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The effect of food on the absorption characteristics of nitrofurantoin from a commercial capsule dosage form containing macrocrystalline drug and a commercial tablet dosage form containing microcrystalline drug was assessed in human subiects by a urinary excretion method. In fa~ting subiects, less nitrofurantoin was absorbed and at a slower rate, and attained lower body levels when the capsule rather than the tablet dosage form was orally administered. When each was administered with food, the absorption of nitrofurantoin was appreciably delayed. Food in the gastrointestinal tract produced an increase in the peak body levels of nitrofurantoin from the macrocrystalline form. No effect of food was observed on the maximum levels after the microcrystalline form. There were increases of 80% and 30% in the bioavailability of nitrofurantoin in nonfasting as compared to fasting subiects, of macro crystalline nitrofurantoin capsules and microcrystalline nitrofurantoin tablets, respectively. There was an increase in the duration of therapeutic urinary concentrations of nitrofurantoin when either form was taken with food. The comman practice of using fasting subiects in bioavailability studies of drug products normally administered with food is questionable.NitrofurantOin, 1-[ (5-nitrofurfurylidene) amino] hydantoin, is a broad-spectrum antibacterial agent used extensively in the treatment of urinary tract infections. It is a weak acid (pKa 7.2) and is poorly soluble at the normal pH of the gastrointestinal (GI) tract. Its dissolution rate, absorption rate, and bioavailabilit y 4, 9, 12, 14 are dependent on its particle size.Adverse reactions associated with nitrofurantoin therapy are nausea and vomiting,

The FDA recently issued a guidance covering practices of scaleup and post approval changes with semisolids (SUPAC-SS). This guidance outlines the steps that must be taken by a company to maintain certification of its semisolid dermatological products after quantitative changes have been made in their compositions and/or after changes have been made in the sourcing of their key ingredients, in their processing, in their batch sizes, and/or after their site of manufacture has been relocated. A key element within the guidance is a release test to be used to determine if the diffusional release of a drug found in a formulation is the same after changes have been made to the formulation as it was prior to implementing the changes. The AAPS-FDA sponsored workshop was set up to explore this qualifying test. The stated aims of the workshop were: a) to illustrate the methodology and techniques of in vitro release testing, b) to show the sensitivity of in vitro release with respect to manufacturing variables and to variations in components and composition (of specific formulations), c) to recognize in vitro release testing as a useful procedure for SUPAC documentation, d) to highlight and evaluate other applications of in vitro release testing, e) to explore the degree to which in vitro release testing and bioavailability may be related, and f) to evaluate the role of in vitro release testing of topical dosage forms as a tool to improve product quality.