Capsule refers to a solid preparation which are filled a raw material medicine or a suitable auxiliary material, and can be divided into hard capsules, soft capsules (gelatin pearl), sustained release capsules, and enteric coated capsules, mainly used for oral medication.

Hard capsule refers to capsules filled with powder, granules, tablets, pellets, semi-solids or liquid prepared from a raw material drug and / or a suitable auxiliary material in a hollow capsule by using a suitable preparation technique.

Soft capsule refers a single piece of capsules that contains liquid raw material medication or the solution, suspension emulsion or a semi-solid that are made by dissolving or dispersing the solid raw material medication in a suitable auxiliary material. Soft capsules can be made by a dropping method or a pressing method, and they are typically made from gelatin, glycerin or other suitable pharmaceutical excipients, either alone or in combination.

Sustained-release capsules are capsules that slowly and non-steadily release drugs in a required release medium. Sustained-release capsules should meet the relevant requirements for sustained-release preparations and should be tested for release.

Controlled release capsule refers to a capsulethat release the drug slowly with a constant rate in the required release medium. Controlled release capsules should meet the relevant requirements and should be tested for release.

Enteric capsule refers to a hard capsule filled by enteric coated particles or pellets or a hard capsule or soft capsule that are enteric coated. Enteric-coated capsules are insoluble in gastric juice, but can disintegrate in intestinal fluid to release active ingredients. Unless otherwise specified, enteric-coated capsules should meet the relevant requirements for delayed-release preparations and be tested for release.

Capsules shall comply with the following regulations during production and storage.

1. The contents of the capsules, including raw materials and excipients, should not cause deterioration of the capsules.

2. Small dose of the raw material medication should be diluted with a suitable diluent and mixed evenly.

3. The hard capsules can be filled with different contents that are made according to the following preparation techniques.

  • Add raw material medicine with a suitable auxiliary material such as a diluent, a flow aid, a disintegrating agent, etc. to make a uniform powder, granule or tablet.
  • The ordinary pellets, the immediate release pellets, the sustained release pellets, the controlled release pellets or the enteric pellets are separately filled or mixed and filled, and if necessary, an appropriate number of blank pellets can be added as well.
  • Directly filled with powder of raw material medication.
  • The raw material drug is made into a clathrate, a solid dispersion, a microcapsule or a microsphere.
  • The solution, suspension, emulsion, etc. can also be filled in the empty capsule with a special filling machine, and sealed if necessary.

4. The capsule should be neat and tidy, and there should be no sticking, deformation, leakage or rupture of the capsule, and should be odorless.

5. The microbial limit of capsules should meet the requirements.

6. According to the characteristics of raw materials and preparations, the dissolution, release, content uniformity etc. of all capsules should meet the requirement, except for the capsules derived from animal and plant components and it is difficult to establish measurement methods of them. If necessary, the coated capsule should be checked for residual solvent.

7. Unless otherwise specified, capsules should be sealed for storage. The storage environment temperature should not be higher than 30 °C, and the humidity should be suitable to prevent moisture, mold and deterioration. The production and quality control of biological products, semi-finished products and finished products shall comply with the relevant varieties.

Capsules should be tested as follows unless otherwise specified.

Moisture

Chinese medicine hard capsules should be tested for moisture.

Take the contents of the test sample and measure according to the moisture measurement method. Unless otherwise specified, the moisture content should not exceed 9.0%.

Liquid or semi-solid in hard gelatin capsules do not need to be checked on moisture.

Difference in capacity

check according to the following methods, and the difference should meet the requirements.

Steps: take 20 samples (10 capsule are filled with Chinese medicines), accurately weigh the weight of each sample, pour out the contents (do not break the capsule shell), use a small brush or other suitable to clean the hard capsules; soft capsules or hard capsules containing semi-solid or liquid content need to be washed with volatile solvents such as ether, be placed in a ventilated place until the solvent is exhausted. Then accurately weight the weight of each capsule shell, and calculate for the capacity of each capsule and the average capacity. Compare the capacity of each capsule to the average capacity, (if there is indicated capacity of capsules, compare the capacity of each capsule to the indicated capacity) there should be no more than 2 capsules beyond the limit of the capacity difference, and no difference is allowed to exceed the limit for 2 times.

Average capacity or indicated capacity Capacity difference limits
less than 0.30g ±10%
0.30g and more than 0.3g ±7.5% (Chinese medicine ±10%)

Capsules that are required to be check with the uniformity of the content, checking for differences in capacity is generally not needed.

Disintegration time limit

unless otherwise specified, the inspection of the disintegration time limit should be based on relevant method, and it shall comply with the regulations.

For capsules that are required to be check with dissolution or release, checking for disintegration time limit: is generally not needed.

Microbial limits

capsules made from non-monomer components derived from animal, plant, mineral-derived, and biologic capsules, should be checked for the microbial limit according to microbical limit inspection of sterile products: microbial counting and control bacteria inspection and microbial limit standards for non-sterile drugs, and should be in compliance with regulations. For biologic capsules need to be checked for miscellaneous bacteria, checking for microbial limits is not necessary.