Why to go for Granulation?

Powders/Granules intended for compression into tablets must possess two essential properties: flow property and compressibility. Some drugs exhibit poor fluidity and compressibility. In such cases binders have to be added for improving flow property and compressibility. Flow property/Fluidity is required to produce tablets of a consistent weight and uniform strength. Compressibility is required to form a stable, intact compact mass when pressure is applied. These two objectives are obtained by adding binder to tablet formulation and then proceeding for granulation process. Granules so formed should possess acceptable flow property and compressibility. Other reasons for Granulation process are to improve appearance, mixing properties, to avoid dustiness, to densify material, to reduce segregation, in general to either eliminate undesirable properties or to improve the physical and chemical properties of fine powders. Granulation Processes The standard methods frequently used today in tablet manufacturing are granulation and direct compression. Granulation technique includes wet granulation and dry granulation/slugging methods wherein binders are added in solution/suspension form and in dry form respectively. In Direct Compression, binders possessing direct compressibility characteristics are used. Binder when used in liquid form gives better binding action as compared to when used in dry form. Mechanism of granule formation Granules are formed in three stages: Nucleation: Here, the particles adhere due to liquid bridges which are the initiation step of Granulation. These adhered particles play a role of nucleus for further enlargement of granules. Transition: Enlargement of nucleus takes place by two possible mechanisms. Individual particle adhere to the nucleus or two or more nuclei combine among themselves. Ball growth or enlargement of the granule: Ball growth occurs either by Coalescence or Breakage or Abrasion Transfer or Layering. In Coalescence- a larger granule is formed when two or more granules are united. In Breakage- granules break and the fragments of granule adhere to other granules. This forms a layer of material over intact granules. In Abrasion Transfer- granule material are abraded through attrition by the agitation of granule bed and abraded material adheres to other granules resulting into enlarged granules. In layering particles adheres to the already formed granules increasing their size.

Factors to be considered in Granulation

Compatibility and Characteristics of the drugs and other excipients 1. Spreading of Binder 2. Type and quantity of Binder 3. Temperature and Viscosity 4. Method of Addition of Binder 5. Mixing Time 6. Material of Construction of Granulator 7. Type of Granulator 8. Process Variables & Apparatus Variables Evaluation tests for Granules It is essential to evaluate the granule characteristics to monitor its suitability for tableting. Particle Size and Particle Size Distribution Surface Area Density % Compressibility Flow Properties Disintegrants

Boavailability of a drug depends on absorption of the drug, which is affected by solubility of the drug in gastrointestinal fluid and permeability of the drug across gastrointestinal membrane. The drugs solubility mainly depends on physical chemical characteristics of the drug. However, the rate of drug dissolution is greatly influenced by disintegration of the tablet. The disintegration test is an official test and hence a batch of tablet must meet the stated requirements of disintegration. The drug will dissolve at a slower rate from a nondisintegrating tablet due to exposure of limited surface area to the fluid. Disintegrants, an important excipient of the tablet formulation, are always added to tablet to induce breakup of tablet when it comes in contact with aqueous fluid and this process of desegregation of constituent particles before the drug dissolution occurs, is known as disintegration process and excipients which induce this process are known as disintegrants. The objectives behind addition of disintegrants are to increase surface area of the tablet fragments and to overcome cohesive forces that keep particles together in a tablet. Mechanism of tablet disintegrants The tablet breaks to primary particles by one or more of the mechanisms listed below:I. By capillary action

II. By swelling III. Because of heat of wetting IV. Due to disintegrating particle/particle repulsive forces V. Due to deformation VI. Due to release of gases VII. By enzymatic action Disintegration of tablet by wicking and swelling

Disintegration by deformation and repulsion

Schematic representation of tablet disintegration and subsequent drug dissolution

Methods of addition of disintegrants : The method of addition of disintegrants is also a crucial part. Disintegrating agent can be added either prior to granulation (intragranular) or prior to compression (after granulation i.e. extragranular) or at the both processing steps. Extragranular fraction of disintegrant (usually, 50% of total disintegrant requires) facilitates breakup of tablets to granules and the intragranular addition of disintegrants produces further erosion of the granules to fine particles.