Dry granulation process

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. 

When compared with direct compression results, the dry granulation processes enhance the flow of the powder and decrease the variability of the AUC, the major response. Nevertheless, this variability and the variability of the drug dissolved at 8 h (T7) are greater than the fixed optimal values, particularly for the compaction processes. From the results it is seen that the wet granulation process gave a powder presenting an adequate or better result than the other processes ... 

FIGURE 23.3 Example process owforthe dry granulation process. 

TABLE 6.12 Process Challenges for Optimizing a Low-Dose Dry Granulation Process... 

Evaluate dry granulation process parameters to achieve a desired target throughput Manufacturability Mass per unit time Mass flow rate (kg/h)... 

Figure 6.5 Low-dose dry granulation process optimization decision tree.

Recognizing that the roll diameter from Eq. (6.1) and roll width from Eq. (6.2) are noncontrollable process parameters for a given dry granulation process equipment, the remaining process parameters identified within these two equations, roll speed, ribbon thickness, and ribbon density, serve to define the dry granulation throughput. 

A fifth process challenge in the optimization of a dry granulation process is to achieve a granulation that is resistant to fluidization and sifting segregation forces. In general, process parameters that influence segregation potential are similar to those that influence variability in sieve cut potency. 

Since the properties that influence granulation blend uniformity (variability in sieve cut potency, segregation potential) have already been established during the dry granulation process, a minor secondary function of the final blending process... 

For low-dose, immediate-release drug products, the formulation should be designed with cohesive diluents, such as lactose, to enhance ordered mixing prior to the dry granulation process. Based on the two case studies reported here, it was also demonstrated that this formulation approach reduced the propensity for the powder blend to segregate. 

In the case where stability issues prevent the pursuit of the preferred formulation, then it becomes more important to optimize the dry granulation process to achieve an improved uniformity of drug as a function of particle size. For these cases, it is important to consider the impact of the optimized granulation on tableting performance. Although it is important to consider the commercial manufacturing efficiency, the process challenges that impact quality are of primary importance. 

However, some excipients have multiple functions. For example, microcrystalline cellulose can function as a filler, a binder, and a disintegrant. As seen in Table 7.3, a typical low-dose formulation could include more than 85% filler—binders. Thus, physical and chemical properties for these specialty excipients are extremely important in a low-dose formulation for manufacturability, product performance, and longterm stability. Because the poor physicomechanical properties of components are not altered during manufacture as they are in the wet or dry granulation process, critical material properties and their impact on product quality attributes should be well characterized and understood.23 Discussion in this section will focus on fillers-binders. For those requiring more information on excipients, several excellent books and review articles are available in the literature.24-27... 

The other two prerequisites—flow and cohesion— can only be achieved by more elaborate techniques and are in fact the reasons why the wet and dry granulation processes were devised. 

When using alginic acid in tablet formulations, the alginic acid is best incorporated or blended using a dry granulation process. 

In oral products, hypromellose is primarily used as a tablet binder, in film-coating, and as a matrix for use in extended-release tablet formulations.Concentrations between 2% and 5% w/w may be used as a binder in either wet- or dry-granulation processes. High-viscosity grades may be used to retard the release of drugs from a matrix at levels of 10-80% w/w in tablets and capsules. 

Compressible sugar is prepared by cocrystallization of sucrose with other excipients such as maltodextrin. Compressible sugar may also be prepared using a dry granulation process. 

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