The Pharmaceutical Journal
Vol 273 No 7329 p852-853
11 December 2004

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· New contract (5)
· PPRS
· Registration exam (4)
· Prescription forms
· Community pharmacy
· Male health
· Competency
· Public health
· Alcohol
· Levithyroxine
· Complementary medicine
· The register (3)
· Retention fee
· The Journal (2)

Letters to the Editor

Levothyroxine

Suspensions are not the solution

From Dr J. I. Wells, MRPharmS

I would like to respond to the letter from Royston Morgan and Zilla Huma (PJ, 27 November, p785). It is not clear from their letter whether they crushed tablets as their source of drug, or bought in the pure drug. If we, however, assume the former, then any presumption of accuracy of dosing is confounded by the extremely low dose and the difficulty in mixing a tableting blend at target. The British Pharmacopoeia will accept a target dose of ±10 per cent on a composite sample, and ±15 per cent on individual tablets. If tablets are crushed in a pestle and mortar, then further dosing errors will occur, especially if a sample of the powder is used, there is non quantitative transfer, there is powder fly and dust generated or rubbing down is incomplete.

However, there is one serious oversight. This product is a solution. The solubility of thyroxine sodium (the salt used in L-thyroxine preparations) is 1 in 600 (Martindale 27th edition, 1977). This translates to 1.666mg ml^-1. Since the target dose is 10mg ml^-1, this is only 0.6 per cent of the equilibrium solubility. There is no need to use Xanthan gum. I would propose the following instead:

· If tablets are used, count out the requisite numbers of tablets for the preparation and allow them to disintegrate and deaggregate in an aliquot of water. Better still, weigh out the pure drug. Most specialist chemical suppliers hold a wide range of pharmacopoeial quality drug substances.

· For neonates, to avoid unnecessary excipient additions, disperse the tablets to dissolve the drug in sterile water, and filter through a 40mm membrane to remove the tableting excipients and then through a sterilising filter (0.47mm) into a sterile amber glass container and store in a refrigerator. Alternatively use a combined prefilter and sterilising membrane unit, remembering to discard the first 5ml to account for potential adsorption losses.

· More elegant solutions could usefully contain 50 per cent sorbitol solution to lower the water activity and improve stability, and 0.1 per cent methyl and 0.02 per cent propyl parabens as preservatives. This choice is dictated by the prevailing pH.

As a general comment, compounders should investigate the solubility and stability profile of any drug, when embarking on extemporaneous preparation from another dosage form. Quite clearly the assumption that an oral liquid derived from solid dosage forms is going to be a suspension is not always true. The residue due to tableting excipients truly clouds the issue. As a play on words: “suspensions are not the solution.”

James I. Wells
Rosemont Pharmaceuticals, Leeds

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