4) and magnesium stearate concentration, w/w (0.6% low and 1.2% high). The response variables evaluated were granulation compactibility, ejection force, normalized granule size, % fines, flowability index, compression speed sensitivity and hardness loss upon storage. Addition of mannitol in the MCC formulation increased compactibility of the final granulation as it decreased the susceptibility of the formulation to compaction loss upon wet granulation. Presence of mannitol in the formulation reduced the compression speed sensitivity and also decreased the susceptibility of the formulation to hardness loss upon storage.
authors.affiliation: Bristol-Myers Squibb Company, Pharmaceutics R & D, New Brunswick, New Jersey 08903, USA. sherif.badawy@bms.com
authors.forename: Sherif I F
authors.initials: SI
authors.lastname: Badawy
authors.forename: Keyur R
authors.initials: KR
authors.lastname: Shah
authors.forename: Madhu S
authors.initials: MS
authors.lastname: Surapaneni
authors.forename: Marta M
authors.initials: MM
authors.lastname: Szemraj
authors.forename: Munir
authors.initials: M
authors.lastname: Hussain
mesh_terms: D002482:Cellulose / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D006244:Hardness; D008353:Mannitol / Q000737:chemistry*; D013229:Stearic Acids / Q000737:chemistry*; D013607:Tablets
chemical_list: D005079:Excipients; D013229:Stearic Acids; D013607:Tablets; D008353:Mannitol; C031183:stearic acid; D002482:Cellulose; C109691:microcrystalline cellulose