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[Galenical possibilities and problems in protraction of drug effects (author's transl)].

In recent years, dosage forms with sustained release have obtained a significant importance. The technological possibilities for manufacturing are described as coating, embedding and matrix procedures. The range of auxiliary substances, which are responsible for the retardation of drug activity, reaches from lipophilic compounds as lipoids, fatty alcohols and compounds which are forming hydrogels as cellulose derivatives and natural polysaccharides to synthetic polymers derived from acrylic acid. The formulation of the dosage forms requires particular care in respect to the amount of initial and maintenance doses. On account of technological processes, for example during manufacturing of tablets, under certain circumstances the liberation rate is altered. In vitro test methods allow comparisons only then when the results can be counter-checked by in vitro experiments. The release of drug follows different mechanisms, which are described, entirely or in part, to be reactions following the time law of zero or first order. In special cases, a linear correlation is observed as a function of square root of time. The calculation of given special equations for events within the dosage form is feasible from blood-level values.

Biological Availability↗

[Pharmacokinetic study of sodium di-n-propylacetate (usual tablet and enteric coated tablet with delayed absorption) (author's transl)].

The authors study the blood levels of DPA after ingestion of the drug in the usual tablet form and after ingestion of an enteric coated tablet with delayed intestinal absorption. They emphasize the fast and very variable absorption of the drug in the usual tablet form which makes necessary the administration of several doses each day. They find a slower absorption from the enteric coated tablet resulting incumulative effects. This form allows an easier administration schedule (one dose in the morning and one dose in the evening). Moreover, the blood levels show less variation during a twenty-four-hour period. Undoubtedly, this new form is an improvement in comparison with the usual tablet.

Adult↗

[Drugs in tablets].

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Biopharmaceutics↗

[Clinical treatment of inflammatory and benign ulcerous diseases of the stomach and duodenum with a new combination preparation (Aci-Tensilan) (author's transl)].

A gastroduodenal combination preparation was introduced at a deliberately high dosage into a clinical treatment schema. A marked improvement of the subjective symptoms already appeared after a short treatment in hospital, pain in particular being rapidly affected. Younger patients tolerated the preparation excellently, older ones had a marked sedation. Because of the danger of concealment, stenoses in the region of the gastrointestinal tract, ileus and preileus are particular contraindications. The dosage of 3 X 3 to 3 X 4 dragees should be reserved for hospital treatment. The dosage of 3 X 1 dragee for ambulant practice and also for prolonged therapy (ca. 6-8 weeks) is unobjectionable, reference being made to possible initial tiredness and disturbances of accomodation.

Adolescent↗

[Potassium chloride and non-specific ulcers in the small intestine].

Gut toxicity due to potassium chloride preparations is well known, but there is little information concerning side effects of the newer slow release preparations. Small bowel ulceration due to the new slow release formulation is described. As far as the authors are aware this is the first such case published in Switzerland.

Administration, Oral↗

An enteric-coated pancreatic enzyme preparation that works.

A new enteric-coated pancreatic enzyme preparation (microspheres) was compared with traditional enzyme tablets in six subjects with severe exocrine pancreatic insufficiency. The microspheres were found to be as effective as traditional enzyme supplements. In most patients in balance studies, the lowest fecal fat values were obtained with microsphere therapy in spite of a smaller amount of lipase administered (6015 vs 10,800-43,200 lipase units per meal). In contrast to enteric-coated tablets, microspheres can be recommended in the treatment of pancreatic steatorrhea.

Adult↗

The effect of oral magnesium chloride therapy on the QTc and QUc intervals of the electrocardiogram.

The effect of magnesium, given orally as enteric-coated magnesium chloride tablets, on the ECG of 25 randomly selected patients was investigated. Each patient, who served as his own control, was given 4--6 tablets, each containing 0,5 g MgCl26H2O, at night for periods varying from 6 weeks to 2 years. Findings included (i) a statistically significant decrease in OTc and QUc intervals; (ii) a progressive shortening of QTc and QUc intervals with continuing therapy; (iii) reversion to normal of ECG abnormalities, especially of ST segments and T waves.

Administration, Oral↗

A trial of micro-encapsulated and enteric-coated aspirin in rheumatoid arthritis.

In a trial of 48 patients with rheumatoid arthritis, enteric-coated aspirin (4.55 g daily( and micro-encapsulated aspirin (4.50 g daily) proved to be equally effective in reducing morning stiffness, relieving pain, increasing grip strength, reducing ESR, and reducing the need for additional analgesic tablets, compared with placebo. Reduction of joint tenderness was also found, but this was not statistically significant. Proximal interphalangeal joint circumference altered little during the trial. Tinnitus and deafness were commoner with enteric-coated aspirin, but gastric side-effects were similar. Of 39 patients completing the trial, there was an equal patient preference for enteric-coated aspirin and micro-encapsulated aspirin. Salicylate side-effects necessitated withdrawal of six patients from the trial and dose reduction in nine patients. It was concluded that the efficacy and side-effects in rheumatoid arthritis of both aspirin preparations were similar.

Administration, Oral↗

Absorption of quinidine from an enteric-coated preparation.

The absorption of quinidine from single and multiple doses of an enteric-coated preparation (Systodin) was studied in seven healthy subjects, and was compared with the pharmacokinetics of intravenously administered quinidine and the results of in vitro dissolution tests of the tablets. Absorption of quinidine began after a variable delay, 2-8 h (mean 4.8) after fasting and 3-10 h (mean 6.1) after food. The rate of absorption varied both in and between individuals. It appeared to be lower when the drug was administered after food. Multiple doses after food gave a pattern of plasma concentration-time curves similar to that found on administration of single doses after food. The delay prior to absorption was prolonged at night. The ratio between the maximum and minimum concentration of quinidine during a dose interval varied from 1.3 to 3.2 (mean 2.0). Bioavailability of quinidine in fasting subjects ranged from 69 to 95% (mean 83); variation was greater when doses were administered after food. The release of quinidine from the enteric-coated preparation was pH dependent and was sustained at low pHs as may be found in the intestines. The results indicate that the absorption of quinidine from the enteric-coated formulation was dependent on the highly variable rate of gastric emptying and the pH of intestinal fluid, and it varied greatly both within and between individuals.

Adult↗

Medical treatment of pancreatic insufficiency.

Treatment of exocrine pancreatic insufficiency with the use of eight tablets of pancreatin with meals consisting of 25 g of fat per meal will generally abolish azotorrhea. Although steatorrhea is not totally corrected, satisfactory nutritional status and relative relief of symptoms are usually achieved. For the occasional patient who continues to lose weight or remains symptomatic even after reduction of dietary fat, the addition of cimetidine to the standard pancreatin treatment will usually provide relief from the steatorrhea and alleviate troublesome diarrhea. In certain circumstances in which gastric pH is more than 4 for 1 hour after a meal, altering the dosage schedule to two tablets hourly may be effective in alleviating the steatorrhea. Conversely, in patients whose upper gastrointestinal tract is acidic for long periods postprandially (gastric pH less than 5, duodenal pH less than 4), Pancrease, an enteric-coated preparation, may be effective. In difficult cases in which symptoms and steatorrhea continue, special intraluminal studies need to be performed to ensure that intraluminal conditions are, in fact, present for certain dosage schedules to be effective or that intraluminal conditions have been altered by adjunctive therapy.

Celiac Disease↗

Incidence of gastric lesions in patients with rheumatic disease on chronic aspirin therapy.

Endoscopy was done in 82 patients with rheumatic disease who were receiving chronic aspirin therapy. Fifty-eight patients were taking at least eight aspirin tablets daily for 3 or more months; 24 patients were taking, in addition to the aspirin, a maximum of one other antiinflammatory, nonsteroidal medication. Endoscopy in 45 normal subjects not taking aspirin showed no ulcers or erosions and a 4% incidence of gastric erythema. In the 82 patients with rheumatic disease, 14 (17%) had gastric ulcers, 33 (40%) had gastric erosions, and 62 (76%) had gastric erythema. Regular aspirin and buffered aspirin users had an ulcer incidence of 23% and 31% respectively, compared with a 6% incidence in enteric-coated aspirin users (P less than 0.05). One third of all patients with gastric ulcer had no gastrointestinal symptoms. Patients taking chronic aspirin therapy for rheumatic diseases have a higher than suspected incidence of gastric ulcer and erosions. Gastric ulcer may exist without symptoms in such patients.

Adult↗