Magnesium Trisilicate Research Articles

Siliceous deposits in human urinary calculi--an E. M. study.

Silica calculi in man are extremely rare; only 12 cases have been reported. In an electron microscopic study of human urinary stones, siliceous deposits were encountered in three out of 180 stones as a discrete component of stones. There were no histories of magnesium trisilicate administration in these cases. Morphology of the deposits was distinctive from any other components of the stones and bore some resemblance to animal silica calculi. Siliceous deposits in human urinary stones appear to be more common than generally recognized.

Use of Cimetidine as an Oral Antacid in Obstetric Anesthesia

The H2-receptor antagonist, cimetidine, was used instead of magnesium trisilicate BPC as routine antacid therapy before both elective and emergency obstetric anesthesia. Two trials of its efficacy in increasing intragastric pH and decreasing the volume of gastric contents in parturients are reported. In the first trial, 400 mg of cimetidine given orally to patients being delivered by elective cesarean section effectively decreased gastric acidity, providing induction of anesthesia occurred 90-150 min after its administration. Of 62 patients requiring emergency anesthesia during active labor and who had been treated with 200 mg of cimetidine orally at 2-h intervals, 80% had gastric contents with a pH higher than 2.5. Failure to decrease gastric acidity to this level was mainly due to anesthesia being required within 60 min of the loading dose, but it also was considered that inaccurate timing of repeat doses and possibly delay in uptake due to gastric stasis by narcotic analgesia played a part. In trial 2 the same cimetidine regimen plus a 15-ml oral dose of 0.3 M sodium citrate given 10 min before induction of anesthesia was studied. All 72 women delivered by elective cesarean section had a low volume of gastric contents with pH greater than 2.5. Only 4% of 135 patients requiring emergency anesthesia had gastric aspirates the pH of which was less than 2.5. The volume (97 +/- 8.4 ml) of gastric contents removed from the latter patients were considered to still pose a hazard at induction of general anesthesia. No maternal or infant side effects related to cimetidine therapy were noted.

Effects of Glycopyrrolate and Atropine Combined with Antacid on Gastric Acidity

Glycopyrrolate, atropine or saline were administered i.v. with oral magnesium trisilicate 1 h before induction of anaesthesia to patients about to undergo Caesarean section. Both anticholinergics greatly reduced gastric acidity. It is suggested that glycopyrrolate should be used in combination with antacid therapy before obstetric anaesthesia and puerperal tubal ligation because of its prolonged duration of action, effect on gastric secretion and failure to cross the placental barrier.

The adsorption of esters of p-hydroxybenzoic acid by magnesium trisilicate

The adsorption of esters of p-hydroxybenzoic acid to magnesium trisilicate and kaolin was examined. Adsorption isotherms at pH 8.0 for 4 esters were linear at low concentration. Adsorption increased with increasing ester chain length. Adsorption was strongly influenced by pH, since the amount of ester adsorbed decreased with increasing pH. Further studies showed that only the non-ionized compound was adsorbed, and this process was Langmuirian. In fact a Langmuirian plot of combined data from the four esters investigated showed that adsorption was independent of the molecular weight and hence the hydrophobicity of the compound. These results suggest that adsorption of the non-ionized compound is a function of the hydroxybenzoate rather than the ester side-chain. In contrast, esters of p-hydroxybenzoic acid were not adsorbed by kaolin.

The effect of activated dimethicone, other antacid constituents, and kaolin on the absorption of propranolol.

A study was made of the effect of 6 commonly used gastrointestinal preparations on the absorption of propranolol using an in vitro experimental model. The constituents examined were activated dimethicone, aluminium hydroxide gel, bismuth carbonate, kaolin, magnesium carbonate, and magnesium trisilicate. A slight decreased propranolol absorption was given by kaolin (-13.0%), the other components showed smaller effects ranging from -6.8% to +6.6%. None of the results were statistically significantly different from control absorption values.

SILICA STONES IN THE URINARY BLADDER

Three urinary bladder stones composed of pure silicon dioxide (silica) were found in a patient who had been taking magnesium trisilicate compound three times a day for 40 years.

Silicate nephrotoxicity in the experimental animal: the missing factor in analgesic nephropathy.

Three silicon-containing compounds (magnesium trisilicate BP, crushed quartz and crushed Arran granite) were added to the drinking water (250 mg/l) of three groups of male guinea pigs for four months. At autopsy all animals receiving magnesium trisilicate showed a focal tubulo-interstitial nephritis mainly affecting the distal nephron. Similar but less intense lesions were encountered in two animals receiving crushed quartz. No renal lesions were found in the control group or in animals receiving crushed Arran granite. The concentration of soluble silicates in drinking water, measured as elemental silicon (Si) by atomic absorption spectroscopy (AAS) was determined for twenty-eight locations in different regions of Britain. Following ingestion of magnesium trisilicate, significant increases in urinary excretion of Si were demonstrated in two healthy adults using atomic absorption spectroscopy.

EFFECTS OF GLYCOPYRROLATE AND ATROPINE COMBINED WITH ANTACID ON GASTRIC ACIDITY

Glycopyrrolate, atropine or saline were administered i.v. with oral magnesium trisilicate 1 h before induction of anaesthesia to patients about to undergo Caesarean section. Both anticholinergics greatly reduced gastric acidity. It is suggested that glycopyrrolate should be used in combination with antacid therapy before obstetric anaesthesia and puerperal tubal ligation because of its prolonged duration of action, effect on gastric secretion and failure to cross the placental barrier.

Effect of Antacids on Activity of Oral Hypoglycemics

The effect of some antacids on the dissolution and hypoglycemic activity of acetohexamide, tolazamide, and tolbutamide tablets was investigated, as was the adsorption of the three drugs onto the antacids. The dissolution rates of the three drugs in the presence of magnesium oxide, aluminum hydroxide, magnesium carbonate, and calcium carbonate increased (0.5-1hr) and then plateaued or decreased (1-3hr). Magnesium trisilicate directly suppressed the dissolution of the three drugs. The antacids reduced the hypoglycemic activity of tolbutamide in the following order: magnesium trisilicate > magnesium oxide > aluminum hydroxide > magnesium carbonate > calcium carbonate. The same order occurred for the first three antacids with acetohexamide and tolazamide. Decreased hypoglycemic activity of the drugs may have been due to their adsorption to the coadministered antacids.

Effect of antacid constituents, kaolin and calcium citrate on phenytoin absorption

The effects of 4 constituents of gastrointestinal medications and calcium citrate on the absorption of phenytoin were examined in vitro using an experimental model based on the everted segment of rat intestine. Bismuth carbonate increased phenytoin absorption by 28.2%; magnesium trisilicate reduced absorption (−6.2%) as also did light kaolin (−60.2%), activated dimethicone (−71.3%) and calcium citrate (−77.2%). The latter 3 values were significantly different from control absorption values ( P < 0.05). Agents which decrease phenytoin absorption markedly in vitro may be implicated in poor phenytoin bioavailability in vivo.

Mixing of antacids with stomach contents. Another approach to the prevention of the acid aspiration (Mendelson's) syndrome.

An investigation was carried out into the readiness with which magnesium trisilicate mixture BPC, Andursil suspension (Geigy) and 0.33 M aqueous sodium citrate mixed with gastric contents, to evaluate their suitability for use as an antacid before the induction of anaesthesia in obstetric patients. Laboratory investigations demonstrated that magnesium trisilicate and Andursil did not mix adequately with gastric contents, whereas sodium citrate mixed readily. A clinical investigation of sodium citrate revealed significant improvement in the mixing of gastric juice with the antacid if the patient was turned into the right lateral position following its administration (p < 0.05), but highly significant improvement followed a rotation through 360 degrees (p < 0.005). It was thought that these findings were caused by the division of the stomach into two sacs, a phenomenon confirmed by radiological studies and the use of a pig's stomach as a model of the human stomach.

In vitro Adsorption Studies of Cimetidine

The adsorption of cimetidine on selected pharmaceuticals including kaolin, activated charcoal, talc, and nonsystemic antacids was determined at pH 5.0 and 25°. The Langmuir and Freundlich adsorption isotherms showed that cimetidine adsorption was significant with activated charcoal, kaolin, talc, and magnesium trisilicate and was virtually nonexistent with magnesium hydroxide and aluminum hydroxide. Equations expressing the Freundlich and Langmuir adsorption isotherms were evaluated for each adsorbent. The approximate amounts of cimetidine adsorbed per gram of adsorbent were 25.6, 0.402, 0.291, and 0.343mg for charcoal, kaolin, talc, and magnesium trisilicate, respectively. These in vitro studies indicate that some cimetidine may be lost when it is administered concomitantly with pharmaceutical adsorbents.

Variation of intra-and inter-particle porosity with degree of compaction

The porosity of compacts of magnesium trisilicate has been determined by low temperature nitrogen adsorption and mercury intrusion methods. An insight into the compaction mechanism has been obtained because the total porosity of the compacts decreases rapidly as the compaction pressure is initially increased, and then becomes progressively slower. The results are in agreement with the porosity-compaction relationship put forward by Bockstiegel.

The interaction of warfarin with antacid constituents in the gut.

A study was made of the effect of 4 constituents of antacid preparations on the absorption of the coumarin derivate warfarin sodium using an in vitro experimental model. The constituents tested were activated dimethiocone (a silicone) magnesium trisilicate, bismuth carbonate and the adsorbant, kaolin. Slight decreased intestinal absorption was shown by magnesium trisilicate (19%) and bismuth carbonate (7%), the other 2 components showing no effects.

Pyrogastrone for oesophagitis

Pyrogastrone (Winthrop) is marketed to relieve symptoms and promote healing in oesophagitis. It is a palatable tablet containing 20 mg carbenoxolone sodium plus aluminium hydroxide, magnesium trisilicate, sodium bicarbonate and alginic acid. The manufacturer recommends that one tablet be chewed thrice daily after meals, with a further two tablets at bedtime. The daily dose of carbenoxolone is 100 mg (less than in the treatment of gastric ulcer) and the daily sodium ‘load’ is 13 mmol.

Effect of magnesium trisilicate on nitrofurantoin absorption.

In vitro adsorption studies revealed that for an identical initial concentration of nitrofurantoin, magnesium trisilicate exhibited the greatest adsorptive capacity with bismuth oxycarbonate, talc, kaolin, and magnesium oxide exhibiting intermediate adsorptive powers, while aluminum hydroxide and calcium carbonate exhibited low or no adsorption properties. Trials to elute the drug with acidic or alkaline solution were unsuccessful. The in vivo absorption characteristics of nitrofurantoin and nitrofurantoin-magnesium trisilicate combination were evaluated in 6 healthy males. Administration of magnesium trisilicate with nitrofurantoin reduced the rate and extent of its excretion reflecting decrease in both rate and extent of absorption. The time during which the drug concentration in the urine was above the minimum effective concentration of 32 microgram/ml was also significantly reduced after administration of the antacid.

Urinary silicon excretion by rats following oral administration of silicon compounds

The rate and extent of urinary excretion of silicon was determined in rats after oral administration of magnesium trisilicate, food-grade sodium aluminosilicate, sodium silicate or Zeolite type increased rapidly after dosing and peak excretion rates occurred within 24 hr in all test groups. Zeolite A had the most rapid urinary excretion rate (half-life, 6–8 hr) followed by magnesium trisilicate (half-life, 16–20 hr), sodium silicate (half-life, 24 hr) and sodium aluminosilicate (half-life, 38 hr). First-order excretion kinetics were followed for all four materials. When expressed as a percentage of dose the total urinary silicon excreted was roughly equal for magnesium trisilicate, sodium silicate and Zeolite A but considerably less for sodium aluminosilicate. Urine of rats dosed with sodium aluminosilicate or Zeolite A did not show any detectable increase in aluminium, indicating that the silicon that was excreted was a breakdown product of the parent molecule. Since it is known that aluminuim when administered either ip or iv is excreted in urine, this is evidence for decomposition of the test material in the gastro-intestinal tract. For all four test materials urinary silicon excretion increased with dose level. However, the magnitude of this increase (two- to eightfold) was not as great as the increase in the amount dosed (25-fold) so that the percentage of silicon excreted decreased as the dose was increased. This suggested that some process in the absorption or excretion of silicon was becoming saturated. These results are discussed with respect to the comparative safety of these four silicates.

Effect of antacids on the dissolution behavior of tetracycline and methacycline.

The effect of antacids on the dissolution behavior of tetracycline hydrochloride and methacycline hydrochloride from commercial capsules was studied. The dissolution of the tetracyclines was found to be markedly retarded by antacids such as aluminium silicate and magnesium trisilicate. An attempt was made to elucidate the mechanism of this effect. The results suggest that the effects of antacids on the dissolution may be due to the adsorption of the drugs on antacid particles as well as to the increased pH of the medium. A study was also carried out to determine the influence of stomachics using Cinnamomi Cortex as a test material. In dissolution experiments on commercial capsules, a significant dissolution inhibition by the stomachic was found.

Interaction of digoxin with activated dimethicone and other antacid constituents

A study was made of the effect of activated dimethicone on the absorption of digoxin in relation to other commonly used antacid constituents using an in vitro experimental model. Dimethicone was found not to affect the absorption of digoxin in relation to aluminium hydroxide, bismuth carbonate, light magnesium carbonate and magnesium trisilicate whose effects on the absorption of digoxin were in agreement with values reported in the literature.

Effect of Concomitant Administration of Magnesium Trisilicate on GI Absorption of Dexamethasone in Humans

The oral absorption of dexamethasone in humans was compared to its absorption when coadministered with magnesium trisilicate. The bioavailability of dexamethasone was estimated by measuring the suppressive effect of the drug on the daily excretion of endogenous steroids. Administration of 1mg of dexamethasone to six healthy male volunteers significantly decreased the urinary excretion of 11-hydroxycorticosteroids. However, the coadministration of magnesium trisilicate with dexamethasone decreased its absorption, as indicated by the increased urinary excretion of 11-hydroxycorticosteroids. The decrease in absorption was attributed to drug adsorption on the antacid surface. These results confirm previous in vitro findings.