Compounding Hotline

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

Aliquot Dilution for Compounding Capsules

Please clarify a method for preparing an aliquot dilution for compounding capsules (specifically liothyronine [T₃]).

?T₃ is administered in microgram doses; using the capsule dilution method often employed (pack 5-10 capsules of the size to be used in the preparation with each of the ingredients; in turn, weigh, compute an average for each, then calculate relative displacement to find the amount of excipient to be used. See: Lloyd AV. Developing a capsule formulation. Int J Pharm Compounding. 2001;(5):392-393). The following steps can be used as an example for 7.5 mcg T₃.

Note that steps 1 and 3 are "the same" for each dose (strength) to be administered; step 2 contains the technical variation. In step 2, the desired dose is a fraction of the mixture in step 1. This is a direct result of the very small active powder weight variation: relative displacement becomes insignificant (ie, displacement factor ~1). Step 1: Make a standard dilution T₃ 0.25 g + corn starch 24.75 g = 25 g (provides 0.010 g of T₃ per 1 g of mixture 1). Step 2: Dilute mixture 1 further: mixture 1 powder 0.75 g + corn starch 99.25 g = 100.000 g. (Mixture 2: contains 7.5 mcg of T₃, or 0.0075 mg of T₃, per 1 g of mixture 2.) Step 3: Make 1 more dilution to incorporate Methocel E4M Premium (which forms a bolus to provide a delayed-release form [not timed- or sustained-release]).

Mixture 2 powder 33 g + Methocel E4M Premium 33 g + cornstarch 51.15 g + silica gel 0.3 g + 117.45 g. Mixture 2 provides 2.475 mg of T₃ per 33 g. Therefore, 355 mg of the mixture contains 0.00748 mg of T₃, or 7.5 mcg, the desired dose. Pack each capsule with 355 mg of mixture 3 to yield a 7.5-mcg dose per capsule. Note the following: Capsule size #1 was determined to contain ~355 mg mixture. For capsule compounding, where Methocel E4M Premium is incorporated, its ratio generally is 1/3 of total theoretical capsule contents.

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