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Compendial Standards and Regulatory Requirements for Capsules

by | September 29, 2020 0

Among solid dosage forms, the capsule is second only to the compressed tablet in frequency of utilization for drug delivery, and the hard shell capsule continues to be the more frequently used form. Because hard shell capsules are often perceived as “simpler” than other oral dosage forms, they are frequently the first dosage form administered to humans and sometimes the final marketed dosage form.

In capsule formulation development and during manufacturing of capsule dosage forms, a number of standard and regulatory requirements are met before they are approved for consumption and marketing. Below are the compendial standards and regulatory requirements for capsules.

i. Added substances

Non-medicinal substances added to official preparations, including capsules, to serve different pharmaceutical purposes thus ensuring product acceptability in terms of manufacturability, appearance and performance may be used only if they:

  1. Are harmless in the quantities used.
  2. Do not exceed the minimum amounts required to provide their intended effect.
  3. Do not impair the product’s bioavailability, therapeutic efficacy, or safety.
  4. Do not interfere with requisite compendial assays and tests.

ii. Disintegration time test for capsules

The compendial disintegration test for hard and soft gelatin capsules follows the same procedure and uses the same apparatus described in the article “Quality Control Tests for Tablets”. The capsules are placed in the basket-rack assembly, which is repeatedly lowered 30 times per minute into a thermostatically controlled bath of fluid at 37˚C and observed over the time described in the individual monograph.

To fully satisfy the test, the capsules disintegrate completely into a soft mass with no firm core and only some fragments of the capsule shell.

iii. Dissolution test for capsules

The compendial dissolution test for capsules uses the same apparatus, dissolution medium, and test as that for uncoated and plain coated tablets. However, in instances in which the capsule shells interfere with the analysis, the contents of a specified number of capsules can be removed and the empty capsule shells dissolved in the dissolution medium before proceeding with the sampling and chemical analysis.

If the capsule floats on the surface of the dissolution fluid, a small, loose piece of nonreactive material, such as a few turns of a wire helix, may be attached to the dosage form to force it to sink to the bottom of the vessel.

Read Also: Quality Control Tests for Capsule Drug Products

iv. Uniformity of weight

The uniformity of dosage units may be demonstrated by determining weight variation and/or content uniformity. The test for uniformity of weight is performed as follows.

a. Hard shell capsules

Ten randomly selected capsules are individually weighed (to obtain their gross weights) and their contents removed. The emptied shells are individually weighed and the net weight of the contents calculated by subtracting the weight of the shell from the respective gross weight.

From the results of an assay performed as directed in the individual monograph, the content of active ingredient in each of the capsules is determined.

b. Soft shell capsules

The gross weight of ten randomly selected intact capsules is determined individually. Then each capsule is cut open with a suitable clean, dry cutting instrument e.g., scissors or a sharp blade, and the contents are removed by washing with a suitable solvent. The solvent is allowed to evaporate at room temperature over a period of about 30 minutes, with precautions taken to avoid uptake or loss of moisture. The individual shells are weighed and the net contents calculated. From the results of the assay directed in the individual monograph, the content of active ingredient in each of the capsules is determined.

v. Content uniformity

Unless otherwise stated in the United States Pharmacopeia (USP) monograph for an individual capsule, the amount of drug substance, determined by assay, is within the range of 85.0 % to 115.0 % of the label claim for nine (9) of ten (10) dosage units assayed, with no unit outside the range of 75.0 % to 125.0 % of the labelled drug content. Additional tests are prescribed when two or three dosage units are outside of the desired range but within the stated extremes.

vi. Stability testing

Stability testing of capsules is performed to determine the intrinsic stability of the active drug molecule and the influence of environmental factors (e.g., temperature, light, humidity), formulation components, and the container and closure system. The battery of stress-testing, long-term stability, and accelerated stability tests help determine the appropriate storage conditions and the product’s anticipated shelf life.

vii. Content labeling requirement

All official capsules must be labeled to express the quantity of each active ingredient in each dosage unit.

viii. Containers for dispensing capsules

There are specifications listed in the USP prescribing the type of container suitable for the repackaging or dispensing of each official capsule and tablet. Depending on the item, the container might be required to be tight, well-closed, and light-resistant and/or a combination of these.

ix. Moisture permeation test

The USP requires determination of the moisture-permeation characteristics of single-unit and unit dose containers to assure their suitability for packaging capsules. The degree and rate of moisture penetration is determined by packaging the dosage unit together with a color-revealing desiccant pellet, exposing the packaged unit to known relative humidity over a specified time, observing the desiccant pellet for color change (indicating absorption of moisture), and comparing the pretest and posttest weight of the packaged unit.

References

  • Allen L. and Ansel H. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia: Lipincott Williams and Wilkins.
  • L. and Hoag, S. (2018). Pharmaceutical Dosage Forms: Capsules. USA: Taylor & Francis Group, LLC.
  • Aulton, M. and Taylor, K. (2013). Aulton’s Pharmaceutics: The Design and Manufacture of Medicines, (4th ed.). Edinburgh: Churchill Livingstone.
  • Dash, A., Singh, S. and Tolman, J. (2014). Pharmaceutics – Basic Principles and Application to Pharmacy Practice. USA: Academic Press.
  • Felton, L. (2012). Remington Essentials of Pharmaceutics. UK: Pharmaceutical press.
  • Ghosh, T. and Jasti, B. (2005). Theory and Practice of Contemporary Pharmaceutics. USA: CRC Press LLC.
  • Hoag, S. (2017). Capsules Dosage Form: Formulation and Manufacturing Considerations. In Y. Qui, Y. Chen, G. Zhang, L. Yu, and R. Mantri (Eds.), Developing Solid Oral Dosage Forms – Pharmaceutical Theory and Practice, (2nd ed.) (pp. 723-747). UK: Elsevier Inc.
  • https://www.capsugel.com/
  • Jones D. (2008). Fasttrack Pharmaceutics – Dosage Form and Design. London: Pharmaceutical Press.

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