Stomach emptying

Avoid long-term use of mineral oil. Daily use of this product may interfere with tiie absorption of some vitamins (vitamins A, D, E, K). Take with the stomach empty, preferably at bedtime... 

In summary, food will delay stomach emptying and, as a result, may decrease the rate of availability of a drug from its oral dosage form. The extent of availability of that drug, however, may be increased, decreased, or unaffected by meals. Thus, it is important for the pharmacist to counsel patients on the importance of timing the taking of their medications relative to their mealtimes. 

Usually, an increase in Cg that would affect the dissolution rate would occur only when another process, such as membrane transport or stomach emptying, becomes the rate-limiting step in drug absorption. As a general rule pharmacists should advise patients to take their oral medications with a full glass of water to ensure that dissolution occurs under optimal conditions. 

The important stages in delivering a drug to its desired target after an oral dose can be summarized as shown in Fig. 6.2. Initially the formulation has to be swallowed and survive the transition to the site of absorption - the gastrointestinal tract (GIT). The time required for this to happen will depend on the stomach emptying time, which in turn will be a function of the fed/fasted state of the subject or animal that is being studied (see for example Ref. [7]). This kind of information can only be obtained from in vivo studies. 

Despite the gastrointestinal absorption characteristics discussed above, it is common for absorption from the alimentary tract to be facilitated by dilution of the toxicant. Borowitz et al. (1971) have suggested that the concentration effects they observed in atropine sulfate, aminopyrine, sodium salicylate, and sodium pentopar-bital were due to a combination of rapid stomach emptying and the large surface area for absorption of the drugs. 

Solubility Stomach emptying rate Dissolution rate... 

Aqueous solubility Stomach emptying Dosage form Metabolism... 

Metoclopramide is frequently used in combination with antacid therapy. It increases the tone of the lower oesophageal sphincter, increases stomach emptying, and because of this may speed absorption of drugs absorbed from the small intestine. 

Opioids induce an inhibitory effect on gastrointestinal motility and fluid secretion (Kromer, 1990). The effect is peripherally and centrally mediated. The peripheral component is related to p- and K-receptors in intestinal organs, which are densely equipped with opioid receptors. They are located at parasympathic ganglia and inhibit the release of acetylcholine, which stimulates the contraction of smooth muscles. Inhibition of the intestinal fluid secretion is mediated via inhibition of adenylate cyclase. The intestinal effects of opioids extend to all parts of the gut and results in inhibition of stomach emptying and inhibition of secretion and motility of duodenum, jejunum, colon and rectum. 

Pramlintide (rINN) is an amyloid analogue (1). It is administered subcutaneously, but it precipitates above pH 5.5 and therefore cannot be co-administered with insulin. It received FDA approval in 2005 for both type 1 and type 2 diabetes. It reduces postprandial glucose excursions, probably by reducing stomach emptying, not by stimulating the release of glucagon-like peptide (GLP-1) (2). It can only be given by injection. 

Thus, it was suggested that pectin may moderate the glucose (and hence the insulin) response by delaying the rate at which stomach emptying occurs. 

Drug release and retention at the site of absorption are very important for the enhancement of the bioavailability, particularly when the absorption sites are localized to a certain area of the GI route. This control of the transition of the drug can be achieved using bioadhesive excipients. Chlorothiazide (CT), a diuretic and antihypertensive drug, was better orally absorbed when administered with mucoadhesive polymers [25], The absorption of CT is considered to be saturable and site-specific, because a low dose is better absorbed, and a decreased stomach emptying rate and slow GI transition rate are better for increased absorption. As chitosan is a mucoadhesive polymer, the absorption of CT is expected to be enhanced... 

In vivo, however, various further aspects have to be taken into account such as variability in stomach emptying, intestinal transit, effect of the dilution of the particle suspension in the Gl-tract fluids, and mixing with ingested food (Ponchel and Irache 1998). 

Gastric emptying assay Stomach emptying in mice or rats (phenol red)... 

Percentage of stomach emptying (Se) is calculated according to the following formula ... 

As the stomach empties, the hydrochloric acid in the material entering the small intestine is neutralized by secretions from the pancreatic ducts, bile, and pancreatic juice. The digestion of the starch dextrins is continued by the action of the pancreatic a-amylase. 

The intestinal phase, which occurs as chyme enters the duodenum. This involves many inhibitory controls neural and endocrine mechanisms limit the rate of stomach emptying so that the secretory and absorptive mechanisms of the small intestine can cope effectively with the entry of gastric contents. 

Whereas solid food delays stomach emptying, liquids tend to accelerate the process. Acceleration results from activation of stretch receptors in the stomach wall. When the fluid is water, activation of the inhibitory receptors is stopped. This results in rapid emptying of stomach contents into the duodenum. 

A drug in a suspension is in solid form, but is finely divided and has a large surface area. Drug particles can diffuse readily between the stomach and small intestine so that absorption is relatively insensitive to stomach emptying rate. 

Tablets may be formulated with coatings such as shellac, resin, or styrene-maleic acid copolymer. These coatings are insoluble in acid but dissolve readily at neutral or alkaline pH. Thus they are ideally suited to prevent drug release until the formulation has passed from the stomach into the small intestine. Preventing drug release in the stomach may protect drugs that are acid labile. It may also protect the patient from irritant substances like iron salts, diethylstilbo-estrol, and some anti-inflammatory agents. Release, and subsequent systemic availability of drugs from these formulations is likely to be highly sensitive to stomach emptying patterns.

The drug dosage form may also be affected by food. For example, enteric-coated tablets may stay in the stomach for a longer period of time because food delays stomach emptying. If the enteric-coated tablet does not reach the duodenum rapidly, drug release and subsequent systemic drug absorption are delayed. In contrast, enteric-coated beads or microparticles disperse in the stomach, are less affected by food, and demonstrate more consistent drug absorption from the duodenum. 

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