GB809015A — Stable aqueous suspensions of tetracycline

USPTO Abstract

Magnesium tetracycline is prepared by reacting tetracycline, or a salt thereof such as the hydrochloride, with a magnesium salt such as the hydrochloride in an aqueous medium at a pH of 7.4 to 9.0 and preferably 8.5. The ratio of tetracycline to magnesium is from 1 : 1 to 1.5 : 1. The aqueous medium may be water, a mixture of water and a water-miscible organic solvent such as methanol, or such a solvent containing as solubilizer a water-soluble carbohydrate, e.g. sucrose. Magnesium tetracycline is stable in aqueous suspension (see Group VI). Specifications 747,779 and 793,558 are referred to.ALSO:A stable, easily resuspended tetracycline preparation of good colour comprises a suspension of magnesium tetracycline in an aqueous vehicle, the insoluble solids in the preparation having a particle size of less than 100, and preferably 10-20 microns. The magnesium tetracycline is such that the ratio of tetracycline to magnesium ions is from 1 : 1 to 1.5 to 1 (see Group IV (b)). The vehicle is an aqueous solution of a sugar such as sucrose or invert sugar, as such, or with the further addition of glycerol or glycol, or other aqueous solution such as sorbitol. Optional additions are (a) synthetic sweetening agents such as sodium cyclohexanesulphamic acid or saccharin; (b) flavouring agents, e.g. chocolate, cocoa, coffee, fruit acids such as citric, ascorbic and tartaric; banana, wild cherry and raspberry flavours; oils of peppermint, spearmint and orange; (c) medicinal dyes (The Merck Index 6th Edition, pages 1112-1116); (d) preservatives such as methyl p-hydroxybenzoic acid, sodium and calcium propionate, cinnamaldehyde, sorbic acid and benzalkonium chloride; (e) antioxidants such as sodium bisulphite and sodium metabisulphite; and (f) other therapeutic agents such as amino acids and vitamins. In one example, a 1 : 1 magnesium tetracycline, sodium cyclohexanesulphamate, methyl- and propyl-p-hydroxybenzoate, sodium metabisulphite, oil of orange, a mixture of red and yellow dye are dispersed in a vehicle containing 60 per cent sucrose and 10 per cent glycerol in water, the preparation being adjusted to pH 7.5 with citric acid. The vehicle may be replaced by a 70 per cent aqueous solution of sorbitol. Specifications 747,779 and 793,558 are referred to.