Antacid Suspension Research Articles

Evaluation of antacid suspensions containing aluminum hydroxide and magnesium hydroxide

Liquid antacid suspensions containing aluminum hydroxide and magnesium hydroxide were evaluated for composition, antacid properties, and product quality. The equivalent aluminum oxide and magnesium hydroxide content was determined by chelatometric titration, and sodium content was determined by flame photometry. Antacid properties measured were acid-consuming capacity, antacid effectiveness (preliminary antacid test, acid-neutralizing capacity test), and pH-stat titration. Content uniformity, consistency of the antacid properties, and microbiological content were examined for each product. Data are presented for 36 products for which samples from four or more lots were obtained. The ratio of percentage of equivalent aluminum oxide to percentage of magnesium hydroxide ranged from 1:0.6 to 1:3.5; this range allows for selection of the desired balance between the laxative effect of magnesium hydroxide and the constipating effect of aluminum hydroxide. Based on a daily dose of 280 meq of antacid, the sodium content of the products tested ranged from less than 2% to approximately 45% of the 500 mg per day of sodium allowed in a sodium-restricted diet. The concept of bioavailability was related to the amount of the antacid reacting at pH 3, 37 degrees C during the estimated gastric residence time of 15 minutes. Antacid suspensions are available which will react almost completely (neutralizing greater than 90% of the theoretical quantity of acid) during the estimated gastric residence time. Approximately 4% of the samples contained unacceptable numbers of bacteria. An antacid suspension cannot be adequately evaluated by a single test; choice of a product should be based on an evaluation that integrates several characteristics including sodium content, time and volume required to neutralize a given amount of acid, and uniformity of content.

COMPARATIVE STUDY OF VARYING REGIMENS TO IMPROVE STEATORRHOEA AND CREATORRHOEA IN CYSTIC FIBROSIS: EFFECTIVENESS OF AN ENTERIC-COATED PREPARATION WITH AND WITHOUT ANTACIDS AND CIMETIDINE

The failure of conventional pancreatic enzyme supplements to correct completely the malabsorption that is caused by pancreatic insufficiency in cystic fibrosis (CF) is partly due to acid-peptic inactivation of ingested enzymes. To compare various methods of preventing acid-peptic inactivation we studied 10 CF patients during four randomised crossover 14-day treatment periods: (i) conventional supplements of pancrelipase (68±5 capsules daily); (ii) pH-sensitive enteric-coated microspheres of pancrelipase (ECMP; 31±3 capsules/day); (iii) ECMP plus cimetidine (20 mg/kg/day); and (iv) ECMP plus antacid suspension. Faecal fat excretion, measured as mmol/24 h and as a percentage of recorded ad-libitum intake, faecal nitrogen excretion, measured as g/24h and as a percentage of intake, and faecal weight/24 h were measured during each treatment period. During the ECMP treatment period there were significant decreases in faecal fat excretion (p<0·001), faecal nitrogen excretion (p<0·001) and faecal weight (p<0·01) compared with the conventional pancrelipase treatment period. Faecal fat excretion (mean±1 SEM) fell from 29·5±4·6% of intake on conventional treatment to 9·6±1·9% of intake on ECMP treatment (normal range [NR]<10%), and faecal nitrogen fell from 15·9±1·2% of intake to 9·1±1·3% of intake (NR<10%). Percentage fat excretion by all 10 patients improved to normal or near-normal levels. ECMP treatment was extremely well accepted nitrogen excretion. Addition of antacid or cimetidine to ECMP therapy made no significant difference, but in those cases where ECMP alone did not fully correct steatorrhoea (n=3) cimetidine caused a large additional improvement to normal levels. ECMP treatment was extremely well accepted because of reduced capsule intake and faecal output. It offers significant advantages over conventional enzyme-replacement therapy at half the capsule dosage. ECMP therapy alone, or in combination with cimetidine, seems able to produce maximum improvement in the digestive activity of pancreatic supplements.

Correlation of in vitro and in vivo methodology for evaluation of antacids.

The rate and extent of acid consumption of an antacid suspension and tablet were evaluated by in vitro and in vivo techniques. Four different test procedures were used to estimate in vitro antacid reactivity. In vivo effects were determined in the fasted and postcibal states in normal human subjects by a radiotelemetry procedure. The duration of elevation of intragastric pH greater than 3 was in agreement with in vitro estimates of total acid consumption of the antacid. There was also good correlation between onset, extent, and duration of in vivo antacid activity and a modified in vitro Beekman antacid test procedure. There was no significant difference in antacid activity of the tablet or suspension in either in vitro or in vivo test procedures. A wide variation in antacid activity was observed between subjects and also in the fasted versus postcibal states. These studies emphasize the requirements for standardization of antacid products by comparactive in vitro and in vivo evaluations to facilitate individualized dose titration of the antacid in each patient and correlation of the acid secretion rate in various types of GI disease with the antacid dose.

Time Course and Dose Dependence of Antacid Effect on Urine pH

Daily administration of a proprietary magnesium and aluminum hydroxides suspension, 15ml four times a day, to normal adult volunteers resulted in a statistically significant increase in urine pH on the 1st day of treatment. The urine pH's on the 2nd and subsequent days of treatment were statistically significantly higher than on the 1st day. A 7.5‐ml dose of the antacid suspension, taken four times a day, had only a small and not statistically significant effect on urine pH, while 30ml four times a day increased urine pH by approximately the same magnitude as the 15‐ml doses. The effect of the antacid on urine pH persisted for at least 1 day after discontinuation of dosing.

Enhancing Fluidity of Concentrated Antacid Suspensions

Highly concentrated antacid suspensions can be fluidized by adding a colloidal polyelectrolyte to alter the charge on antacid particles from positive to negative. A deflocculated state is assumed to exist in such preparations, as supported by electrophoretic and viscometric analyses. When viscosity is directly correlated with the ζ-potential, viscometry becomes particularly useful in confirming that the suspension has been maximally fluidized.

Pharmacology and clinical use of antacids

The pharmacology of antacids, with particular reference to their clinical use in treating acid-peptic disease, is discussed. Liquid antacid suspension should be given at least as often as one hour after each meal and at bedtime. Inthe treatment of the acute phase of acid-peptic disease, hourly antacid is recommended. The dose should be planned in terms of milliequivalents of acid neutralizing capacity and should be adjusted according to the type of disease under treatment. All antacids have side effects, the most serious of which are metabolic. In clinical terms, the harmful sustemicside effects of calcium carbonate and sodium bicarbonate outweigh their benefit as neutralizing agents; they should rarely be employed in the treatment of acid-peptic disease. The more common antacid side effects of diarrhea (magnesium hydroxide) and constipation (aluminum hydroxide) are best managed by appropriately alternating the agents or by using one of the various antacid mixtures.

Effect of Antacid on Absorption of Enteric-Coated Aspirin

To the Editor.— Modification of the gastrointestinal absorption of one drug by another may be an important factor in patients receiving multiple drug therapy, especially with the increasing use of over-the-counter medications. We report the influence of administration of antacids on the release of aspirin from an entericcoated formulation. Enteric-coated aspirin (Ecotrin) was administered to six healthy subjects (aged 21 to 32 years) with and without coadministration of a magnesium and aluminum hydroxide oral suspension (Maalox) in a crossover manner. At least one week separated each study. After an overnight fast and one hour prior to the administration of the aspirin, 15 ml of antacid suspension was taken with 85 ml of water. At the time of aspirin administration, 15 ml of antacid suspension was again administered with 85 ml ofwater. The control studies consisted of administration of 100 ml of water one hour prior to and concomitantly with

Intragastric pH Evaluation with Radiotelemetry

Jóhannesson, E., Magnusson, P.-O., Sjöberg, N.-O. & Skov-Jensen, A. 1973. Intragastric pH Evaluation with Radiotelemetry. Scand. J. Gastroent. 8, 65-69.Different techniques have been used to study the effect of drugs influencing gastric pH. Still, methods for direct measurement of hydrogen ion concentrations in vivo have required some form of intubation; therefore there are certain limitations: the patients suffer considerable discomfort, and there is also a risk that the measuring equipment per se by irritating the gastric mucosa may induce gastric secretion or cause regurgitations from the duodenum. The acid-neutralizing effect of an antacid suspension has been studied in vivo with the Heidelberg capsule to give the outlines of some methodological aspects relating to this radiotelemetrical technique.

The effect of combined antacid-anticholinergic treatment on the intragastric pH in peptic ulcer disease.

The effect of antacid suspensions and supplementary anticholinergic treatment has been tested by the intragastric pH method in 14 cases of peptic ulcer disease. Common antacids do not usually influence the intragastric pH for more than 5-10 minutes in states of hypersecretion. Antacid suspensions tend to give a more prolonged effect on pH. The combined action of antacid suspensions and anticholinergic substances has been carefully studied in strictly controlled experiments. When these patients were treated basically with anticholinergic drugs even small amounts of antacid suspensions caused a satisfactory and prolonged increase of intragastric pH.

Sorbitol and mannitol: Chemical Industries, 38, 57.

This chapter discusses the description, methods of preparation, physical properties, excipient studies, stability, and methods of analysis of sorbitol. Sorbitol is an odorless powder that is white or almost colorless. Various grades based on particle size are available, and it is obtained in various forms such as flakes, granules, pellets, or powder. Sorbitol is a hexahydric alcohol that is isomeric with mannitol. It has been described as a humectant, plasticizer, sweetening agent, and tablet and capsule diluent. It is used extensively in the pharmaceutical, cosmetics, and food industries, because it has a sweet taste and approximately 50–60% the sweetness of sucrose. In pharmaceutical applications, sorbitol is used as a tablet diluent in wet granulation or dry compression formulations. It is commonly used in chewable tablets because of its sweet taste, and it is used as a plasticizer for gelatin in capsule formulations. Sorbitol is utilized in sugar-free liquid preparations and as a stabilizer for drug, vitamin, and antacid suspensions. When it is used in syrups, crystallization around bottle caps is prevented. Sorbitol has also been used in injectable and topical products, and has a therapeutic use as an osmotic laxative.