Stabilized modified release vitamin D formulation and method of administering same
AssigneeOpko Ireland Global Holdings, Ltd.
InventorsJay A. White, Samir P. Tabash, Sammy A. Agudoawu, Joel Z. Melnick
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Abstract
A stabilized formulation for controlled release of a vitamin D compound is disclosed. The formulation comprises one or both of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 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.
Claims28
A stabilized formulation for extended release of a vitamin D compound in the gastrointestinal tract of a subject which ingests the formulation, the formulation comprising a mixture of:
- one or both of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in an extended release lipophilic matrix, the lipophilic matrix further comprising a cellulosic stabilizing agent to stabilize the matrix against changes in dissolution release characteristics over time;
- wherein the cellulosic stabilizing agent is a cellulose ether and is present in an amount of about 5 wt % to about 30 wt % of the stabilized formulation;
- wherein the formulation is characterized by providing a mean baseline-adjusted in vivo Cmax per microgram of 25-hydroxyvitamin D administered to humans in a range of about 0.0133 ng/mL to about 0.04 ng/mL.
A stabilized formulation for extended release of a vitamin D compound in the gastrointestinal tract of a subject which ingests the formulation, the formulation comprising a mixture of:
- one or both of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in an extended release lipophilic matrix, the lipophilic matrix further comprising a cellulosic stabilizing agent to stabilize the matrix against changes in dissolution release characteristics over time;
- wherein the cellulosic stabilizing agent is a cellulose ether and is present in an amount of about 5 wt % to about 30 wt % of the stabilized formulation;
- wherein the formulation, when administered to adult humans having CKD Stage 3 with secondary hyperparathyroidism and vitamin D insufficiency, and at daily oral doses of 30 mcg, is characterized by providing a baseline-adjusted AUC0-6 wk of the administered vitamin D compound having a mean of about 700 ng·d/mL.
A stabilized formulation for extended release of a vitamin D compound in the gastrointestinal tract of a subject which ingests the formulation, the formulation comprising a mixture of:
- one or both of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in an extended release lipophilic matrix, the lipophilic matrix further comprising a cellulosic stabilizing agent to stabilize the matrix against changes in dissolution release characteristics over time;
- wherein the cellulosic stabilizing agent is a cellulose ether and is present in an amount of about 5 wt % to about 30 wt % of the stabilized formulation;
- wherein the formulation, when administered to adult humans having CKD Stage 3 with secondary hyperparathyroidism and vitamin D insufficiency, and at daily oral doses of 60 mcg, is characterized by providing a baseline-adjusted AUC0-6 wk of the administered vitamin D compound having a mean of about 1500 ng·d/mL.
A stabilized formulation for extended release of a vitamin D compound in the gastrointestinal tract of a subject which ingests the formulation, the formulation comprising a mixture of:
- one or both of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in an extended release lipophilic matrix, the lipophilic matrix further comprising a cellulosic stabilizing agent to stabilize the matrix against changes in dissolution release characteristics over time;
- wherein the cellulosic stabilizing agent is a cellulose ether and is present in an amount of about 5 wt % to about 30 wt % of the stabilized formulation;
- wherein the formulation, when administered to adult humans having CKD Stage 3 with secondary hyperparathyroidism and vitamin D insufficiency, and at daily oral doses of 90 mcg, is characterized by providing a baseline-adjusted AUC0-6 wk of the administered vitamin D compound having a mean of about 2100 ng·d/mL.
Dependencies are inferred from the claim text.