# Patent

## Title
Laxative gel composition

## Abstract

An edible, gel composition of a PEG and a gel forming agent wherein the composition is prepared by mixing together the PEG with gel forming agent to form the edible gel composition, and the edible gel composition has laxative properties.

## Background
CLAIM OF PRIORITY
This application claims the benefit of priority of U.S. Provisional Application Ser. No. 61/620,707, filed on Apr. 5, 2012, which application is herein incorporated by reference in its entirety.


BACKGROUND
Polyethylene glycol (PEG), particularly PEG 3350 is a known osmotic laxative. PEG 3350 is sold in US in laxative compositions which typically are to be combined with an aqueous medium. For example 17 g of PEG powder is dissolved in about 8 ounces of aqueous beverage and consumed to provide a laxative dosage. Examples of such products include Miralax® (MSD consumer care) and Gavilax® (Gavis Pharmaceuticals, NJ).
Formulation of PEG as a beverage or in an aqueous medium is inconvenient, unsatisfying and uncomfortable to the consumer. The aqueous formulation has an undesirable mouth-feel and can create a bloated, overwhelmed feeling in the consumer's stomach. The aqueous formulation is also not a drink that can be discretely consumed so that consumers typically use restrooms in which to mix and drink the formulation. This practice is uncomfortable, disagreeable and ill tasting. The discomfort and inconvenience leads to reduction of dose compliance of the product as directed. Thus, there is a need for more conveniently dosed polyethylene glycol.
While there are certain products, for example Movicol® (Norgine Ltd, Middx UB9 6NS, UK) that are sachets for combination with aqueous media, they contain in addition to polyethylene glycol, electrolytes such as sodium chloride, sodium bicarbonate and potassium chloride. These salts do not impart good taste and suffer from the same discomfort and inconvenience as an aqueous formulation containing only PEG.
Other laxatives formulated for oral consumption suffer from the same problems. All have disagreeable tastes, cause a bloated feeling in the stomach and require inconvenient mixing as aqueous formulations. Chief among these are the laxative preparations with water insoluble substances such as psyllium, bran husk, microcrystalline cellulose and the like. These all form gritty distasteful aqueous formulations that leave thick residue in the glass when drunk. Therefore, there is a need to provide a laxative dosage form that has a good taste and would enhance patient compliance.
SUMMARY OF INVENTION
The present invention is directed to a laxative based edible, gel composition. An aspect of the invention is the composition of such ingredients as a laxative, a gel forming agent and optional sweetening, coloring and flavoring agents.
A further aspect of the invention provides that the gel composition is formed as an edible gel by mixing the ingredients to form a fluid dispersion in water and to form a gel. In particular, and preferably, another aspect of the invention provides that the gel forming agent is first dispersed or otherwise converted into a flowable viscous to fluid state in water. The laxative is then combined with the fluid and mixed to form the gel dispersion. An aspect of invention is a sweetening agent, a flavor, and a coloring agent are added to the fluid dispersion. The fluid dispersion is added to containers preferably sized to produce one dose of laxative per container and allowed to cool to ambient temperature. Another aspect of the invention is to add sweetening agents, flavors and coloring agents before addition of laxative. Optionally, a preservative such as sodium benzoate, benzoic acid or parabens can be added. Preferably the preservatives after addition of laxative.
According to yet another aspect of the invention, the dispersion constituting the edible composition is gel at ambient temperature.
Additional aspects of the invention provide that the composition may optionally include sweeteners, flavoring agents, coloring agents and preservatives that can also be added to the composition as appropriate.


DETAILED DESCRIPTION
The objective was to develop a gel formulation that can be eaten with a spoon from a cup. The gel contains polyethylene glycol (PEG) of low (eg. 200) to high (eg. 40000) average molecular weight, preferably from about 200 to about 35000, more preferably from about 400 to about 10000, most preferably from about 400 to about 8000, especially most preferably about 400 to about 6000. PEG in this formulation acts as a laxative.
Several polymers such as sodium Carboxy Methyl cellulose sodium, Xanthan gum and carbopol were tried to form gel with PEG. With Carboxy methyl Cellulose Sodium, the gel separated into two layers. With Xanthan gum there was no gel formation at all. It is theorized that probably PEG itself is a water loving polymer and that could be the reason for the separation of the gel into two layers. Unexpectedly, carbopol polymer was very much compatible with PEG and formed a good gel. But even with Carbopol polymer, Citric acid and electrolytes were found to interfere in the gel formation. The striking observation was that Carbopol could form a good gel even at low concentration level in the formulation. It formed gels at less than 0.5 g and even up to levels below 0.05 g per dose of PEG of about 15 to 20 g. The process of preparation of the gel was very critical and needed much attention and care. It was found that Carbopol and PEG have to be added slowly with stirring. Also, it is preferable to add Carbopol and form dispersion before addition of PEG. Addition of PEG before Carbopol showed tendency of separation of PEG. It was also found that it is preferable to add sweetening agents, colorings agents and flavorings as appropriate, before addition of Carbopol for easier dispersion. Additionally, it was found surprisingly that addition of preservatives is preferable as the last step as it was found to interfere with gel formation if added earlier. RB-115-131 was chosen as the proto-type formula for further development.







TABLE 1







Gel formulations (Selection of polymers)









Per Unit dose (gm)













RB115-
RB115-
RB115-


Item
Ingredients
117
121
118














1
PEG 3350
17.000
17.000
17.000


2
Purified water
20.000
20.000
20.000


3
Citric acid
0.600
—
—


4
Sucralose
0.042
—
0.050


5
Sod.carboxy
10.000
—
—



methyl cellulose


6
Xanthan Gum
—
4.000
—


7
Carbopol 71G NF
—
—
0.500


8
Orange flavor
0.100
—
—


9
Orange color
0.001
—
—


10
Red # 40
—
—
0.001


11
Strawberry Flavor
—
—
0.100



Total Wt
47.743
41.000
37.651



Comments
No gel
No gel
Good Gel




formation
formation with
forms with




with Sodium
Xanthan gum
Carbopol.




carboxy

Carbopol has




methyl

been selected




cellulose

for further






experiments





Procedure:


Purified water was taken and kept under stirring. Citric acid and Sucralose (if present in the formulation), color and flavors were added one by one and dissolved. Polymer (Sodium carboxy methyl cellulose or Xanthan gum or Carbopol) was added and dispersed. PEG 3350 was then added and dissolved.


A good Gel was formed in case of the polymer carbopol and there was no gel formation with respect to other polymers tried.













TABLE 2







Gel formulations (effect of Citric acid and Electrolytes)









Per Unit dose (gm)










Item
Ingredients
RB115-119
RB115-123













1
PEG 3350
17.000
13.125


2
Purified water
22.000
20.000


3
Citric acid
0.500
—


4
Sodium chloride
0.100
0.351


5
Pot.chloride
—
0.049


6
Sod.bi carbonate
—
0.179


7
Sucralose
0.060
—


8
Sugar
—
5.000


9
Carbopol 71G NF
0.500
0.500


10
Red # 40
0.001
0.001


11
Strawberry
0.150
0.200



Flavor





Total Wt
40.311
39.405



Comments
No gel formation
No gel formation





Procedure:


Purified water was taken and kept under stirring. Citric acid, Sucralose or Sugar (if present in the formulation), 3 Electrolytes, color and flavors were added one by one and dissolved. Polymer carbopol was added and dispersed PEG 3350 was then added and dissolved.


No gel was formed. Citric acid lowerered pH less than 3.


Electrolytes also affect gel formation.













TABLE 3







Gel formulations with Carbopol Polymer (per unit dose gm)
















#
Ingredient
RB115-120
RB115-122
RB115-124
RB115-125
RB115-126
RB115-127
RB115-128
RB115-129



















1
PEG 3350
17.000 
17.000 
17.000
17.000
17.000
17.000
17.000
17.000


2
Purified
20.000 
20.000 
20.000
20.000
20.000
20.000
20.000
20.000



water


3
Sucralose
0.060
—
—
—
—
—
—
—


4
Sugar
—
5.000
 5.000
 5.000
 5.000
 5.000
 5.000
 5.000


5
Carbopol
0.500
0.500
 0.500
 0.400
 0.300
 0.200
 0.100
 0.050



71G NF


6
Vanilla
—
—
 0.200
 0.200
 0.200
 0.200
 0.200
 0.200



flavor


7
Red # 40
0.001
0.001


8
Strawberry
0.200
0.200
—
—
—
—
—
—



Flavor











Total Wt
37.761 
42.701 
42.700
42.600
42.500
42.500
42.500
42.250



Comments
Thick
Thick
Thick
Thick
Thick
Viscous
Thin gel
Thin gel




viscous
viscous
viscous
viscous
viscous
Good gel
pH 5.47
pH 6.0




Good gel
Good gel
Good gel
Good gel
Good gel
pH 5.18
Good
Good




pH 4.80
pH 4.80
pH 4.85
pH 4.90
pH 4.90
Good
taste
taste




Not good
Not good
Not good
Not good
Moderate
taste




taste
taste
taste
taste
taste





Procedure:


Purified water was taken and kept under stirring. Sucralose or Sugar (if present in the formulation) was added and dissolved. Color and flavor were added and dissolved. Polymer carbopol was added slowly over a period of 45 minutes and dispersed well. PEG 3350 was then added over a perod of 15 minutes and dissolved.


Considering the appearance, pH of the formulation and viscosity of the gel, Formulation RB-115-127 was selected for further experiments.













TABLE 4







Gel with Strawberry Flavor RB-115-131









#
Ingredients
10 units (gm)












1
PEG 3350
170.000


2
Purified Water
200.000


3
Carbopol 71G NF
2.000


4
Sugar
60.000


5
Red # 40
0.020


6
Strawberry Flavor
2.000



TOTAL WEIGHT
434.020



Comments
A good palatable viscous gel. pH: 5.3









Procedure:

Purified water was taken and kept under stirring. Sugar was added and dissolved. Color and flavor were added and dissolved. Polymer carbopol was added slowly over a period of 45 minutes and dispersed well. PEG 3350 was then added over a period of 15 minutes and dissolved. Poured into containers.







TABLE 5







Gel with Strawberry Flavor RB-115-137









#
Ingredients
10 units (gm)












1
PEG 3350
170.000


2
Purified Water
200.000


3
Carbopol 71G NF
2.000


4
Sugar
60.000


5
Purple color
0.020


6
Flavors
2.000


7
Sodium Benzoate
1.000



TOTAL WEIGHT
434.020



Comments
A good palatable viscous gel. pH: 5.3



Observation
When sodium Benzoate was added before




addition of Carbopol, good gel did not form.









Procedure:

Same as 131. Sodium benzoate was added after addition of PEG.

## Claims

1. An edible laxative composition, consisting essentially of:
a polyethylene glycol (PEG);
carbopol;
water; and
optional sweetening, color and flavor agents;
wherein the weight percentage of carbopol relative to the weight of PEG is in the range of from about 1.17% to about 1.2%, the weight percentage of carbopol to the combined weight of PEG and water is in the range of from about 0.5% to about 0.6%, the composition is free of citric acid and pharmaceutically acceptable electrolytes, the composition tastes good and the composition has the physical form of a viscous gel that is consumable by spoon and cup.

2. The composition according to claim 1 wherein the pH of the composition is in a range of from about 4.8 to about 6.0.

3. The composition according to claim 1 wherein the composition is free of pharmaceutically acceptable electrolytes which include potassium chloride, sodium chloride, sodium bicarbonate or any combination thereof.