Compounding Hotline

SEPTEMBER 01, 2008
Martin A. Erickson III, RPh

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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