Dry Granulation of Pharmaceuticals

Dry Granulation of Pharmaceuticals

Application: In case of low bulk densities, bad flowing properties and the risk of segregation of the mixture tableting machines have problems to press high quality tablets which are required in the Pharmaceutical Industry. To press these mixtures a granulation technology is required to change the material behavior to god flowing, higher bulk density and reduce the tendency of segregation.

Tableting machines can typically operate with granules at higher speeds than with powders. The cheapest way of granulation in case of high amount of active ingredient is dry granulation where on liquid binder are necessary.

Process: The pharmaceutical blend is fed into the feed hopper of the compactor where an auger is feeding the material into the nip of the rolls. Between the rolls the powder is pressed to so called flakes. In a subsequent Flake Crusher the flakes will be broken to granules. The typical granule size varies to 10 to 18 mesh. Typical these processes requires machines which are easy to clean and guarantee a high quality of the produced granules. The quality of the granules needs to be validated.

Example: Feeding material: Pharmaceutical blend, bulk density: 200 – 350 g/l, due to very fine active ingredients the flowing will be very bad.

  • Pharmapaktor APC L 200/50 for throughputs 80 to 120 kg/h
  • Pharmapaktor APC K Series
  • Size 200 for throughputs up to 250 kg/h
  • Size 300 for throughputs up to 800 kg/h
  • Pharmapaktor APC C 250
  • For throughputs from 100 to 300 kg/h for various products which require very different settings

Granulation is carried out for various reasons, one of which is to prevent the segregation of the constituents of powder mix. Segregation is due to differences in the size or density of the component of the mix. Normally, the smaller and/or denser particles tend to concentrate at the base of the container with the larger and/or less dense ones on the top. An ideal granulation will contain all the constituents of the mix in the correct proportion in each granule and segregation of granules will not occur.

Many powders, because of their small size, irregular shape or surface characteristics, are cohesive and do not flow well. Granules produced from such a cohesive system will be larger and more isodiametric, both factors contributing to improved flow properties.

Some powders are difficult to compact even if a readily compactable adhesive is included in the mix, but granules of the same powders are often more easily compacted. This is associated with the distribution of the adhesive within the granule and is a function of the method employed to produce the granule.

The dry granulation process is used to form granules without using a liquid solution because the product granulated may be sensitive to moisture and heat. Forming granules without moisture requires compacting and densifying the powders. In this process the primary powder particles are aggregated under high pressure. Sweying granulator or a high-shear mixer-granulator can be used for the dry granulation.

Dry granulation can be conducted under two processes; either a large tablet (slug) is produced in a heavy duty tabletting press or the powder is squeezed between two counter-rotating rollers to produce a continuous sheet or ribbon of materials (roller compactor, commonly referred to as a chilsonator which received its name from its inventor, Francis Xavier Chilson).

When a tablet press is used for dry granulation, the powders may not possess enough natural flow to feed the product uniformly into the die cavity, resulting in varying degrees of densification. The roller compactor (granulator-compactor) uses an auger-feed system that will consistently deliver powder uniformly between two pressure rollers. The powders are compacted into a ribbon or small pellets between these rollers and milled through a low-shear mill. When the product is compacted properly, then it can be passed through a mill and final blend before tablet compression.]