GB730249A - Procaine penicillin crystals - Google Patents

Abstract

Procaine penicillin of enhanced stability in the presence of moisture is prepared by crystallizing procaine penicillin at a temperature within the range of 20 DEG to 30 DEG C., and preferably 25 DEG C., and maintaining the resulting crystals within said range until at least 40 per cent of said crystals have a particle size of greater than 300 microns in length, e.g. for at least one hour. A preferred method is adding an aqueous solution of procaine hydrochloride at 25 DEG C. to an aqueous solution of sodium penicillin maintained at 25 DEG C. until 1/3 to 2/3 of the procaine hydrochloride has been added, seeding the reaction mixture with crystals of procaine penicillin, adding the remainder of the aqueous solution of procaine HCl to the reaction mixture, and maintaining the mixture at 25 DEG C. for at least one hour. Any water-soluble penicillin salt may be used, e.g. the sodium, potassium, calcium and ammonium salts; and amine salts such as those of ethylamine, triethylamine and N-ethyl piperidine. The penicillin may be a particular penicillin, e.g. penicillin G or a mixture of penicillins. Water-soluble procaine salts are the hydrochloride, hydrobromide, hydroiodide, sulphate, nitrate, phosphate, acetate or formate. Solvents other than water which may be used are methanol, formamide and dioxane. Preferably the reaction takes place in buffered solution, e.g. phosphate buffer. After the main ageing operation, increased yields are obtained by p adding to the reaction mixture over a period of 20 to 30 minutes a salting-out agent such as sodium chloride, sodium nitrate, sodium sulphate, calcium chloride, ammonium nitrate, or ammonium sulphate. The procaine penicillin when dried to a moisture content of 7 per cent is suitable for incorporation in an animal feed supplement. The procaine penicillin particles are such that at least 40 per cent are greater than 300 microns in length, at least 70 per cent are over 200 microns in length, at least 85 per cent are over 150 microns in length and substantially all are over 100 microns in length.ALSO:Procaine penicillin crystals of enhanced stability suitable for animal feed supplements are obtained by crystallizing procaine penicillin at 20-30 DEG C. and maintaining the crystals at this temperature until they have attained more than 300 microns in length.