Dry granulation, methods

Both wet and dry granulation methods of tablet manufacture are complex multistage processes, but are necessary to convert the components of the formulation into a state that can be readily compressed into acceptable tablets. If, however, a major component of the formulation already possesses the necessary degree of fluidity and compressibility, granulation would be unnecessary. This is the basis of the direct compression method of tablet manufacture. ... 

A faulty batch of tablets can sometimes be recovered by grinding up the tablets and recompressing them, a process which is known as reworking and is analogous to the dry granulation method of tablet manufacture. This can sometimes cause problems with a direct compression formulation. Many direct compression diluent particles are in the form of aggregates, e.g., spray-dried lactose is composed of small crystals of lactose embedded in amorphous lactose. If these aggregates are compressed, their structure may be broken down to such an extent that subsequent recompression will result in impaired tablet quality. 

Selkirk AB, Ganderton D. Influence of wet and dry granulation methods on the pore structure of lactose tablets. J Pharm Pharmacol 1970 22 86S-94S. 

Recently, two novel procedures have been described for the isolation of PHA granules based on air classification [81] or centrifugal fractionation [82] (Fig. 8). These two processes are related to the well established wet and dry milling methods used in the corn industry for the fractionation of corn seeds into endosperm, germ, and hull and for the isolation of starch grains [83]. 

Full Scale Giatt Mixing. The fluidized bed granulator is one of the most important granulation methods available today, because it combines the unit operations of mixing, granulating, and drying into... 

Gereg and Capolla developed process parameters determined by a model laboratory bench scale Carver press, model C (Carver Inc. Savannah, Georgia, U.S.A.), which were translated to production scale compactor parameters (6). Their study provided a method to predict whether a material is suitable for roller compaction. Their study objectives were to characterize properties of the material to identify process parameters suitable to achieve the necessary particle size and density using the dry granulation process and then translate laboratory information to a production scale roller compactor. Actually, information developed from a Carver press was correlated and scaled-up to a production scale Fitzpatrick roller compactor. Model IR 520 (Fitzpatrick Co., Elmhurst, Illinois, U.S.A.) The compactor produced very similar powder granule characteristics as the Carver press. Various lactose materials, available as lactose monohydrate or spray dried lactose monohydrate, were used as the model compounds. Results indicated that a parametric correlation could be made between the laboratory bench Carver press and the production scale compactor, and that many process parameters can be transferred directly. 

Dry granulation is a process which consists of granulating a powder by compression, avoiding the wetting and drying steps. The advantages and drawbacks of this process were described by Sheth et al. [1]. The two methods used for dry granulation are compaction and double compression [2,3]. 

Granulation. Granulation methods can be wet or dry. Wet granulation cannot be used for drugs that are sensitive to moisture and heat. The powered drug and diluent are blended with a dispersion of the binder... 

Oscillation of the dried granulation and lubricant was accomplished in every instance using a no. 10 wire screen. Reference to the no. 12 screen, the alternative method for pulverizing the batch, must be deleted from the manufacturing instructions for the process to be validated retrospectively. 

Direct compression is a simpler alternative tablet manufacturing method. With direct compression, tablets are compressed directly from a powder mixture of an API and appropriate excipients. Like granulation methods, this approach is also based on the required flow, compressibility, and compactibility of a formulation. Direct compression offers both time and economic advantages by eliminating intermediate granulating and drying steps. 

The first direct compression excipient, spray-dried lactose, was introduced in the early 1960s as a filler specifically designed for direct compression processes. Over many years, more direct compression API and excipients, especially diluents and binders, were developed. Since these are now commercially available, design of direct compression formulations is readily possible. However, despite the simplicity of the direct compression process, the pharmaceutical industry still produces most tablets by wet granulation methods.1... 

Slugs or preforms are usually 1 to 2 in. diameter in pharmaceutical manufacture. Suited to granulation of moisture-sensitive materials and those unable to withstand high temperature of drying in wet granulation methods. 

---