PHARMACEUTICAL COMPOSITIONS
The present invention provides for a method of treatment of IgA nephropathy, which method comprises: (i) identifying a pharmaceutically acceptable composition intended to treat IgA nephropathy comprising budesonide and one or more pharmaceutically-acceptable excipients that provide for a modified release of said budesonide after administration to the gastrointestinal tract, which composition fulfils the following requirements in a standard in vitro USP<711>/Ph.Eur. 2.9.3 dissolution test using a dissolution apparatus according to Apparatus 2 (Paddle Apparatus) of said test; (a) the composition fulfils the requirement that no more than about 10% of the budesonide is released into the dissolution medium within about 120 minutes, when the dissolution medium is aqueous and has a pH of about 1.2; (b) the composition fulfils the requirement that no more than about 10% of the budesonide is released into a pharmaceutically-relevant dissolution medium within about 30 minutes; and (c) the composition fulfils the requirement that at least about 70% of the budesonide is released into the pharmaceutically-relevant dissolution medium within about 120 minutes; (ii) wherein the method comprises the step of administering said composition to a patient with IgA nephropathy in need of said treatment.
1 . (canceled)
2 . A method of treatment of IgA nephropathy in a subject in need thereof, comprising:
orally administering to said subject, in the morning at least one hour before the first meal of the day, a dose of about 16 mg of budesonide, which dose is contained in one or more pharmaceutical compositions comprising budesonide, which one or more pharmaceutical compositions comprise:
a plurality of cores comprising budesonide encapsulated within a capsule comprising an enteric coating, wherein the plurality of cores are each coated with an extended release pharmaceutically-acceptable polymeric blend comprising a water-insoluble polymer having a solubility in water (at 25° C.) of less than about 0.1 mg/mL and a water-soluble polymer having a solubility in water (at 25° C.) of at least about 10 mg/mL, wherein the water-insoluble polymer is present in an amount of from about 45 wt. % to about 90 wt. % of the extended release pharmaceutically-acceptable polymeric blend and the water-soluble polymer is present in an amount of from about 35 wt. % to about 5 wt. % of the extended release pharmaceutically-acceptable polymeric blend;
wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from 5 wt. % to about 18 wt. % of the total coated core weight.
3 . The method according to claim 2 , wherein the water-insoluble polymer is present in an amount of from about 45 wt. % to about 65 wt. % of the extended release pharmaceutically-acceptable polymeric blend and the water-soluble polymer is present in an amount of from about 35 wt. % to about 15 wt. % of the extended release pharmaceutically-acceptable polymeric blend.
4 . The method according to claim 2 , wherein the water-insoluble polymer is present in an amount of from about 47 wt. % to about 56 wt. % of the extended release pharmaceutically-acceptable polymeric blend and the water-soluble polymer is present in an amount of from about 32 wt. % to about 22 wt. % of the extended release pharmaceutically-acceptable polymeric blend.
5 . The method according to claim 2 , wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from 6 wt. % to about 16 wt. % of the total coated core weight.
6 . The method according to claim 2 , wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from 6 wt. % to about 12 wt. % of the total coated core weight.
7 . The method according to claim 2 , wherein the water-insoluble polymer is an alkyl cellulose.
8 . The method according to claim 7 , wherein the alkyl cellulose is an ethyl cellulose.
9 . The method according to claim 2 , wherein the water-soluble polymer is selected from polyethylene glycol (PEG), hydroxypropylmethyl cellulose (HPMC), and hydroxypropyl cellulose (HPC).
10 . The method according to claim 2 , wherein the water-insoluble polymer is an alkyl cellulose and the water-soluble polymer is selected from polyethylene glycol (PEG), hydroxypropylmethyl cellulose (HPMC), and hydroxypropyl cellulose (HPC).
11 . The method according to claim 2 , where the enteric coating is present in an amount of from about 34 mg to about 46 mg per capsule.
12 . The method according to claim 2 , wherein the method comprises orally administering to the subject the pharmaceutical composition at a daily dose of about 16 mg of budesonide.
13 . The method according to claim 2 , wherein the pharmaceutically-acceptable polymeric blend is cured.
14 . The method according to claim 2 , wherein the combination of the enteric coating and the polymers in the extended-release component result in the pharmaceutical composition releasing budesonide substantially to the ileum region of the small intestine to reduce the formation by mucosal B cells in Peyer's patches in the ileum of secretory galactose-deficient IgA antibodies that drive immune complex formation in IgA nephropathy, to treat said IgA nephropathy, and limiting systemic exposure of said budesonide.
15 . A method of treatment of IgA nephropathy in a subject in need thereof, comprising orally administering to said subject a daily dose of about 16 mg of budesonide, which dose is contained in one or more pharmaceutical compositions comprising budesonide and an extended-release component present on said budesonide,
the extended-release component comprising a pharmaceutically-acceptable cured polymeric blend of a water-insoluble polymer having a solubility in water (at 25° C.) of less than about 0.1 mg/mL and a water-soluble polymer having a solubility in water (at 25° C.) of at least about 10 mg/mL; and
the composition further comprising an enteric coating,
wherein the combination of the enteric coating and the cured polymeric blend in the extended-release component result in the pharmaceutical composition releasing budesonide substantially to the ileum region of the small intestine to reduce the formation by mucosal B cells in Peyer's patches in the ileum of secretory galactose-deficient IgA antibodies that drive immune complex formation in IgA nephropathy, to treat said IgA nephropathy, and limiting systemic exposure of said budesonide.
16 . The method according to claim 15 , wherein the composition is in the form of one or more capsules or tablets.
17 . The method according to claim 16 , wherein the enteric coating is located at the exterior of the composition.
18 . The method according to claim 15 , wherein the composition is in the form of one or more capsules.
19 . The method according to claim 18 , wherein the one or more capsules each contain a plurality of cores comprising budesonide, and the plurality of cores are coated with the extended release pharmaceutically-acceptable cured polymeric blend.
20 . The method according to claim 19 wherein the water-insoluble polymer is present in an amount of from about 45 wt. % to about 90 wt. % of the extended release pharmaceutically-acceptable cured polymeric blend and the water-soluble polymer is present in an amount of from about 35 wt. % to about 5 wt. % of the extended release pharmaceutically-acceptable cured polymeric blend.
21 . The method according to claim 19 , wherein the water-insoluble polymer is present in an amount of from about 45 wt. % to about 65 wt. % of the extended release pharmaceutically-acceptable cured polymeric blend and the water-soluble polymer is present in an amount of from about 35 wt. % to about 15 wt. % of the extended release pharmaceutically-acceptable cured polymeric blend.
22 . The method according to claim 19 , wherein the water-insoluble polymer is present in an amount of from about 47 wt. % to about 56 wt. % of the extended release pharmaceutically-acceptable cured polymeric blend and the water-soluble polymer is present in an amount of from about 32 wt. % to about 22 wt. % of the extended release pharmaceutically-acceptable cured polymeric blend.
23 . The method according to claim 19 , wherein the extended release pharmaceutically-acceptable cured polymeric blend is present in an amount of from 5 wt. % to about 18 wt. % of the total coated core weight.
24 . The method according to claim 19 , wherein the extended release pharmaceutically-acceptable cured polymeric blend is present in an amount of from about 6 wt. % to about 16 wt. % of the total coated core weight.
25 . The method according to claim 19 , wherein the extended release pharmaceutically-acceptable cured polymeric blend is present in an amount of from about 6 wt. % to about 12 wt. % of the total coated core weight.
26 . The method according to claim 15 , wherein the water-insoluble polymer is an alkyl cellulose.
27 . The method according to claim 26 , wherein the alkyl cellulose is an ethyl cellulose.
28 . The method according to claim 15 , wherein the water-soluble polymer is selected from polyethylene glycol (PEG), hydroxypropylmethyl cellulose (HPMC), and hydroxypropyl cellulose (HPC).
29 . The method according to claim 19 , wherein the enteric coating is on the plurality of cores.
30 . The method according to claim 18 , wherein the enteric coating is on the one or more capsules.
31 . The method according to claim 18 , where the enteric coating is present in an amount of from about 34 mg to about 46 mg per capsule.