Patent GB-984114-A (GB)
Title: Controlled release compositions and their preparation
IPC: A61K9/16
Filed: 1961-05-09
Abstract: A controlled release composition is made by dissolving an acetate-phthalate ester of cellulose or starch in a non-polar/polar solvent mixture containing at least 50% by volume non-polar solvent, separately dissolving an aluminium salt of a carboxylic acid containing 2-22 carbon atoms in the same or another portion of the same solvent mixture, combining the solutions and removing solvent from the gel which forms and thereafter breaking the gel into particles.  The non-polar solvent may be a halogenated hydrocarbon, e.g. methylene chloride, ethylene dichloride, chloroform, or carbon tetrachloride and the polar solvent may be an alcohol or ketone having 1-4 carbon atoms, e.g. methanol, ethanol, the propanols, and acetone.  The solvent mixture may range from 50-95% by weight non-polar solvent and 50-5% by weight polar solvent, especially 80-90% non-polar solvent and 20-10% polar solvent.  A preferred solvent mixture comprises 90% methylene chloride and 10% methanol, by volume. Aluminium salts specified include the acetate, hexoate, octoate, stearate and palmitate.  A therapeutic agent, oil, or other substance may be incorporated in one of the solutions prior to mixing.  Specified agents include Vitamin B12, the polyvinyl pyrrolidineiodine complex, "Pyridium" (Registered Trade Mark) (phenylazo-a a -diamino-pyridine mono-hydrochloride), hydroxazine, hydrochloride, phenmetrazine hydrochloride, the phenothiazines, the corticosteroids, ataraxyhydrochloride, phenobarbital, methylene blue, corn oil, and ferrous sulphate.  The gel structure may be formed in the cold, or by heating to about 60 DEG  C.  The rate of release of the therapeutic agent or other substance is predetermined by varying the relative proportions of gel to therapeutic agent (the larger the proportion of gel to therapeutic agent the slower the rate of release of the drug in acid or alkaline media), and cellulose acetate phthalate to therapeutic agent and to aluminium salt (the higher the proportion of cellulose acetate phthalate to therapeutic agent and to aluminium salt the slower the rate of release of that agent into artificial gastric juice or other acid medium, and the faster the release of that agent into artificial intestinal fluids or other alkaline medium). Proportions of cellulose acetate phthalate to aluminium salt may vary from 50-1 parts cellulose acetate phthalate to 1-50 parts aluminium salt, especially 10-1 parts cellulose acetate phthalate to 1-10 parts aluminium salt.ALSO:A controlled release composition is made by dissolving an acetate-phthalate ester of cellulose or starch in a non-polar/polar solvent mixture containing at least 50% by volume non-polar solvent, separately dissolving an aluminium salt of a carboxylic acid containing 2-22 carbon atoms in the same or another portion of the same solvent mixture, combining the solutions and removing solvent from the gel which forms and thereafter breaking the gel into particles.  The non-polar solvent may be a halogenated hydrocarbon, e.g. methylene chloride, ethylene dichloride, chloroform, or carbon tetrachloride and the polar solvent may be an alcohol or ketone having 1-4 carbon atoms, e.g. methanol, ethanol, the propanols, and acetone.  The solvent mixture may range from 50-95% by weight non-polar solvent and 50-5% by weight polar solvent, especially 80-90% non-polar solvent and 20-10% polar solvent.  A preferred solvent mixture comprises 90% methylene chloride and 10% methanol, by volume. Aluminium salts specified include the acetate, hexoate, octoate, stearate and palmitate.  A therapeutic agent, oil, or other substance may be incorporated in one of the solutions prior to mixing.  Specified agents include Vitamin B12, the polyvinyl pyrrolidineiodine complex, "Pyridium" (Registered Trade Mark) (phenylazo-a ,a -diamino-pyridine monohydrochloride), hydroxazine hydrochloride, phenmetrazine hydrochloride, the phenothiazines, the corticosteroids, ataraxhydrochloride, phenobarbital, methylene blue, corn oil, and ferrous sulphate.  The gel structure may be formed in the cold, or by heating to about 60 DEG  C.  The rate of release of the therapeutic agent or other substance is predetermined by varying the relative proportions of gel to therapeutic agent (the larger the proportion of gel to therapeutic agent the slower the rate of release of the drug in acid or alkaline media), and cellulose acetate phthalate to therapeutic agent and to aluminium salt (the higher the proportion of cellulose acetate phthalate to therapeutic agent and to aluminium salt the slower the rate of release of that agent into artificial gastric juice or other acid medium, and the faster the release of that agent into artificial intestinal fluids or other alkaline medium).  Proportions of cellulose acetate phthalate to aluminium salt may vary from 50-1 parts cellulose acetate phthalate to 1-50 parts aluminium salt, especially 10-1 parts cellulose acetate phthalate to 1-10 parts aluminium salt.