Advantages of Mannitol in Pharmaceutical Granulation Processes – A Comparison of Different Polymorphic Forms

Granulation is employed during production of oral dosage forms to convert small particles of powder ingredients and the active pharmaceutical ingredient (API) into large, free-flowing, dust-free, compressible granules, ensuring uniform distribution of ingredients throughout the resulting mixture. There are several granulation processes available; the most widely used in the pharmaceutical industry is wet granulation.

The wet granulation process generally includes blending, wetting, wet mass stage, drying and sizing. Several types of process equipment can be used:

Low-shear processes use very simple mixing equipment. This approach can take a considerable amount of time to achieve a uniformly mixed state.
High-shear processes use equipment that mixes the powder and liquid at a very fast rate using high shear forces, and thus accelerate the manufacturing process.
Twin-screw granulation can continuously manufacture wet granulate powders at higher spacetime yield and improved product consistency.
Fluidized bed granulation is a multiple-step process in which the powders are pre-heated, granulated and dried in the same vessel.

This approach allows close control of the granulation process. Success of a wet granulation process depends on selection of appropriate excipients and choice of suitable process parameters which lead to excellent binding and compaction properties and flow. Among the most widely used fillers and binders in oral dosage forms are lactose, cellulose derivatives and calcium phosphates.

Interest in the use of mannitol as a filler/binder, however, is increasing due to its physicochemical properties such as low hygroscopicity in comparison to other commonly used filler/binder excipients (Figure 1) and chemical inertness as well as its advantageous tableting behavior including compactibility and the ability to form extremely robust tablets.1 It also has a good taste and mouthfeel enabling its use for chewable, sublingual and orodispersible tablet formulations.

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