Stabilized modified release Vitamin D formulation and method of administering same
A stabilized formulation for controlled release of a vitamin D compound is disclosed. The formulation comprises one or both of 25-hydroxyvitamin D 2 and 25-hydroxyvitamin D 3 and a cellulosic compound. The stabilized formulations exhibit a stable dissolution profile following exposure to storage conditions and demonstrate improved pharmacokinetic parameters compared to unstabilized formulations.
1. A pharmaceutical composition comprising a storage-stabilized formulation for sustained release of a vitamin D compound, wherein the storage-stabilized formulation comprises a mixture of: a vitamin D compound; and a stabilizing agent comprising a cellulose ether in an amount of about 5 wt % to about 30 wt % of the storage-stabilized formulation, wherein the stabilizing agent maintains a difference of less than 30% between the amount of vitamin D compound released at any given time point after four hours during in vitro dissolution after two months exposure to storage conditions of 25° C. and 60% relative humidity and the amount released at the same dissolution time point during in vitro dissolution conducted prior to exposing the formulation to the storage conditions,
wherein the storage-stabilized formulation comprises a lipophilic matrix comprising the vitamin D compound.
2. The pharmaceutical composition of claim 1 , wherein the lipophilic matrix comprises a wax.
3. The pharmaceutical composition of claim 1 , wherein the storage-stabilized formulation is an oral formulation for sustained release of the vitamin D compound in the gastrointestinal tract of a subject which ingests the formulation.
4. The pharmaceutical composition of claim 1 , wherein the storage-stabilized formulation comprises a matrix that releasably binds and controllably releases the vitamin D compound.
5. The pharmaceutical composition according to claim 1 , wherein the cellulose ether comprises one or more of methylcellulose, hydroxyl propyl methylcellulose, hydroxyl ethyl methylcellulose, hydroxyl ethyl cellulose, and hydroxyl propyl cellulose.
6. The pharmaceutical composition according to claim 4 , wherein the cellulose ether comprises hydroxyl propyl methylcellulose.
7. The pharmaceutical composition according to claim 1 , wherein the vitamin D compound is one or more of vitamin D 3 (cholecalciferol), vitamin D 2 (ergocalciferol), 25-hydroxyvitamin D 3 , 25-hydroxyvitamin D 2 , 25-hydroxyvitamin D 4 , 25-hydroxyvitamin D 5 , 25-hydroxyvitamin D 7 , 1α,25-dihydroxyvitamin D 3 , 1α,25-dihydroxyvitamin D 2 , 1α,25-dihydroxyvitamin D 4 , 1,25-dihydroxy-19-nor-vitamin D 2 , and 1α-hydroxyvitamin D 3 .
8. The pharmaceutical composition according to claim 7 , wherein the vitamin D compound comprises one or both of 25-hydroxyvitamin D 2 and 25-hydroxyvitamin D 3 .
9. The pharmaceutical composition according to claim 1 , wherein the vitamin D compound comprises 25-hydroxyvitamin D 3 .
10. The pharmaceutical composition of claim 1 , wherein the storage-stabilized formulation is in the form of a capsule, tablet, sachet, dragee, or suppository.
11. The pharmaceutical composition of claim 10 , wherein the storage-stabilized formulation is in the form of a capsule.