Extended release formulation and method of treating adrenergic dysregulation
View Patent ↗A composition and method of treating adrenergic dysregulation by administering the composition is disclosed, wherein the composition comprises a a2-adrenergic receptor agonist; a pharmaceutically acceptable hydrophilic matrix and a release-retardant of a metal alkyl sulfate. In embodiments, the composition provides a sustained release of the agonist, wherein after administration of the composition no more than once about every 12 hours to a subject having a steady state plasma concentration of the a2-adrenergic receptor agonist, the agonist's plasma concentration peak-to-trough ratio is no greater than about 1.9.
1. An oral dosage form comprising:
(a) clonidine or a pharmaceutically acceptable salt thereof in an amount between about 0.001 wt % and 0.5 wt % of said oral dosage form; and
(b) a pharmaceutically acceptable hydrophilic matrix comprising:
(i) at least one hydroxypropyl methylcellulose ether in an amount between 20 wt % and 80 wt % of said oral dosage form;
(ii) at least one of starch, lactose, or dextrose in an amount between 20 wt % and 80 wt % of said oral dosage form; and
(iii) sodium lauryl sulfate in an amount of about 5 wt % of said oral dosage form;
wherein after administration of said dosage form no more than once about every 24 hours to a subject having a steady state plasma concentration of clonidine, the clonidine plasma concentration peak-to-trough ratio is no greater than about 1.9.
2. The oral dosage form of claim 1 , wherein said clonidine or a pharmaceutically acceptable salt thereof is clonidine hydrochloride.
3. The oral dosage form of claim 1 , wherein said amount of clonidine is between about 0.01 wt % to about 0.3 wt % of said oral dosage form.
4. The oral dosage form of claim 1 , wherein said amount of clonidine or a pharmaceutically acceptable salt thereof is between about 0.025 mg to about 0.4 mg.
5. An oral dosage form comprising:
(a) clonidine or a pharmaceutically acceptable salt thereof in an amount between about 0.001 wt % and 0.5 wt % of the oral dosage form;
(b) a pharmaceutically acceptable hydrophilic matrix comprising,
(i) at least one hydroxypropyl methylcellulose ether in an amount between 20 wt % and 80 wt % of the oral dosage form;
(ii) at least one of starch, lactose, or dextrose in an amount between 20 wt % and 80 wt % of the oral dosage form; and
(iii) sodium lauryl sulfate in an amount of about 5 wt % of said oral dosage form; and
(c) a metal stearate and/or colloidal silica;
wherein after administration of said dosage form no more than once about every 24 hours to a subject having a steady state plasma concentration of clonidine, the clonidine plasma concentration peak-to-trough ratio is no greater than about 1.9.
6. The oral dosage form of claim 5 , wherein said clonidine or a pharmaceutically acceptable salt thereof is clonidine hydrochloride.
7. The oral dosage form of claim 5 , wherein the amount of clonidine is between about 0.01 wt % to about 0.3 wt % of the oral dosage form.
8. The oral dosage form of claim 5 , wherein said amount of clonidine or a pharmaceutically acceptable salt thereof is between about 0.025 mg to about 0.4 mg.
9. The oral dosage form of claim 5 , comprising:
(a) clonidine hydrochloride in an amount between about 0.001 wt % and 0.5 wt % of the oral dosage form;
(b) a pharmaceutically acceptable hydrophilic matrix comprising,
(i) at least one hydroxypropyl methylcellulose ether in an amount between 30 wt % and 50 wt % of the oral dosage form;
(ii) at least one of starch, lactose, or dextrose in an amount between 50 wt % and 70 wt % of the oral dosage form; and
(iii) sodium lauryl sulfate in an amount of about 5 wt % of said oral dosage form; and
(c) a metal stearate and/or colloidal silica.
10. An oral dosage form consisting essentially of:
(a) clonidine hydrochloride in an amount between about 0.001 wt % and 0.5 wt % of the oral dosage form;
(b) a pharmaceutically acceptable hydrophilic matrix comprising,
(i) at least one hydroxypropyl methylcellulose ether in an amount between 30 wt % and 50 wt % of the oral dosage form;
(ii) at least one of starch, lactose, or dextrose in an amount between 50 wt % and 70 wt % of the oral dosage form; and
(iii) sodium lauryl sulfate in an amount of about 5 wt % of said oral dosage form; and
(c) a metal stearate and/or colloidal silica;
wherein after administration of said dosage form no more than once about every 24 hours to a subject having a steady state plasma concentration of clonidine, the clonidine plasma concentration peak-to-trough ratio is no greater than about 1.9.