Pharmaceutical composition comprising eliglustat
The present invention relates to a pharmaceutical composition comprising glucosylceramide synthase inhibitor and a one or more pharmaceutically acceptable excipients. The present invention specifically relates to a sublingual pharmaceutical composition of eliglustat or a pharmaceutically acceptable salt thereof and a one or more pharmaceutically acceptable excipients. Moreover, the present invention further relates to a pharmaceutical composition of eliglustat or a pharmaceutically acceptable salt thereof which is used in the treatment of individual with lysozymal storage diseases selected from the group consisting of, Gaucher disease, Sphingolipidoses, Farber disease, Krabbe disease, Fabry disease, Schindler disease, Tay-Sachs disease and Niemann-Pick disease.
1 . A sublingual pharmaceutical composition comprising from about 45% to about 80% of eliglustat or a pharmaceutically acceptable salt thereof by weight of the sublingual composition and at least one or more pharmaceutically acceptable excipients; wherein the sublingual composition comprises an amount of from about 0.1 mg to about 30 mg of eliglustat or a pharmaceutically acceptable salt thereof; wherein the sublingual composition, following administration to a subject, provides an increase in AUC (0-inf) of eliglustat of at least about 20 times compared to the AUC (0-inf) of eliglustat provided by administration of an oral pharmaceutical composition absorbed through the gastrointestinal tract of the subject that comprises the same dose of the eliglustat or a pharmaceutically acceptable salt thereof as the sublingual composition; and wherein the sublingual composition is formulated in the form of sublingual film comprising a polymer and a plasticizer.
2 . The sublingual pharmaceutical composition according to claim 1 , wherein the sublingual composition, following administration to a subject, provides an increase in Cmax of eliglustat of at least about 1.5 times as compared to the Cmax of eliglustat provided by administration of an oral composition absorbed through the gastrointestinal tract of the subject that comprises the same dose of eliglustat or a pharmaceutically acceptable salt thereof as the sublingual composition .
3 . The sublingual pharmaceutical composition according to claim 1 , wherein the increase in the AUC (0-inf) of eliglustat is from about 20 times to about 80 times.
4 . The sublingual pharmaceutical composition according to claim 3 , wherein the increase in the AUC (0-inf) of eliglustat is from about 20 times to about 30 times.
5 . The sublingual pharmaceutical composition according to claim 2 , wherein the increase in the Cmax of eliglustat is from about 2 times to about 60 times.
6 . The sublingual pharmaceutical composition according to claim 5 , wherein the increase in the Cmax of eliglustat is about 24 times.
7 . A method of treating Gaucher's disease type 1 in a subject in need thereof, comprising administering to the subject a sublingual pharmaceutical composition comprising from about 45% to about 80% of eliglustat or a pharmaceutically acceptable salt thereof by weight of the sublingual composition and at least one or more pharmaceutically acceptable excipients; wherein the sublingual composition comprises an amount of from about 0.1 mg to about 30 mg of eliglustat or a pharmaceutically acceptable salt thereof; and wherein the sublingual composition, following administration to a subject, provides an increase in AUC (0-inf) of eliglustat of at least about 20 times as compared to AUC (0-inf) of eliglustat provided by administration of an oral pharmaceutical composition absorbed through the gastrointestinal tract of the subject that comprises the same dose of the eliglustat or a pharmaceutically acceptable salt thereof as the sublingual composition; and wherein the sublingual composition is formulated in the form of sublingual film comprising a polymer, and a plasticizer.
8 . The method of treating Gaucher's disease type 1 according to claim 7 , wherein the therapeutically effective dose in the sublingual composition is about 60% to about 99% lower than the oral composition.
9 . The method of treating Gaucher's disease type 1 according to claim 7 , wherein the sublingual pharmaceutical composition provides an increase in the AUC (0-inf) of eliglustat of about 20 times to about 30 times.
10 . The method of treating Gaucher's disease type I according to claim 7 , wherein the sublingual pharmaceutical composition comprises from about 0.1 mg to about 10 mg of eliglustat or a pharmaceutically acceptable salt thereof.
11 . A sublingual pharmaceutical composition comprising from about 45% to about 80% of eliglustat or a pharmaceutically acceptable salt thereof by weight of the sublingual composition and at least one or more pharmaceutically acceptable excipients; wherein the sublingual composition comprises an amount of from about 0.1 mg to about 30 mg of eliglustat or a pharmaceutically acceptable salt thereof; and wherein the sublingual composition has a therapeutically effective dose of eliglustat or a pharmaceutically acceptable salt thereof of about 50% to about 99% lower than that of an oral pharmaceutical composition of eliglustat or a pharmaceutically acceptable salt thereof absorbed through the gastrointestinal tract of a subject; wherein the lower therapeutically effective dose of eliglustat or a pharmaceutically acceptable salt thereof provides an equivalent or better therapeutic efficacy in comparison to the oral pharmaceutical composition; wherein the sublingual composition, following administration to a subject at a same therapeutic dose as the oral composition absorbed through the gastrointestinal tract of the subject, provides an increase in AUC (0-inf) of eliglustat of at least about 20 times compared to the AUC (0-inf) of eliglustat provided by administration of the oral composition; and wherein the sublingual composition is formulated in the form of sublingual film comprising a polymer in an amount from about 10% w/w to about 60% w/w, a plasticizer in an amount of about 0.5% w/w to about 40% w/w, and a sweetening agent in an amount of about 10% w/w or less.
12 . The sublingual pharmaceutical composition according to claim 11 , wherein the therapeutically effective dose of eliglustat or a pharmaceutically acceptable salt thereof in the sublingual composition is about 60% to about 99% lower than that of the oral pharmaceutical composition.
13 . The sublingual pharmaceutical composition according to claim 1 , wherein the composition provides an increase in AUC (0-inf) of eliglustat of at least about 20 times and an increase in Cmax of eliglustat of at least about 20 times as compared to the AUC (0-inf) and Cmax provided by an oral pharmaceutical composition absorbed through the gastrointestinal tract that comprises the same dose of eliglustat or a pharmaceutically acceptable salt thereof.
14 . The sublingual composition according to claim 1 , wherein the polymer is a water-soluble polymer selected from the group consisting of hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, water-soluble chemical derivatives of starch, sodium hyaluronate, gelatin, and mixtures thereof.
15 . The sublingual composition according to claim 14 , wherein the plasticizer is selected from the group consisting of polyethylene glycol, polypropylene glycol, polyethylene-propylene glycol, glycerol, glycerol monoacetate, glycerol diacetate, glycerol triacetate, triacetin, polysorbate, cetyl alcohol, propylene glycol, sorbitol, sodium diethylsulfosuccinate, triethyl citrate, tributyl citrate, and mixtures thereof.
16 . The sublingual composition according to claim 15 , wherein the polymer is hydroxypropylmethyl cellulose and the plasticizer is propylene glycol.
17 . The sublingual composition according to claim 7 , wherein the polymer is hydroxypropylmethyl cellulose and the plasticizer is propylene glycol.