COMPOUNDING HOTLINE

Pharmacy Times, Volume 0, 0

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 veryslightly 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 readilyabsorbed when given by mouth. Peak blood levels are attainedwithin 1 hour, with half-life ~100 minutes. Given orally, HCacetate is not well absorbed; HC and HC acetate intramuscularinjections are poorly absorbed. Poor absorption from synovialspace and soft tissue, however, provides a long duration of actionwhen it is injected for local inflammation. HC acetate isemployed for intra-articular injection and sodium phosphate orsuccinate forms for soft-tissue injections. The metabolism of HCis hepatic; excretion is urinary, chiefly as glucuronides andsome HC. In adrenocortical insufficiency, 10 to 30 mg of HCis given orally in divided doses, with a larger morning dose tomimic normal circadian rhythm. The salts (HC sodium succinateor HC sodium phosphate) are given intravenously for rapidonset in emergency situations.

HC and several esters are used topically; usual concentrationsare HC 0.1% to 2.5%, butyrate 0.1%, and valerate0.2%. Evaluation of skin condition is imperative before therapybecause damaged skin readily absorbs HC and esters. Compoundersshould wear protection when handling these drugs.Reports of HC suspensions include Fawcett JP, Boulton DW, etal. Stability of hydrocortisone oral suspensions prepared fromtablets and powder. Ann Pharmacother. 1995;29(10):987-990,in which HC 2.5-mg/mL oral suspensions were stored in thedark (3 temperatures/91 days). Reportedly, only the formulationprepared from tablets exhibited significant HC decomposition;patients responded well to the formulations. The authorsconcluded that the suspension would be stable for at least 30days 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 carboxymethylcelluloseNa 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 powderin (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 Suspensionreformulation (xanthan gum substituted for tragacanth)bioinequivalence resulted in a lack of congenital adrenal hyperplasiacontrol in children. The authors noted a Cortef Oral Suspensionrecall (Merke DP, Cho D, et al. Hydrocortisone suspensionand hydrocortisone tablets are not bioequivalent in thetreatment of children with congenital adrenal hyperplasia. J ClinEndocrinol Metab. 2001;86[1]:441-445).

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