A capsule only works once it opens and its contents dissolve. Two pharmacopoeial tests measure this: disintegration and dissolution. Here is what each test means for hard gelatin capsules, how gelatin behaves in the body, and the formulation and storage factors that can speed up or slow down drug release.
The short answer
Disintegration is how quickly the capsule shell breaks apart; dissolution is how quickly the drug inside dissolves. Hard gelatin shells dissolve readily at body temperature, and Universe Capsules shells disintegrate in not more than 15 minutes in purified water at 37 °C. Release can be slowed by the fill formulation and by gelatin cross-linking caused by poor storage.
Disintegration vs dissolution
| Disintegration | Dissolution | |
|---|---|---|
| What it measures | The time for the capsule to break apart | How much drug dissolves over time |
| Typical apparatus | Basket-rack disintegration tester | Basket (apparatus 1) or paddle (apparatus 2) with a sinker |
| Conditions | Liquid at 37 °C, units moved up and down | Set volume of medium at 37 °C, sampled at time points |
| Result | Pass or fail within a time limit | Percentage of drug released at each time |
| Who relies on it | Capsule shell quality control | Finished product release and bioequivalence work |
How a hard gelatin capsule opens in the body
Gelatin is a protein that dissolves readily in water at body temperature. When a capsule reaches the stomach, the shell softens within moments, the thinner areas around the cap and body ends open first, and the fill is released, usually within minutes. Below about 30 °C gelatin swells rather than dissolving, which is why disintegration and dissolution tests are run at 37 °C to mimic the body.
In practice, the speed at which the drug becomes available depends far more on the fill than on the shell. A free-flowing powder that wets easily disperses quickly; a tightly packed, water-repellent plug can take much longer.
Pharmacopoeial requirements
Pharmacopoeias such as the IP, USP and BP describe standard disintegration and dissolution methods. For plain hard capsules, a disintegration limit of 30 minutes is common unless an individual monograph says otherwise. The limits for dissolution are set product by product, typically as a minimum percentage of drug dissolved within a stated time. Universe Capsules empty shells are tested to IP, USP and BP requirements and are made to disintegrate in not more than 15 minutes in purified water at 37 °C.
What slows down drug release from a capsule?
Gelatin cross-linking
Aldehydes from some excipients or packaging, and storage at high heat and humidity, can link gelatin chains together. A tough skin, or pellicle, forms that is slower to dissolve.
Water-repellent excipients
Too much lubricant such as magnesium stearate, or long blending times, can coat the powder and stop water reaching the drug.
Tight plugs
Heavy compaction on automatic filling machines creates a dense plug that disperses slowly once the shell has opened.
Poor drug solubility
A drug that dissolves poorly will release slowly whatever the shell. Particle size reduction and wetting agents can help.
Cross-linking and two-tier dissolution testing
Cross-linked gelatin can make a capsule fail its dissolution test even though the drug and formulation are unchanged. Pharmacopoeias allow for this with a two-tier test: if a gelatin capsule fails, the test is repeated with enzymes added to the medium, such as pepsin in acidic media or pancreatin in neutral media. The enzymes digest the cross-linked gelatin, much as digestive enzymes would in the body. The best defence is prevention: control aldehyde-forming excipients, and store capsules correctly.
How to keep release consistent
- Store capsules correctly: sealed, at 15 to 25 °C and 35 to 65 percent relative humidity. See how to store empty capsules.
- Check excipient compatibility with gelatin, especially for ingredients that can contain or form aldehydes.
- Keep lubricant levels low and blending times controlled.
- Control compaction on automatic filling machines; see our guide to capsule filling problems.
- Run stability studies that include dissolution testing at accelerated conditions.
Frequently asked questions
How long does a hard gelatin capsule take to dissolve?
The shell usually opens within a few minutes in the stomach. Universe Capsules shells disintegrate in not more than 15 minutes in purified water at 37 °C.
What is the difference between disintegration and dissolution?
Disintegration is the time for the capsule to break apart. Dissolution measures how much of the drug inside actually dissolves over time.
Why does a gelatin capsule sometimes fail a dissolution test?
Often because of gelatin cross-linking from aldehydes or poor storage, or because of the fill formulation. A two-tier test with enzymes can show whether cross-linking is the cause.
Does capsule size affect dissolution?
Slightly. Larger capsules hold larger plugs that can take longer to disperse, but the formulation has a much bigger effect than the size.
Do coloured capsules dissolve more slowly?
Permitted colourants and opacifiers do not meaningfully change how quickly a hard gelatin shell dissolves.
Need capsules with consistent disintegration?
Our empty hard gelatin capsules are tested to IP, USP and BP requirements, with a certificate of analysis for every batch. Ask us for a sample and our specification.
Request samples and a CoA
