Gastric fluid

FIGURE 2.16 pH versus enzymatic activity. The activity of enzymes is very sensitive to pH. The pH optimum of an enzyme is one of its most important characteristics. Pepsin is a protein-digesting enzyme active in the gastric fluid. Trypsin is also a proteolytic enzyme, but it acts in the more alkaline milieu of the small intestine. Lysozyme digests the cell walls of bacteria it is found in tears. 

A complication here, however, is noted with those drugs that exhibit a limited chemical stability in either acidic or alkaline fluids. Since the rate and extent of degradation is directly dependent on the concentration of drug in solution, an attempt is often made to retard dissolution in the fluid where degradation is seen. There are preparations of various salts or esters of drugs (e.g., erythromycin) that do not dissolve in gastric fluid and thus are not degraded there but which dissolve in intestinal fluid prior to absorption. A wide variety of chemical derivatives are used for such purposes. 

As discussed previously, drug absorption may be impaired or improved when food is present in the GIT. Food may reduce the rate or extent of absorption by virtue of reduced gastric-emptying rate, which is particularly important for compounds unstable in gastric fluids and for dosage forms designed to release drug... 

Fig. 6 Dissolution of digoxin tablets containing different fillers (in simulated gastric fluid at 37°C). (From Ref. 45.)...

Healy MA, Harrison PG, Aslam M, et al. 1982. Lead sulfide and traditional preparations Routes for ingestion, and solubility and reactions in gastric fluid. J Clin Hosp Pharmacol 7 169-173. 

Hamel S.C., Buckley B., Lioy P.J. Bioaccessibility of metals in soils for different liquid to solid ratios in synthetic gastric fluid. Environ Sci Technol 1998 32 358-362. 

Fig. 10. Controlled release of insulin in vitro from P(MAA-g-EG) microparticles simulated gastric fluid (pH = 1.2) for the first two hours and phosphate buffered saline solutions (pH = 6.8) for the remaining three hours at 37°C (243).

In the stomach, carotenoids are exposed to acid environments. This can lead to carotenoid isomerization, which can change carotenoid antioxidant properties, solubility, and absorption. In humans, (3-carotene absorption is reduced when the pH of the gastric fluids is below 4.5 (Tang and others 1995). Vitamin E consumption seems to reduce carotenoid absorption in animals, presumably because vitamin E and carotenoids compete for absorption (Furr and Clark 1997). Dietary sterols, such as those in sterol-supplemented functional foods, are also known to decrease carotenoid absorption. 

Fig. 15 Effect of phenytoin (PHT) particle size on (a) dissolution in simulated gastric fluid, pH 1.2, 37°C and (b) bioavailability in human volunteers after oral administration of 300 mg PHT. Dark circles lot with particle size range 74-350 /u.m open circles lot with particle size range 177-350 /am. (From Ref. 64.)...

The U. S. Dispensatory26 reports maximum serum levels of 0.2 ijg./ml. 1 hour after administration of a 250 mg. dose, 0.6 (ig./ml. 2 hours after a 500 mg. dose, and 1.2 ug./ml. 2 hours after a 1 g. dose. Higher blood levels are achieved on a multiple dosage schedule. Since it is acid labile, a resistant coating is used in tablet formulations to overcome the deleterious effect of gastric fluid on erythromycin base or the stearate salt is prepared which does not dissolve readily in the stomach. 

Consider how a weak electrolyte is distributed across the gastric mucosa between plasma (pH 7.4) and gastric fluid (pH 1.0). In each compartment, the Henderson-Hasselbalch equation gives the ratio of acid-base concentrations. The negative logarithm of the acid dissociation constant is designated here by the symbol pAa rather than the more precisely correct pK1. 

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