CA1090251A - Dried amorphous antacid aluminum hydroxide gel - Google Patents
Dried amorphous antacid aluminum hydroxide gelInfo
- Publication number
- CA1090251A CA1090251A CA290,242A CA290242A CA1090251A CA 1090251 A CA1090251 A CA 1090251A CA 290242 A CA290242 A CA 290242A CA 1090251 A CA1090251 A CA 1090251A
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- Canada
- Prior art keywords
- gel
- accordance
- organic solvent
- aluminum hydroxide
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Abstract
ABSTRACT OF THE DISCLOSURE
Dried amorphous aluminum hydroxide gels having substantial acid reacting capability over an extended period of time are pre-pared by drying the gel after contacting the aqueous liquid gel with an inert organic solvent of sufficient solubility in water to replace water in the gel. The dried gel product and pharma-ceutical compositions comprising the gel are also novel.
Dried amorphous aluminum hydroxide gels having substantial acid reacting capability over an extended period of time are pre-pared by drying the gel after contacting the aqueous liquid gel with an inert organic solvent of sufficient solubility in water to replace water in the gel. The dried gel product and pharma-ceutical compositions comprising the gel are also novel.
Description
BACKGROU~D OF TI~E _VENTION
Aluminum hydroxide gel is a widely used antacid. It possesses many of the properties of an ideal antacid such as acid consuming capacity and non-absorbability. Many effective antacid fluid dosage forms currently rnarketed utilize aluminum hydroxide gel. However, when aqueous aluminum hydroxide gel is used to produce a dried gel which can be formulated into solid dosage forms, its total antacid reactivity, as well as acid reaction rate~ is decreased. Of even greater potential significance, the aging of dried aluminum hydrox-ide gel at ambient or elevated temperature results in significantlosses in antacid reactivity. An antacid preparation which is ini-tially active can become inactive over a relatively short period of time. Ilowever, the convenience of a solid antacid dosage form over a fluid dosage form is readily appreciated and makes highly desirable the development of an initially acid reactive dried aluminum hydrox-ide gel which maintains its acid reactivity for an extended period of time.
SUMMARY OF THE INVENTION
In accordance with this invention there is a process for pre-paring a dried amorphous antacid aluminum hydroxide gel which com-prises contacting an amorphous aqueous aluminum hydroxide gel with an inert nrganic solvent of sufficient solubility in water to re-place water in the gel; removing the inert organic solvent; drying the amorphous aluminum hydroxide gel to an acid reactant stable amorphous powder having substantial acid reacting capability over an extended ~eriod of time.
A further aspect of the invention is a composition which comprises a dried aluminum hydroxide gel with a surface area mini-mum of 150 m /gm. and a pH stat tso value of from about six to about twenty minutes.
Aluminum hydroxide gel is a widely used antacid. It possesses many of the properties of an ideal antacid such as acid consuming capacity and non-absorbability. Many effective antacid fluid dosage forms currently rnarketed utilize aluminum hydroxide gel. However, when aqueous aluminum hydroxide gel is used to produce a dried gel which can be formulated into solid dosage forms, its total antacid reactivity, as well as acid reaction rate~ is decreased. Of even greater potential significance, the aging of dried aluminum hydrox-ide gel at ambient or elevated temperature results in significantlosses in antacid reactivity. An antacid preparation which is ini-tially active can become inactive over a relatively short period of time. Ilowever, the convenience of a solid antacid dosage form over a fluid dosage form is readily appreciated and makes highly desirable the development of an initially acid reactive dried aluminum hydrox-ide gel which maintains its acid reactivity for an extended period of time.
SUMMARY OF THE INVENTION
In accordance with this invention there is a process for pre-paring a dried amorphous antacid aluminum hydroxide gel which com-prises contacting an amorphous aqueous aluminum hydroxide gel with an inert nrganic solvent of sufficient solubility in water to re-place water in the gel; removing the inert organic solvent; drying the amorphous aluminum hydroxide gel to an acid reactant stable amorphous powder having substantial acid reacting capability over an extended ~eriod of time.
A further aspect of the invention is a composition which comprises a dried aluminum hydroxide gel with a surface area mini-mum of 150 m /gm. and a pH stat tso value of from about six to about twenty minutes.
-2-;3~5~
A still further aspect of the invention is a pharmaceutical composition which comprises in association with a solid pharmaceu-tical carrier, a dried amorphous aluminum hydroxide gel, said gel having a minimum surface area of 150 m /gm. and a pH stat tSo value of about six to about twenty minutes.
DETAILED DESCRIPTION OF THE INVENTION
The aqueous amorphous aluminum hydroxide gel which is dried is a standard acid reactive aqueous gel which can be obtained from various manufacturers such as Chattem Chemical Company, Reheis, Barcroft, and J. T. Baker. An amorphous aqueous aluminum hydroxide gel which meets the United States Pharmacopeia l9th Revision speci-fication is preferably employed. If it is desirable to initially prepare an aqueous amorphous aluminum hydroxide gel rather than purchasing a commercially prepared gel, art-known methods for pre-paring an acid reactive gel can be employed. For example, antacid active amorphous aqueous gels are prepared through the reaction of a water soluble aluminum salt such as aluminum chloride, aluminum sulfate or the like, and a basic aqueous solution such as an alkali metal carbonate or bicarbonate solution. Although the reason is not clearly understood, gels of higher antacid activity are prepared from carbonate or bicarbonate-containing bases.
Once the aqueous gel is obtained, it is contacted with an inert organic solvent of sufficient water solubility to replace water in the gel. The term inert as used herein refers to the lack of re-activity of the organic solvent with the gel. Examples of organic solvents which can he employed in this invention are those solvents which are miscible with water, for example, methanol, ethanol, propanol, isopropol, acetone, acetaldehyde, dimethylformamide, formamide, tetrahydrofuran, 1,3-dioxane, 1,4-dioxane, pyridine and other organic solvents miscible in water. Inert organic solvents 2~
which are not miscible in water but which can be employed are higher alcohols such as butcmols and pentanols, esters such as ethyl acetate, and higher hc ~ logues thereof having one to three carbon atc~s attached to the acyl moiety; keton~s haviny four to six carbon atcms, inclusive, and the like. For convenience and ease of handling the gel, the inert organic solvent should be added to the aqueous gel in such quantities that a single liquid phase is present. By definition, a water miscible solvent will only form a single phase with water. For practical reasons, the single phase should exist for other organic solvents not miscible in water when the solvent is added in quantities up to a l:l ratio with respec-t to the volume of aqueous gel. It should be noted that c~rganic solvents may be used in mixtures for replacement of the water in the gel. For example, a 1:1 ratio, ethanol (50%~, benzenet50~):aqueous gel volume, still maintains a single phase with the aqueous gel even though benzene, aclded alone to the aqueous gel, would create two phases.
The organic solvent may be added to the gel in varlous proportions and the addition oE solvent repeated after removal as well. For preparing a dried gel with high acid reactivity as measured by the pH-stat t50 value, as well as the Rossett-Rice test, ethanol should be added to the aqueous gel at a volume of 3:1. The water and ethanol are removed by decantation, vacuum filtration, or preferably centrifugation, and the entire treatment step should be repeated twice. As a balance between cost, handling and acid reactivity, ethanol should be added to the gel at a volume ratio of 2:1, water and ethanol removed and then followed by a l:l addition of ethanol. The secondary treatment volumes of organic solvent are measured on the basis of the original gel volume.
3Q At each treatment step, the alunN num hydroxide gel is maintained " ' .
~L~ 5 1 as a moist cake. Following the final solvent treatment, the gel is dried using standard means such as spray drying, vacuum drying, forced air drying, drum drying, and the like.
The dried amorphous aluminum hydroxide gel prepared by this process has high antacid reactivity as measured by the Rossett-Rice time and the pH stat tSo time. Rossett-Rice time is the length of time a quantity of the dried gel equ;valent to 300 mgs.
of aluminum Qxide dispersed in 70 milliliters of O.lN hydrochloric acid and 30 milliliters of water at 37 C. remains at a pH between
A still further aspect of the invention is a pharmaceutical composition which comprises in association with a solid pharmaceu-tical carrier, a dried amorphous aluminum hydroxide gel, said gel having a minimum surface area of 150 m /gm. and a pH stat tSo value of about six to about twenty minutes.
DETAILED DESCRIPTION OF THE INVENTION
The aqueous amorphous aluminum hydroxide gel which is dried is a standard acid reactive aqueous gel which can be obtained from various manufacturers such as Chattem Chemical Company, Reheis, Barcroft, and J. T. Baker. An amorphous aqueous aluminum hydroxide gel which meets the United States Pharmacopeia l9th Revision speci-fication is preferably employed. If it is desirable to initially prepare an aqueous amorphous aluminum hydroxide gel rather than purchasing a commercially prepared gel, art-known methods for pre-paring an acid reactive gel can be employed. For example, antacid active amorphous aqueous gels are prepared through the reaction of a water soluble aluminum salt such as aluminum chloride, aluminum sulfate or the like, and a basic aqueous solution such as an alkali metal carbonate or bicarbonate solution. Although the reason is not clearly understood, gels of higher antacid activity are prepared from carbonate or bicarbonate-containing bases.
Once the aqueous gel is obtained, it is contacted with an inert organic solvent of sufficient water solubility to replace water in the gel. The term inert as used herein refers to the lack of re-activity of the organic solvent with the gel. Examples of organic solvents which can he employed in this invention are those solvents which are miscible with water, for example, methanol, ethanol, propanol, isopropol, acetone, acetaldehyde, dimethylformamide, formamide, tetrahydrofuran, 1,3-dioxane, 1,4-dioxane, pyridine and other organic solvents miscible in water. Inert organic solvents 2~
which are not miscible in water but which can be employed are higher alcohols such as butcmols and pentanols, esters such as ethyl acetate, and higher hc ~ logues thereof having one to three carbon atc~s attached to the acyl moiety; keton~s haviny four to six carbon atcms, inclusive, and the like. For convenience and ease of handling the gel, the inert organic solvent should be added to the aqueous gel in such quantities that a single liquid phase is present. By definition, a water miscible solvent will only form a single phase with water. For practical reasons, the single phase should exist for other organic solvents not miscible in water when the solvent is added in quantities up to a l:l ratio with respec-t to the volume of aqueous gel. It should be noted that c~rganic solvents may be used in mixtures for replacement of the water in the gel. For example, a 1:1 ratio, ethanol (50%~, benzenet50~):aqueous gel volume, still maintains a single phase with the aqueous gel even though benzene, aclded alone to the aqueous gel, would create two phases.
The organic solvent may be added to the gel in varlous proportions and the addition oE solvent repeated after removal as well. For preparing a dried gel with high acid reactivity as measured by the pH-stat t50 value, as well as the Rossett-Rice test, ethanol should be added to the aqueous gel at a volume of 3:1. The water and ethanol are removed by decantation, vacuum filtration, or preferably centrifugation, and the entire treatment step should be repeated twice. As a balance between cost, handling and acid reactivity, ethanol should be added to the gel at a volume ratio of 2:1, water and ethanol removed and then followed by a l:l addition of ethanol. The secondary treatment volumes of organic solvent are measured on the basis of the original gel volume.
3Q At each treatment step, the alunN num hydroxide gel is maintained " ' .
~L~ 5 1 as a moist cake. Following the final solvent treatment, the gel is dried using standard means such as spray drying, vacuum drying, forced air drying, drum drying, and the like.
The dried amorphous aluminum hydroxide gel prepared by this process has high antacid reactivity as measured by the Rossett-Rice time and the pH stat tSo time. Rossett-Rice time is the length of time a quantity of the dried gel equ;valent to 300 mgs.
of aluminum Qxide dispersed in 70 milliliters of O.lN hydrochloric acid and 30 milliliters of water at 37 C. remains at a pH between
3 to 5 as n.lN hydrochloric acid is added to the mixture at a rate of 4 milliliters per minute. The pH stat test is a more sensitive test of ac;d react;v;ty. Thls test measures the volume of acid required to maintain p~l at a preset value as a funct;on of time.
The t!,o ;s the time required for one-half of the antacid to be consumed. The rate of loss of antacid activity as measured by Rossett-Rice time of gels prepared after drying from water is sub-stantially greater than for gels prepared after drying from an inert organic solvent. The rate constant for loss or reactivity for gels dried from water is about 0.4~/month at 40 C. in contrast to about 0.071/month at 40 C. for gels dried from the organic solvent.
This is a significant difference wh;ch is reflected in a much greater retention of acid reactivity at room temperature by the gels of the invention. This difference illustrates the stability of the product prepared by this process over an extended period of time.
The term "extended period of time" as used in this specification and claims, indicates a period of time over which the dried gel is capable o`f neutralizing acid at such a rate and at such a pH that a ph.lrmaceu-tical composition comprising that gel would have a useful shelF life. A period of at least two years is contemplated. It is this extended antacid activity which distinguishes the amorphous 16P~ 5 1 gel prepared by the process of this invention from the gels of the art dried from water and allows the preparation of a potent antacid for therapeutic purposes.
This extended antacid activity is manifested by the com-position characteristics of an increased surFace area over gels prepared by drying from water in combination with certain p~l-stat tr,o values. A minimum surface area of l50 m /gm. of aluminum hydroxide gel as measured by nitronen adsorbtion apnears to be necessary. A minimum sur-face area above l70 m /gm. is preferred.
The composition has a pH-stat tSo time of about six to about twenty ; rninutes. A pH-stat t~ of about six to about fifteen minutes is preferred. The aluminum oxide content of the gel, as measured by the United States Pharmacopeia l8th Revision assay system can vary significantly and still provide gels which are antacid active for an extended period of time. For example~ aluminum oxide weight percentages can vary from about 40 to about 63% and still maintain antacid active gels. A preferred range of aluminum oxide is 45 to 59'~,. The 18th Revision of the United States Pharmacopeia discloses a range of 50-57.5~. Dried gels within this range are active and stable. The percentage aluminum oxide is dependent upon the drying time and does not appear to be intrinsically associated with extended antacid activity. ~-lowever, amorphous gels dried from water seem to be required to fall with the 50-57.5~, range of the U.S.P. to be active for even a short period of time.
The dried amorphous aluminum hydroxide gel of this specifica-tion is compounded into oral solid dosage nharmaceutical compositions for administration to individuals requiring antacid therapy. These oral, solid dosage forms are chewable or swallowable, the latter being preferred because of the chalky nature of the conventional 3() chewable dosa~e form. The swallowable dosage form can be either a 1~ ;25~L
tciblet or a capsule. ~len formula-t~d into tab~et forml the usual excipients cc~l be ~mplo~ed, however, a strong disinteyrant such as Starex is pref~rred for appropriate antiacid action Following is an example in accordance with the invention, This example is intended to illustrate the invention concepts but not limit them.
Example 1 In a five liter beaker, an 11.4~ aqueous solution containing 0.755 moles of aluminum chloride hexahydrate is added to an aqueous solution containing 2.8% sodium carbonate (0,57 moles) and 4.5%
sodium bicarbonate (1.336 moles). The mixture is stirred for a few ~inutes at room t~perature; and the aluminum hydroxide gel formed is washed several times with deionized water to remove the residual salts.
The gel is then treated three times with a volume of ethanol eclual to the volume of aluminum hydroxide gel (about 500 ml.) by thoroughly dispersing the gel in the alcohol and filtering through a Buchner funnel using #l filter paper, being careful to mRintain the aluminum hvdroxide as a moist cake. The final prcduct is dried at an elevated temperature.
- The Rossett-Rice time, lag time, acid consuming capacity, and pH-stat t,o on aging of the above dried amorphous aluminum hydroxide gel indicate a substantially more potent product than similarly prepared gels dried from water. The Rossett-Rice time and pH-stat t50 tests were previously defined. The lag time is the length of time required for the pH to reach 3.0 after starting the addition of the hydrochloric acid in the Rossett Rice time detenmination. Acid consuming capacity is the method used in U.S.P. l9th Revision.
The pH-stat t,o values in this specification are obtained }m~
'' ~Lq`~ ~?~5~l 3~63 under the followinc3 conditions. A sample of dried aluminum hydroxide gel containing 38 m~. of aluminum hydroxide, as measured by the essay procedure of the United States Pharmacopeia, l9th Revision~ is dispersed in twenty-two (22) ml. of distilled water in a fifty (50) ml. beaker. The pH-stat tso value for a pll oF 3 is then obtained for this sample using a typical pll-stat titrator assembly with a stirrer operating at 900 rpm. The particular pH-stat titrator assembly is not unduly significant. Such asseml)lies are available from Mettler, Beckman and Radiometer A/S (Copenha~en, Denmark). The specific assembly components used were obtained from Radiometer and are:
pH meter RHM 26 Titrator TTT II
Autoburet ABU12 (2.5 ml.) Titration Assembly TTA3 Recorder SBR 2
The t!,o ;s the time required for one-half of the antacid to be consumed. The rate of loss of antacid activity as measured by Rossett-Rice time of gels prepared after drying from water is sub-stantially greater than for gels prepared after drying from an inert organic solvent. The rate constant for loss or reactivity for gels dried from water is about 0.4~/month at 40 C. in contrast to about 0.071/month at 40 C. for gels dried from the organic solvent.
This is a significant difference wh;ch is reflected in a much greater retention of acid reactivity at room temperature by the gels of the invention. This difference illustrates the stability of the product prepared by this process over an extended period of time.
The term "extended period of time" as used in this specification and claims, indicates a period of time over which the dried gel is capable o`f neutralizing acid at such a rate and at such a pH that a ph.lrmaceu-tical composition comprising that gel would have a useful shelF life. A period of at least two years is contemplated. It is this extended antacid activity which distinguishes the amorphous 16P~ 5 1 gel prepared by the process of this invention from the gels of the art dried from water and allows the preparation of a potent antacid for therapeutic purposes.
This extended antacid activity is manifested by the com-position characteristics of an increased surFace area over gels prepared by drying from water in combination with certain p~l-stat tr,o values. A minimum surface area of l50 m /gm. of aluminum hydroxide gel as measured by nitronen adsorbtion apnears to be necessary. A minimum sur-face area above l70 m /gm. is preferred.
The composition has a pH-stat tSo time of about six to about twenty ; rninutes. A pH-stat t~ of about six to about fifteen minutes is preferred. The aluminum oxide content of the gel, as measured by the United States Pharmacopeia l8th Revision assay system can vary significantly and still provide gels which are antacid active for an extended period of time. For example~ aluminum oxide weight percentages can vary from about 40 to about 63% and still maintain antacid active gels. A preferred range of aluminum oxide is 45 to 59'~,. The 18th Revision of the United States Pharmacopeia discloses a range of 50-57.5~. Dried gels within this range are active and stable. The percentage aluminum oxide is dependent upon the drying time and does not appear to be intrinsically associated with extended antacid activity. ~-lowever, amorphous gels dried from water seem to be required to fall with the 50-57.5~, range of the U.S.P. to be active for even a short period of time.
The dried amorphous aluminum hydroxide gel of this specifica-tion is compounded into oral solid dosage nharmaceutical compositions for administration to individuals requiring antacid therapy. These oral, solid dosage forms are chewable or swallowable, the latter being preferred because of the chalky nature of the conventional 3() chewable dosa~e form. The swallowable dosage form can be either a 1~ ;25~L
tciblet or a capsule. ~len formula-t~d into tab~et forml the usual excipients cc~l be ~mplo~ed, however, a strong disinteyrant such as Starex is pref~rred for appropriate antiacid action Following is an example in accordance with the invention, This example is intended to illustrate the invention concepts but not limit them.
Example 1 In a five liter beaker, an 11.4~ aqueous solution containing 0.755 moles of aluminum chloride hexahydrate is added to an aqueous solution containing 2.8% sodium carbonate (0,57 moles) and 4.5%
sodium bicarbonate (1.336 moles). The mixture is stirred for a few ~inutes at room t~perature; and the aluminum hydroxide gel formed is washed several times with deionized water to remove the residual salts.
The gel is then treated three times with a volume of ethanol eclual to the volume of aluminum hydroxide gel (about 500 ml.) by thoroughly dispersing the gel in the alcohol and filtering through a Buchner funnel using #l filter paper, being careful to mRintain the aluminum hvdroxide as a moist cake. The final prcduct is dried at an elevated temperature.
- The Rossett-Rice time, lag time, acid consuming capacity, and pH-stat t,o on aging of the above dried amorphous aluminum hydroxide gel indicate a substantially more potent product than similarly prepared gels dried from water. The Rossett-Rice time and pH-stat t50 tests were previously defined. The lag time is the length of time required for the pH to reach 3.0 after starting the addition of the hydrochloric acid in the Rossett Rice time detenmination. Acid consuming capacity is the method used in U.S.P. l9th Revision.
The pH-stat t,o values in this specification are obtained }m~
'' ~Lq`~ ~?~5~l 3~63 under the followinc3 conditions. A sample of dried aluminum hydroxide gel containing 38 m~. of aluminum hydroxide, as measured by the essay procedure of the United States Pharmacopeia, l9th Revision~ is dispersed in twenty-two (22) ml. of distilled water in a fifty (50) ml. beaker. The pH-stat tso value for a pll oF 3 is then obtained for this sample using a typical pll-stat titrator assembly with a stirrer operating at 900 rpm. The particular pH-stat titrator assembly is not unduly significant. Such asseml)lies are available from Mettler, Beckman and Radiometer A/S (Copenha~en, Denmark). The specific assembly components used were obtained from Radiometer and are:
pH meter RHM 26 Titrator TTT II
Autoburet ABU12 (2.5 ml.) Titration Assembly TTA3 Recorder SBR 2
Claims
The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:
A process for preparing a dried amorphous antacid aluminum hydroxide gel which comprises contacting an amorphous aqueous alu-minum hydroxide gel with an inert organic solvent of sufficient solubility to replace water in the gel; removing the inert organic solvent; drying the amorphous aluminum hydroxide gel to an acid reactant stable amorphous powder having substantial acid reacting capability over an extended period of time.
A process in accordance with Claim 1 wherein the inert organic solvent is miscible with water.
A process in accordance with Claim 1 wherein the organic solvent is methanol, ethanol, propanol, isopropanol, acetone, acetaldehyde, dimethylformamide, formamide, tetrahydrofuran, 1,3-dioxane, 1,4-dioxane or pyridine.
A process in accordance with Claim 3 wherein the solvent is methanol, ethanol, propanol, isopropanol or acetone.
A process in accordance with Claim 4 wherein the solvent is methanol or ethanol.
A process in accordance with Claim 1 wherein the organic solvent is of sufficient solubility in water to maintain a single phase when contacted in a 1:1 volume ratio with the aqueous gel.
A process in accordance with Claim 6 wherein the organic solvent is a mixture of organic entities.
A process in accordance with Claim 1 wherein the powder is from about 40 to about 63 weight percent aluminum oxide.
A process in accordance with Claim 8 wherein the powder is from about 45 to about 59 weight percent aluminum oxide.
A composition which comprises a dried aluminum hydroxide gel with a surface area minimum of 150 m2/gm. and a pH stat t50 value of about six to about twenty minutes.
A process for preparing a dried amorphous antacid aluminum hydroxide gel which comprises contacting an amorphous aqueous alu-minum hydroxide gel with an inert organic solvent of sufficient solubility to replace water in the gel; removing the inert organic solvent; drying the amorphous aluminum hydroxide gel to an acid reactant stable amorphous powder having substantial acid reacting capability over an extended period of time.
A process in accordance with Claim 1 wherein the inert organic solvent is miscible with water.
A process in accordance with Claim 1 wherein the organic solvent is methanol, ethanol, propanol, isopropanol, acetone, acetaldehyde, dimethylformamide, formamide, tetrahydrofuran, 1,3-dioxane, 1,4-dioxane or pyridine.
A process in accordance with Claim 3 wherein the solvent is methanol, ethanol, propanol, isopropanol or acetone.
A process in accordance with Claim 4 wherein the solvent is methanol or ethanol.
A process in accordance with Claim 1 wherein the organic solvent is of sufficient solubility in water to maintain a single phase when contacted in a 1:1 volume ratio with the aqueous gel.
A process in accordance with Claim 6 wherein the organic solvent is a mixture of organic entities.
A process in accordance with Claim 1 wherein the powder is from about 40 to about 63 weight percent aluminum oxide.
A process in accordance with Claim 8 wherein the powder is from about 45 to about 59 weight percent aluminum oxide.
A composition which comprises a dried aluminum hydroxide gel with a surface area minimum of 150 m2/gm. and a pH stat t50 value of about six to about twenty minutes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA290,242A CA1090251A (en) | 1977-11-04 | 1977-11-04 | Dried amorphous antacid aluminum hydroxide gel |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA290,242A CA1090251A (en) | 1977-11-04 | 1977-11-04 | Dried amorphous antacid aluminum hydroxide gel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1090251A true CA1090251A (en) | 1980-11-25 |
Family
ID=4109956
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA290,242A Expired CA1090251A (en) | 1977-11-04 | 1977-11-04 | Dried amorphous antacid aluminum hydroxide gel |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1090251A (en) |
-
1977
- 1977-11-04 CA CA290,242A patent/CA1090251A/en not_active Expired
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