RETARDATION OF WEAKLY BASIC DRUGS WITH DIFFUSION TABLETS

In the increasing pH milieu of the gastrointestinal fluid, the release of weakly basic dmgs such as noscapine from diffusion dosage forms with polymethacrylate mixture film-coatings is problematical. Once their pKa or the pH value at which precipitation occurs is exceeded by intestinal fluid, precipitation of the poorly soluble free bases takes place within the dosage form. Precipitated drug is no longer capable of diffusing through the film-coating. This problem of ensuring pharmaceutical availability could be solved, in the case of noscapine HCl, by the addition of organic acids such as succinic, adipic, tartaric or citric acids to the tabletting mass. By maintaining the pH value within the diffusion coating below the precipitating pH of noscapine, an improvement in release is achieved over the pH range 1.2 (first hour) to 7.5 (eighth hour), that depends on the type and amount of acid added. © 1990.