Pediatric dosage forms, methods of making and using
Pediatric and modified release dosage forms of vitamin D compounds, and methods of making and using the same.
1. A solid extended release oral dosage form, the dosage form comprising a 25-hydroxyvitamin D compound in a solid hydrophilic matrix comprising
about 30 wt. % to about 50 wt. % microcrystalline cellulose;
about 5 wt. % to about 60 wt. % ethylcellulose;
about 5 wt. % to about 40 wt. % glyceryl behenate;
about 1 wt. % to about 20 wt. % polyglycolized glycerides; and
about 1 wt. % to about 15 wt. % methylcellulose.
2. The oral dosage form of claim 1 , in the form of a plurality of particles having a particle size characterized by a diameter in a range of about 0.2 mm to about 2.8 mm.
3. The oral dosage form of claim 1 , wherein the microcrystalline cellulose is characterized by a crystallinity in a range of about 60% to about 80%, a mean particle size in a range of about 10 microns to about 200 microns.
4. The oral dosage form of claim 1 , wherein the microcrystalline cellulose is present in an amount of at least 35 wt. % to about 50 wt. %.
5. The oral dosage form of claim 1 , wherein the ethylcellulose is characterized by a viscosity in a range of 9 to 11 cP.
6. The oral dosage form of claim 1 , wherein the ethylcellulose is characterized by an ethoxyl content of in a range of about 48% to 49.5%.
7. The oral dosage form of claim 1 , wherein the glyceryl behenate is present in an amount of at least 15 wt. % to about 40 wt. %.
8. The oral dosage form of claim 1 , wherein the polyglycolized glycerides component is selected from a mixture of lauroyl macrogolglycerides and lauroyl polyoxylglycerides, or a caprylocaproyl macrogol-8-glyceride.
9. The oral dosage form of claim 1 , wherein the polyglycolized glycerides component comprises PEG-32 mono and diesters of stearic and palmitic acid.
10. The oral dosage form of claim 1 , wherein the methylcellulose has a methoxyl content in a range of about 19% to about 30%.
11. The oral dosage form of claim 1 , wherein the methylcellulose is further hydroxypropyl substituted.
12. The oral dosage form of claim 11 , wherein the methylcellulose has a hydroxypropyl content in a range of about 5% to about 15%.
13. The oral dosage form of claim 1 , wherein the methylcellulose has a 2% aqueous viscosity at 20° C. in a range of about 2 cP to about 6 CP.
14. The oral dosage form of claim 1 , wherein the matrix is an extruded, spheronized matrix.
15. The oral dosage form of claim 1 , wherein the matrix further comprises medium chain triglycerides and the medium chain triglycerides are present in an amount in a range of about 1 wt. % to about 20 wt. %.
16. A method of treating a vitamin D responsive disease or condition, a mammal in need of vitamin D supplementation, or a mammal at risk for vitamin D insufficiency or deficiency comprising administering the dosage form according to claim 1 to a mammal in need thereof.
17. The method of claim 16 , wherein the mammal is in need of vitamin D supplementation.
18. The method of claim 16 , wherein the mammal is at risk for vitamin D insufficiency or deficiency.
19. The method of claim 16 , wherein the vitamin D-responsive disease comprises one or more in the group of hyperparathyroidism, hyperparathyroidism secondary to Chronic Kidney Disease (“CKD”), hyperparathyroidism secondary to CKD in mammals undergoing hemodialysis, or tertiary hyperparathyroidism, cancer, autoimmune diseases, including type I diabetes, multiple sclerosis, rheumatoid arthritis, polymyositis, dermatomyositis, scleroderma, fibrosis, Grave's disease, Hashimoto's disease, acute or chronic transplant rejection, acute or chronic graft versus host disease, inflammatory bowel disease, Crohn's disease, systemic lupus erythematosis, Sjogren's Syndrome, eczema and psoriasis, dermatitis, including atopic dermatitis, contact dermatitis, allergic dermatitis and/or chronic dermatitis.