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Dissolution testing measures how much of a drug is released from a solid dosage form, such as a tablet or capsule, into a liquid medium under controlled conditions over time. FDA guidance describes three uses for immediate release products: assessing lot-to-lot quality, guiding development of new formulations, and ensuring continuing quality and performance after certain changes.
Short answer
Dissolution testing is an in vitro quality and development test. A dosage form is placed in a defined apparatus, medium and temperature, and the percentage of drug released is measured at set times. Its results feed a specification for routine quality control, and, when two products must be compared, a profile comparison using the f1 and f2 factors.
Definition and scope
The FDA Center for Drug Evaluation and Research (CDER) guidance Dissolution Testing of Immediate Release Solid Oral Dosage Forms (August 1997) states that in vitro dissolution tests for immediate release solid oral dosage forms, such as tablets and capsules, are used to (1) assess the lot-to-lot quality of a drug product, (2) guide development of new formulations, and (3) ensure continuing product quality and performance after certain changes, such as changes in formulation, manufacturing process, manufacturing site, or scale-up.
The guidance explains why release matters: absorption of a drug from an oral product depends on release of the drug from the product, dissolution under physiological conditions, and permeability across the gastrointestinal tract. For that reason it says in vitro dissolution may be relevant to the prediction of in vivo performance. For generic products, it notes that acceptable bioequivalence data and comparable in vitro dissolution and chemistry, manufacturing and controls (CMC) data are required for approval of an abbreviated new drug application under 21 CFR 314.94. See our guide to the FDA ANDA application for that pathway.
This page covers immediate release solid oral dosage forms as described in that 1997 guidance. It is not a restatement of the current USP general chapter text.
How dissolution testing is used in practice
FDA scientists writing in The AAPS Journal (2011) describe in vitro dissolution testing as an important tool used for development and approval of generic dosage forms, and say the USP describes seven different dissolution apparatuses from which an appropriate method can be developed. They add that a method should be adequately discriminating to distinguish any changes that could affect the product’s in vivo performance.
The 1997 guidance, in its Appendix A, identifies the two most commonly employed methods: the basket method (Apparatus 1) and the paddle method (Apparatus 2), described as simple, robust, well standardized, and used worldwide. FDA also maintains a searchable Dissolution Methods database, organised by drug name, which lists the methods the agency recommends.
Apparatus 1 and 2 and the test conditions FDA describes
| Item | Basket (Apparatus 1) | Paddle (Apparatus 2) |
|---|---|---|
| Common agitation speed in the 1997 guidance | 50 to 100 rpm | 50 to 75 rpm |
| Temperature for immediate release tests | 37 ± 0.5 °C for both | |
| Capsule note | – | Capsules tend to float; a wire helix (USP) is suggested |
Other conditions from the same appendix: where a simulated intestinal fluid medium is used, the guidance describes pH 6.8, with a higher pH to be justified and in general not exceeding pH 8.0. Apparatus calibration with calibrators is recommended at least twice a year and after any significant equipment change or movement, and switching between basket and paddle may call for recalibration.
Single-point specifications versus profile comparisons
The guidance separates two different jobs that people often blur together. A specification is the pass criterion applied to each batch in routine quality control. A profile comparison asks whether two products release drug in a similar way across time.
| Routine specification | Profile comparison | |
|---|---|---|
| Question answered | Does this batch meet the release criterion? | Are test and reference products similar over time? |
| Form in the 1997 guidance | Single point for highly soluble, rapidly dissolving drugs (BCS classes 1 and 3): not less than 85% (Q = 80%) in 60 minutes or less. Slowly dissolving or poorly soluble drugs need a two-point specification. | Difference factor f1 and similarity factor f2, using 12 units each of test and reference |
| Thresholds | Q = 80% in 60 minutes or less | f1 of 0 to 15 and f2 of 50 to 100 ensure sameness or equivalence |
| Practical conditions | Compendial immediate release standards are single-point | Most suitable with three or four or more time points, the same conditions and time points for both products, and only one measurement after both products reach 85% dissolved |
The guidance also notes that a product reaching 85% dissolution in 15 minutes in 0.1 N HCl under mild conditions behaves like a solution, the rationale behind treating BCS class 1 and 3 drugs differently. The class definitions and the related biowaiver logic are covered in our guide to the Biopharmaceutics Classification System.
Where it matters for labs and quality units
- Routine release: the compendial specification is the lot-to-lot check. A failing result is handled as an out-of-specification event; see OOS investigations.
- After a change: the 1997 guidance lists formulation, process, site and scale-up changes as occasions for dissolution testing to confirm continuing quality.
- Equipment control: because the guidance asks for calibration at least twice a year and after significant equipment change or movement, the apparatus belongs in the instrument qualification programme described in USP 1058 analytical instrument qualification.
- Analytical finish: the measurement of released drug is itself an analytical procedure, so it falls under validation expectations such as ICH Q2(R2).
Common misunderstandings
- It does not by itself prove bioequivalence. For ANDAs, the guidance says acceptable bioequivalence data and comparable dissolution and CMC data are both required.
- One similarity factor is not a universal pass. The f1 and f2 ranges apply to the procedure described, with the unit counts and time points above.
- The 1997 numbers are not the whole current picture. The agency guidance dates from 1997, and the compendial chapter is maintained separately by the USP; check the current compendium before applying any acceptance criterion.
FAQ
What is dissolution testing used for?
FDA lists lot-to-lot quality assessment, guiding development of new formulations, and ensuring continuing quality after changes such as formulation, process, site or scale-up.
Which apparatus is most common?
The basket (Apparatus 1) and paddle (Apparatus 2) methods, which the 1997 FDA guidance calls the most commonly employed.
What temperature is used?
Immediate release tests in the guidance are conducted at 37 ± 0.5 °C.
What do f1 and f2 mean?
f1 is the difference factor and f2 the similarity factor used to compare dissolution profiles. The guidance says f1 values of 0 to 15 and f2 values of 50 to 100 ensure sameness or equivalence.
Sources
- FDA CDER, Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms, August 1997: fda.gov/media/70936/download (checked 2026-10-29).
- Anand O, Yu LX, Conner DP, Davit BM. Dissolution Testing for Generic Drugs: An FDA Perspective. The AAPS Journal 2011;13(3):328: PMC3160163 (checked 2026-10-29).
- FDA Dissolution Methods database: accessdata.fda.gov/scripts/cder/dissolution (checked 2026-10-29).
