Characterization of Antacid Compounds Containing Both Aluminum and Magnesium. I. Crystalline Powders

The composition and antacid properties of 10 samples of crystalline antacids containing both aluminum and magnesium were determined. The composition was found to vary significantly, even within the same type of antacid. For example, three of four hydrotalcite samples exhibit evidence of the presence of a minor phase of amorphous aluminum hydroxide. Almagate and almagcit, which are claimed to be unique compounds, were found to be composed of hydrotalcite, magnesium hydroxycarbonate, and/or magnesium carbonate and amorphous aluminum hydroxide. All three magaldrate samples examined contained a minor phase of amorphous aluminum hydroxide. All 10 samples passed the preliminary antacid test and had high acid neutralizing capacities. However, the rate of acid neutralization varied between samples. In some cases the rate of acid neutralization at a dose of 400 mg was too slow to raise the pH to 3.0 as required by the Rossett–Rice test.     

The effect of an antacid on the bioavailability of indomethacin

Summary The biovailability of indomethacin from two indomethacin-antacid (aluminum hydroxide magnesium carbonate and magnesium hydroxide) combinations was compared with the bioavailability of oral indomethacin. Relative bioavailability was estimated by three methods: comparison of plasma concentrations at various times, comparison of areas under plasma concentration time curves, and comparison of the amount of drug excreted unchanged in the urine. A double blind three-way crossover study was conducted in twelve healthy volunteers. The combination with the slightly smaller amount of antacid (preparation A) showed significantly decreased bioavailability by all three methods in comparison with indomethacin alone (preparation C). The combination with the larger amount of antacid (preparation B) was also less bioavailable than preparation C. This effect was significant only for the comparison of areas under curves and not for plasma levels, although the mean plasma levels produced by preparation B at all times were lower than those for preparation C. These findings suggest that aluminum hydroxide magnesium carbonate and magnesium hydroxide decrease the bioavailability of indomethacin.A preliminary report has been published as an abstract in Clin. Res.23, 219, 1975     

pH-stat titration of aluminum hydroxide gel.

The pH-stat titration of aluminum hydroxide gel was evaluated and was affected by pH, temperature, concentration, and ionic strength. Control of these parameters resulted in a highly sensitive and reproducible in vitro antacid test. The utility of the pH-stat test was illustrated by monitoring the aging of several carbonate-containing aluminum hydroxide gels and by comparing the antacid properties as measured by the pH-stat titration, the acid-consuming capacity, the Rossett-Rice test, and the test proposed by the food and Drug Administration Drug Evaluation Panel. The pH-stat titration also was useful for relatively nonreactive aluminum hydroxide gels. The use of sodium fluoride as the reaction medium extended the capability of the pH-stat titration to monitor the aging of chloride-containing gels. The pH-stat titrigram was interpreted in terms of a previously published polymer model of the structure of a chloride-containing aluminum hydroxide gel. The acid reactivity of relatively nonreactive gel is believed to be due totally to the chemical neutralization of acid, because the milliequivalents of aluminum ion appearing in solution is the same as the milliequivalents of acid neutralized throughout the ph-stat titration.     

Effect of interaction of aluminum hydroxycarbonate gel and magnesium hydroxide gel on acid neutralization.

Acid neutralization by mixtures of aluminum hydroxycarbonate gel and magnesium hydroxide gel differs from the sum of the acid neutralization of each gel. Acid neutralization by magnesium hydroxide gel in the mixture is not observed until after a substantial portion of the aluminum hydroxycarbonate gel has reacted with acid, even though magnesium hydroxide gel is the faster reacting of the two gels. It is hypothesized that amorphous aluminum hydroxycarbonate forms a coating on the crystalline magnesium hydroxide particles due to electrostatic attraction. This coating prevents protons from reaching the highly reactive magnesium hydroxide until the coating is dissolved by the acid neutralization of aluminum hydroxycarbonate.     

In vitro acid reactivity of three commercial antacid tablets.

The in vitro acid reactivity of three commercial brands of aluminum and magnesium hydroxide antacid tablets was determined by two methods. A pH-stat test was used to examine the rate and extent of acid neutralization at a constant pH of 3.0. A modified Rossett-Rice test was used to record the length of time during which the antacid products maintained the pH of a simulated gastric solution at between 3.0 and 5.0. Acid neutralization by product A was faster and more complete than that by product B or C. The percent of theoretical acid consuming capacity at 30 minutes of product A (86.8%) was significantly greater than that of product B (56.1%) and product C (57.0%) tablets. The 32-minute Rosett-Rice time A was significantly longer than the 16- and 12-minute times of products B and C, respectively. The differences observed may be attributed to different reactivities of the raw materials used in the products, or formulation and processing variables. It is not known how the data relate to in vivo performance.     

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 two antacids on the bioavailability of paracetamol

Summary The effect of two antacids on the bioavailability of paracetamol has been investigated in 12 young healthy volunteers. Following a random cross over design, each subject swallowed, on three separate occasions, one weak apart, 500 mg paracetamol alone, or together with two different aluminium hydroxide, magnesium hydroxide preparations (Dimalan and Maalox). Plasma paracetamol levels were measured by HPLC. The bioavailability of paracetamol was not altered by either antacid, but they both delayed the time to peak plasma concentration (0.85 h; 1.43 h; 1.25 h, without antacid, with Dimalan and with Maalox respectively). The peak plasma concentration was not affected by concurrent antacid administration.     

Dissolution characteristics of pH-dependent antacid granules agglomerated in high speed agitation type granulator

Antacid granules were prepared by agglomeration and powder coating method in high speed agitation type granulator. The compositions of the test antacids were sodium bicarbonate and magnesium carbonate and a coating material was powder of polyvinylacetal diethylaminoacetate (AEA) and an additive material was talc powder. The dissolution characteristics of base from the antacid granules were investigated to evaluate neutralization capacity of hydrochloric acid and timed-release properties of the antacid granules. From the examination on the dissolution profile of base and neutralization behavior, the following results were obtained: The prepared granules showed a pH-dependent dissolution pattern of a base. The dissolution profile of a base was varied with addition of talc powder as well as coating amount of AEA. The relationship between the ratio of dissolution retarded time for 20% and 10% AEA coated granules θ₂₀/θ₁₀ and the diameter reduction of the granules was explained by the rate process of neutralization of hydrochloric acid.     

Kinetics of acid neutralization by aluminum hydroxide gel.

The rate of acid neutralization by an aluminum hydroxide gel prepared by the reaction of aluminum chloride solution and strong ammonia solution was studied. The decrease in acid-consuming capacity during aging as measured by the USP test is due to a decrease in the rate of reaction rather than to a decrease in equilibrium reactivity. The reactivity profile has three phases, which are shown to be related to the structure of the gel. The rate of loss of reactivity is directly related to the extent of washing.     

氢氧化铝片的物理结构和药物性能的研究

本文研究了制片压力对氢氧化铝片(包括直接压缩的原粉片)的物理结构和药物性能的影响。测定了样品的比表面、表观密度、孔隙率、平均孔半径、硬度、崩解度和制酸力,并对实验结果进行了讨论。     

Spectrophotometric and chromatographic determination of omeprazole in pharmaceutical formulations

The purpose of this study was to determine the stability of the pH sensitive drug, omeprazole, within different solid oral pharmaceutical formulations and to determine whether the addition of antacid and surfactant agents, at varying concentrations, influenced drug stability and release. Spectrophotometric and chromatographic techniques were used for evaluation purposes, giving good results concerning linearity, precision and specificity within the range of concentrations used in this study. However, the results show that the degradation products of omeprazole interfere with spectrophotometric evaluation, making this technique insufficiently selective for omeprazole. On the other hand, liquid chromotography proved to be more sensitive, accurate and precise. Additionally, in an attempt to improve the administration form of the drug, an extemporaneous suspension was designed, which after evaluation proved to be a satisfactory administration vehicle. The best formulation of omeprazole studied is: omeprazole: 0.5%; corn starch 34.2%; aluminum hydroxide 26%; magnesium hydroxide 13%; simple syrup 24.8%; SDS 1%.     

Studies on the in vitro interaction of D-penicillamine with antacids

Interactions of D-penicillamine with various antacids (aluminum hydroxide-magnesium hydroxide, AH-MH; aluminum hydroxide-calcium carbonate, AH-CC; dihydroxy sodium aluminum carbonate, DSAC; aluminum hydroxide, AH) were studied in vitro. Only a small binding to AH-MH (29.2 +/- 7.2 mumol/g antacid) and AH (13.6 +/- 4.0 mumol/g antacid) and no adsorption at all to AH-CC and DSAC were observed. Bile salts and bicarbonate as well as the pH did not influence binding. Although extrapolations from in vitro studies to in vivo conditions are hazardous, clinically relevant interactions of D-penicillamine with antacids in patients ingesting both drugs in the usual dose range simultaneously appear unlikely.     

Effect of antacid suspension on the pharmacokinetics of ibuprofen

The effect of antacid administration on the pharmacokinetics of ibuprofen was evaluated in a randomized, crossover study of eight healthy volunteers. Doses of 62 mL of aluminum and magnesium hydroxide suspension and single doses of ibuprofen 400 mg were used. Subjects received each of the following treatments at one-week intervals: ibuprofen alone; ibuprofen administered concurrently with one dose of antacid; antacid administered one hour after the ibuprofen dose; and antacid administered concurrently with the ibuprofen dose, plus three more antacid doses given every five hours. Blood samples were taken at various time intervals up to 24 hours after the ibuprofen dose. Serum samples were assayed for ibuprofen content using high-performance liquid chromatography. Values for AUC, Cmax, tmax, and k were not significantly different among treatment groups. The ranges of mean (+/- S.D.) values were 113.97 +/- 21.5 to 127.53 +/- 29.3 micrograms.hr/mL for AUC, 35.30 +/- 6.40 to 41.00 +/- 10.00 micrograms/mL for Cmax, 0.95 +/- 0.30 to 1.28 +/- 0.54 hr for tmax, and 0.346 +/- 0.026 to 0.388 +/- 0.040 hr-1 for k. For the doses used, concurrent administration of aluminum and magnesium hydroxide suspension and ibuprofen does not alter ibuprofen pharmacokinetics.     

Effect of antacid on the bioavailabiity of lithium carbonate

The effect of an antacid on the bioavailability of lithium carbonate was determined in six healthy men in a crossover study. The volunteers were given single 300-mg doses of lithium carbonate alone and with 30 ml of an antacid containing aluminum and magnesium hydroxides with simethicone. Blood samples were collected at various times for 0-24 hours after each dose. The plasma samples were analyzed for lithium using a spectrophotometer, and bioavailability variables were calculated from plasma lithium concentration-time curves. There were no significant differences in peak plasma lithium concentration, time to peak concentration, area under the concentration-time curve from 0 to 24 hours, first-order absorption rate constant, and first-order elimination rate constant between the two treatments. Concurrent administration of antacids and lithium carbonate should not affect lithium blood concentrations.     

抗酸药研究进展

综述了传统抗酸剂与一类铝镁复合物新型抗酸剂。指出新型抗酸剂具有温和、持久的抗酸性能 ,在消化溃疡的治疗中疗效确切 ,不良反应小 ,是一种值得研究开发的新型抗酸药     

Antacids and Sotalol Absorption

Abstract: The effect of concurrent administration of antacids on the relative bioavailability of sotalol has been examined in five healthy volunteers. Each subject received an oral 160 mg dose after an overnight fast in four different experimental schedules. Venous blood samples were drawn 1,2,3,4,5,6,7,8,12,24, and 32 hrs after the drug administration, and sotalol concentrations were determined fluorometrically. The results show that concurrent administration of calcium carbonate or aluminium hydroxide with sotalol has negligible pharmacokinetic consequences. The adsorption of sotalol onto magnesium hydroxide leads to somewhat decreased biovailability but in long term use the phenomenon is not likely to be of clinical importance.     

Interactions between ciprofloxacin and antacids--dissolution and adsorption studies

Ciprofloxacin is a fluorinated quinolone antibacterial agent extensively used against both Gram-positive and Gram-negative microorganisms. In certain polytherapy programs, ciprofloxacin can be administered with some antacids that could modify its dissolution rate and reduce its absorption leading to therapeutic failure. The aim of this study was to evaluate the influence of some antacids on the availability of ciprofloxacin. The release of ciprofloxacin from tablets in the presence of antacids, such as sodium bicarbonate, calcium hydroxide, calcium carbonate, aluminum hydroxide, magnesium hydroxide, magnesium carbonate, magnesium trisilicate and magaldrate was studied on BP 2002 dissolution test apparatus. These studies were carried out in simulated gastric and intestinal juices for 3 hours at 37 degrees C. The results confirmed that the dissolution rate of tablets was markedly retarded in the presence of all the antacids studied. Magaldrate and calcium carbonate in simulated gastric juice exhibited relatively higher adsorption capacities, as did magnesium trisilicate and calcium hydroxide in simulated intestinal juice.     

Action of hydrochloric acid on aluminum hydroxide-magnesium hydroxide gels and magaldrate: 27Al NMR and pH-stat studies

Neutralization of mixtures of aluminum hydroxide-magnesium hydroxide gels and of magaldrate by hydrochloric acid were studied by 27Al NMR under conditions of both equilibrium and kinetic control. Under conditions where equilibrium has been attained, an aluminum NMR signal is detectable for suspensions of the mixed gels and magaldrate only after enough acid has been added to exhaust the acid-neutralizing capacity of the magnesium hydroxide. Mixed gels seem to form several soluble aluminum-containing species as neutralization proceeds. Under the conditions of the modified Beekman neutralization procedure, in which the species concentrations reflect neutralization kinetics, mixed gels show a sharp burst of the hexaaquoaluminum cation as acid is added followed by a slow loss of that cation from solution and an accompanying slow rise in pH. Magaldrate shows a steady increase in the hexaaquoaluminum cation with added acid. Differences between magaldrate and mixed gels are also apparent in pH-stat titrations in which magaldrate displays a biphasic response, contrasting to the two burst phases with an intervening lag phase observed for mixed gels. The results of the 27Al NMR and pH-stat titrations are consistent with the hypotheses that magaldrate is a homogeneous substance with a hydrotalcite-like structure and that mixed gels consist of a magnesium hydroxide core surrounded by aluminum hydroxide.     

The effects of antacid and propantheline on the absorption of oral ranitidine

The effects of propantheline bromide and an aluminum hydroxide/magnesium hydroxide suspension on absorption of ranitidine were evaluated in 12 healthy volunteers according to a Latin square design. Ranitidine 150 mg was administered alone, with 30 ml antacid or preceded by 15 mg propantheline. Ten serum samples were obtained over 12 hours during each treatment period for measurement of ranitidine concentration. The antacid had no significant effect on ranitidine absorption, but propantheline increased the relative bioavailability of ranitidine by 22%. In addition, there was a trend, although not statistically significant, for propantheline to increase the maximum ranitidine serum concentration and the time to maximum serum concentration. Ranitidine can be administered concomitantly with the evaluated doses of antacid and propantheline without a clinically significant alteration in its absorption.     

Effect of chloroquine adsorption on acid reactivity of magnesium trisilicate.

Due to the adsorption of chloroquine by magnesium trisilicate, both the BP acid absorption test and the rate of hydrochloric acid uptake, as monitored by pH measurements, were significantly reduced. This reduction was dependent on the amount of chloroquine adsorbed, since multilayer adsorption produced relatively more suppressive effects than did monolayer adsorption. The presence of adsorbed chloroquine also decreased the amounts of magnesium released in an acid medium. The inhibition of the antacid property due to chloroquine adsorption may be attributed to the occupation of the reactive sites of the antacid surface by chloroquine and to a reduction of the surface of the antacid due to flocculation of the particles.