Epsom salt USP food grade pharma grade API is supplied as magnesium sulfate heptahydrate, MgSO₄·7H₂O, CAS 10034-99-8, molecular weight 246.47 g/mol. The product is offered as model MGS·7H₂O-USP/FCC for oral solid dosage and food-grade use and as model MGS·7H₂O-USP-PAR for controlled parenteral-grade material. The material appears as colorless or white efflorescent crystals or crystalline powder, with a theoretical water of crystallization content of 51.2%. It is freely soluble in water and practically insoluble in ethanol. Both models are produced in a GMP-aligned crystallization, centrifugation, drying, and milling line with metal detection and finished-particle sieve control. The designation “USP food grade pharma grade API” indicates that the material is released against the current USP–NF magnesium sulfate monograph and the FCC monograph, but it does not imply that the non-sterile powder is ready for injection without additional processing.

What Limits Differentiate USP–NF, FCC, and Technical-Grade Magnesium Sulfate Heptahydrate?

Technical-grade magnesium sulfate heptahydrate is not manufactured under pharmaceutical change control and commonly shows broader particle-size distribution, higher iron and chloride residues, and no endotoxin or particulate-matter testing. Production-scale failure modes observed on gravimetric feeders include bridging when mean particle size exceeds 500 µm, while tablet surface specking from insoluble iron oxides becomes visible when iron is present above 0.005%. Food-grade material meeting FCC limits is suitable for dietary supplement and food processing, but it is not required to meet parenteral endotoxin limits under USP <85>, sterility under USP <71>, or particulate matter under USP <788>. USP–NF grade material is manufactured with documented cleaning between technical and food-grade campaigns, container-closure integrity testing, and stability data generated under ICH Q1A(R2) conditions. The table below summarizes the critical differentiating attributes.

The release specification for the USP–NF grade is controlled by a compendial identity test based on magnesium and sulfate reactions, a complexometric assay with 0.05 M edetate disodium, and loss on drying by USP <731> at 450°C for 3 hours. The heptahydrate loses water of crystallization at high drying temperatures; therefore the loss on drying range of 48.0–52.0% confirms the correct hydrate form rather than free surface moisture. Free moisture in milled product is separately controlled below 0.5% by Karl Fischer titration at the filling line. Particle-size distribution is measured by laser diffraction per USP <429> and is specified as d10 not more than 30 µm, d50 between 90 µm and 160 µm, and d90 not more than 300 µm for direct-compression formulations. These particle-size values are typical release ranges, not compendial limits; they should be confirmed against the finished-product process capability.

Solid Oral Dosage Processing Parameters and Water-of-Hydration Control in Tablet and Capsule Formulation

MgSO₄·7H₂O is used in oral tablets, capsules, and granules as a magnesium source and as an osmotic laxative component. In tablet formulations, free moisture content should remain below 0.5% to avoid picking and sticking on rotary tablet presses. Direct compression is preferred when the particle-size specification is within d50 90–160 µm; outside this range, wet granulation may require vacuum drying at 40–60°C with air dew point below 0°C to avoid premature dehydration. Capsule formulations require flowability measured by Carr index or Hausner ratio; a typical accepted range is Carr index 15–25%. Granule formulations should be sieved through 20–60 mesh after dry granulation to maintain blend uniformity. Magnesium sulfate heptahydrate is incompatible with strong alkali and carbonate salts in aqueous granulating fluids because insoluble magnesium hydroxide or carbonate precipitates can form.

When the same formulation uses anhydrous magnesium sulfate or a lower hydrate, the conversion factor from anhydrous MgSO₄ to heptahydrate is 2.047. A formulation requiring 100 mg anhydrous equivalent therefore requires 204.7 mg of MgSO₄·7H₂O. This difference is a frequent source of label claim error in scale-up when the hydrate form is not explicitly stated on the master batch record. Batch-to-batch variation in water of hydration can also shift assay; when drying exceeds 50°C, partial conversion to lower hydrates changes the effective molecular weight and may cause content uniformity failure. Production-scale observation indicates that tablet capping becomes more frequent when free moisture exceeds 0.8% or when granule d50 exceeds 200 µm in direct-compression trials; these limits should be verified on the specific press and tooling configuration.

If the API Is Intended for Injectable Formulation, What Additional Controls Apply?

Use of magnesium sulfate heptahydrate in injectable formulations is restricted to parenteral-grade material that is further processed by dissolution in Water for Injection, pH adjustment with diluted sulfuric acid if necessary, depyrogenation, sterile filtration through 0.22 µm or 0.2 µm rated filters, and terminal sterilization or aseptic filling. The non-sterile API is not for direct injection. Injectable solutions must meet USP <1> Injections, including sterility testing per USP <71>, bacterial endotoxins per USP <85>, particulate matter per USP <788>, and package integrity testing. The API should be released with a bacterial endotoxin limit agreed with the finished-product manufacturer; because the compendial API monograph does not set a universal endotoxin limit, the finished parenteral specification governs. Production-scale issues include endotoxin carryover in piping and heat exchanger dead legs; equipment should use sanitary stainless steel 316L with minimal threaded connections and passivation per ASTM A967. Compatibility with other injectable drug solutions must be confirmed case by case; published data for this specific configuration is limited.

The material is packaged in polyethylene-lined fiber drums with low moisture-vapor transmission, typically 25 kg net weight. Storage in unopened original containers at 15–25°C and relative humidity below 60% is recommended. Open containers should be reclosed immediately, because the heptahydrate can lose water of hydration in very dry air or adsorb surface moisture in humid conditions. The product should not be stored adjacent to strong oxidizing agents, strong acids, or alkaline agent vapors.