Disintegration and Dissolution
Disintegration is a physical process that occurs when a dosage form (e.g. tablet or gelatine capsule) breaks up into smaller particles. It usually takes place in two steps; the content breaks up into small granules which then disaggregate. For immediate release drug products in vivo this breaking up process of the dosage form usually starts in the stomach where it may be completed depending upon the formulation, duration and volume of gastric fluid. If the dosage form passes rapidly into the small intestine, then the process may continue there. Disintegration can usually be observed in the laboratory in dissolution apparatus. Actual QC disintegration methods, however, use specific pieces of equipment described in USP <701> and USP <2040>.
Dissolution requires disintegration of the dosage form to occur first then drug particles to dissolve. It is the rate (amount of drug and time) at which the drug dissolves. In vivo dissolution starts as soon as the drug in the dosage form is wetted with gastrointestinal fluids. However, the rate and extent of dissolution are governed by the properties of the drug and type of gastrointestinal fluid in contact with the drug. Dissolution rates in the various gut fluids have a significant influence on absorption and resultant pharmacokinetics. There are many different dissolution apparatus used to establish how much drug dissolves and how long this takes. The standard apparatus are also described in USP <701>.
Quality Control (QC) Tests
Disintegration and dissolution laboratory studies can both be used as QC tests. Disintegration was first introduced more than 100 years ago in the Swiss Pharmacopeia well before dissolution testing. For highly water-soluble drugs, disintegration can occasionally be used to replace dissolution provided:
1. the relationship between disintegration and dissolution has been established
2. the drug product is immediate release
3. the drug is highly soluble across the physiological pH range
4. the drug is rapidly soluble across the physiological pH range
Rise of in vitro dissolution testing
Most modern-day drugs are far less water soluble so the disintegration technique has fallen out of favour. Laboratory dissolution testing is far and away the most common method of assessing drug release from drug products both during development and as a QC method.
Biorelevant disintegration and dissolution
Biorelevant disintegration and dissolution tests enable you to conduct these experiments using media that simulate the appropriate gastrointestinal fluids closely. Biorelevant dissolution is a generally more useful in vitro test than disintegration. This is because it gives information not just on disintegration of the dosage form but also quantitative release of the drug into the surrounding simulated gut fluids.