Use of Mannitol as a Filler in Wet Granulation
A study was conducted to evaluate mannitol as a filler along with microcrystalline cellulose (MCC) in wet granulated tablet formulation, in situations in which lactose cannot be included in the formulation because of 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 to MCC ratio, water to intragranular solids ratio, and magnesium stearate concentration. The response variables evaluated were granulation compactibility, ejection force, normalized granule size, percentage of fines, flowability index, compression speed sensitivity, and hardness loss upon storage. Addition of mannitol in the MCC formulation increased compactibility of the final granulation because 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 decreased the susceptibility of the formulation to hardness loss upon storage.