The adsorption of atropine sulfate and selected opium alkaloids and sulfonamides by kaolin

The adsorption interactions between kaolin and chlorpromazine hydrochloride, codeine phosphate, morphine sulfate, atropine sulfate, and four sulfonamides were studied in vitro. With the exception of chlorpromazine hydrochloride and three of the sulfonamides, these test drugs have been combined with kaolin into antidiarrheal preparations. Due to solubility problems, the adsorption of the sulfonamides by kaolin was investigated in 1:12.5 hydrochloric acid solution. All other studies were carried out in water and in pH 1.2, 3.0, and 5.0 hydrochloric acid solutions and at a temperature of 37.0°C. The data for adsorbed drugs could, in most instances, be represented graphically on the basis of either the Freundlich or Langmuir adsorption equations. However, several of the adsorption isotherms were classified according to the system outlined by Giles and his co-workers (1960). Desorption studies for adsorbed drugs were carried out in aqueous solution. Under the experimental conditions cited, the sulfonamides were not adsorbed by kaolin. All other test drugs were adsorbed by this clay. In general, adsorption varied with the pH of the adsorption medium. With the exception of atropine sulfate, the adsorption of chlorpromazine hydrochloride and the opium alkaloids appears to be a reversible process. On the basis of data obtained, it was estimated that over 90% of a normal dose of chlorpromazine hydrochloride, atropine sulfate, morphine sulfate, or codeine phosphate would be adsorbed by a normal dose (six gm.) of kaolin if the drug and the adsorbent were allowed to equilibrate in 40 ml. of water. The in vivo significance of these results is not known. However, on the basis of in vivo data for lincomycin hydrochloride (Wagner, 1966) and a limited number of other drugs, decreases in plasma levels following concurrent administration of kaolin containing preparations are greater than those that might be predicted by in vitro data. This may, therefore, imply that the incorporation of opium alkaloids or atropine sulfate into antidiarrheal preparations containing kaolin is undesirable but the final proof of such an assumption must be based on carefully controlled studies in man. This abstract represents the true contents of the thesis submitted.Pharmaceutical Sciences, Faculty ofGraduat