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TABLETS

Tablets are solid oral dosage forms usually prepared with the aid of suitable pharmaceutical excipients. They may vary in size, shape, weight, hardness, thickness, disintegration and dissolution characteristics and in other aspects, depending on their intended use and method of manufacture.

Single tablet unit

Pharmaceutical industries prefer tablet dosage form in the first instant due to its scalability, flexibility, low production cost and patient compliance.

Here we are going to explain you the common methods of preparation of tablet formulation in industries.


Direct Compression Method

Direct compression method does not involve any addition of fluid before the compression of the tablets. This method should be the first choice of any tablet formulation because of its uncomplicated manufacturability and cost effectiveness. Other advantages of this technique are getting the drug product with less disintegration time and faster dissolution rate, better stability of an API in a drug product due to less processing steps and a good choice for moisture sensitive drug.

A tablet can be made by direct compression method in the following way

  • Sift an API, diluent /diluents, binder, disintegrant, lubricant, others separately through sieves of an appropriate pore size.
  • Transfer the above mixer except lubricant in a blender of appropriate capacity. Note that the occupancy in the blender should be at least 30 % to the maximum of 70 % of total capacity. More occupancy will lead to improper mixing whereas very less occupancy will lead to segregation of materials.
  • For higher dose drugs normally 10 to 15 minutes of mixing is sufficient.
  • At the end of the blending process, add lubricant and mix the blend for the appropriate time. Avoid mixing lubricant for longer period of time as it may increase the hydrophobicity of the blend by coating API and other ingredients.
  • For lower dose drugs, fix the blending time by gradually increasing the time of mixing say every 10 minutes. Collect the samples from five different points (four corners and one in the center) in a blender every 10 minutes. Collect the samples till 30 to 45 minutes.
  • Analyze the sample for content uniformity. Choose the blending time at which you get a good content uniformity.

Contact us to get more information on a suitable direct compression method for your formulation.


Granulation Method

Granulation method is used to get the granules of uniform and equal size in order to avoid variation in filling of dies in compression machines which in turn avoids the variation in tablet weight.

Generally there are two methods of granulation adopted in industries:


Dry Granulation Technique

By dry granulation technique, the powder mixture is compacted in large pieces and subsequently broken down or sized into granules. For this method, either the active ingredient or the diluent must have cohesive properties. Dry granulation is especially applicable to materials that can not be prepared by wet granulation because they degrade in moisture or the elevated temperature required for drying the granules.

  • Weigh API and other excipients along with lubricant and compact them through the roller compactor or make slugs.
  • Mill the compacted blend / slugs in multi-mill or quadro comil through sieve of appropriate pore size.
  • Mix the sieved blend with weighed quantity of lubricant in a blender for an appropriate time.
  • Finally compress the blend into tablets.

Note: If the materials during compaction are sticking inside the compaction machine then add some amount of lubricant with API and other excipients during compaction process itself.


Wet Granulation Technique

Wet granulation technique involves addition of fluid to form granules. Wet granulation technique improves the flow of the powder and increases mechanical strength of the tablet. Wet granulation process is used when the drug is not very much sensitive to moisture. Wet granulation is done in rapid mixer granulator (RMG) or Fluid bed process (FBP) in industries.


Wet granulation using Rapid mixer granulator
  • For wet granulation process, weigh the required materials separately and pass them through the sieve of appropriate pore size (normally ASTM Sieve no. # 30).
  • Transfer the sieved materials to RMG of appropriate capacity and mix for 10 minutes at particular RPM. The RPM of the RMG should be fixed at a point when slight whirlpool is visible in the blend to ensure the mixing of the blend from top to bottom.
  • Add the binder solution slowly to the blend within 2 to 3 minutes. Further run the machine for 1 minute after addition of binder for the uniform distribution of fluid in the blend.
  • Stop the machine. Mix the blend manually with S.S. spatula or S.S. spoon. This process is known as racking. Racking is necessary to remove the materials which are stuck to the sides of RMG and caking at the bottom.
  • You can further run the machine for 1 to 2 minutes after racking either adding extra quantity of solvent (in case granules are not formed) or without adding extra solvent (in case granules are almost formed).
  • Document every action such as quantity of binder solution used, set RPM, time of addition of binder, racking, time of mixing the blend after addition of solvent, time of addition of extra solvent and quantity of extra solvent. These parameters are important for the reproducibility of the batch and understand the nature of API.
  • Normally binder containing 10 % w/w of solid content is preferred. The percentage of solid content can be decreased or increased based on observation of granules formation.
  • The amount of binder can be increased if the granules formed are softer and the amount of binder can be reduced if the granules formed are harder.
  • You can use aqueous solution of binder where HPMC, HPC, PVP etc. can be used as binder. Out of above mentioned binders HPMC is required to be dispersed initially in warm water as HPMC forms lumps in cold water and takes long time to dissolve.
  • Once the granules are formed, they are unloaded from RMG and dried in fluid bed drier or tray drier at a temperature where the drug will not degrade. Most of the drugs are stable at 60 ̊ C temperature. Generally the granules are dried till its LOD is less than 4 %w /w.

Wet granulation using Fluid bed processor

Wet granulation can also be done by using fluid bed processor. Granules made in FBP are uniform, porous and small in size. Granulation process in FBP is briefly explained below:

  • The weighed and sieved ingredients (API and other excipients) are loaded in FBP and mixed at low blower speed for 5 minutes or more.
  • Set the spray RPM, atomization pressure, blower speed, inlet temperature, product temperature and exhaust temperature.
  • In the beginning, keep the blower speed low as the blend will be in powder form and increase in blower speed will cause the finer materials to stick to the filter bag and escape through the exhaust of FBP.
  • Start spraying the binder solution and observe the granulation process. Spray rate of the binder solution can be adjusted through an observation of the granulation process. Avoid lumping of granules.
  • At the end of the granulation process dry the granules till its LOD is less that 4 % w/w.

Contact us to get more information on a suitable wet granulation technique for your formulation.


Preparation of final blend
  • The dried granules are passed through sieve of appropriate pore size to get uniform granules.
  • The sieved granules are lubricated with lubricant in a blender and finally compressed into tablets.

Compression Process

Compression process is the final step in tablet preparation.

  • Appropriate size of punches and dies are selected and fixed in compression machine.
  • Fill the blend in the hopper. Observe the flow of the blend from hopper to the turret of the compression machine.
  • Initially adjust the weight of a tablet by keeping lower hardness. Once the weight is set, adjust the hardness and thickness of the tablet. Hardness and thickness are inversely proportional to each other.
  • Keep checking the weight of tablets in between the compression process.
  • Collect the tablets in appropriate container.
  • You can install dehumidifier in the compression room for moisture sensitive products or install sodium vapour lamp for light sensitive products.

Minitablets
  • The preparation of minitablets is similar to that of single unit tablet except the size of the granules is smaller and more uniform.
  • For minitablet the punch and die size will be from 1 to 3 mm in size. Smaller granule size is necessary to avoid more void spaces between granules and avoid weight variation.
  • Check the compression load in case of minitablets as the punches are thin and less stronger than bigger punches.
  • Check the weight of each minitablet in between the compression process.
  • Fill the Minitablets into capsules.

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