Dissolution Medium Preparation Calculator (HCl, Buffers, SGF, SIF)

About the Dissolution Medium Preparation Calculator (HCl, Buffers, SGF, SIF)

A dissolution run starts with litres of medium made exactly to recipe. Choose the medium — hydrochloric acid of any strength (0.1 N HCl and others), the pH 1.2 fluids, the 0.05 M acetate buffer pH 4.5, the phosphate buffers pH 6.8, simulated gastric fluid with or without pepsin and simulated intestinal fluid without enzyme, water, or your own method’s recipe — and the number of vessels, the volume per vessel (500, 900 or 1000 mL), the runs and any extra, and the calculator scales every component: grams of salts, millilitres of acid and stock solutions, with the stock solutions to make first, a surfactant such as SLS by % w/v, the form of the salt you actually hold (hydrates converted by molar mass) and the batches your flasks allow.

The preparation lists the steps, the pH to check (within 0.05 unit for buffered media, as the harmonized dissolution test asks), the deaeration note and the temperatures, and ends with a preparation record to fill in by hand: reagent lots, weights, pH reading, signatures. Several media can be planned at once, with the reagents added up.

The free preview shows the recipe per 1000 mL as the pharmacopoeia writes it, the steps and the rules, with every amount worked out for your vessels, your acid or your hydrate hidden; the amounts, the PDF record, the workbook and the printed record need a Premium pass.

Common uses

• QC laboratories preparing media for a day’s dissolution runs.
• Method transfer and development: the same medium for profiles at pH 1.2, 4.5 and 6.8.
• Biowaiver and similarity studies needing three media at once.
• Converting a recipe to the hydrate or the acid strength on the shelf.
• Training analysts with a printed preparation record.

The recipes

Per 1000 mL, as the pharmacopoeias write them:

• JP 1st fluid for dissolution test (pH about 1.2): 2.0 g sodium chloride and 7.0 mL hydrochloric acid, water to 1000 mL (JP).
• Simulated gastric fluid without enzyme (pH 1.2 ± 0.1): 2 g sodium chloride in 100 mL water, 7 mL hydrochloric acid, diluted to 1000 mL; with pepsin: plus 3.2 g purified pepsin, pH about 1.2 (Brazilian Pharmacopoeia).
• 0.05 M acetate buffer pH 4.5: 2.99 g sodium acetate trihydrate and 1.66 mL glacial acetic acid to 1000 mL, pH adjusted if needed (Brazilian Pharmacopoeia).
• Phosphate buffer pH 6.8: 250 mL of 0.2 M potassium dihydrogen phosphate (27.22 g/L) and 112 mL of 0.2 M sodium hydroxide (8.0 g/L) to 1000 mL; simulated intestinal fluid without enzyme has the same composition, pH 6.8 ± 0.1 (Brazilian Pharmacopoeia; the 0.2 mol/L solutions as in the JP).
• JP phosphate buffer solution (pH 6.8): 3.40 g potassium dihydrogen phosphate and 3.55 g anhydrous disodium hydrogen phosphate to 1000 mL; the JP 2nd fluid for dissolution test is that buffer and water, 1:1.
• Hydrochloric acid of c mol/L: c × 36.46 g of HCl per litre, from concentrated acid of known content and density (the JP monograph allows 35.0–38.0 % HCl, specific gravity about 1.18) or by diluting a standardized solution.

pH, deaeration and temperature

The harmonized dissolution test (JP 6.10 with Ph. Eur. 2.9.3 and USP <711>) says:

• the volume specified refers to measurements made between 20 and 25 °C;
• a buffered medium is adjusted to within 0.05 unit of the specified pH;
• dissolved gases can cause bubbles that change the results: where they influence the results, remove them. One method: heat the medium to about 41 °C while stirring gently, filter at once under vacuum through a filter of 0.45 µm or finer with vigorous stirring, and continue stirring under vacuum for about 5 minutes; other validated methods may be used;
• the test runs at 37 ± 0.5 °C.

A medium with a surfactant such as SLS foams under vacuum, so the preparation adds the surfactant after any deaeration, unless your method orders the steps otherwise.

Choosing the medium

Use the medium your monograph or approved method names; the FDA Dissolution Methods Database lists the media and volumes FDA recommends for many products. The FDA guidance on immediate-release dosage forms describes volumes of generally 500, 900 or 1000 mL and aqueous media of pH 1.2 to 6.8 — pH 1.2 without enzymes to simulate gastric fluid and pH 6.8 for intestinal fluid — with enzymes only where justified (pepsin or pancreatin to dissolve the pellicles gelatin capsules may form), and a surfactant such as sodium lauryl sulfate for poorly soluble drugs, its need and amount justified. Media of the same name can differ between pharmacopoeias, so check the recipe against your method.

Limitations

• The recipes are the Japanese and Brazilian pharmacopoeias’ as written; use the one your method names, or enter it as your own recipe.
• Simulated intestinal fluid with pancreatin and other enzyme media follow your method (the enzyme’s activity matters): enter them as your own recipe.
• How long a prepared medium may be kept, and the grade of the reagents, are set by your procedure.
• Inputs stay on this page until you reload it; nothing is saved or uploaded.

Privacy

On this device; its files download once

Everything is worked out in your browser: the media and volumes you choose are never uploaded or stored.