Soft gelatin encapsulated pharmaceutical composition of cis-5,8,11,14,17-eicosapentaenoic acid in free acid form and cis-7,10,13,16,19-docosapentaenoic acid in free acid form

Abstract

Shelf life of soft gelatin capsules comprising a soft gelatin shell encapsulating a pharmaceutical formulation comprising cis-5,8,11,14,17-eicosapentaenoic acid (C20:5 n-3; “EPA”) in free acid form in an amount from 25 wt % to 99 wt % of the formulation and cis-7,10,13,16,19-docosapentaenoic acid (C22:5 n-3; “DPA”) in free acid form in an amount from 1 wt % to 75 wt % of the formulation in which the gelatin component of the shell is Type B gelatin, is improved by replacing up to 75 wt % of the gelatin component with porcine Type A gelatin.

1 - 37 . (canceled) 
     
     
         38 : A soft gelatin capsule, comprising:
 a soft gelatin shell encapsulating a pharmaceutical formulation,   wherein the pharmaceutical formulation comprises polyunsaturated fatty acids (PUFAs) in free acid form including
 cis-5,8,11,14,17-eicosapentaenoic acid (C20:5 n-3; “EPA”) in free acid form in an amount of from 45 wt % to 65 wt % of the pharmaceutical formulation, 
 cis-7,10,13,16,19-docosapentaenoic acid (C22:5 n-3; “DPA”) in free acid form in an amount of from 1 wt % to 75 wt % of the pharmaceutical formulation, 
 cis-4,7,10,13,16,19-docosahexaenoic acid (C22:6 n-3; “DHA”) in free acid form in an amount of from about 15 wt % to about 25 wt % of the pharmaceutical formulation, and 
 at least one omega-6 PUFA in free acid form, 
 wherein the total combined amount of omega-6 PUFAs in free acid form is no more than 10 wt %, 
 wherein the amount of all PUFAs in said pharmaceutical formulation does not exceed 100 wt %, 
   wherein the soft gelatin shell comprises a gelatin component made up of porcine Type A gelatin and a Type B gelatin, and   wherein the porcine Type A gelatin is present in an amount of no more than about 75 wt % of the gelatin component.   
     
     
         39 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the porcine Type A gelatin is present in an amount of no more than about 50 wt % of said gelatin component.   
     
     
         40 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the porcine Type A gelatin is present in an amount of no less than about 10 wt % of the gelatin component.   
     
     
         41 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the porcine Type A gelatin is present in an amount of no less than about 25 wt % of the gelatin component.   
     
     
         42 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the Type B gelatin is bovine Type B gelatin.   
     
     
         43 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the DPA in free acid form is present in the pharmaceutical formulation in an amount of at least 2 wt %.   
     
     
         44 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the DPA in free acid form is present in the pharmaceutical formulation in an amount of at least 3 wt %.   
     
     
         45 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the DPA in free acid form is present in the pharmaceutical formulation in an amount of at least 4 wt %.   
     
     
         46 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the DPA in free acid form is present the pharmaceutical formulation in an amount of no more than about 50 wt %.   
     
     
         47 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the DPA in free acid form is present in the pharmaceutical formulation in an amount of no more than about 25 wt %.   
     
     
         48 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the DPA in free acid form is present in the pharmaceutical formulation in an amount of no more than about 10 wt %.   
     
     
         49 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the DPA in free acid form is present in the pharmaceutical formulation in an amount of no more than about 8 wt %.   
     
     
         50 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the DPA in free acid form is present in the pharmaceutical formulation in an amount of from about 3 wt % to about 7 wt %.   
     
     
         51 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the DPA in free acid form is present in the pharmaceutical formulation in an amount of from about 4 wt % to about 6 wt %.   
     
     
         52 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the pharmaceutical formulation comprises EPA in free acid form and DHA in free acid form in a total combined amount of from about 60 wt % to about 90 wt % of the pharmaceutical formulation.   
     
     
         53 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the pharmaceutical formulation comprises at least one further omega-3 PUFA in free acid form.   
     
     
         54 : The soft gelatin capsule as claimed in  claim 53 , wherein
 the at least one further omega-3 PUFA is selected from the group consisting of α-linolenic acid (C18:3 n-3); moroctic acid (C18:4 n-3); eicosatetraenoic acid (C20:4 n-3); heneicosapentaenoic acid (C21:5 n-3); and eicosatrienoic acid (C20:3 n-3).   
     
     
         55 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the total combined amount of omega-3 PUFAs in free acid form in the pharmaceutical formulation is from about 80 wt % to about 95 wt % of said formulation.   
     
     
         56 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the at least one omega-6 PUFA is selected from the group consisting of dihomo-gamma-linolenic acid (C20:3 n-6); arachidonic acid (C20:4 n-6); linoleic acid (C18:2 n-6); docosapentaenoic acid (C22:5; n-6); gamma-linolenic acid (C18:3 n-6); and eicosadienoic acid (C22:2 n-6).   
     
     
         57 . The soft gelatin capsule as claimed in  claim 38 , encapsulating from about 100 mg to about 2000 mg of the pharmaceutical formulation. 
     
     
         58 : The soft gelatin capsule as claimed in  claim 38 , wherein
 the capsule is coated with a polymeric film coating to control release of the pharmaceutical formulation in the intestines.   
     
     
         59 : A process for manufacturing a soft gelatin capsule according to  claim 38 , said process comprising encapsulating said pharmaceutical formulation in said soft gelatin shell. 
     
     
         60 : A method of treatment or prophylaxis of a condition, said method comprising:
 administering a therapeutically effective amount of at least one soft gelatin capsule according to  claim 38  to a subject in need thereof;   wherein said condition is at least one selected from the group consisting of chronic inflammatory conditions, hyperlipidaemia, hypertriglyceridaemia, asthma, bipolar disorder, and neoplastic disease.   
     
     
         61 : A soft gelatin capsule, comprising:
 a soft gelatin shell encapsulating a pharmaceutical formulation,   wherein the pharmaceutical formulation comprises polyunsaturated fatty acids (PUFAs) in free acid form including
 cis-5,8,11,14,17-eicosapentaenoic acid (C20:5 n-3; “EPA”) in free acid form amount of from 45 wt % to 65 wt % of the pharmaceutical formulation, 
 cis-7,10,13,16,19-docosapentaenoic acid (C22:5 n-3; “DPA”) in free acid form in an amount of from 1 wt % to 75 wt % of the pharmaceutical formulation, 
 cis-4,7,10,13,16,19-docosahexaenoic acid (C22:6 n-3: “DHA”) in free acid form in an amount of from about 15 wt % to about 25 wt % of the pharmaceutical formulation, and 
 at least one omega-6 PUFA in free acid form, 
 wherein the total combined amount of omega-6 PUFAs in free acid form is no more than 10 wt %, 
 wherein the amount of all PUFAs in said pharmaceutical formulation does not exceed 100 wt %, 
   wherein the soft gelatin shell comprises a gelatin component made up of porcine Type A gelatin and a Type B gelatin, and   wherein the porcine Type A gelatin is present in an amount of no less than about 10 wt % to no more than about 75 wt % of the gelatin component.   
     
     
         62 : A soft gelatin capsule, comprising:
 a soft gelatin shell encapsulating a pharmaceutical formulation,   wherein the pharmaceutical formulation comprises polyunsaturated fatty acids (PUFAs) in free acid form including
 cis-5,8,11,14,17-eicosapentaenoic acid (C20:5 n-3; “EPA”) in free acid form amount of from 45 wt % to 65 wt % of the pharmaceutical formulation, 
 cis-7,10,13,16,19-docosapentaenoic acid (C22:5 n-3; “DPA”) in free acid form in an amount of from 1 wt % to 75 wt % of the pharmaceutical formulation, 
 cis-4,7,10,13,16,19-docosahexaenoic acid (C22:6 n-3; “DHA”) in free acid form in an amount of from about 15 wt % to about 25 wt % of the pharmaceutical formulation, and 
 at least one omega-6 PUFA in free acid form, 
 wherein the total combined amount of omega-6 PUFAs in free acid form is no more than 10 wt % 
 wherein the amount of all PUFAs in said pharmaceutical formulation does not exceed 100 wt %, 
   wherein the soft gelatin shell comprises a gelatin component made up of porcine Type A gelatin and a Type B gelatin, and   wherein the porcine Type A gelatin is present in an amount of no less than about 0.5 wt % to no more than about 75 wt % of the gelatin component.