Granulating composition and method

The invention involves a granulating composition composed of an aqueous solution of magnesium sulfate heptahydrate and sodium hexametaphosphate. This composition can be used to prepare granules of ingredients for inclusion in any formulation for which rapid disintegration or dispersion are important factors. It is useful for tablets containing ingredients which are difficult to compress and is particularly useful for formulating swallowable tablets of a single non-soluble ingredient such as calcium carbonate. Disintegration times are markedly decreased.

FIELD OF THE INVENTION 
The invention relates to a granulating composition and method of 
granulation which provides good granule formation, good tablet formula, 
compressibility and efficient disintegration of formulations in water. In 
particular, the invention can be used to decrease disintegration time of a 
swallowable tablet in the stomach or of an effervescent tablet in water. 
BACKGROUND OF THE INVENTION 
Tableting has always required balancing the need for a tablet which will 
withstand the stress of manufacturing, packaging and storage without 
breaking or fracturing with the need for a tablet which will to make the 
ingredient available for dissolution disintegrate and absorption. It is 
known that a hard compact tablet can be produced which will pass 
completely through the body. 
The solution to this problem has been approached in many ways. One method 
is to use so called "super disintegrators" such as Ac-Di-Sol.RTM., 
available from FMC Corp., Philadelphila, Pa., a modified cellulose gum 
which promotes disintegration of a swallowable tablet in the stomach. 
This invention provides another answer to the problem with a granulating 
composition which promotes active disintegration, can be used with normal 
tablet manufacturing procedures and provides a tablet with suitable 
handling characteristics. The composition can also be used advantageously 
with ingredients which are difficult to compress with normal tableting 
procedures. 
SUMMARY OF THE INVENTION 
The invention provides a granulating composition and a method of 
granulating. 
The composition includes magnesium sulfate and sodium hexametaphosphate in 
aqueous solution. Magnesium sulfate heptahydrate is a readily available 
form of magnesium sulfate and ratios of sulfate to phosphate and total 
weight percentages given herein were calculated on the basis of the 
heptahydrate. 
The composition can be used in a granulating procedure, comprising the 
steps of: 
a. mixing a granulating composition, composed of an aqueous solution of 
magnesium sulfate heptahydrate and sodium hexametaphosphate in a ratio of 
about 10:1 to about 2:1 by weight with a total solid content of about 10 
to 60% by weight, with an ingredient to be granulated to produce a 
uniformly wetted mixture; 
b. drying the wetted mixture at a temperature between 40 and 100 degrees 
centigrade; and 
c. sizing the dried mixture to form a dried granulation mixture. 
The granulated ingredient may then be used in any tablet formulation 
desired, effervescent or swallowable, or may be used in the granular form 
as desired.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION 
The granulating composition as used herein is defined as an aqueous 
solution. The composition of the invention is composed of magnesium 
sulfate heptahydrate, sodium hexametaphosphate and water. The composition 
is primarily composed of the three ingredients with a total solid content 
of approximately 10 to 60% by weight. Other ingredients which are to be 
added to a final formulation in only a small amount may also be added to 
the composition. 
This composition and method of granulating provide a tablet formulation 
which has both good compressibility and good disintegration 
characteristics. It is believed, but not relied upon, that the magnesium 
sulfate acts as a binder and that the sodium hexametaphosphate acts both 
to augment the binding property of the composition and to improve the 
disintegration time. The ratio of sulfate to hexametaphosphate can be 
varied between about 10 to 1 to about 2 to 1 by weight depending on the 
desired characteristics of the final formulation. A preferred ratio is 
about 4 to 1 by weight for ingredients with particular compression 
problems such as calcium carbonate, magnesium hydroxide or acetaminophen. 
The total solid content of the composition can vary from about 10 to 60% 
by weight. A preferred solid content of the composition for granulating 
calcium carbonate or magnesium hydroxide is about 40 to 50% by weight. 
All ratios and weight percentages given are calculated on the basis of 
magnesium sulfate heptahydrate. However, it is to be understood that while 
this is a readily available commercial form of magnesium sulfate, 
anhydrous magnesium sulfate could be used making the easily calculated 
allowance for the difference in molecular weight to calculate the ratios 
to be used. Therefore, as used herein, magnesium sulfate heptahydrate is 
equivalent to magnesium sulfate or any of the various hydrated forms. 
The composition and method are particularly advantageously used in a single 
non-soluble ingredient formulation such as a calcium carbonate tablet. 
This granulating composition provides a calcium carbonate tablet with a 
decreased disintegration time and provides an improved formulation for 
BIOCAL.RTM., available from MILES INC, Elkhart, Ind. However, the 
composition can also be used to formulate other difficult to granulate 
ingredients such as magnesium hydroxide for addition to vitamin 
formulations such as STRESSGARD.RTM., also available from MILES INC, or 
for effervescent ingredients such as sodium bicarbonate and citric acid 
useful in effervescent formulations. 
The composition and method are not limited in use to tableting but may be 
used in powdered drink formulations where increased dispersibility will 
provide added ease of use. 
The method of granulating particularly preferred ingredients includes the 
steps of 
a mixing an ingredient chosen from calcium carbonate, magnesium hydroxide, 
acetaminophen, sodium bicarbonate or citric acid with an aqueous 
granulating composition composed of magnesium sulfate heptahydrate and 
sodium hexametaphosphate in a ratio of about 4 to 1 by weight with a solid 
content of 40 to 50% by weight until a uniformly wetted mixture is 
produced; 
b. drying the wetted mixture at a temperature between 40 and 100 degrees 
centigrade; and 
c. sizing the dried mixture to produce a free flowing dried granulation. 
Mixing may be accomplished in any suitable mixer. For commercial 
manufacture a high intensity mixer such as a Littleford Lodige 
mixer/granulator is preferred. Other equipment such as a fluid bed 
granulator or a spray drier may also be used. In the latter cases drying 
of the mixture is accomplished with the same equipment as mixing and the 
sizing step may not be required. 
The mixture is then dried to drive off water used as a solvent; and when 
desired, some or all of the water of hydration of the magnesium sulfate. 
In order to remove the about four moles of water of hydration, the 
temperature should be in excess of 70.degree. C. but below 100.degree. C. 
Other temperatures and periods of drying may be used as long as the degree 
of drying is suited to the needs of the end product. Drying is commonly 
accomplished in a kiln on trays at approximately 90 degrees centigrade for 
a period of not less than 12 hours. The mixture may also be dried in a 
fluid bed drier. 
The dried mixture is then sized by passing it through a suitable milling 
machine to produce a free flowing granulation. It has been found that the 
finished dried granulation mixture is composed of particles of the 
granulated ingredient coated with the sulfate/phosphate composition. 
The finished dried granulation may be used as an ingredient in desired 
tablet formulations and may be used to produce tablets by normal 
manufacturing methods. The dried granulation may also be used directly if 
a powder is preferred. 
The following examples describe granulation formulations which were 
prepared. While the examples serve to illustrate the invention, they are 
not to be interpreted as limiting its scope, which is defined solely by 
the claims. One skilled in the art will be able to make such variations, 
substitutions and changes in the components of the granulating 
compositions, ingredients to be granulated and of the conditions of 
granulation as may seem desirable. 
EXAMPLES 
Calcium Carbonate Granulation 
Calcium carbonate is granulated with the granulating composition of the 
invention as follows: 
1.44 kilograms of sodium hexametaphosphate (Vitrafos.RTM., Stauffer 
Chemical Co., Westport, Conn.) is dissolved in 7.2 kilograms of water with 
mixing. 5.76 kilograms of magnesium sulfate heptahydrate (Epsom Salt USP, 
Dow Chemical USA, Midland, Mich.) are added to the previous solution and 
dissolved to produce a granulating composition containing a 4:1 ratio of 
the sulfate to phosphate with a total solid content of approximately 50% 
(as calculated including the waters of hydration). 
14.4 kilograms of the granulating composition is placed in a solution 
transfer tank. A Lodige Mixer Model FM-130-D, Littleford Bros., Inc., 
Cincinnati, Ohio, is charged with 68.18 kilograms of calcium carbonate 
(Whiton F.RTM., HM Royal, Inc., Trenton, N.J.). The solution is 
transferred from the tank to the mixer while the mixer is running. The 
mixer is run for approximately twelve minutes or until densification of 
the powder is apparent and the wetted mixture is discharged into 
collection drums. The wet granulation is spread on kiln trays. The trays 
are placed in a kiln and dried at 90.degree. C. for twelve hours. 
The dried granulation is removed from the kiln and assayed for moisture 
content. The dried mixture is passed through a Fitzpatrick Comminutor 
(Model D), WJ Fitzpatrick Co., Chicago, Ill. equipped with a swinging 
blade milling head , knives forward. For a calcium carbonate tablet the 
milling head of the Fitzpatrick is set at about 2500 rpm with a 2A screen. 
The coating in the final granulation is about 5 to 10% of the total solid 
content by weight. 
The granulated material is then used in normal tableting procedures to 
produce a swallowable tablet. 
Magnesium Hydroxide Granulation 
Magnesium hydroxide is granulated as above with the exception that 68.0 
kilograms of magnesium hydroxide is mixed with the granulating 
composition. Again, the coating comprises about 5 to 10% of the total 
solids by weight in the final dried granulation. The granules of magnesium 
hydroxide produced using the composition of this invention have been used 
with other ingredients to prepare a vitamin/mineral tablet. 
Obviously, many modifications and variations of the invention as set forth 
may be made without departing from the spirit or scope of the invention.