A stable, non-caking suspension of cortisone acetate in an isotonic aqueous vehicle and the process of preparing said composition

摘要

A stable, non-caking suspension of cortisone acetate in an aqueous vehicle is obtained by milling the cortisone acetate with the vehicle until stable crystals of reduced particle size are produced. The crystals show the following X-ray diffraction data:-Interplanar spacing-15.5 A, 8.65, 5.94, 5.64, 5.01, 4.78, 4.41, 4.15, 4.09, 3.95, 3.82. It is preferred that 90 per cent of the crystals have a size of 0 to 10 microns in length and none is greater than 50 microns. Preferably 5 to 15 parts of cortisone acetate are milled with 95 to 85 parts of aqueous vehicle using a hard glass mill e.g. 6 litre "Pyrex" (Registered Trade Mark) bacteria grinding jar and aseptic conditions. The mill charged with the steroid compound, the vehicle, and glass beads is rotated at a rate of 25 to 45 revolutions per minute at a temperature of 20 DEG C. If desired, before milling, the mixture may be "seeded" with a suspension of the stable crystalline form of cortisone acetate. Preferably the aqueous vehicle is rendered isotonic by e.g. the addition of sodium chloride, and also contains a suspending agent, a surface active agent and a preservative. The suspending agent may be sodium carboxymethylcellulose, methyl cellulose, gelatin or sodium alginate; the preservative-benzyl alcohol or phenol; the surface active agent-sodium lauryl sulphate, cetyl trimethyl ammonium bromide, high alkyl (C8-C18) dimethyl benzyl ammonium chloride or polyoxyalkylene derivatives of sorbitol anhydride long chain fatty acid ester e.g. polyoxyalkylene derivatives of sorbitan monooleate. In one example, isotoxnicity is produced by the addition of sodium citrate and N/10 hydrochloric acid. Cortisone is 11-dehydro-17-hydroxy corticosterone.