SUSTAINED RELEASE OF DRUGS FROM ION EXCHANGE RESINS

THE development of preparations to give sustained release of drugs in the body when administered by mouth, has been recently reviewed’. Most of these preparations are based on physical methods for retarding the release of drug as, for example, by making tablets which disintegrate slowly or by coating pellets with slowly soluble films213. A more continuous and uniform release over a long period is likely to result if the drug is chemically bound to a solid carrier, from which it is slowly released by the action of the digestive fluids. The slowness of the uptake and release of alkaloids from ion exchange resins has been noted by Saunders and Sr i i ra~tava~>~ and it was thought that these resins might provide suitable chemical carriers for drugs in sustained release preparations. Ion exchange resins are extremely insoluble in aqueous liquids and have no toxic effects unless they are given in large enough quantities to disturb the calcium content of the body fluids. When they are administered by mouth, they are likely to spend about two hours in the stomach in contact with an acid fluid of concentration of about 0-1N hydrochloric acid. They will then be moved to the intestine where they will be in contact with a fluid of approximately neutral pH and ionic strength of about that of 0.1N sodium chloride, for several hours. An outline of the properties and structures of ion exchange resins has been given in a review by Saunderse. The common cation exchangers contain either carboxyl or sulphonic acid groups distributed throughout the resin particles. Both types in the hydrogen form (the “form” of a resin is named after the exchangeable ion contained in it) absorb alkaloids from solution, forming resin salts, in which the alkaloid is chemically combined with the exchanger anion. RSO,-H+ + Alk = RS0,-AlkH+