Effect of spray-dried mannitol on the performance of microcrystalline cellulose-based wet granulated tablet formulation.

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.

Form conversion of anhydrous lactose during wet granulation and its effect on compactibility.

The purpose of this study was (a) to evaluate the factors affecting the form conversion of anhydrous lactose to the monohydrate form during wet granulation using water as the granulating agent and (b) study the effect of lactose form conversion on its compaction properties. A two-level full factorial design with two center points was used to evaluate the factors affecting form conversion. The three variables evaluated were percentage of microcrystalline cellulose (low 0 and high 20), water to intragranular solids ratio (low 0.10 and high 0.18) and drying conditions (tray drying and fluid bed drying). The presence of microcrystalline cellulose in the formulation did not provide any benefit in reducing the percent lactose conversion. But, the conversion was significantly reduced by decreasing the amount of water added to the granulation and/or by decreasing the drying time, using a fluid bed dryer compared to a tray dryer. In the second part of the study, complete conversion of the anhydrous lactose to monohydrate was achieved by storing the anhydrous form under 25 degrees C/97% RH for 4 weeks. Physical characterization (compactibility, surface area and surface morphology) was performed on the form converted material and compared to the as received anhydrous lactose. The physical characterization results indicated that even though anhydrous lactose undergoes complete form conversion to monohydrate form under high humidity and/or during wet granulation, it retains its inherent higher as received material compactibility and the BET surface area and porosity of the form converted material are higher than that of the as received anhydrous lactose.

Assessment of segregation potential of powder blends.

Pharmaceutical blends consist of several components each with its own unique characteristics, with different size, shape, density, and particle-particle interactions. With so many degrees of complexity, prediction of segregation behavior becomes intractable. The objective of this study was to develop a segregation test method or a segregation tool that would assess the segregation potential of blends. Literature reports generally seek to predict the segregation behavior based on only one mechanism by which the segregation occurs, primarily sifting or fluidization. This study makes an attempt to combine both of these mechanisms by which segregation occurs. A test is developed and used to assess the segregation behavior of blends at large scale and compare the content uniformity results of tablets with the results of the segregation test. The segregation testing model was successful in predicting the segregation tendency of the formulation and also in rank ordering large scale formulation blends based on their segregation potential. A segregation risk classification system is proposed to assess the potential of segregation at large scale.