Dissolution testing, the lab check behind many tablet recalls

FDA's weekly Enforcement Report for Oct. 28, 2026, listed three generic tablets recalled for the same kind of lab failure: amitriptyline, an amlodipine and olmesartan combination, and cinacalcet. FDA's stated reason for two of them was "Failed dissolution specifications." For the third it was "Out of specification due to dissolution." Since Sept. 2, FDA has posted 11 drug recall records citing dissolution.

A dissolution test measures how much of a tablet's or capsule's active ingredient comes out into a liquid over a set time. It is one of the routine checks in most tablet and capsule specifications, run on each batch before release. When a batch that has already shipped fails it, usually in a manufacturer's own long-term stability testing, the result is often a recall.

GxRadar found 414 drug recall records since June 2012 whose reason mentions dissolution, in an openFDA search of the recall file¹. This piece explains how the test works, how FDA and the U.S. Pharmacopeia set the pass mark, and what the recall records show about which products fail.

How the test works

The method lives in USP General Chapter <711>. The U.S. Pharmacopeia's entry² for the chapter says it is harmonized with the European and Japanese pharmacopeias, which "have undertaken to not make any unilateral change to this harmonized chapter." The harmonized text³ describes four kinds of apparatus: a rotating basket (Apparatus 1), a paddle that stirs the liquid (Apparatus 2), a reciprocating cylinder (Apparatus 3) and a flow-through cell (Apparatus 4). The liquid, called the dissolution medium, is held at 37 ± 0.5 degrees Celsius, roughly body temperature. A "dosage unit" is one tablet or one capsule.

Technicians drop a unit into each vessel, start the apparatus and draw samples at set times. Each sample is analyzed for how much drug has dissolved, as a percentage of the amount on the label.

FDA's 1997 guidance, Dissolution Testing of Immediate Release Solid Oral Dosage Forms⁴, explains why this matters. Absorption of a drug taken by mouth "depends on the release of the drug substance from the drug product, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract." The guidance lists three uses for the test: to "assess the lot-to-lot quality of a drug product," to "guide development of new formulations," and to "ensure continuing product quality and performance after certain changes," such as a new manufacturing site.

The same guidance gives common settings of 50 to 100 rpm for the basket and 50 to 75 rpm for the paddle. For quick-dissolving products whose drug is highly soluble, a 2018 FDA guidance⁵ set a standard method: 500 mL of 0.1N hydrochloric acid, the basket at 100 rpm or the paddle at 50 rpm, and an acceptance criterion of "Q=80% in 30 minutes."

Passing in stages

Q is the amount of drug that a product's specification says must be dissolved by the test time, expressed as a percentage of the labeled content. USP's acceptance table lets a batch pass at the first stage or move to larger samples.

Source: USP <711> Acceptance Table 1 (harmonized text), for immediate-release dosage forms.

For a product with Q of 80 percent, all six tablets in the first round must reach 85 percent. A batch that fails at S3 fails the test. Extended-release products have their own table in the chapter. Their limits are ranges at several time points, so a batch can fail by releasing drug too fast as well as too slowly. Delayed-release products get separate tables for an acid stage and a buffer stage.

Why generic makers live by this test

For a generic, dissolution sits next to bioequivalence. FDA's 1997 guidance states that "acceptable bioequivalence data and comparable in vitro dissolution and CMC data are required for approval" of generic applications, citing 21 CFR 314.94. To compare a changed product with the original, the guidance uses a similarity factor called f2. Two curves are considered similar when f2 is between 50 and 100. Our explainers on bioequivalence and generic approval cover the human studies that sit alongside these lab tests.

When USP has no dissolution method for a product, FDA publishes one. The Dissolution Methods Database⁶ lists methods "presently recommended" by FDA reviewers and is updated quarterly. Its FAQ⁷ says that by the last sampling time FDA generally recommends "at least 70-85% (Q) of the labeled content" be dissolved, and that it provides the database "to aid industry personnel in developing generic drug products." FDA's product-specific guidances set out the separate study plan for each generic.

Why a failed test becomes a recall

CGMP rules require testing before release. Under 21 CFR 211.165⁸, each batch needs "appropriate laboratory determination of satisfactory conformance to final specifications" before it ships. Testing continues afterward. 21 CFR 211.166⁹ requires a written stability program whose results "shall be used in determining appropriate storage conditions and expiration dates," which is why manufacturers keep pulling samples from marketed batches for months or years. Our piece on expiration dates covers that program.

A batch that drifts out of specification before its expiration date has stopped meeting the standard printed on its approval. FDA's FY2024 Report on the State of Pharmaceutical Quality¹⁰ said most failed-specification recalls that year "were discovered during stability testing," and that dissolution failures made up 36 percent of them. In the recall file, 92 of the 325 dissolution events mention stability in FDA's reason text, often naming the time point, as in a September 2026 prasugrel recall that "failed to meet 18-month stability testing acceptance criteria."

Most of these recalls sit in the middle tier. Of the 414 records, 284 are Class II, 121 are Class III and nine are Class I. An openFDA search for Class II records with the exact phrase "failed dissolution specifications" returns 237¹.

Source: GxRadar analysis of openFDA drug enforcement records whose reason mentions dissolution, by Enforcement Report date. 2012 (from June) adds 7 records in 6 events.

Which products fail

Tablets account for 229 of the 325 dissolution events and capsules for 77, by GxRadar's sort of product descriptions. Products described as extended-release, delayed-release or controlled-release make up 187 events, more than half. Each of their time points is another chance to fall outside a limit.

Source: GxRadar analysis of openFDA recall records, June 2012 to Oct. 28, 2026.

An openFDA search for bupropion dissolution recalls¹ confirms 23 records. Most date from 2012 to 2017, and several cite the 8-hour time point for extended-release tablets. One 2013 record says results at that point "were above approved specification limits," meaning the drug came out faster than allowed. GxRadar's drug pages for metoprolol succinate ER, doxycycline, glipizide and nitrofurantoin list recalls alongside price history.

A dissolution recall says a lot failed a lab standard. It does not say anyone was harmed, and Class II and III assignments reflect FDA's judgment that serious harm is remote or unlikely. Anyone wondering whether a medicine at home is affected can match the lot number using our recall lookup guide and ask a pharmacist about next steps. FDA says it updates the Dissolution Methods Database quarterly, by the fifth working day of the first month of each quarter, so the next refresh is due in early January 2027. New dissolution recalls appear on the GxRadar feed each week.