Dissolution testing is a laboratory method that measures how quickly and how completely the active ingredient of a solid dosage form, such as a tablet or capsule, dissolves in a liquid medium under defined conditions. It is used in development to compare formulations, in production to monitor consistency between batches and in quality control to show that a product meets its specification. This guide summarises the basic idea of the test, the apparatus types defined in the pharmacopoeias and what to look at on the accessory side of a test set-up.
What is dissolution testing used for?
An active ingredient in a solid dosage form has to dissolve before it can be absorbed. Dissolution testing follows this behaviour in vitro, outside the body and under controlled conditions. The result is not a clinical outcome on its own, but it is a basic quality tool: it shows that every batch behaves in the same way and allows the method to be compared with the limits set in the relevant monograph. The FDA guidance on dissolution testing of immediate release solid oral dosage forms is one of the documents often consulted for general practice.
Pharmacopoeial chapters and apparatus types
The details of the method are set out in the pharmacopoeias: the General Chapter <711> Dissolution of the USP, chapter 2.9.3 (dissolution test for solid dosage forms) of the European Pharmacopoeia and the corresponding general test of the Japanese Pharmacopoeia. Ph. Eur. 2.9.3 describes the basket apparatus, the paddle apparatus, the reciprocating cylinder and the flow-through cell; on the USP side the numbering runs from 1 to 7. The table below summarises the common apparatus types and their general use. The conditions that apply must always be taken from the monograph and from the current edition of the pharmacopoeia.
| Apparatus | Name | General use |
|---|---|---|
| Apparatus 1 | Basket | Capsules, tablets, chewables, extended release forms |
| Apparatus 2 | Paddle | Same forms as Apparatus 1, plus suspensions and powder-filled capsules |
| Apparatus 3 | Reciprocating cylinder | Extended release products |
| Apparatus 4 | Flow-through cell | Poorly soluble, modified or extended release products; oral and non-oral forms |
| Apparatus 5 and 6 | Paddle over disk and rotating cylinder | Transdermal patches |
| Apparatus 7 | Reciprocating holder | Osmotic systems, transdermal patches |
Source: the pairing of apparatus and use is based on summaries in manufacturer and industry publications (see References). The monograph or the approved method decides which apparatus is used.
The difference between Apparatus 1 and Apparatus 2
The two most common apparatus share the same instrument body and differ only in the stirring element. In Apparatus 1 the dosage form sits inside a rotating basket, which holds forms that tend to float, such as capsules, or that break up as they disintegrate. In Apparatus 2 the dosage form settles on the bottom of the vessel and a rotating paddle stirs the medium. A sinker is used to keep floating capsules at the bottom. The apparatus, rotation speed and medium volume are given by the method; a laboratory is not expected to change them freely.
The parts of a test set-up
A standard set-up consists of a water bath or heating system with temperature control, vessels that are usually of 1000 mL capacity, a rotation mechanism, a basket or paddle, the medium and a sampling system. Sources often quote 37 °C ± 0.5 °C for the medium temperature; the exact values a method requires are given in the monograph. The reliability of the results depends not only on the instrument but also on mechanical details such as vessel geometry, basket and paddle dimensions, shaft alignment and centring.
- Vessel: inner diameter, bottom curvature and concentricity tolerances affect the result. Glass-rimmed and plastic-rimmed versions and small volume vessels are available.
- Basket and paddle: their dimensions must conform to the figures in the pharmacopoeia; the connection differs by instrument make.
- Shaft and centring: the shaft must rotate on the axis of the vessel to give consistent hydrodynamic conditions.
- Sinker: holds floating dosage forms in the vessel.
- Sampling cannulae and cannula filters: allow the sample to be taken from the medium through a filter.
Media and sampling
The dissolution medium is prepared at the pH and composition given in the method; preparation steps such as degassing are also defined in the method. Ready media concentrates containing hydrochloric acid, phosphate, acetate and citrate buffers and SLS are diluted with purified water and help to standardise media preparation. Where biorelevant media are needed, the FaSSIF and FeSSIF powders are on the Biorelevant page.
Samples are taken through a cannula at the time points given in the method and filtered before analysis. The cannula and filter material must not retain the active ingredient, so the filter type (PVDF, PTFE, nylon or PES, for example) is chosen during method development and confirmed during validation.
Instrument compatibility when choosing accessories
Most accessories have a connection that is specific to the make and model of the instrument, so the make, model and apparatus type (1 or 2) should be given when ordering. The Dissolution Accessories products supplied by YGT Laboratory are listed as compatible with instruments from makers such as Agilent, Caleva, Distek, Electrolab, Erweka, Teledyne Hanson, Pharmatest and Sotax. The manufacturer states that its products comply with the requirements of the USP, EP, BP and JP and are supplied with a certificate of compliance; this is the manufacturer's statement, and the documents are requested from the manufacturer's source.
Product pages for frequently used parts: baskets, paddles and shafts, vessels and vessel accessories, sinkers and sampling cannulae and cannula filters. Small volume vessels and conversion kits are also available for reduced-volume applications.
Verifying the instrument: qualification and calibration
A mechanically correct dissolution instrument is a precondition for reliable results. Parameters such as height, verticality, centring, rotation speed and temperature are checked at regular intervals. ASTM and USP qualification tools, height gauges and calibrated shafts are used for these checks; they are listed under calibration and qualification tools. For calibration and maintenance of the instrument, see the technical service page.
Instruments
On the instrument side, RIGGTEK offers the Dissilio dissolution testers, the DissoPrep media preparation stations and the Sampilio automatic sampler. Media preparation and sampling can be automated to reduce operator influence compared with manual steps; details are on the pages for dissolution testers and media preparation and automated sampling.
Short checklist
- Confirm the apparatus (1, 2 or another), rotation speed and medium volume given in the method.
- Choose a vessel, basket or paddle that is compatible with the make and model of the instrument.
- Check in the method whether a sinker is needed for floating forms.
- Confirm during method validation that the cannula and filter material does not retain the active ingredient.
- Check that the concentrate and water used for the medium are of the quality the method requires and that the medium is degassed as the method describes.
- Make sure that qualification and calibration records are up to date.
References
- USP-NF, General Chapter <711> Dissolution (United States Pharmacopeia)
- European Pharmacopoeia, 2.9.3 Dissolution test for solid dosage forms (EDQM)
- FDA, Dissolution Testing of Immediate Release Solid Oral Dosage Forms (1997)
- Copley Scientific, Choosing the right dissolution apparatus for oral solid dosage forms
- Dissolution Accessories (ProSense B.V.), manufacturer website
Quotation
Product selection and quotations
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