US3208906A - Glycine-stabilized aluminum hydroxidemagnesium compound codried gel antacids and process of making the same - Google Patents

Description

Sept. 28, 1965 s. M. BEEKMAN 3,208,906

GLYCINE-STABILIZED ALUMINUM HYDROXIDE-MAGNESIUM COMPOUND CODRIED GEL ANTACIDS AND PROCESS OF MAKING THE SAME Filed June 6, 1963 3 Sheets-Sheet l ATOMIC RATIO AI Mg 2=| 10 CODE EXAMPLE! DRY BLEND lac 4 k O 40 80 I20 I60 200 In ATOMIC RATIO Al=Mg=l=l zo CODE H EXAMPLE 2 DRY BLEND 2 Grn I v 1 0 4O 80 I20 I60 200 TIME IN MINUTES Sept. 28, 1965 M. BEEKMAN 3,

GLYCINE-STABILIZED ALUMINUM HYDROXIDE-MAGNESIUM COMPOUND CODRIED GEL ANTACIDS AND PROCESS OF MAKING THE SAME Filed June 6, 1963 5 Sheets-Sheet 2 I" ATOMIC RATIO y" A|:M =o.5=| I Mi I EXAMPLE 3 I DRY BLEND I l I50 I F762 3 Q I I I I I I O 40 80 I20 I60 200 TIME IN MINUTES 9.0 h I I I I I T ATOMIC RATIO AI=Mg=2=I A I M CONTROL A f DRY BLEND I I I Gm\ I Grn 2 Gm I I I I I I I I I O 40 80 I20 I60 200 TIME IN MINUTES Sept. 28, 1965 s. M. BEEKMAN 3,208,906

GLYCINE-STABILIZED ALUMINUM HYDROXIDE-MAGNESIUM COMPOUND CODRIED GEL ANTACIDS AND PROCESS OF MAKING THE SAME Filed June 6, 1963 3 Sheets-Sheet 3 9.0 I I I l I I I j ATOMIC RATIO l Al=Mg=I l 7' 7.0 -I I CODE II CONTROL 5 l H DRY BLEND o 40 so I20 I60 200 TIME IN MINUTES h A ATOMIC RATIO i I CONTROL 0 r DRY BLEND o 40 80 I20 I60 200 TIME IN MINUTES United States Patent Office 3 208 906 GLYCINE-STABILIZEli AIlUMmUM HYDROXHDE- MAGNESIUM COMPOUND CODRIED GEL ANT- ACIDS AND PROCESS OF MAKHNG THE SAME Stewart M. lleelcman, Chatham, NHL, assignor, by mesne assignments, to Armour Pharmaceutical Company, Chicago, Ill., a corporation of Delaware Filed June 6, 1963, Scr. No. 286,074 14 Claims. (Cl. 16755) This invention relates to antacid compositions, and, more particularly, to antacid compositions comprising aluminum hydroxide and magnesium carbonate, hydroxide or silicate, mixed as wet gels and codried, and stabilized by the addition of glycine, and to a process of preparing the same.

Antacid preparations are now quite generally employed for the treatment of peptic ulcers, gastric hyperacidity and dyspepsia. Gwilt, Livingstone and Robertson in the Journal of Pharmacy and Pharmacology, X, No. 12,770- 775 (1958), describe the characteristics of an ideal antacid. They point out that it should show its maximum neutralizing effect in the shortest possible time, that it should neutralize an adequate amount of gastric hydrochloric acid and maintain its action during the normal period of gastric digestion, that any excess however great beyond the amount required to neutralize free gastric acid should not cause alkalization, that it should raise the pH of the gastric contents to a level at which pepsin activity is reduced significantly but not totally inhibited, that adequate and repeated doses should be palatable to the hyperacid patient, and that its use should not lead to laxative, constipating or other side effects such as gastric irritation. In addition to these factors the antacid composition should be inexpensive and it should not deteriorate significantly in any respect on aging. These workers summarize the various statements in the literature as to the pH ranges desirable for the ideal antacid, and conclude that a pH within the range from about 3.5 to about 4.5 is apparently the optimum to ensure adequate relief from hyperacidity, particularly if an ulcer site is present, and at the same time permits sufficient residual pepsin activity to avoid secondary digestive disturbances.

Edwards in The Chemist and Druggist, Dec. 14, 1957, page 647, also discusses the properties of an ideal antacid, and suggests that the nearest approach to the ideal attained as of that date was wet activated alumina gel. Dr. Edwards views of the properties of the ideal antacid are in substantial agreement with those expressed by Gwilt et al.

Liquid aluminum hydroxide gel closely approaches the ideal for an antacid but its liquid form makes it inconvenient to use, especially in the case of ambulatory patients. The liquid gel is quite rapid in its action and gives a prolonged antacid effect in the optimum pH range. It is not significantly affected in its antacid properties by pepsin and it also does not significantly lose its antacid characteristics in aging. However, as Edwards and others have pointed out, it may have a mildly constipating effect which many have sought to remedy by combining it with other ingredients such as magnesium hydroxide or carbonate.

The advantages of the dried gel are obvious. However, the obvious material, dried aluminum hydroxide gel, is actually far from an ideal antacid. It exhibits a lag in its rate of reaction with stomach acids. It does not give a prolonged antacid in the optimum pH range and its antacid properties are severely affected by pepsin. Also, its antacid activity is less than that of the liquid gel, being decreased by the drying and the reduced activity decreases further with aging. These disadvantages have been noted by Gwilt et al. and other workers in this field.

Rossett and Flexner, Ann, Internal Med. 21 119 (1944) reported that mixtures of milk of magnesia (magnesium hydroxide) with aluminum hydroxide gel were more 3,208,906 Patented Sept. 28, 1965 effective gastric antacids than aluminum hydroxide alone. These conclusions were based on in vivo experiments on humans, together withextensive clinical experience. Rossett and Rice, Gastroenterology, 26 490 (1954), Morrison, Am. J. Gastro'enterology, 21 301 (1954), and Jankelson, Am. J. Dig. Dis., 14 11 (1947) reported that liquid aluminum magnesium hydroxide gels were effective for the treatment of peptic ulcer, hyperacidity, heartburn, spasticity and gastritis. However, simple mixtures of aluminum hydroxide and magnesium hydroxide dried gels have the disadvantage that they result in a high un desirable initial rise in pH, and they also show a rapid diminution in antacid activity on aging. This property is characteristic also of aluminum hydroxide dried gels.

In accordance with the invention, there is provided an antacid composition composed of a codried mixture of aluminum hydroxide and a magnesium compound selected from the group consisting of magnesium carbonate, magnesium hydroxide, and magnesium trisilicate, together with a proportion of glycine. Such compositions have a more prolonged antacid activity in the optimum pH range of from 3 to 5 than corresponding dry blends containing the same basic components in the same proportions, and they do not display a high undesirable initial rise in pH. Furthermore, the compositions of the invention are relatively stable, and retain a very high antacid activity on aging, even after two years of storage.

The aluminum hydroxide-magnesium compound codried gels in accordance with the invention approach the theoretical requirements for an ideal antacid in dried form, because they are capable of rapidly increasing the pH of gastric juice to within the optimum pH range of from 3 to 5, and maintain the, pH within the optimum range for very long periods of time, of the order of two hours and more. They do not display the initial high pH rise characteristic of the magnesium components. They are non-systemic, and do not upset the acid-base balance of the blood. They are not adversely affected by pepsin in antacid action. They are non-irritating to the gastrointestinal tract. They have a desirable, mild astringent effect, with a minimal constipating or laxative effect. They are palatable, with very little chalkiness, and rehydrate and swell in Water to provide a gelatinous, positively charged protective coating for inflamed membranes. Furthermore, they can be prepared at moderate cost, because of the process of their preparation.

The proportions of aluminum hydroxide and magnesium compound in the codried gel are quite critical in developing and maintaining a fast antacid action within the pH range of from 3 to 5. The molecular ratio is expressed herein, for simplicity, as the atomic ratio AlzMg, and this should be within the range from 2:1 to 0.25:1. Proportions of aluminum hydroxide to give an AlzMg ratio in excess of 2:1 can be used, without the disadvantageously affecting pH, but with the detriment that the composition is greatly slowed in its antacid action, so that the desired pH is not reached until a considerable time following administration, which is undesirable. The proportion of magnesium compound can exceed the AlzMg ratio of 0.25: 1, but when it does, the maximum pH following administration of the composition may rise to considerably in excess of 5, which is undesirable. Thus, the stated range represents the optimum proportions of the essential ingredients for effective and prompt antacid action.

The magnesium component can be a mixture of two or three of magnesium hydroxide, magnesium carbonate and magnesium trisilicate in any proportions. However, the total magnesium content is Within the above-stated AlzMg ratio range.

The composition can be prepared in any of several ways. The only prerequisite is that the aluminum hydroxide or aluminum hydroxy carbonate and magnesium carbonate,

'3 hydroxide or trisilicate be in hydrous, gelatinous form at the time of mixing. The components must not have been dried prior to use, i.e., they must contain a sufficient amount of the original gel water to make them moist,

The method of Holbert, Noble and Grote, J. Am. Pharm. Assn. 36 149 (1947), 37 292 (1948), Murphey, ibid. 41 361 (1952) uses a test sample of antacid added to 150 ml. of pH 1.5 hydrochloric acid containing 2 g. of pepusually at least 5%. Any available aluminum hydroxide 5 sin N.F. per liter (artificial gastric juice) at 375 C. 20 gels can be used, but the preferred gel is a highly reactive, ml. of the artificial gastric juice is withdrawn every ten freshly precipitated aluminum hydroxide containing some minutes and replaced with an equal volume of fresh gastric carbonate. Any of the available magnesium carbonates, juice. The modified test procedure used in the work rehydroxides and trisilicates can be used, provided they are ported in this and the following examples, however, was in moist gel form. A preferred magnesium hydroxide carried out by continuously introducing fresh artificial gel is a 30% magnesium hydroxide paste obtained by congastric juice and removing the antacid-gastric juice mixtrolled precipitation from pure aqueous solutions of mag V ture by overflow at the rate of 2 ml. per minute. The antnesium sulfate and sodium hydroxide followed by filtraacid effect is determined by measuring the pH of the artition, washing and mixing the washed hydrogel. ficial gastric juice during the test period, which is until the Usually, it will be convenient to employ a separately pH drops below 2.5. precipitated aluminum hydroxide and magnesium com- The method of Bachrach used was as reported by pound, but the magnesium compound may also be co-pre- Hinkel, Fisher and Tainter, J. Am. Pharm. Assn., 48 380 cipitated with the aluminum hydroxide or aluminum hy- (1959). This method consists essentially of adding didroxy carbonate from a common reaction solution, conlute hydrochloric acid to the antacid at 375 C. at such a taining hydroxyl, carbonate, silicate, magnesium and alurate as to maintain a pH of 3.5. This method gives a minum ions, as required for the desired magnesium comdirect estimate of the speed of action and total available pound, such as a mixture of sodium hydroxide, magneactivity, whereas the Holbert, Noble and Grote test prosium sulfate, and aluminum sulfate, in the case of'an alucedure demonstrates primarily the buifering effect, as minum hydroxide-magnesium hydroxide cogel. measured by pH and duration of action. In the test pro- The combined precipitates are filtered, and washed free cedure as used in this work, the acid used was 0.0875 N of soluble salts. The mixed hydrous gels are then preferhydrochloric acid, containing 2 grams of sodium chloride ably subjected to a highly intensive shear at room temper liter. perature, and then reduced to finely divided powder form, EXAMPLES 1 To 3 such as by spray drying at a temperature below th t t A series of six codried gel antacids, three controls (A, which the gels are adversely affected, or by low tempera- B and and three in accordance With e invention ture air-drying, together with line pulverizing. The gly- (Examples 2 and a P p in accordance with cine is added to the mixed gels before mililng or shearing. The following Procedure Highly reactive aluminum y- Gl ci can b dd d to h h d 1 i lid form, droxide U.S.P. and pure gelatinous magnesium hydroxide preferably finely pulverized, or in the form of an aqueous were Separately Precipitated to form Slurries- The solution, and thoroughly mixed therewith to ensure uni- 3 Slurries were Combined in the Proportions given in Table f di ib i throughout h i i Th I, filtered, and washed free of soluble salts. The mixed amount of glycine is not critical, but enough is used to hydrous gels were then Subjected to highly intensive Shear give the desired effect on stability and pH. The amount at room temperature, and reduced to finelydivided P can be within the range from 2 to 200%, preferably withder form y P Y' Y Glycine P i the range fr 15 to by weight f h hydrous 40 gram of final powder weight) was added to three of these gels, calculated without the water content so as to correcompositions at the 1hue the Shlrries were combinedspond to h fi l d i d iti i ht The resulting codried gels were then analyzed for alu- The final composition of the invention is in the form minum Oxide and magnesium Oxide, and the atomic ratio of a codried gel which in finely divided or powdered form AliMg determined from the data cbtairled- The acidis generally soft, white, smooth, tasteless and odorless, Consuming p y of each antacid composition was and which reacts readily with gastric strength acid containtermined, and is given in Table I.

TABLE I Proportions of components, relative Product analysis amount per gm. Antacid activity. acid Example No. R consuming A1(OH)3: Approximate analysis, capacity, Al(OH) 1 Mg(OH)z Glycine Mg(OH)z Atomic percent 0.1 N (mg. mg.) (mg) ratio, HCl/g.

Al:Mg

A1701 MgO 773 227 3. 4:1 2:1 39. 4 15.8 305 618 182 200 3. 4:1 2:1 31. 5 12.6 250 629 371 1. 7 :1 1:1 32.1 25. 6 310 504 296 200 1. 7:1 1:1 25. 7 20. 4 254. 459 541 0. 85:1 0. 5:1 23. 4 a7. 4 314 Example 3 367 433 200 0. 85:1 0. 5:1 18.7 30. 0 260 1 AI(OH)3 U.S.P. calculated as 51% A1203. ing pepsin. The pH of aqueous suspensions of the Stabi1 Rock salt infra red spectra (2 to 16 microns) were run ized gels in accordance with the invention is from about on C l A and Example e alummum 9 to about 96 when aluminum hydroxy carbonate is used droxide dried gel U .S.P. used as the starting material, the as the source of aluminum hydroxide. The carbonate e g hydroxlde gel used. as the Startmg content of the final mixture will be within the range from L i an crfilstanme g Nulol and l about 5 to about 12%, dependent principally upon the 3 1 122 2 z r ma an Samples run at Caplnary {method of The Spray'dned samgles have Spher' The infra red spectra showed that both Control A and ically shaped particles and are free-flowing. The tray- Example 1 were Sim 1 p e mixtures. drled and drum-rifled composltlons tend to be l l or 70 Antacid activity of the various gels was determined usflaky but can be reduced Powder pulvenemging the Holbert, Noble and Grote procedure, as de- The followlrlg P In the 0P1r110 r1 of h lrlven'wr, scribed above, and the samples were evaluated on the represent thebest m dtments of the lnventl-on. basis of one and two gram dosage levels. The results The antacid characteristics were determined by two for the three gel pairs, A and 1, B and 2, and C and 3, methods. are given in Table II.

TABLE II-PART C The Table II data, for Examples 1 to 3, is plotted in FIGURES 1 to 3, and the data for the three codried gels In each figure, for

A to C is plotted in FIGURES 4 to 6.

d at mmm ywh I g D 3 a m 1 oh. mww xfl. 0 E H m g M m h w g A We n m 0 aw l we a C 1 s h w N m m e .1 m m e e m m m E D T w e d l D e g m mhm 2 .DHCII S ww r g g m D 1 n 1 e g a e e d w 1 mmm 2 e g e. w ll 1 a 1 .Wm O X g g aA H E 1 mnT m g DtwR M mm 2. m A h m 2 OMWP A .W Cp Cm Mm g I 1 h t C E 1 e n e L mam u mB mm .maA tm IS E a T wcm H m h o t u n in m m fS n w 0 "M u n n h m 0 0 p P m e mm a S m X 0 pd E D T 55814752854 L5 5 6 6 4Am92 22 It is apparent from the data in Table II and in the figures that the codried gels of the invention with glycine (Examples 1 to 3) are in every case superior to the codried gels without 5370387316953 Li5 6 6 4 44 4-&2 2 2 glycine (Controls A to C), as well h and Without glycine (Controls D This is so despite the fa had only 80% of the antacid co The initial rise is considerabl time within which the as the dry blends wit to I).

TABLE IIPART B AlzMg ratio, 1:1

ct that Examples 1 to 3 ntent of Controls A to C. y lower, and the period of emains within the optimum is correspondingly extended.

y blend with glycine pHr d m ho 5C e mm a; w a CC V 0h u e 6 con I 3 r gels containing glycine did not initially give a pH increase lim to beyond the permissible it of 5, and the period during which the pH remained S, d g d .m r w me e m n "a m 1mg a f o a a Pm we 06 mm t 6 am m k 3 k 6 v0 0T 10 a t ey were stored in glass containers which were kept ve months. gram samples was then determined Noble and Grote test method The closed at ambient temperatures for fi antacid activity of one b and comy prepared samples.

y the Holbert pared with values obtained on freshl The results are shown in Table III.

no glycine Example No. Control B Time minutes:

' from the data in Table III that whereas ls which did not contain is apparent e ge glycine showed a loss of after five months storage,

.1 nea m wum m% um 6W mo t a ec t4 C w na a med.. m .mo m e C W I W h c IV. mnb mh n mww my 0 MP ea om C mvi. nmf ad a dw o mm mmm C hP SI manmma wi h .m See E w .mL 0 CB hm y m d w M e wn T nm m ail I mmmm l m cev 55 activity of from to In a second series of aging tests,.samples of the gels of Examples 1, 2 and 3 were stored in closed bottles at room temperature for two years, and the antacid activity then determined in accordance with the Holbert, Noble and Grote test procedure. The results are given in Table IV, on the basis of equal weights of active antacid ingredient.

TABLE IV Atomic ratio, Atomic ratio, Atomic ratio, AlzMg=2z1 Al:Mg=1:1 Al:Mg=1-.2

Example No A 1 B 2 C 3 1.5 1.5 1.5 1.5 1.5 1.5 3.1 3.9 4.0 4.1 4.5 4.1 4.3 4.3 5.0 4.5 5.8 4.4 4.4 4.7 5.4 5.1 6.0 5.1 4.2 4.6 4.4 4.8 4.8 4.7 4.0 4.4 4.3 4.5 4.5 4.5 3.9 4.2 4.1 4.4 4.3 4.4 3.8 4.0 3.2 4.2 4.1 4.3 3.1 3.9 2.5 4.1 3.2 4.1 2.7 3.9 2.3 4.0 2.7 3.9 2.5 3.7 2.2 3.8 2.4 3.7 3. 4 3. 4 2. 2 V 3. 3 3.0 3.1 2 1 3. 3 2. 7 2. 8 2. 7 2. 5 2. 6 2. 6 170 2. 5 2. 5 Time to pH 3 Sec 58 56 58 37 36 34 Time above pI-I 101 133 83 140 103 140 Time above pH 2.5, min 118' 150 98 158 116 158 The improvement in stability is evident from this data. Whereas Control A was capable of maintaining the pH above 3 only for approximately 100 minutes, Example 1 could maintain the pH above 3 for more than /2 hour longer. Similarly, Control B could maintain the pH above 3 only for approximately an hour and a half, whereas Example 2 was capable of maintaining the pH 8 EXAMPLE 4 Aluminum hydroxide-magnesium carbonate-glycine cdried gel AlzMg atomic ratio 2:120% glycine in dry product Magnesium carbonate gel-57 pounds of magnesium chloride flakes MgCl 6H O was dissolved in 250 pounds of water and filtered into a 60 gallon reactor vessel provided with a 4" turbine type agitator with speed of 800 rpm. and at 21 C. Sodium carbonate solution (16.4 B., equivalent to 11.9% Na CO 243 pounds was added to the magnesium chloride solution at 0.45 gallon per minute. The resulting slurry was filtered and washed using a plate and frame filter press at 40 p.s.i.g. The magnesium carbonate gel filter cake was analyzed and found to contain 8.5% MgO.

483 pounds of an aluminum magnesium hydroxy carbonate gel containing 9.33% A1 0 1.4% MgO, and 3.4% CO made in accordance with US. Patent No. 2,797,978, 128 pounds of a magnesium carbonate gel containing 8.5% MgO (prepared as above), 31.3 pounds of glycine and757.3 pounds water were mixed for one hour in a 150 gallon Hamilton double motion hemispherical stainless steel kettle after which the white somewhat viscous gel was pumped to a 750 gallon Haveg tank provided with a Premier HP. Duplex Dispersator and mixed for minutes additional at 3600 r.p.m. The homogeneous slurry contained 12% product solids.

1350 pounds of the above was spray-dried in a Bowen 7 foot spray dryer using a 7" CSE atomizer at 21000 rpm. under diiferent conditions. One portion was sprayed at a feed rate of 15.2 pounds a minute with in-.

let temperature of 250 F. and outlet temperature 275 F. 121 pounds of product were recovered from this portion.

above 3 for 2 hours and minutes. Control C could A 27.7 maintain the pH above 3 only for somewhat over 100 MgO 11.4 minutes, whereas Example 3 could maintain the pH at CO 20.2 3 for 2 hours and 20 minutes. Apparent density g./ml. 0.3-9 A second series of comparative antacid activity tests Screen test through 325 mesh 99.7 was carried out on Controls A to C and Examples 1 to 3, pH (4% suspension) 8,3 employing the method of Bachrach on 2 gram samples. Acid consuming capacity The test data is given in Table V, on the basis of -1 g. (ml. 0.1 N HCl/g.) 221 active antacid. Reaction velocity (Reheis) sec. 2

TABLEV Amount of acid added (1111.)

Time (minutes) Control Control Control Example Example Example A B o v 1 2 3 2=1 111 0.51. 2:1 1:1 0.51

It is apparent from the data of this test that the acid consuming capacity, the total available activity and the speed of action are considerably greater for the compositions of the invention, Examples 1 to 3, as compared to the codried control gels without glycine. The total acid consumed per hour is 12% to 37% greater.

The in vitro antacid evaluation test by the modified 70 Holbert, Noble. and Grote test after. 14 months of aging gave the following results:

9 v EXAMPLE 5 Aluminum hydroxide-magnesium hydroxide-magnesium trisilicate glycine codried gel containing equal weights of aluminum hydroxide U.S.P. dried gel (51 A1 magnesium hydroxide N.F. (98% Mg(OH) magnesium trisilicate U.S.P. (22% MgO) and 20% glycine 136.0 pounds of aluminum hydroxide compressed gel Reheis Type F-1000 containing 10.0% A1 0 84.5 pounds of magnesium hydroxide gel (31% Mg(OH) 26.7 pounds magnesium trisilicate U.S.P. powder (super bulky grade), 19.3 pounds of glycine and 4.00 pounds of water were mixed for one hour in a Hamilton double motion 150 gallon stainless steel kettle. The slurry was pumped to a second tank and agitated with a high shear mixer for an additional 15 minutes. The resulting homogeneous gel containing 159% product solids was spraydried in a Bowen 7 foot dryer using a feed rate of 15.5 pounds per minute, a 7" CSE atomizer at 21000 r.p.m., inlet temperature of 750 F. and outlet temperature of 275 F.

The finely-divided white powder retained only 1% on a 45 micron screen. The analysis showed that it contained 13.5% A1 0 24% MgO, 13.3% SiO 5.8% C0 The acid consuming capacity was 197 ml. 0.1 N HCl per gram, which is close to the theoretical value of 199. The AlzMg atomic ratio was 0.28: 1.00.

The antacid properties were determined by the in vitro method of Holbert, Noble and Grote on the basis of 1.0 gram sample. The results are as follows:

TABLEVIII Time, (minutes): pH 0 1.5 l 3.9 2 3.9 4.0 10 4.1 4.2 4.2 4.1 4.1 4.0 3.9 3.9 3.6 3.4 3.1 2.8 Time to pH 3.0, sec 28 Time above pH 3.0 112 Time above pH 2.5

The Bachrach method was also used to determine the speed of reaction and total antacid activity. The following data shows the number of milliliters of 0.0875 N HCl per 1.0 gram active ingredient as a function of time.

TABLE 1X Time, (minutes): Vol., 0.0875 N HCl, ml. 0 0 5 105 10 159 15 214 20 254 25 268 30 271 40 273 50 273 60 273 As previously indicated, the compositions in accordance with the invention are useful in the treatment of internal conditions where excess acidity is to be encountered, such as gastric acidity in the stomach, in, for

example, the treatment of gastric and peptic ulcers. For this purpose, the dry compositions are readily administered in the form of slurries, or as dry powders or tablets, with an excipient, if desired, which are suitably taken orally or added to a liquid carrier such as water.

It is usualy most convenient to prepare the compositions in tablet form, and since the compositions are relatively inert and store well, tablets are easily prepared by conventional procedures. The composition can be tabletted as such, or with an excipient mixture of conventional type. The following is a typical tablet formulation:

Antacid composition grams 32000 Lactose do 62620 Starch do 6800 Monosodium phosphate do 1130 Stearic acid do 1130 The quantity indicated is suflicient to prepare approximately 48,000 tablets, containing 10 grains each of the antacid composition.

The following is claimed:

1. An antacid composition capable as determined by the modified Holbert, Noble and Grote test method of maintaining the pH of artificial gastric juice within the range from about 3 to about 5 for at least one hour, comprising the codried combination of a hydrous gelatinous aluminum hydroxide material selected from the group consisting of aluminum hydroxide and aluminum hydroxy carbonate and a gelatinous magnesium compound selected from the group consisting of magnesium carbonate, magnesium hydroxide and magnesium trisilicate in an atomic ratio AlzMg Within the range from about 2:1 to about 0.25:1, and from 2 to 200% by weight of the hydrous gels, calculated sans water, of glycine to increase the stability of the composition to aging.

2. An antacid composition in accordance with claim 1 in which the aluminum hydroxide is a hydrous gelatinous aluminum hydroxy carbonate.

3. An antacid composition in accordance with claim 1 in which the gelatinous magnesium compound is magnesium hydroxide.

4. An antacid composition in accordance with claim 1 in which the gelatinous magnesium compound is magnesium carbonate.

5. An antacid composition in accordance with claim 1 in which the gelatinous magnesium compound is magnesium trisilicate.

6. An antacid tablet comprising a composition in accordance with claim 1 and an excipient.

7. A process for preparing an antacid composition capable as determined by the modified Holbert, Noble and Grote test method of maintaining the pH of artificial gastric juice within the range from about 3 to about 5 for at least one hour, which comprises mixing a moist hydrous gelatinous aluminum material selected from the group consisting of aluminum hydroxide and aluminum hydroxy carbonate and a moist gelatinous magnesium compound selected from the group consisting of magnesium carbonate, magnesium hydroxide and magnesium trisilicate in an atomic ratio AlzMg within the range from about 2:1 to about 0.25:1 and from 2 to 200% by weight of the hydrous gels, calculated sans water, of glycine to increase the stability of the composition to aging, and drying the resulting mixture.

8. A process in accordance aluminum hydroxide bonate gel.

9. A process in accordance with claim 7 in which the aluminum hydroxide gel and magnesium hydroxide gel are formed in situ by coprecipitation from a common solution.

with claim 7 in which the gel is an aluminum hydroxy car- 10. A process in accordance with claim 7 in which the gelatinous magnesium compound is magnesium carbonate.

11. A process in accordance with claim 7 in which the gelatinous magnesium compound is magnesium hydroxide.

12. A process in accordance with claim 7 in which the gelatinous magnesium compound is magnesium trisilicate.

13. An antacid composing according to claim 1 containing, by weight of the hydrous gels and calculated sans water, from 15 to 35 percent glycine.

12.v 14. A process according to claim 7 in which is added, by Weight of the hydrous gels and calculated sans water, from 15 to 35 percent glycine.

References Cited by the Examiner JULIAN S. LEVITT, Primary Examiner. FRANK CACCIAPAGLIA, IR., Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent N00 3,208,906 September 28, 1965 Stewart MC Beekman It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below Column 10, line 58, after "aluminum" insert hydroxide Signed and sealed this 19th day of July 1966 n (SEAL) Attest:

ERNEST W. SWIDER EDWARD J. BRENNER Attesting Officer Commissioner of Patents

Claims (1)

1. AN ANTACID COMPOSITION CAPABLE AS DETERMINED BY THE MODIFIED HOLBERT, NOBLE AND GROTE TEST METHOD MAINTAINING THE PH OF ARTIFICIAL GASTRIC JUICE WITHIN THE RANGE FROM ABOUT 3 TO ABOUT 5 FOR AT LEAST ONE HOUR, COMPRISING THE CODRIED COMBINATION OF A HYDROUS GELATINOUS ALUMINUM HYDROXIDE MATERIAL SELECTED FROM THE GROUP CONSISTING OF ALUMINUM HYDROXIDE AND ALUMINUM HYDROXY CARBONATE AND A GELATINOUS MAGNESIUM COMPOUND SELECTED FROM THE GROUP CONSISTING OF MAGNESIUM CARBONATE, MAGNESIUM HYDROXIDE AND MAGNESIUM TRISILICATE IN AN ATOMIC RATIO AL:MG WITHIN THE RANGE FROM ABOUT 2:1 TO ABOUT 0.25:1, AND FROM 2 TO 200% BY WEIGHT OF THE HYDROUS GELS, CALCULATED SANS WATER, OF GLYCINE TO INCREASE THE STABILITY OF THE COMPOSITION TO AGING.

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