Knowledge Centre



CAPSULES

Capsules are alternate dosage form of tablet dosage form. Hard gelatin Capsules can be filled with powder, granules, pellets and minitablets.

Powder filling

In case of powder filling, the drug and the excipients are simply mixed in a blender and filled in capsules.

Granules filling

Here the granules are prepared similar to the procedure mentioned in wet granulation process under single table unit section.

The prepared granules are simply filled in capsules.

Pellets filling

Pellets preparation is another challenging process and widely adopted by many pharmaceutical industries. Pellet formulation has many pharmacological advantages. Pellets distribute freely and independently in gastrointestinal tract avoiding dose dumping and high local concentration of drug, which may be irritating to stomach. Pellets maximize drug absorption, reduce peak plasma fluctuations, minimize potential side effects and reduce inter and intra subject variability of plasma profiles.

Pellet preparation involves the following process:

Drug containing pellets

Drug containing pellets are prepared by Extrusion/spheronization method.

  • The pellet formulation mainly involves an ingredient with good plasticity such as microcrystalline cellulose.
  • To get pellets with good sphericity, it is recommended to have 50 % to 70 % of MCC in the formulation.
  • Weigh the drug and diluents and pass them separately through sieve of appropriate pore size.
  • Transfer the blend in to RMG of appropriate capacity. For dry mix, run the RMG till 10 minutes at RPM which can form a mild whirlpool in the center.
  • The blend should be over granulated to acquire plastic property.
  • The wet mass is immediately transferred to extruder. Set the extruder at required RPM so that uniform extrudates are formed.
  • Transfer the extrudates immediately to spheronizer and set the required RPM of the spheronizer.
  • Avoid higher RPM at initial stage for spheronization as it will lead to bigger and uneven pellets. Lower RPM initially helps the extrudates to break into smaller and uniform size. The heat generated in spheronizer slowly evaporates the moisture from the extrudates thereby avoiding the sticking of pellets to each other.
  • The extrudates under centrifugal force changes to dumble shape and finally to spheres.
  • If the pellet formation is stopped in dumble shape then try doing following things:
    • Decrease the binder amount as higher binder content may make the extrudates harder.
    • Increase the moisture content of the blend.
    • Increase the plastic ingredient in your formulation.
  • Dry the completely formed pellets at appropriate temperature till the LOD of the pellets is less than 2 %w/w.

Drug loading pellets

In drug loading process, readily available pellets of appropriate size are coated with the drug solution or suspension. The readily available pellets (Placebo pellets) may be MCC pellets (celphere) or sugar spheres (Non pareil seeds).

  • Weigh the required amount of placebo pellets and load them in FBP containing wurster assembly.
  • Set the inlet temperature, Exhaust temperature, product temperature, spray RPM, blower speed, atomization and column height.
  • Dry the placebo pellets for 5 minutes to remove excess moisture. Weigh the dried pellets again and note it as actual weight of the pellets.
  • Prepare the drug solution or suspension with drug, binder and solvent with appropriate % of solid content.
  • Check the spray rate by starting the spray pump without atomization and collecting the solution in a tared beaker for one minute. Weigh the collected solution and note it as wt/min.
  • Be sure of proper flow of pellets in and out of wurster column forming a fountain pattern. Start spraying the drug solution to load the drug on the pellets.
  • At the end of the spraying process, dry the drug loaded pellets in FBP till their LOD is less than 2% w/w and finally unload them. Weigh the drug loaded pellets to check the proper loading of the drug.
  • Less loading of the drug on the pellets indicates spray drying, leakage of the solution and pellets loss during the coating process.

Polymer coating of pellets

Modified release polymer is coated over drug containing pellets or drug loaded pellets to get a desired drug release profile.

  • Prepare the coating solution containing appropriate percentage of solid content.
  • Coating solution should have control release polymer or delayed release polymer, pore former, plasticizer and solvent.
  • Make sure that the all the solid ingredients are dissolved properly in case of coating solution or else it will give uneven film over pellets which in turn will give uneven drug release.
  • Prepare 20 % to 30 % extra coating solution so that you do not run out of solution during the process due to some process loss.
  • Check the spray rate as mentioned in drug loading pellets process.
  • Start spaying the coating solution on drug pellets and fix the time of spraying as mentioned below.
  • For e.g. if you want to load 6 % w/w coating material on 300 gm of drug pellets and the spray rate of the solution is 0.1gm/min at particular spray pump RPM then to get 318 gms of coated pellets (which contains 6 % W/W of coating material on drug pellets) the solution need to be sprayed till 180 minutes at that particular RPM.
  • At the end of spraying process, dry the coated pellets in FBP till their LOD is less than 2 % w/w and then unload them. Weigh the dried pellets.
  • If the pellets do not weigh the required weight then you need to spray the coating solution further till you get the required weight.
    For e.g. if you are getting 316 gm of coated pellets instead of 318 gm in180 minutes then to coat 2 gm of extra material you need to further spray the solution based on observation of the first coating time i.e. approx. 22 min.
  • Document the details in the lab note book. With this experiment you can fix all the parameters required for coating the material on the pellets for the next batch.
  • Finally fill the coated pellets in capsule by using capsule filling machine.

Contact us to get more information on preparation and coating of pellets.

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