Enteric-coated products

GI complaints are the most common adverse effects of NSAIDs. Minor complaints such as nausea, dyspepsia, anorexia, abdominal pain, flatulence, and diarrhea occur in 10% to 60% of patients. NSAIDs should be taken with food or milk, except for enteric-coated products (milk or antacids may destroy the enteric coating and cause increased GI symptoms in some patients). 

Oral pancreatic enzyme supplements are available as powders, uncoated or coated tablets, capsules, enteric-coated spheres and microspheres, or enteric-coated microtablets encased in a cellulose or gelatin capsule (Table 28-2). Microencapsulated enteric-coated products are not superior to recommended doses of conventional non-enteric-coated enzyme preparations. The quantity of active lipase delivered to the duodenum appears to be a more important determinant in pancreatic enzyme replacement therapy than the dosage form. GI side effects appear to be dose related but occur less frequently with enteric-coated products. 

The solubility should be measured at all of these pH values with a suitable, validated method such as shake-flask or pSol (2) at 37°C to determine whether the (envisaged) dose of the drug can be completely dissolved at all points of interest in the GI tract (see Chapter 11 for more discussion of solubility determination). Typically, this would be the upper GI pH (stomach and proximal small intestine) for immediate release (IR) products, the pH in the small intestine for enteric-coated products and, additionally for MR dosage forms intended to release over a period of six hours or more, the pH in the proximal colon. 

Some studies suggest the microencapsulated preparations are less likely to cause Gl damage however, evidence conflicts and a specific recommendation of one solid oral product over another cannot be made. Avoid enteric coated products. 

Enteric Coated Intended to delay the release of the drug (or drugs) until the dosage form has passed through the stomach. Enteric coated products are delayed release dosage forms. 

Shellac.2 This is a naturally occurring polymer obtained from a gummy exudation produced by female insects. The pH at which drug is released is about 7, which may well be too high for most enteric-coated products. It is not recommended for developing a new product. 

The influence of a single dose of omeprazole on the pharmacokinetics of enteric-coated ketoprofen tablets was tested [65], There was no significant difference with or without single-dose omeprazole administration for the systemic bioavailability of the ketoprofen products. A trend in higher plasma concentrations with omeprazole indicates a possibility of drug release from enteric-coated products at potentially elevated stomach pH values. 

M. E. M. van Golderen, M. Oeling, D. M. Barends, J. Meulenbelt, P. Salomons, A. G. Rauws, The bioavailability of diclofenac from enteric coated products in healthy volunteers with normal and artificially decreased gastric acidity, Biopharm Drug Disp 75 775-788 (1994). 

Pharmacopoeias generally do not require a dissolution profile to be determined but do specify that a certain amount of drug must dissolve (or not dissolve in the case of enteric-coated products) within a specified time. Should a single-time specification be stated, the test may be concluded in a shorter time if the requirement for a minimum amount dissolved is met. If two or more times are specified, then the samples should be withdrawn with a tolerance of 2% of the stated time. For Digoxin Tablets BP, when there is more than one tablet per test, all six replicate runs should release at least 75% of the stated amount within 60 minutes. 

Gastric irritation may occur from direct GI contact or through systemic mechanisms (i.e., irritation may occur with suppositories or enteric coated products)... 

Oral pancreatic enzyme supplements are available as a powder, uncoated or coated tablet, capsule, enteric-coated sphere (ECS) and microsphere (ECMS), or enteric-coated microtablet (ECMT) encased in a cellulose or gelatin capsule (Table 39-8). Recommended dosages of microencapsulated enteric-coated products are not necessarily more effective than recommended dosages of the non-enteric-coated enzyme preparations. This is because a lesser quantity of lipase is usually administered at each meal with the enteric-coated preparations. 

E. Pharmacokinetics. Acetylsalicylic acid is well absorbed from the stomach and small intestine. Large tablet masses and enteric-coated products may dramatically delay absorption (hours to days). The volume of distribution of salicylate is about 0.1-0.3 L/kg, but this can be increased by acidemia, which enhances movement of the drug into cells. Elimination is mostly by hepatic metabolism at therapeutic doses, but renal excretion becomes important with overdose. The elimination half-life is normally 2—4.5 hours but as long as 18-36 hours after overdose. Renal elimination is dependent on urine pH. See also Table 11-59 (p 381). 

---