compounding HOTLINE

MARCH 01, 2008
Martin A. Erickson III, RPh

Mr. Erickson is director of professional affairs at Gallipot Inc.

I am compounding a few tablets using a hand press; the formulation requires calcium phosphate dibasic, and both anhydrous and dihydrate are available. Which should I use?

Tablet formulation can require pharmaceutical engineering at the production level due to incompatibilities or other difficulties. A hand press is advised here for FDA regulatory purposes.

Anhydrous dibasic calcium phosphate USP has a molecular weight of 136.06 and is a white, odorless, tasteless powder/crystalline solid (density 2.89 g/cm3; decomposes at 425°C to calcium pyrophosphate). It contains only adsorbed moisture 0.1% to 0.2% and cannot be rehydrated to form the dihydrate. It is practically insoluble in water, ethanol, and ether, but is soluble in dilute acids; is nonhygroscopic and stable, but should be stored in a closed container in a dry place; and is used as nutritional supplement for calcium and phosphorus and as a tablet and capsule diluent. Incompatibilities include tetracyclines. The milled material's surface is alkaline—do not use with drugs sensitive to pH >7. The unmilled form has an acidic surface and may affect drug stability, especially when particle size changes. Although it flows well, high pressure can cause lamination and "capping."

Dibasic calcium phosphate dihydrate USP has a molecular weight of 172.09 (appearance of the anhydrate; density 2.389 g/cm3). It dehydrates, losing 2 molecules of water, below 100°C; exhibits solubility as the anhydrous form; is nonhygroscopic and stable, but can lose water of crystallization; and should be stored in well-closed container in a cool, dry place. It is used as a capsule and tablet diluent. It is probably the better choice for your formulation. Incompatibilities include tetracyclines, ampicillin, aspartame, aspirin, cephalexin, erythromycin, and indomethacin. The surface is alkaline—do not use with drugs unstable at pH >7.

Both forms are abrasive, and formulations should use a lubricant to preserve tableting equipment.

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