Soft gel capsule preparations

Abstract

The disclosure relates to a pharmaceutical or dietary composition in the form of a soft gel capsule comprising a liquid or semisolid fill and a shell, the fill comprising at least one active ingredient or dietary supplement, dissolved, suspended or solubilized in a solution comprising water and alcohol, and a solubilizer and thickening agent. The disclosure furthermore relates to methods of reducing brittleness and fragility of such soft gel capsules.

1 . A pharmaceutical or dietary supplement composition in the form of a soft gel capsule, the capsule comprising a liquid or semisolid fill and a shell,
 wherein the fill comprises   a) at least one active ingredient or dietary supplement dissolved, suspended or solubilized in a solution comprising less than 50% (w/w) of water and less than 5% (w/w) of alcohol,   b) at least one solubilizer, wherein the solubilizer is selected from the group consisting of low molecular weight polyethylene glycol (PEG) having a molecular weight of 300 to 600 and plant oils selected from the group consisting of soybean oil, sunflower oil, olive oil, maize oil, medium-chain triglycerides and combinations thereof; and   c) at least one thickening agent, wherein the thickening agent is selected from the group consisting of high molecular weight polyethylene glycol, beeswax, glycerol monostearate 40-55 (Type I) EP/Mono, colloidal silicone dioxide, hard fat, lauroyl polyoxyl-32 glycerides, or stearoyl macrogol-32 glycerides, and combinations thereof, and   
       wherein the shell comprises an edible polymer and optionally one or more of a plasticizer, an opacifier and colorants. 
     
     
         2 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein the solution comprising water and alcohol comprises
 i. less than 5% (w/w), less than 4% (w/w), less than 3% (w/w), less than 2%, less than 1% (w/w), less than 0.5% (w/w), or less than 0.25% (w/w) of alcohol, wherein the alcohol is ethanol; and   ii. less than 50% (w/w), less than 45% (w/w), less than 40% (w/w), less than 35% (w/w), less than 30% (w/w), less than 25% (w/w), less than 20% (w/w), or less than 15% (w/w) of water.   
     
     
         3 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein the solution comprising water and alcohol comprises
 i. between 5% to 0.2% (w/w), between 4% to 0.5% (w/w), between 3% to 1% (w/w), between 2% to 1% (w/w), between 2% to 0.5% (w/w), or between 1% to 0.2% (w/w) of alcohol wherein the alcohol is ethanol; and   ii. between 10% to 50% (w/w), between 20% to 50% (w/w), between 30% to 50% (w/w), between 35% to 50% (w/w), between 40% to 50% (w/w), between 45% to 50% (w/w), between 15% to 49% (w/w), between 20% to 48% (w/w), between 25% to 47% (w/w), between 30% to 46% (w/w), or between 35% to 45% (w/w) of water.   
     
     
         4 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein
 a) the active ingredient is dissolved, suspended or solubilized in a solution comprising less than 2% (w/w) of alcohol, wherein the alcohol is ethanol and less than 50% (w/w) of water; and   b) the at least one solubilizer is selected from the group consisting of MACROGOL 600, sunflower oil, olive oil, maize oil, and combinations thereof; and   c) the at least one thickening agent is selected from MACROGOL 4000, GELEOL™ Mono and Diglycerides NF, colloidal silicone dioxide, beeswax, and combinations thereof; and   wherein the shell comprises an edible polymer and optionally one or more of a plasticizer, an opacifier and colorants.   
     
     
         5 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein the active ingredient is a hydrophilic plant extract. 
     
     
         6 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein the active ingredient is a plant extract selected from the group consisting of  Matricaria  flower liquid extract, Peppermint leaves liquid extract, Liquorice root liquid extract, Caraway fruit liquid extract, Bitter candytuft fresh plant liquid extract, Melissa leaf liquid extract, Chamomile flowers liquid extract, Lemon balm leaf liquid extract,  Angelica  root liquid extract, Celandine herb liquid extract, Milk thistle fruit liquid extract, and combinations thereof. 
     
     
         7 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein the active ingredient is a plant extract comprising  Matricaria  flower liquid extract, Peppermint leaves liquid extract, Liquorice root liquid extract, Caraway fruit liquid extract, Bitter candytuft fresh plant liquid extract and Melissa leaf liquid extract. 
     
     
         8 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein the active ingredient is a plant extract comprising Chamomile flowers liquid extract, Peppermint leaves liquid extract, Liquorice root liquid extract, Caraway fruit liquid extract, Bitter candytuft fresh plant liquid extract, Lemon balm leaf liquid extract,  Angelica  root liquid extract, Celandine herb liquid extract and Milk thistle fruit liquid extract. 
     
     
         9 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein the active ingredient is a plant extract selected from the group consisting of American aspen or aspen stem bark and leaves liquid extract, Common ash stem bark liquid extract, European goldenrod herb liquid extract, and combinations thereof;
 e) The pharmaceutical or dietary supplement composition of  claim 1 , wherein the edible polymer is selected from the group consisting of gelatine, gelatine RXL, gelatine GELITA® RXL R2 and non-animal derived compounds, selected from the group consisting of SEAGEL® CAP 203, carrageenan, vegetable starch, and combinations thereof.   
     
     
         10 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein
 a) the active ingredient is IBEROGAST N concentrate;   b) the at least one solubilizer is selected from the group consisting of MACROGOL 600, sunflower oil, olive oil, maize oil, and combinations thereof;   c) the at least one thickening agent is selected from the group consisting of MACROGOL 4000, GELEOL™ Mono and Diglycerides NF, colloidal silicone dioxide, beeswax, and combinations thereof; and   d) wherein the shell comprises an edible polymer selected from the group consisting of gelatine, gelatine RXL, gelatine GELITA® RXL R2 and non-animal derived compounds selected from the group consisting of SEAGEL® CAP 203, carrageenan, vegetable starch, and combinations thereof.   
     
     
         11 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein the plasticizer is selected from the group consisting of glycerine, propylene glycol, mannitol, sorbitan, sorbitol, low molecular weight polyols, and combinations thereof. 
     
     
         12 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein the opacifier is selected from the group consisting of starch, titanium dioxide, calcium carbonate, zinc oxide, tricalcium phosphate, iron oxides, and combinations thereof. 
     
     
         13 . The pharmaceutical or dietary supplement composition of  claim 1 , wherein
 (i) a water activity value of the fill is between 0.30 and 0.60, between 0.35 and 0.50, between 0.37 and 0.47, or between 0.38 and 0.45; or   (ii) the water activity value of the fill is between 0.70 and 0.90, between 0.73 and 0.85, between 0.74 and 0.84, or between 0.75 and 0.83.   
     
     
         14 . A method of reducing brittleness of a soft gel capsule  claim 1 , wherein a solubilizer is added to the fill before encapsulation with the shell, wherein the solubilizer is selected from the group consisting of MACROGOL 400, MACROGOL 600, plant oils and combinations thereof, wherein said plant oils are selected from the group consisting of soybean oil, sunflower oil, olive oil, maize oil, and combinations thereof. 
     
     
         15 . A method of reducing the fragility of pharmaceutical or dietary compositions in the form of a soft gel capsule as claimed in  claim 1 , the method comprising adding a solubilizer to the fill before encapsulation with the shell, wherein the solubilizer is selected from the group consisting of MACROGOL 400, MACROGOL 600, plant oils and combinations thereof, wherein said plant oils are selected from the group consisting of soybean oil, sunflower oil, olive oil, maize oil, and combinations thereof. 
     
     
         17 . A pharmaceutical or dietary supplement composition according to  claim 1 , for use in the treatment of functional disorders of a gastrointestinal (GI) tract, wherein the functional disorders of the GI tract are selected from the group consisting of functional dyspepsia (FD), irritable bowel syndrome (IBS), minor gastro-intestinal complaints, functional impairments of the GI tract and combinations thereof. 
     
     
         18 . The pharmaceutical or dietary supplement composition of  claim 5 , wherein the active ingredient is a highly concentrated hydrophilic plant extract. 
     
     
         19 . The pharmaceutical or dietary supplement composition according to  claim 1 , for use in the treatment of the functional disorders of the gastrointestinal (GI) tract according to  claim 17 , wherein the minor gastro-intestinal complaints are selected from the group consisting of bloating, minor spasms, burning sensations, pain, inflammations, swelling and combinations thereof. 
     
     
         20 . The pharmaceutical or dietary supplement composition according to  claim 1 , for use in the treatment of the functional disorders of the gastrointestinal (GI) tract according to  claim 17  further comprising accompanying diseases of the locomotor apparatus of rheumatic origin, wherein said accompanying diseases are selected from a group consisting of rheumatoid arthritis, arthroses, spinal syndromes, epicondylitis, periarthritis, Bechterew's disease, lumbago and combinations thereof.