Capsules are solid preparations in which drug substance(s) and/or excipients are enclosed in either a soft or hard soluble shell. The shell is normally made from gelatin or other suitable polymeric material and results in a simple, tasteless, odourless, elegant, easy-to-swallow dosage form without need for a secondary coating step. Depending on the composition of the capsule shell, capsules may be classified as either hard or soft capsule, with soft capsules possessing a flexible, plasticized gelatin film. The shells may be composed of two pieces in the form of cylinders closed at one end; the shorter piece, called the ‘cap’ and the longer piece, called the ‘body’, or they may be composed of a single piece. The two-piece capsules and one-piece capsules are commonly referred to as hard-shell capsules and soft-shell capsules respectively.
Capsule fill materials
Capsules may be filled with a range of formulation types including dry powders, semisolids, nonaqueous liquids, and other dosage forms such as beads, mini-tablets, and even mini capsules most of which are intended for oral administration. There are also specialty applications such as capsules that can be loaded into dry-powdered inhalers, add reagents as part of a diagnostic kit, and occasionally soft-shell capsules intended for rectal or vaginal insertion as suppositories.
The first capsule prepared from gelatin was a one-piece capsule patented in France by Pharmacist Joseph Gerard Dublanc and Francois Achille Barnabe Mothes (a pharmacy student) in 1834. Although the shells of these early capsules were not plasticized, such capsules likely would be classified today as soft gelatin capsules based on shape, contents, and other features. In 1848, James Murdock invented the two-piece telescoping (hard gelatin) capsule patented in England in 1865.
- 1 Types of capsules
- 2 Difference between hard gelatin capsules and soft gelatin capsules
- 3 Compendial standards and regulatory requirements for capsules
- 3.1 i. Added substances
- 3.2 ii. Disintegration time test for capsules
- 3.3 iii. Dissolution test for capsules
- 3.4 iv. Uniformity of weight
- 3.5 v. Content uniformity
- 3.6 vi. Stability testing
- 3.7 vii. Content labelling requirement
- 3.8 viii. Containers for dispensing capsules
- 3.9 ix. Moisture permeation test
- 4 Advantages of capsules
- 5 Disadvantages of capsules
- 6 References
Types of capsules
i. Hard gelatin capsules
Hard gelatin capsules also known as two-piece capsules, hard shell capsule or dry-filled capsules are solid dosage forms in which one or more drug substances and/or excipients are enclosed within a small shell. The shell consists of two parts: the body designed to contain the drug and the diluent, and the cap that is approximately half as long as the body. Drugs and granulations to be encapsulated are filled into the body and the shell is closed by bringing the body and the cap together.
Hard gelatin capsules are made from gelatin or hydroxypropyl methylcellulose (HPMC) and other materials used either to enable capsule formation or to improve their performance. The capsules contain 13 – 16 % water, but the water content can vary, depending on the storage conditions. When the humidity is low, the capsules can become brittle; if stored at high humidities, the capsules can become ﬂaccid, sticky, and lose their shape. Storage in high-temperature areas can also affect the quality of hard gelatin capsules.
Hard shell capsules are available in a variety of standard sizes and are designated by numbers from 000 to 5. The size of the 000 capsule is the highest and that of the number 5 capsule is the smallest.
ii. Soft gelatin capsules
Soft gelatin capsules also referred to as soft shell capsule, soft elastic capsule, or softgel are single-unit solid dosage form, consisting of a liquid, semi-solid, dry powders, or even preformed tablets fill enveloped by a one-piece hermetically sealed elastic outer shell. Similar to hard gelatin shells, Soft gelatin capsules are made from shells of gelatin to which plasticizers such as glycerol, polyols or other suitable materials have been added. Other components may include dyes, opacifiers, flavours and preservatives (often included in the capsule shell formulation to prevent microbial or fungal growth).
The distinctive feature of this type of capsule is its one-piece construction. The feeding and sealing are achieved by only one machine. Filled soft gelatin capsules are commercially available in a wide variety of shapes (e.g. round, oblong, tubular). They may be single coloured or two-toned and may be imprinted with identifying markings. The size of soft gelatin capsules represents its nominal capacity in minims, for example, a 30 oval softgel can accommodate 30 minims (or 1.848 cm3).
Difference between hard gelatin capsules and soft gelatin capsules
- Hard gelatin capsules have two separate parts namely a body and a cap whereas soft gelatin capsules are hermetically sealed one-piece capsules and cannot be separated.
- Hard shell capsules are manufactured in a two-step process; the shells are manufactured by one type of machine and the filling achieved by a different machine whereas the manufacture, feeding and sealing of soft gelatin capsules are achieved by only one machine.
- Hard gelatin capsules usually contain dry powders, slightly compressed plugs, granules, or tablets. whereas soft gelatin capsules typically contain liquids and semisolids.
- Hard gelatin capsules are cylindrical in shape while soft gelatin capsules are available in round, oval and tubular shapes.
- The ratio of plasticizer to gelatin is less in a hard gelatin capsule (0.4 : 1.0) than in soft gelatin capsule (0.8 : 1.0).
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:
- Are harmless in the quantities used.
- Do not exceed the minimum amounts required to provide their intended effect.
- Do not impair the product’s bioavailability, therapeutic efficacy, or safety.
- 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.
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 labelling requirement
All official capsules must be labelled 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 colour-revealing desiccant pellet, exposing the packaged unit to known relative humidity over a specified time, observing the desiccant pellet for colour change (indicating absorption of moisture) and comparing the pretest and posttest weight of the packaged unit.
Advantages of capsules
- Capsules are convenient means of eliminating unpleasant taste and odour of drugs by enclosing ingredients in an almost tasteless and odourless shell.
- Capsules are elegant in appearance
- They are relatively easy to swallow (suitable shape and slippery when moistened)
- Consumer preference regarding ease of swallowing, convenience, and taste can improve compliance.
- They are easily filled either extemporaneously or in large quantities commercially.
- Capsules (generally soft shell capsules) may be formulated to increase the bioavailability of poorly soluble drugs.
- Capsules offer opportunities for product differentiation via colour, shape, and size and product line extension.
- Capsules are made from gelatin; hence they are therapeutically inert.
- The stability of therapeutic agents may be improved in a capsule formulation.
Disadvantages of capsules
- Capsules are unsuitable for very small children
- They cannot be used for substances that react with or dissolve gelatin, the major component
- Capsules become brittle under very dry conditions and may crack during the filling process.
- They absorb moisture and soften under high humidity.
- Potential stability problems may be associated with capsules containing liquid fills.
- The manufacture of capsules (generally softgels) require specialist manufacture and incur high production costs.
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