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.

Description:
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&#39;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.