Dry Syrup Formulation: How to Spec the In-Use Window

A dry syrup is powder or granules that a pharmacist or caregiver mixes with water to make an oral suspension. US labels name these products "for suspension" (see the DailyMed listing for azithromycin). The reconstituted window decides the rest, because every other choice has to hold up for that many days.

The formulation has five parts:

• Active pharmaceutical ingredient (API): the drug itself.
• Bulking base: such as powdered sucrose.
• Suspending agent: keeps undissolved drug evenly spread after mixing.
• Flavor and sweetener.
• Preservative.

One US patent for powders of beta-lactam antibiotics (the class that includes penicillins and cephalosporins) shows the scale. It claims 80 to 95 wt% (percent by weight) powdered sugar, a d50 (the median particle diameter; half the particles are smaller) of 50 to 150 µm, a d90 (90% of the particles are smaller) below 200 µm, and water of at most 3 wt%. Its description prefers a d50 of 40 to 150 µm, water below 0.7 wt% and 0.5 to 1.5 wt% colloidal silicon dioxide. The examples are cefixime and amoxicillin (US9566337B2). Treat these as one patent's ranges for one drug family, not a standard.

Across 15 common actives on current US labels, reconstituted windows run from 10 to 35 days, and some other actives, such as mycophenolate mofetil at 60 days, are longer. Nine of the 15 print 14 days. The window depends on the active and, for some, on refrigeration.

Selection: the 15 actives are the common antibacterial, antifungal, antiviral and acid-suppressant for-suspension products in DailyMed whose manufacturer label prints a discard window in its reconstitution text. We searched 11 further actives and left them out. Linezolid was left out because we read its window only on a repackager label. Other for-suspension products, such as mycophenolate mofetil, were not searched.

Method: for each active we recorded the discard time from the reconstitution text of the linked label, read in October 2026. Labels differ by manufacturer, so check your reference product.

The count: 3 actives at 10 days, oseltamivir at 10 to 17, 9 at 14, famotidine at 30 and erythromycin ethylsuccinate at 35, which makes 15. Where the same labels print dry-powder storage (cephalexin, azithromycin and fluconazole), it is 20 to 25 °C.

Buyers get the window wrong by assuming one number fits the whole dosage form. Because 9 of the 15 actives in the table print 14 days, 14 feels standard. For the other 6 it is wrong. In our recommendation, never write a window into an RFQ that is not tied to the specific active and its storage condition.

The reason is chemistry. The study shows why temperature matters for this pair: in a peer-reviewed study of commercial amoxicillin/clavulanic acid suspensions, clavulanic acid degraded by up to 12.9% at 8 °C and up to 72.3% at 28 °C over 7 days (Mack et al., Antibiotics 2021). It did not test the label's 10-day window, so the window itself must come from stability data on your own product. The study measured suspensions sold in Switzerland, so it shows the mechanism, not a limit for your product. Erythromycin ethylsuccinate sits at the other end: its label allows 35 days with no refrigeration.

Two further mistakes to avoid:

• Setting the window from the formulation alone. The window has to be demonstrated by stability data on the finished powder in its final bottle, stored as the label will say.
• Ignoring facility. Penicillin actives must be made in separate facilities under 21 CFR 211.42(d).

A dry syrup RFQ should state the reconstituted window first, then nine further tested attributes, each with a pass condition. Copy the table into your RFQ and replace the bracketed items. The numbers in brackets are for you to set from your active's stability data. Our recommendation is not to accept a supplier's defaults.

Terms used below: excipient is any non-drug ingredient. Redispersion is how easily settled powder returns to an even suspension on shaking.

Checks 4, 7 and 8 and the particle-size limit follow FDA's inspection guide; the other checks are our recommendation. The guide says bottles from the beginning, middle and end of filling should not be composited. It also calls for continuous or periodic agitation during filling, particle-size specifications, and testing for objectionable organisms, with particular concern for infants and immunocompromised patients. It also says stability bottles should be stored on their side or inverted to test the closure (FDA, Oral Solutions and Suspensions, 1994, content reviewed 2014).

For the pass criteria, the independent references are USP <51> Antimicrobial Effectiveness Testing for check 6, the USP <61> and <62> microbial limits for check 7, and ICH Q1A(R2) for check 8 and the stability data behind check 1.

Why does facility segregation matter for a dry syrup?

Penicillin work must be done in separate facilities. The rule says penicillin operations "shall be performed in facilities separate from those used for other drug products for human use" (21 CFR 211.42(d)). FDA's 2013 guidance, which the June 2022 draft revises, recommends complete separation of cephalosporins and other non-penicillin beta-lactams from other drugs. It is guidance, not a regulation, unlike the penicillin rule in 21 CFR 211.42(d). Of the 15 actives in the table, amoxicillin, amoxicillin/clavulanate, cefdinir, cefixime, cefpodoxime, cefprozil, cefadroxil and cephalexin are beta-lactams: 8 of 15.

We list dry syrup among our finished-dose categories and run oral-dose development through commercial manufacturing as a contract development and manufacturing organization (CDMO). A request follows our buying route: inquiry, feasibility review, commercial quotation, development or technical transfer, production and quality control, packaging, and dispatch.

For a feasibility review, send us the filled spec sheet above with:

• the active and strength per 5 mL;
• the target window and storage condition;
• the destination market.

We quote product by product, so pricing comes with the quotation. Buyers confirm local registration and import requirements for their market before commercial supply.

To discuss your product, use our contact form. For how a contract manufacturing quote is assembled, see Third Party Manufacturing Pharma.