CA1063935A - Antacid tablets and processes for their preparation - Google Patents

Abstract

ABSTRACT
An antacid tablet is prepared which contains a combination of an antacid ingredient, sugar, and fat and which has a hardness requiring no more than 9 pounds peak force to cause a blunt probe to penetrate its sur-face. Included also are processed for preparing such a tablet in which an antacid ingredient, sugar, and melted fat are mixed, cooled and milled to produce a powdered mixture, and the mixture formed into tablet, Further improvements include using a fine sugar, 90% of which will pass a 200 mesh screen; maintaining the plungers and dies of the tableting machine above the melting point of the fat; and utilizing a limited pressure (50 to 600 pounds per square inch) in the compressing of the tab-lets. Another feature involves controlling the moisture to within 3 to 10% based on the weight of the tablet.

Description

This invention relates to antacid tablets and to processes ~or their preparation. More particularly, the invention deals with such tablets containing the com-bination of an antacid ingredient, sugar and a high pro-portion of ~at.

BACKGROUND
Antacid compositions have been prepared in a wide vaxiety of forms such as suspensions, solutions, emul-sions, powders and tablets. In each case the composition includes an ingredient which is an effective antacid sub-stance and such substances include calcium carbonate, mag-nesium carbonate, magnesium hydroxide, magnesium trisili-cate, magnesium oxide, sodium bicarbonate, aluminum hydrox-ide, aluminum carbonate, aluminum hydroxycarbonate, alumin-um magnesium glycinate, dihydroxy aluminum amino acetate, and magnesium aluminate. Many other compounds also come to be useful as antacid ingredients in compositions of this type. One such ingredient is aluminum hydroxide-magnesium carbonate composition which is prepared as a dry gel by Reheis Chemical Company and sold under the trademark FMA-40. Another such composition having somewhat different proportions of the same ingredients is sold under the trade mar~-FMA-ll. In the specification and claims we use the term "antacid ingredient" to mean any of the above-mentioned antac~d substances and mixtures thereo$, together with any compounds which include any of the above as a part of a chemical complex.

10~;3935 Antacid compos~tions containing the antacid in-gredients above referred to may be more effecti~e when made up in solutions or suspensions because liquid medication can more easily reach the affected areas where treatment is needed whereas in the case of powders or tablets, these do not break up into the fine particle size of liquid suspen-sions and some of the medication may never reach the areas where treatment is needed. This is true especially as to tablets which require mastication in the mouth. In ~ome csses antacid tablets or portions of them may even pass into the body in solid for~ without giving up any substan-tial medical benefit. Also, antacids in tablet form are as a general rule slower to take effect and slower to give relief from symptoms of hyperac.tidy than if the same medica-ments were contained in the form of solutions or suspensions.
However, the tablet form of antacid medication is much more convenient to the patient. The tablets may be carried in small containers or in a purse and may be taken as needed without any need for extra equipment or for the measuring of dosages. Despite limitations in giving relief, the convenience of the tablet form of the antacid make this form a popular kind of antacid composition.
What has been needed is an antacid tablet which - is more effective in giving relief to symptoms of hyper-acidity, a tablet which will release its benefits more rapidly, which will pass easily to the areas where treat-ment iL needed, =nd which will also yield benefit= to rhe ~3 : ~ , ~ , ' .
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~063935 patient over a longer period of time. At the same time lt i5 desirable that the ingestion of the tablet be pleasant and without discomfort to the patient such as would be caused by grittiness or other unpleasant feeling in the patient's mouth.
Accordingly, applicants have set out to discover an improved antacid tablet which will meet the needs above expressea.
Applicants conceived the idea that an improved tablet containing fat in combination with an antacid ingredient and sugar, the fat being contained in a relatively high proportion in the tablet; also that the tablet have a very limited hardness;
but according to the prior teachings and the prior practice in the tableting art, such a tablet could not be prepared. For one thing, a material having such a high proportion of fat along with sugar and antacid would be expected to stick to the cavity walls and to the punches of the tableting presses so that the tablets could not be ejected from the press.
Accordingly applicants set out to provide a process for preparing the improved antacid tablets which avoids the difficulties facing the art, a process by which the tablets may be made with ease.
SUMMARY
In one particular aspect the present invention provides an antacid tablet containing an antacid ingredient in an amount of from 5 to 40%, sugar in an amount of from 15 to 80%, fat in an amount of from 15 to 30%, and water in an amount of from 2 to 12%, said percentages being by weight based on the total weight of the tablet.
In another particular aspect the present invention provides in a process for preparing an antacid tablet in which an antacid ,j , : , :, ingre~ient in an ~mount of from 5 to 40%, sugar -in arl amount of from 15 to 80%, fat in an amount of 15 to 30%, and water in an amount of from 2 to 12% are combined to provide a powdered mixture, said percentages being by weight based on the total weight of the mixture, the step comprislng compressing said mixture into tablets under a pressure from 150 to 200 pounds per square inch, using a conventional tableting machine having at least those parts of the machine contacting said tablets at a temperature at or above the melting point of the fat contained in said tablets.
We are aware that each of the antacid ingredients, the sugar, and the fat have separately been formed into tablets, but believe that their combination in accordance with disclosures herein contained constitutes a basic improvement in this art.
DETAILED DESCRIPTION
As the antacid ingredient we may use any of the substances which have been used in the prior practice in making antacid compositions including any of those which we have mentioned above under "Background" but we prefer combinations of aluminum hydroxide, magnesium oxide and magnesium carbonates, particularly that combination sold under the trade mark FMA-40. Such substances may be in the form of a fine powder, the size of the particles in terms of density being something of the order of .15 grams per millimeter plus or minus .1 grams.
As the sugar ingredient we prefer to use sucrose.

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~ 5-, We may use also dextrose, lactose, fructose, galactose, manitol, sorbitol, maltose or sugars of other particular types. It is pos~ible that the dextrose and other sugar~, other than sucrose, may give some difficulty by browning, We prefer also that the sugar be in the form of fine powder - ~ometimes called "fondant sugar" whlch i8 of a fineness such that at least 50% will pass through a 200 mesh screen. It is better that at least 90% of the sugar pass through a 200 mesh screen. This sugar ingredient may contain a small C amount of a material such as starch in the form of cornstarch or tapioca--we prefer pregelatinized tapioca--as an anti-caking agent in the amount o about 2.9% of the weight o the finished tablet.
As the fat ingredient we may use any natural or synthetic fat such as animal or vegetable fats and shorten-ings. We prefer that the fat have a meiting point not higher than 115F, and find that fat having a melting point of the order of 101 to 103F is most useful.
In addition to the antacid, sugar and fat ingredi-ents, we may add a suita~le dye to provide a desired color, common salt and a flavoring agent to provide a desired fla-vor, and water as needed in the processing. All materials should be of pharmaceutically acceptable quality.
- To combine the ingredients, we may put a quantity of water, for example about 25 liters, into a suitable mixing container, and add the dye and salt in a water solution and mix to attain a complete solution. Water may be added to ~,' -.... .

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10~3935 give the desired amount of water, ~or example, abou~ 27 liters, mixing thoroughly.
The sugar, containing a small amount of an anti-caking agent, may be placed in a mixer, the mixer qtarted and the dye qolution added s~owly, mixing for a few mlnutes until the batch has a creamy consistency and uniform color.
The improved antacid tablets prepared in accord-ance with our invention may contain the following percent-ages of essential ingredients:
Usable Preferred IngredientPercenta~ePercenta~e Antacfd 5 to 40 12 to 30 Sugar 15 to 80 35 to 65 Starch 0 to 6 1 to 5 Fat 3 to 40 15 to 30 Water 2 to 12 4.5 to 9 The percentage values of ingredients above given are by weight based on the weight of the tablets which are prepared.
From the above information as to the primary con-stituents of the finished tablets, specific amounts of the ingredients may be selected from the ranges given and the amount of the respective antacid, sugar and fat starting materials may be calculated to ma~e the desired proportions in the finished tablets.
The fat may be heated to a temperature above the . ~
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-melt~ng point of the fat, of the ordcr of 120 to 130F(49 to 54C) to change the fat to a liquid, and the flavor-ing agent may then be mixed in.
Then the melted fat having the flavoring therein and the powdered antacid ingredient may be thoroughly mixed to produce a uniform dispersion o antacid throughout thé
fat. The water, coloring and salt are thoroughly mixed with the sugar ~o form a fondant-like mixture. These two separate mixes may then be blended until they are completely dispersed in each other. Any powdered flavoring agent which it is desired to use may also be mixed in at this point. The batch is now ready for granulation.
The batch in the mixer may be cooled a8 it i8 being mixed by the addition of dry ice until the temperature of the batch has dropped to something below 40F, or example, to about 35 to 40F (2 to 4C).
The hammermill, one type of which is known as a Fitzmill, may be prepared by passing dry ice through it while operating at high speed with impact forward.
The cooled batch may then be passed through the hammermill operating at high speed with impact forward. The cooled temperature may be maintained by the introduction of a coolant uch as liquid nitrogen. Preferably the tempera-ture of the batch as it comes from the hammer is near or below 0C. The temperature may be substantially below O~C, there being no limit on the lower side except that when the , , ' ' ' ' ' ' , , , temperature is very low, heat ~s required to bring it back to the temperature at which continued processing can take place.
The material rom the h~mermill may be put ~nto a dryer and drlet at a temperature, for example, o about 70 to 75F. The moisture may be brouzht down at this point to about 8 to 10% based on the weight of the material. Then we prefer to pass the dried material through an agglomerator to make a more uniform size of particles. We prefer that the operation be continued until all of it will paQs through à 4 mesh screen so that a maximum of 15% will pass a 40 mesh screen. If desired, the agglomerated material may be fur-ther dried to as low as 3% moisture, desirably in the range of about 6.8 to 7.8% based on the weight of the material has proved to be quite satisfactory.
The foregoing detailed description of the prepar-ation of material for tableting sets forth what Applicants believe to be the best procedure but it will be apparent that this procedure may be abbreviated by omission of non-essential steps. For example, the flavoring and dye ingredi-ents may or may not be included and the material prepared using only the essential antacid ingredient, the sugar and the fat along with a small amount of moisture Also, the various-detailed steps may be varied or changed in many respects in accordance with the knowledge of the art.
- The proportions of the antacid ingredient, the .

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fat, from 15 to 80% sugar, with the preferred fat range being from 15 to 30% and water in the proportion of from

2 to 12% with from 4.5 to 9~ preferred. Pregelatinized tapioca starch may be included in the preferred range of 1 to 5%. All of the above percentages are weight amounts based on the total weight of the mixture after drying.
The quantities of these ingredients for any particular batch may be determined as required to result in the selected proportion of ingredients, the size of the batch, etc.
The antacid powder composition prepared as above described may be compressed into tablets of desired form using a standard tableting machine by operating the machine in a prescribed way. It is important first that the tablet-ing machine, or at least those parts of the machine which contact the tablets under compression, be maintained at a temperatu~e at or above the melting point of the fat con-tained in the tablets. This may be don~ by heating the room in which the tableting operation is performed to an elevated temperature above normal room temperature and above the melting point of the fat, suitably about 110 to 125F (~3 to 51C), or by enclosing the tableting machine in a shroud and maintaining the temperature within the shroud at the elevated temperature just referred to. The dies and punches of the press are maintained at a temperature which keeps the fat liquid at the punch/tablet interface and -10- .

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, allows the tablets to come off the tableting machine with-out sticking. This may be accomplished by the use of lamps which direct infrared light toward the machine, I
the temperature of the punches on the tableting machine is below the melting point of the fat, then the fat wh~ch melts at the interface on compression solidifies before the tablet is released, causing sticking of the tablet to the punches.
C It is also important to limit th2 pressure used in forming the tablets. The pressures commonly used in tableting are of the orter of 2000 or 3000 pounds per square inch, but we find it advantageous in forming our improved antacid tablets to use pressures substantially lower than this and within the range of from about 50 to 600 pounds per square inch, preferably from about lS0 to 400 pounds per square inch.
The tablets which are formed using the conditions above described may be collected, packaged and distributed through regular trade channels.
The improved tablets have been found to be very effective in use. We believe this is due in part to the use of fat in the tablets in combination with the antacid ingredient and sugar constituents. This gives the tablets a better eating quality and mouth feeling, and helps to form a coating which lines the esophagus and which resists the effects of stomach acid juices. The fat also helps to ~,., . ' -11~
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,~ , , . . , densify the s~tive antacid ingredient in thé process o manufscture since the fat and antacld are premixed and th$s permits the whole batch to be more easily mixed in a uni-form manner. Further, it is believed that the efect of the fat extends the time during which the tablet gives beneficial effect. Also, the lower values oi~ hardness are believed to contribute to the easy breakup o the tablet in the' mouth, and this provides more surface area of ant-acid material and therefore quicker and more complete action.
The following specific examples demonstrate the practice of our invention in the preparation of the improved antacid tablets:

Example I
A dye solution was prepared using the following supplies:
Constituent Quantity Percent C Dye, PD&C Yellow #56.38 g .0226 - ~ye, FD&C Blue ~12.13 g .0076 Sodium Chloride USP1215. g' 4.3049 Tap water 27.0 L 95.6649 Total28.225 Kg 100.00 %
25 liters of filtered tap water was placed in a --mixer and the dye solution added to it. Water was added to make 27 liters.

44.65 Kg of powdered sucrose having a fineness such'that more than 90% passes a 200 mesh'screen and :' . ~ , .

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containing 2.6 Kg of pregelatinized tapiocaj was placed in a Si~ma Day mixer, the mixer started and the dye solution added to the sucrose, Mixing was continued until the batch had a creamy consistency.

22.5 Kg of hydrogenated vegetable ~at ~having the trade mark Duromel) was liquefied by heating to 120F.
20.0 g of spearmint oil and 35.0 g of peppermint oii were added to the fat and mixed in.
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C ` 13.5 Kg of FMA-4~rwere intermixed and added to the Sigma Day mixer. Mixing was continued until the mass became completely uniform. Dry ice was added to keep the batch at a temperature of between 35 and 40F,.
, The batch was put through a hammermill operated at high speed with impact forward while introducing liqui~
nitrogen to maintain the batch temperature at about -10 -to -20F. The temperature of the batch coming from the ham-mermill was about 0 to -10C.

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The batch was then transferred to a fluid bed drier operated at about 70- ?5 F until the batch came to this same temperature and a moisture of 8 to 8.6%. The batch was then transferred to a blender where agglomeration took place and the agglomerated mass was then classified by passing the same through a No. 4 screen, and then further dried to a moisture content of about 7%.

In the tableting operation we used a tableting ~achine preheated to 120F and a shroud of polyethylene ' .

film about the tableting machine and heated the air within the shroud to about 75 to 100F, and used a pres6ure on the plungers of the machine of 300 pounds pex square inch, We used heating lamps to maintain the machine temperature of from 105 to 120F.

Then the batch material was fed to the tableting machine and tablets formed. The tablets were collected and packaged in polyethylene-lined cans.

Example II
1212 g of dried fondant sugar were blended with 10.5 g of salt and 43 g water containing 15 drops of color and 30 drops of peppermint flavor. 319.05 g of ~inely powdered antacid material (FMA-l~ and FMA-40~ each of which is a mixture of aluminum hydroxide and magnesium carbonate) was dispersed in 584.85 g of melted shortening (melting point 102-105F). The two abo~e-described mix-tures were blended together and allowed to cool and solid-ify. The cooled mass was ground in a Fitzpatrick hammer-mill using liquid nitrogen injected into the milling head as a coolant. The mill was operated at 5800 rpm and the.
screen through which the material must pass was .0156 inches in diameter. The resulting powder was used to make antacid tablets using a compression pressure of 250 pounds per square inch with the machine shrouded by a polyethylene film and the temperature of the machine maintained at 100 to 125F.

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~xample III
606 g of dr~ed fondant sugar, 60 g of corn ~yrup, 5.5 g of salt and 25 g of water were mixed together ln a Hobart mixer. To this mixture was added gradually 292,5 g of melted shortening having a melting point of 102 to 105F, To this was added 7 drops of green food coloring and 15 drops of peppermint flavor. Mixing was continued until the .
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~0 639 3 5 mass was uniform. At this point 399 g of FM~-ll was added This was mixed in thoroughly and the mass allowed to cool and crystallize out. The cooled, crystallized mass was put through a "finishing machine" (a swept screen type of machine in which the material is forced through the screen by revolv-ing blades). The powder from this procedure wa~ tableted as set forth in Example II.

Example IV
2 pounds of fondant sugar (fine enough that 90%
or more will pass a 200 mesh screen), 1/4 oz. of salt, 2-1/2 oz. of water, and ll drops of green ood coloring were mixed together in a Hobart mixer. 8-1/2 oz. of finely powdered antacid mixture (FMA-ll) were dispersed in 15-1/2 oz. of melted shortening (102 to 105F melting point). The shortening and antacid mixture was added to the ~obart mixer with the sugar mixture, and mixing was continued until a homogenous smooth mass was obtained. The mass was allowed to cool and crystallize out. It was then ground through a hammermill equipped for liquid nitrogen injection into the grinding chamber. The mill was operated at 5800 rpm-and had a .0156 inch screen. The powder from this procedure was tableted as set forth in Example IX.

Example V
2 pounds of fondant sugar, il4 oz. of salt, 10 oz.
. , of finely powdered antacid mixture (FMA-ll), 1 pound 2 oz.- -of melted shortening, 3-1/2 oz. water, 6 drops of green food ~ .
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, - ,, ~063935 coloring and 23 drops of peppermint flavor were mixed together and rolled into dough of desired thickness. Pi~ls were cut into tablets using a cookie cutter and the resulting tablets allowed to dry.
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Example VI
21 oz. of sucrose and 4.1 g of salt were dissolved in 8 oz. of water. The solution was brought to a boil and kept boiling until a temperature of about 2S6F was reached.
At this point the heated mass was cooled on a marble slab.
4 oz. of butter was melted and m~xed with 1 oz. of cotton-seed oil. 3-1/2 oz. of finely powdered antacid mixture - -(designated F~-ll and composed of a mixture of aluminum hydroxide and magnesium carbonate) was then dispersed throughout the liquid mixture using a Hobart mechanical mixer. The antacid and fat mixture was then foIded into the cooled boiled sugar mass along with 17 drops of pepper-mint oil and 7 drops of green food coloring. This mass was then pulled until crystallization began to take place.
At this point the mass was formed into ropes and cut into pillow shapes.
' To demonstrate the "hardness" of the tablets made as in Example I, we subjected the tablets to tests on the Instron testing machine using a probe having a cone-shaped end with rounded end tip and measured the peak force neéded to drive the probe 0.075 inches into the tablet at a 8peed of 0.5 inches per minute.

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~063935 A critical element of such a test is the shape of the end of the probe which is pressed into the surface of the tablet. In our har~ness tests, we used a probe having a blunt point resembling a half sphere with a diame-ter of .175 inches and this blunt tip was pre8Bed 810wly into ehe surface of the tablet at a rate of 0.5 inches per minute. The peak force necessary to move the tip to a depth of .075 inches was then taken as a measure of the hardness of the tablet.
( We find that tablets made as set forth in Example I have a peaX penetration force of less than 9 pounds whereas any other antacid tablet known to us and in com-mercial use today requires much higher force for this stan-dard penetration under similar test conditions.
Table I contains data obtained by testing the improved tablets of this invention and comparing these with other antacid tablets known to the trade.

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~063935 , TABLE I
Peak Force Required (lbs. per sq. in,) for Penetration .075 inches Make of Tablet in Surface of Tablet Tablet as prepared in Example I:
Average of 40 sample from 8 lots 3.5 Mylanta II
Avexage of 10 samples 28.4 Di-Gel~9 Average of 10 samples 23.8 `: Maalox No. 2 Average of 7 samples 34.?
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Average of 6 samples 15.2 Alka~2 .
Average of 6 samples 15.~
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. While our invention has been set forth and demon-`. strated in terms of certain embodiments, it must bé under-: stood that other embodiments may be utilized, and many - changes and variations may be made both as to the ~rmula-tion of the improved tablets and as to their process of -manufacture all within the spirit of the invention and within the scope of the appended claims.

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Claims (18)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. An antacid tablet containing an antacid ingredient in an amount of from 5 to 40%, sugar in an amount of from 15 to 80%, fat in an amount of from 15 to 30%, and water in an amount of from 2 to 12%, said percentages being by weight based on the total weight of the tablet.

2. A tablet as set forth in Claim 1 wherein said fat has a melting point from about 101 to 115°F.

3. A tablet as set forth in Claim 1 wherein said antacid ingredient is a mixture of aluminum hydroxide and magnesium carbonate.

4. An antacid tablet as set forth in Claim 1 in which said sugar is sucrose and in which said tablet contains pre-gelatinized tapioca starch.

5. An antacid tablet as set forth in Claim 1 having a hardness which can be probed to a depth of .075 inches by a probe having a rounded end of 0.175 inches diameter at a rate of 0.5 inches per minute, with a peak force of less than 9 pounds.

6. An antacid tablet as set forth in Claim 1 which contains moisture of from 3 to 10% by weight based on the total weight of the tablet.

7. In a process for preparing an antacid tablet in which an antacid ingredient in an amount of from 5 to 40%, sugar in an amount of from 15 to 80%, fat in an amount of 15 to 30%, and water in an amount of from 2 to 12% are combined to provide a powdered mixture, said percentages being by weight based on the total weight of the mixture, the step comprising:

compressing said mixture into tablets under a pressure from 150 to 200 pounds per square inch, using a conventional tableting machine having at least those parts of the machine contacting said tablets at a temperature at or above the melting point of the fat contained in said tablets.

8. A process as set forth in Claim 7 wherein said fat is in liquid form and a mixture of the ingredients formed and then cooled to a temperature below 40°F and passed through a mill to obtain the powdered mixture.

9. A process as set forth in Claim 8 wherein the plungers and dies of said machine are maintained at a temperature of from 110 to 125°F.

10. A process as set forth in Claim 9 in which said temperature of said dies and plungers is maintained by heating the room in which said machine is contained to maintain said room at said temperature.

11. A process as set forth in Claim 9 in which said temperature of said plungers and dies is maintained by placing said machine under a shroud and maintaining the temperature of the machine at said temperature.

12. A process as set forth in Claim 8 wherein said sugar has a fineness such that 90% will pass a 200 mesh screen.

13. A process as set forth in Claim 12 in which said sugar contains pregelatinized tapioca starch as an anti-caking ingredient.

14. A process as set forth in Claim 8 in which said cooling of the mixture is accomplished by the introduction of dry ice into the mixer.

15. A process as set forth in Claim 8 in which each of said antacid ingredient and said sugar has a fineness such that at least 90% of it will pass a 200 mesh screen.

16. A process as set forth in Claim 8 in which said mill is of the hammermill type.

17. A process as set forth in Claim 7 in which said fat has a melting point of about 101 to 115°F.

18. A process as set forth in Claim 7 in which said powdered mixture is passed to a fluid bed dryer, and is agglomerated, prior to being compressed into tablets.