Dosage forms with controlled gastrointestinal passage — studies on the absorption of nitrofurantoin

Abstract

The aim of the present investigation was to describe theoretically the influence of the rate of gastrointestinal passage on the absorption of drugs after peroral administration and to use this description in the practical development of new types of dosage forms. The intention in these studies was to devise peroral dosage forms that display a delayed gastrointestinal passage through the release of a passage-influencing excipient. The saturated fatty acid myristic acid was used as a substance for controlling gastrointestinal passage, since this acid, as a constituent of fat-rich food, delays transit through the alimentary tract. The ammonium salt was used to optimise the properties of myristic acid for use in oral dosage forms. In a comparative in vivo study with 5 healthy subjects, the effects of 107.5 mg ammonium myristate on the absorption of nitrofurantoin after the administration of sustained release preparations (dose: 100 mg) was determined indirectly on the basis of the renal excretion of the drug. A commercially available sustained release preparation in capsule form was used, that was given with and without ammonium myristate in a larger hard gelatine capsule. The addition of ammonium myristate led to an average increase of 23.8% of the total amount of nitrofurantoin excreted in the urine compared to the values obtained from the reference dosage form without the additional substance. The increase in renal excretion was statistically significant ( P < 0.01). On evaluating the time course of urinary excretion of the drug, the amounts of nitrofurantoin excreted after administration of the dosage form with myristic acid were significantly higher ( P < 0.05) in the 5th, 6th, 7th and 9th hours after dosage.