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An instrumental syst.em for continuous automatic colorimetric analysis, 1 he ..Zu toAnalyzer,* has been describedThe unit consists of a proportioning pump for metering reagents and sample. Continuous dialysis of the sample after addition of the reagents is used to achieve separation from interfering materials. The reagent mixture is heated so that the reaction may take place, and then it passes into the continuous flow cuvette of thc colorimeter, where optical densities are measured and a ratio recording is obtained.This system was applied by Ferrari et a1.T to continuous chemical monitoring of blood glucose concentrat ions, and the effect of pharmacological agents on these levels was measured in rabbits. An intravenous iieedle was insert ed into the jugular vein and polyethylene tubing was introduced inside thc needle. The tubing was tied in place and the needle removed. In the same way, a second cannula was then inserted in the vein. The first cathcter used for the continuous removal of blood and the second one, for the continuous infusion of a sedative-anticoagulant medication. The first catheter w a s connected through a variable-speed proportioning pump to the sampling side of the manifold. A second channel of the pump was used for the cont inuous infusion of the sedative-anticoagulant mixture a t the same rate.'This accomplishment suggested a technique for use in human subjects. The purpose of this study was to demonstrate the feasibility of automatic, continuous determinations of blood glucose in patients, and to show the difference between the type of curve resulting and the intermittent measurements in standard use for many years. Materials and MethodsFor this study, it was important to obtain a continuously aiiticoagulatetl sample of blood from the subjects. This wits accomplished by using a modified double-lumen needle. This needle, originally proposed by Duncan A.HoladayJ was made of metal, and modification was required to eliminate its positional sensitivity..4 double cannula was constructed from polyethylene tubing, as illustrated in FIGURE 1. On the side arm of the glass H was attached a length of 0.034 * 'Technicon Instruments Corp., Chauncey, N. Y.t See article elsewhere in this monograph.

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Dissolution studies have for many years been performed by many different techniques. In each case, the objectives are the same; namely, to desive an in vitro means of testing both the rate at which a drug-is dissolved and the active ingredient made available for absorption by the mucosa of the gastrointestinal tract. Unfortunately, the mucosae in different portions of the gastrointestinal tract behave differently. Dissolution and absorption are also affected by the composition and pH of the gastrointestinal fluids. The composition of the gastrointestinal fluid will, of course, vary according to the contents; i.e., the presence or absence of food and the nature of any food present.The gastrointestinal tract is divided into the following: the stomach and pylorus; the duodenum, jejunum, and ileum, which comprise the small intestine; the cecum, the dilated intestinal pouch into which open the ileum, the colon, and the appendix veriformis; and the colon, rectum, and anus, which comprise the large intestine.As stated, composition of the fluids will vary throughout the gastrointestinal tract; thus, absorption conditions will vary. Absorption from the gastrointestinal tract is accomplished in several ways. The first route through which absorption takes place is through the pores of the cell's membrane; i.e., through the waterfilled pores of the cell membrane. It must, however, be recognized that while the diffusion coefficiency can be calculated under experimental conditions with the use of synthetic membrane, such is not the case for diffusion across the cell membranes. This is due to the fact that diffusion must occur across many barriers. These barriers, of course, are the two cell walls, or membranes of the cell, and the basal membrane of the gastrointestinal tract to which these cells are attached. Variation in cell size, shape, and type make calculation difficult. When one speaks of diffusion in general, one must consider that the area of the membrane and the concentration differences across the membrane affect the degree of diffusion that will take place. Another factor that must not be ignored is the molecular weight of the material being diffused. Both in the case of the membrane of the biological system and of in rirro methods, experimental systems are affected by the pH of the fluid in contact with the membrane and with many other external environmental conditions including composition of the media surrounding, or in contact with, the membrane. Another fact that should be considered is that cellular permeability is far greater for undissociated molecules than it is for ionized forms. Therefore, in view of all these varying and uncontrollable conditions, it

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