Dissolution Testing

Dissolution testing places one tablet in a vessel of liquid at 37 ± 0.5°C, stirs it with a basket (United States Pharmacopeia, USP, Apparatus 1) or a paddle (Apparatus 2), and measures how much drug is in solution at set times. Q is the amount dissolved at the stated time, expressed as a percentage of the labeled content, per USP general chapter <711>. Sampling must fall within ±2% of the stated time, per the same USP–NF <711> chapter.

FDA's 1997 guidance describes typical IR conditions:

• Basket at 50 to 100 revolutions per minute (rpm), or paddle at 50 to 75 rpm.
• 500, 900 or 1000 mL of medium between pH 1.2 and 6.8.
• A surfactant such as sodium lauryl sulfate for poorly soluble drugs, with the amount justified.

As of October 2026, FDA's 1997 dissolution guidance and its August 2018 high-solubility guidance are the agency's current published recommendations for IR tablets.

Two confusions matter. Disintegration only checks that the tablet breaks apart; dissolution measures drug in solution. And dissolution is a laboratory (in vitro) test. FDA describes its specifications as a way to ensure batch-to-batch consistency and to signal potential problems with bioavailability, not as proof of absorption.

USP <711> tests IR tablets in up to three stages. With Q=80%, all six stage 1 tablets must reach 85%, which is Q+5%. "Plus 5%" means five percentage points, not 5% of 80. The table below applies the staged rule as published in the USP text. As of October 2026, USP–NF <711> uses the S1, S2 and S3 limits shown.

Stage 1 pass rule for an IR tablet

Q+5% is the first hurdle, not the specification. The pass rates below come from a simulation of 200,000 batches per row, run in October 2026, in which each tablet was drawn from a normal distribution around the batch mean with a fixed relative standard deviation (RSD, spread as a percentage of the mean), then scored with the three rules above. Values were not capped at 100%. Real batches are less tidy, so read this as a model, not a measurement.

A batch that meets Q on average can still run 12 tablets every time, and at 12% spread about 4 in 100 such batches fail outright. The recommended approach is to cut spread before chasing a higher average.

FDA bases the specification on the batches that proved the product: clinical, bioavailability or bioequivalence batches (FDA 1997). Three routes follow.

• New product: the method follows the drug's pH-solubility profile. For fast, highly soluble drugs (Biopharmaceutics Classification System, BCS, classes 1 and 3), a single point of at least 85% (Q=80%) in 60 minutes or less is enough. For poorly soluble drugs (class 2), FDA recommends two points: one at 15 minutes, one at 30, 45 or 60.
• Generic: the specification is generally the reference listed drug's, confirmed on the bioequivalence batch.
• High-solubility IR tablet: FDA's August 2018 guidance offers a standard test: basket at 100 rpm or paddle at 50 rpm, 500 mL of 0.1N hydrochloric acid, no surfactant, 37 ± 0.5°C, criterion Q=80% in 30 minutes. This guidance is nonbinding. A product is eligible only if its highest strength dissolves in 250 mL or less across pH 1 to 6.8; it is not a narrow therapeutic index product, not one where time to peak plasma concentration is critical (rapid-onset or rescue labels), and not an orally disintegrating or sublingual tablet; its excipients are in amounts consistent with their function; and its manufacturing and stability history shows it meets Q=80% in 30 minutes.

Whichever route applies, the product should comply throughout its shelf life (FDA 1997).

They break on small, undocumented details. The industry consortium paper records cases such as:

• A buffer concentrate diluted twice, which produced an out-of-specification (OOS) result.
• A paddle slipped below its 25 mm height onto the sinker (the wire coil that holds a tablet down).
• Two autosamplers of the same model that gave profiles nearly 40 points apart at 5 minutes on 12-month stability samples.
• Six non-compliant five-coil sinkers mixed into a box of 36 compliant seven-coil sinkers, which gave random fast tablets.

SUPAC-IR (FDA's 1995 scale-up and postapproval changes guidance) treats a move to a different campus (a site not on the same contiguous property or in adjacent city blocks) as a Level 3 change. It asks for a multi-point profile (SUPAC-IR's "Case B") at 15, 30, 45, 60 and 120 minutes, or until a plateau, on at least 12 units. It also expects a satisfactory current Good Manufacturing Practice (CGMP) inspection of the new site and a changes-being-effected supplement filing, with long-term stability data in the annual report. The profiles at both sites should be similar, meaning f2, FDA's similarity factor for comparing two dissolution profiles, is between 50 and 100. FDA's 1997 guidance adds two conditions: use only one point after 85% dissolved, and keep the coefficient of variation (CV) within 20% at the earliest point and 10% after.

Agree ten items in writing before the first batch. This term sheet is built from the sources below. Each line passes only if the condition is met. Line 7 follows FDA 1997. Lines 8 and 9 are recommended practice rather than regulatory text. Line 10 reflects 21 CFR 211.165, which requires each batch to be tested against its final specifications before release. For line 6, see pharmaceutical technology transfer.

We are a technology-driven CDMO for oral dosage forms, and tablets are one of our finished-dose categories. Our process runs from inquiry through development or technical transfer to production and quality control; see third-party manufacturing and pharmaceutical technology transfer for how those stages work. Send the method card and specification (items 2 and 3 of the term sheet) with your inquiry so the feasibility review can address them.

Reach us through our contact form, by email to sunil@aarisepharma.com, or by WhatsApp on +91 9899783330. Pricing is quoted per project.