MARCH 01, 2005
Martin A. Erickson, III, RPh

Q Cortef Suspension (Pharmacia & Upjohn) is unavailable. Can we compound it?

A Hydrocortisone (HC) (17-hydroxycorticosterone, mw 362.5), a white/almost white, odorless, crystalline powder, is very slightly water-soluble and soluble 1 in 40 in ethanol. To store it, protect it from light in a well-closed container. HC is the main adrenal cortex glucocorticoid. It is readily absorbed when given by mouth. Peak blood levels are attained within 1 hour, with half-life ~100 minutes. Given orally, HC acetate is not well absorbed; HC and HC acetate intramuscular injections are poorly absorbed. Poor absorption from synovial space and soft tissue, however, provides a long duration of action when it is injected for local inflammation. HC acetate is employed for intra-articular injection and sodium phosphate or succinate forms for soft-tissue injections. The metabolism of HC is hepatic; excretion is urinary, chiefly as glucuronides and some HC. In adrenocortical insufficiency, 10 to 30 mg of HC is given orally in divided doses, with a larger morning dose to mimic normal circadian rhythm. The salts (HC sodium succinate or HC sodium phosphate) are given intravenously for rapid onset in emergency situations.

HC and several esters are used topically; usual concentrations are HC 0.1% to 2.5%, butyrate 0.1%, and valerate 0.2%. Evaluation of skin condition is imperative before therapy because damaged skin readily absorbs HC and esters. Compounders should wear protection when handling these drugs. Reports of HC suspensions include Fawcett JP, Boulton DW, et al. Stability of hydrocortisone oral suspensions prepared from tablets and powder. Ann Pharmacother. 1995;29(10):987-990, in which HC 2.5-mg/mL oral suspensions were stored in the dark (3 temperatures/91 days). Reportedly, only the formulation prepared from tablets exhibited significant HC decomposition; patients responded well to the formulations. The authors concluded that the suspension would be stable for at least 30 days stored in the dark at 5° and 25° C.

The suspension preparation is as follows:

Step 1 (Vehicle): Dissolve methyl hydroxybenzoate 0.020 g

Propyl hydroxybenzoate 0.080 g

Citric acid monohydrate 0.600 g

Simple syrup 10.000 mL

In hot water, mix and allow to cool, then triturate with carboxymethylcellulose Na 1.000 g, and allow to stand overnight.

Step 2: Separately triturate:

Hydrocortisone 0.250 g

Polysorbate 80 0.500 mL

Step 3: Add suspending vehicle from (1) to wetted HC powder in (2), triturate well, and add purified water to make 100 mL. Package in amber high-density polyethylene bottles.

A later study concluded that the 1998 Cortef Oral Suspension reformulation (xanthan gum substituted for tragacanth) bioinequivalence resulted in a lack of congenital adrenal hyperplasia control in children. The authors noted a Cortef Oral Suspension recall (Merke DP, Cho D, et al. Hydrocortisone suspension and hydrocortisone tablets are not bioequivalent in the treatment of children with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2001;86[1]:441-445).

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