Most of a capsule or tablet is not the botanical, and every other ingredient needs a legal basis, a place on the label and a job

A botanical extract is rarely dosed alone. Fillers bring a small dose up to a mass a machine can fill or press; binders hold compressed particles together; disintegrants break the tablet apart once it is wet; flow agents (glidants) keep powder moving through hoppers, which the Scale-up and tech transfer page grades with a USP <1174> flow classifier; lubricants stop it sticking to steel; coatings and shells protect, mask and identify the unit.

FDA's list of functional effects in 21 CFR 170.3(o) names several of these jobs. Paragraph (o)(14), “Formulation aids”, covers “carriers, binders, fillers, plasticizers, film-formers, and tableting aids”; (o)(1) covers “Anticaking agents and free-flow agents”; (o)(18) covers “Lubricants and release agents: Substances added to food contact surfaces to prevent ingredients and finished products from sticking to them.” The list has no separate term for a disintegrant.

Li and Wu (2014) report that “magnesium stearate and stearic acid are the most frequently used lubricants in the pharmaceutical industry”, used at “usually 0.25%–5.0%, w/w”. Desai, Liew and Heng (2016) describe the disintegrant as “responsible for ensuring the break-up of the tablet matrix upon ingestion”.

Sources: 21 CFR 170.3(o); Li J, Wu Y. Lubricants 2014;2(1):21–43, doi:10.3390/lubricants2010021; Desai PM, Liew CV, Heng PWS. J Pharm Sci 2016;105(9):2545–2555, doi:10.1016/j.xphs.2015.12.019.

Sampling. DSLD held 214,780 labels on October 24, 2026, of which 121,959 were marked on market. Label identifiers were drawn at random without replacement from 1 to 330,000 (seed 20261024); an identifier with no label, or with a label marked off market, was skipped; the first 600 on-market labels were kept after 1,800 draws. The range excludes about 850 on-market labels (0.7%) added in the latest update, whose identifiers run to 340,294.

Classes. An entry counts toward a class when its name, or a listed form, matches a fixed name pattern (for example “silicon dioxide” or “silica”, but not “silicate”). A label counts once per class. A match shows that the label lists the substance, not why it was added. Entries DSLD stores as ingredients but which are headings (“Contains 2% or less of”, “None”) are not counted; 16 labels (2.7%; 95% interval 1.6–4.3%) used such a 2% heading, and 67 listed no other ingredient.

Limits. DSLD transcribes labels as printed, so spelling varies and some entries are bundled. Intervals are Wilson 95% intervals for a simple random sample. The script, the label records and the aggregates are published with the site code (src/modules/acexc/compute/).

Source: NIH Office of Dietary Supplements, Dietary Supplement Label Database, https://dsld.od.nih.gov, API https://api.ods.od.nih.gov/dsld/v9/ (version 9.5.0, May 2026; index of September 25, 2025), retrieved October 24, 2026.

• “Other dietary ingredients” (101.36(b)(3))≠“Other ingredients” (101.4(g))
• Listed below the panel≠approved by FDA

21 CFR 101.4(g) reads: “When present, the ingredient list on dietary supplement products shall be located immediately below the nutrition label, or, if there is insufficient space below the nutrition label, immediately contiguous and to the right of the nutrition label and shall be preceded by the word ‘Ingredients,’ unless some ingredients (i.e., sources) are identified within the nutrition label in accordance with § 101.36(d), in which case the ingredients listed outside the nutrition label shall be in a list preceded by the words ‘Other ingredients.’ Ingredients in dietary supplements that are not dietary ingredients or that do not contain dietary ingredients, such as excipients, fillers, artificial colors, artificial sweeteners, flavors, or binders, shall be included in the ingredient list.”

Order. 101.4(a)(1) requires listing “in descending order of predominance by weight”, and lets dietary ingredients already in the panel go unrepeated. Under 101.4(a)(2), ingredients at 2 percent or less may instead follow “Contains __ percent or less of”, with a threshold of 2, 1.5, 1.0 or 0.5 percent, and “No ingredient to which the quantifying phrase applies may be present in an amount greater than the stated threshold.”

The rule cited for this in some summaries, 101.36(g), concerns where nutrition information sits on the label (by reference to 101.2); the ingredient-list rule is 101.4(g), with 101.36(d) for sources.

FDA's guide. In its Dietary Supplement Labeling Guide (April 2005), FDA answers that a magnesium salt used as a binder belongs in the ingredient statement below the panel, not in the panel (Chapter IV, Nutrient Declaration, Question 5).

Sources: eCFR, 21 CFR 101.4 and 101.36 (up to date as of October 22, 2026); FDA, Dietary Supplement Labeling Guide, Chapter IV.

FDA's position, quoted. “Section 201(s) of the FD&C Act (21 U.S.C. § 321(s)) exempts dietary ingredients used in dietary supplements from the food additive definition. … However, other ingredients intended for use in dietary supplements, such as binders, excipients, and fillers, are not exempt from the food additive definition and must meet the same requirements as substances added to conventional foods. In other words, non-dietary ingredients added to a dietary supplement must be used in accordance with a food additive regulation or be GRAS for their intended use (unless they qualify for another exception to the food additive definition).”

Titanium dioxide. 21 CFR 73.575 lists it as a color additive exempt from certification, at no more than 1 percent by weight of the food. A 2023 petition asks FDA to revoke that listing (88 FR 27818, May 3, 2023); no final action was found in the Federal Register as of October 24, 2026. In the EU, Commission Regulation (EU) 2022/63 ended its authorization as a food additive from August 7, 2022, after EFSA concluded in May 2021 that it “can no longer be considered safe when used as a food additive” (as reported by the Food Safety Authority of Ireland).

Where these parts sit. The CFR atlas summarizes every part cited here, from 21 CFR 101 to 40 CFR 180, in one line each.

GRAS reform. A proposed rule of August 11, 2026 would make GRAS notification mandatory for human food substances (91 FR 51834); comments close December 9, 2026. As of October 2026, independent GRAS conclusions remain lawful.

Supplier qualification. For components that are not dietary ingredients, 21 CFR 111.75(a)(2) requires the manufacturer to confirm identity and specifications by its own tests, or to rely on a supplier's certificate of analysis after qualifying that supplier.

Pharmacopeial monographs. The Pharmacopoeial Discussion Group (USP, Ph. Eur., JP) harmonizes excipient monographs; EDQM's table of September 1, 2026 lists 69. Colloidal silicon dioxide is still in elaboration; maltodextrin, acacia and titanium dioxide are not on the list. 21 CFR 101.36(d)(3) allows a label to state that a source “conforms to an official compendium”, for example “calcium carbonate USP”.

Sources: FDA guidance (January 2014), https://www.fda.gov/media/87680/download; 21 CFR 73.575, 111.75, 101.36 (eCFR); Federal Register 88 FR 27818 and 91 FR 51834; FSAI news, July 15, 2022; EDQM PDG status table.

Why carriers. Many extracts are sticky or hygroscopic once the solvent is gone, so a carrier such as maltodextrin or gum arabic is added before or during drying; the spray-dryer stickiness (glass transition) explorer on Scale-up and tech transfer shows why. FDA lists maltodextrin as affirmed GRAS with a dextrose equivalent below 20, made from corn, potato or rice starch (21 CFR 184.1444), and acacia (gum arabic) with maximum levels by food category (184.1330).

EMA definitions, quoted. “Genuine (Native) herbal preparation: refers to the preparation without excipients, even if for technological reasons the genuine herbal preparation is not available.” The ratio of herbal substance to genuine herbal preparation (DER genuine) “is the ratio of the quantity of the herbal substance to the quantity of the resulting genuine herbal preparation.” “Other excipients are technological excipients (e.g. carrier substances) which may be part of herbal preparations.”

The worked example. EMA's “Dry extract from Valerian root”: genuine extract 80%, DER genuine 3–6 : 1, other excipients 20%, 200 mg per capsule; the declaration reads “Each capsule contains 160 mg of extract (as dry extract) … (equivalent to 480 mg – 960 mg of Valerian root).”

U.S. rule for liquids. 21 CFR 101.36(b)(3)(ii)(B) describes “y:z” as the weight of starting material to the volume of solvent, and “if the original extract was 1:5 and 50 percent of the solvent was removed, then the final concentration shall be stated as 1:2.5.” For an extract dried to remove the solvent, “the weight of the ingredient shall be the weight of the dried extract” (101.36(b)(3)(ii)(C)).

Sources: EMA, Guideline on declaration of herbal substances and herbal preparations in herbal medicinal products/traditional herbal medicinal products, EMA/HMPC/CHMP/CVMP/287539/2005 Rev.1; 21 CFR 101.36, 184.1330, 184.1444 (eCFR, October 22, 2026).

The harmonized text calls the indices “not intrinsic properties of the powder” and lists what moves them: cylinder diameter and mass, number of taps, drop height, sample mass and rotation. It recommends a 250 mL cylinder with 100 g of sample. On angle of repose it notes “examples in the literature of formulations with an angle of repose in the range of 40-50 degrees that manufactured satisfactorily. When the angle of repose exceeds 50 degrees, the flow is rarely acceptable for manufacturing purposes.”

Lubricants work mainly by boundary lubrication: “they decrease friction at the interface between a tablet's surface and the die wall during ejection” (Li and Wu 2014). The same review warns that “use of too much lubricant in tablet formulations can impact the product performance by decreasing tablet dissolution” and that “over-mixing often causes dissolution delay”; it gives a typical lubricant mixing time of 0.5–5 minutes.

Sources: PDG harmonized text “Powder Flow” (003-2003PDG), https://www.pmda.go.jp/files/000233963.pdf; Li and Wu 2014, doi:10.3390/lubricants2010021.

The lead in the example comes mostly from two colorants and a filler: titanium dioxide 0.5 µg, calcium phosphate 0.35 µg and iron oxide 0.15 µg of 1.205 µg. Iron oxide supplies 6 of the 9.5 µg of vanadium, and the drug substance 10 of the 12.5 µg of nickel. The elemental budget calculator in Course 6 reproduces this table.

Allergens. FDA lists nine major food allergens: “milk, eggs, fish, Crustacean shellfish, tree nuts, peanuts, wheat, soybeans, and sesame”; sesame became the ninth under the FASTER Act, effective January 1, 2023. FDA states that the labeling law applies to dietary supplements. The food source is declared “in parentheses following the name of the ingredient”, e.g. “lecithin (soy)”, or in a “Contains” statement.

Sources: ICH Q3D(R2), https://database.ich.org/sites/default/files/Q3D-R2_Guideline_Step4_2022_0308.pdf; FDA, https://www.fda.gov/food/nutrition-food-labeling-and-critical-foods/food-allergies.

40 CFR 152.3: “Inert ingredient means any substance (or group of structurally similar substances if designated by the Agency), other than an active ingredient, which is intentionally included in a pesticide product, except as provided by § 174.3 of this chapter.” An inert ingredient that may leave residues in food needs a tolerance or an exemption from one, listed in 40 CFR 180 Subpart D.

EPA PR Notice 97-6 lets registrants replace the heading “Inert ingredients” with “the more neutral term ‘Other ingredients’”, because many consumers took “inert” to mean “water or other harmless ingredients”. EPA adds that “some inert ingredients are not benign to human health or the environment.”

A boundary in the text. 40 CFR 180.950(a)(2)(iv) excludes dietary supplements from the “commonly consumed food commodities” that are exempt as minimal-risk pesticide ingredients.

Sources: eCFR, 40 CFR 152.3 and 180.910–180.960; EPA, PRN 97-6, https://www.epa.gov/pesticide-registration/prn-97-6-use-term-inert-label-ingredients-statement.

Excipient

Any constituent of a dosage unit other than the active or dietary ingredient, added for manufacture, stability or use.

Other ingredients

The heading of a supplement's ingredient statement when sources are named in the Supplement Facts panel (21 CFR 101.4(g)).

Other dietary ingredients

Dietary ingredients without Daily Values, declared inside the panel (101.36(b)(3)); not the same as “Other ingredients”.

Filler (diluent)

Bulk that brings a small dose to a mass a machine can fill or compress.

Binder

A material that holds particles together in a granule or tablet.

Disintegrant

A material that breaks a tablet apart once it is wet.

Glidant (flow agent)

Fine particles that reduce cohesion so a powder flows; in food law, an anticaking or free-flow agent.

Lubricant

A material that lowers friction between powder and tooling, such as magnesium stearate.

Carrier

A technological excipient, such as maltodextrin, added to an extract, often to make drying possible.

DER genuine

The ratio of herbal substance to the genuine extract obtained, excluding excipients (EMA definition).

GRAS

Generally recognized as safe by qualified experts for a stated use; exempt from the food-additive definition.

Inert ingredient (EPA)

Any intentionally added substance in a pesticide product other than an active ingredient (40 CFR 152.3).