JPWO2020148271A5 - - Google Patents

Claims (41)

(i) a phosphodiesterase inhibitor,
(ii) one or more pharmaceutically acceptable hydrophilic matrix-forming agents;
(iii) one or more pharmaceutically acceptable excipients selected from the group consisting only of fillers, glidants and lubricants; and (iv) optionally, pharmaceutically acceptable A modified release tablet formulation comprising a coating system comprising: 2. The modified release tablet formulation of claim 1, wherein the hydrophilic matrix-forming agent comprises hydroxypropylmethylcellulose, hydroxypropylcellulose, or mixtures thereof. 2. The modified release tablet formulation of claim 1, wherein the hydrophilic matrix-forming agent comprises one or more hydroxypropylmethylcelluloses, or mixtures thereof. 4. The modified release tablet formulation of claim 3 , wherein the hydroxypropyl methylcellulose is hypromellose 2910, hypromellose 2208, or mixtures thereof. Said hydrophilic matrix forming agent is from about 10% w/w to about 30% w/w of hydroxypropyl methylcellulose, such as from 15% w/w to about 25% w/w, especially 17.5% w/w. The modified release tablet formulation according to any one of claims 1 to 4 , which is present at a concentration of 6. Any one of claims 1-5 , wherein said one or more pharmaceutically acceptable excipients comprises a filler selected from lactose monohydrate , microcrystalline cellulose , and mixtures thereof . A modified release tablet formulation as described. 7. The modified release tablet of claim 6 , wherein the filler is present at a concentration of about 30% to about 78% w/w lactose monohydrate and 0 to about 40% w/w microcrystalline cellulose. pharmaceutical formulation. 8. The modified release tablet formulation of Claim 7, wherein the filler is lactose monohydrate. 9. The modified release tablet formulation of claim 8, wherein lactose monohydrate is present at a concentration of about 30% to about 78% w/w. The modified release tablet formulation of any one of claims 6-9, wherein the lactose monohydrate is present at a concentration of about 71% w/w. The modified release tablet formulation of any one of claims 1-10 , wherein one of said pharmaceutically acceptable excipients is a glidant . 12. The modified release tablet formulation of claim 11, wherein the glidant is colloidal silicon dioxide. said glidant is from about 0.1% w/w to about 2% w/w of colloidal silicon dioxide, such as from about 0.2% w/w to about 1% w/w, especially 0.5% 13. The modified release tablet formulation of claim 11 or 12 , present in a w/w concentration. The modified release tablet formulation of any one of claims 1-13 , wherein one of said pharmaceutically acceptable excipients is a lubricant. 15. The modified release tablet formulation of Claim 14, wherein the lubricant is magnesium stearate. The lubricant is from about 0.1% w/w to about 2% w/w magnesium stearate, such as from about 0.5% w/w to about 1.5% w/w, especially 1.0% w/w. 16. The modified release tablet formulation of claim 14 or 15 , present in a concentration of % w/w. (i) a phosphodiesterase inhibitor,
(ii) a hydrophilic matrix-forming agent, wherein said hydrophilic matrix-forming agent is hydroxypropyl methylcellulose present at a concentration of about 15% w/w to about 25% w/w;
(iii) from about 30% w/w to about 78% w/w of lactose monohydrate;
(iv) optionally, one or more pharmaceutically acceptable excipients selected from the group consisting of glidants and lubricants; and
(v) optionally, a pharmaceutically acceptable coating system;
A modified release tablet formulation comprising: 18. The coating system of any one of claims 1-17, wherein the coating system is selected from a hydroxypropylmethylcellulose-based coating system, a polyvinyl alcohol-based coating system, a polyvinyl alcohol-polyethylene glycol-based coating system, and an ethylcellulose-based functional membrane coating system. A modified release tablet formulation as described in . Modified release tablet formulation according to any one of claims 1 to 18, comprising a coating system. The modified release tablet formulation of any one of claims 1-19, comprising a film coating. 21. The modified release tablet formulation of claim 19 or 20, wherein the coating is present in an amount that provides a weight gain of about 3% to about 5% of the tablet formulation. The modified release tablet formulation of any one of claims 1-21, wherein the phosphodiesterase inhibitor is a PDE4 inhibitor. wherein the PDE4 inhibitor is a compound of formula (I)

or a pharmaceutically acceptable salt or polymorphic form thereof. The compound of formula (I) is 2-(3,5-dichloro-1-oxide-pyridin-4-yl)-1-(7-difluoromethoxy-2′,3′,5′,6′-tetrahydro -spiro[1,3-benzodioxol-2,4′-(4H)-thiopyran-1′,1′-dioxido]-4-yl) ethanone , polymorphic form E, claim 23 A modified release tablet formulation as described in . The modified release tablet formulation of any one of claims 1-24 , wherein the compound is in micronized form. The formulation contains about 3.3% w/w micronized 2-(3,5-dichloro-1-oxide-pyridin-4-yl)-1-(7-difluoromethoxy-2′,3′, 5′,6′-tetrahydro-spiro[1,3-benzodioxol-2,4′-(4H)-thiopyran-1′,1′-dioxido]-4-yl) ethanone , about 17. 5% w/w hypromellose, about 77.7% w/w lactose monohydrate, about 0.5% w/w colloidal silicon dioxide, about 1.0% w/w magnesium stearate, and optionally optionally a polyvinyl alcohol - based coating system. The formulation contains about 10.0% w/w micronized 2-(3,5-dichloro-1-oxide-pyridin-4-yl)-1-(7-difluoromethoxy-2′,3′, 5′,6′-tetrahydro-spiro[1,3-benzodioxol-2,4′-(4H)-thiopyran-1′,1′-dioxido]-4-yl) ethanone , about 17. 5% w/w hypromellose, about 71.0% w/w lactose monohydrate, about 0.5% w/w colloidal silicon dioxide, about 1.0% w/w magnesium stearate, and optionally optionally a polyvinyl alcohol - based coating system. wherein the phosphodiesterase inhibitor is D ₅₀ 28. The modified release tablet formulation of any one of claims 1-27, having a particle size distribution of ≤5 μm. 29. The modified release tablet formulation of any one of claims 1-28, wherein the phosphodiesterase inhibitor is present in an amount of about 5 mg to about 60 mg. 30. The modified release tablet formulation of any one of claims 1-29, wherein the phosphodiesterase inhibitor is present in an amount of 10 mg, 20 mg, 30 mg, or 40 mg. The modified release tablet formulation according to any one of claims 1-30, which is coated with a polyvinyl alcohol-based coating system. 32. The modified release tablet formulation of claim 31, wherein the coating is present in an amount of about 3% to about 5% weight gain of the tablet formulation. 32. The modified release tablet formulation of claim 31, wherein the coating is present in an amount of 4% weight gain of the tablet formulation. A modified release tablet formulation according to any one of claims 1 to 33 for treating, preventing or alleviating a disease or condition of the skin. Proliferative and inflammatory skin disorders, dermatitis, psoriasis, plaque psoriasis (plaque psoriasis), atopic dermatitis, seborrheic dermatitis, contact dermatitis, cancer, epidermal inflammation, alopecia, alopecia areata skin disease or condition selected from the group consisting of skin atrophy, steroid-induced skin atrophy, skin aging, skin photoaging, acne, urticaria, pruritus, and eczema. Modified release tablet formulation according to any one of claims 1 to 33, for Modified release tablet formulation according to any one of claims 1 to 33 for the treatment of inflammatory skin disorders. A modified release tablet formulation according to any one of claims 1-33 for the treatment of psoriasis. 38. A modified release tablet formulation according to claim 37 for the treatment of psoriasis vulgaris. 38. The modified release tablet formulation of claim 37, wherein the psoriasis is moderate to severe plaque psoriasis. Modified release tablet formulation according to any one of claims 1-33 for the treatment of atopic dermatitis. The modified release tablet formulation according to any one of claims 34 to 40, wherein the modified release tablet formulation is for oral administration.