Sustained release compositions of endoxifen
AssigneeAtossa Therapeutics, Inc.
InventorsSteven C. QUAY, Naresh Kumar Reddy VUTUKURU, Srinivasan SHANMUGAM
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Abstract
The present disclosure provides sustained release compositions of (Z)-endoxifen and polymorphs and salts thereof and methods of making sustained release compositions of (Z)-endoxifen and polymorphs and salts thereof. The present disclosure also provides methods for treating disorders susceptible to (Z)-endoxifen, including hormone dependent disorders and mood disorders.
Claims71
A sustained release composition comprising a therapeutic agent and a sustained release agent, wherein the therapeutic agent is (Z)-endoxifen free base, a polymorph of (Z)-endoxifen, a salt of (Z)-endoxifen, or a combination thereof, and wherein the therapeutic agent has at least two percentage dissolution parameters selected from:
- a percentage dissolution of less than 20% at 2 hours;
- a percentage dissolution of less than 40% at 7 hours;
- and
- a percentage dissolution of at least 30% at 12 hours,
- as measured at 37° C. in simulated gastric fluid at pH 1.2 from hours 0 to 2 and in simulated intestinal fluid at pH 6.8 after 2 hours.
A sustained release composition comprising:
- a therapeutic agent, and
- a sustained release agent,
- wherein the therapeutic agent is (Z)-endoxifen free base, a polymorph of (Z)-endoxifen, a salt of (Z)-endoxifen, or a combination thereof, and wherein the sustained release agent is selected from the group consisting of hydroxyalkyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose.
A sustained release composition comprising a tablet and an enteric coating enclosing the tablet, wherein the tablet comprises:
- a therapeutic agent;
- and
- a sustained release agent,
- and wherein the enteric coating comprises:
- a delayed release agent;
- a plasticizer;
- an anti-tacking agent;
- or
- a combination thereof,
- wherein the therapeutic agent is (Z)-endoxifen free base, a polymorph of (Z)-endoxifen, a salt of (Z)-endoxifen, or a combination thereof, wherein the sustained release agent is selected from the group consisting of hydroxyalkyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose.
A sustained release composition comprising a tablet and an enteric coating enclosing the tablet, wherein the tablet comprises a therapeutic agent and hypromellose, wherein the therapeutic agent comprises at least 90% (Z)-endoxifen, and wherein the enteric coating comprises a poly(meth)acrylate polymer and triethyl citrate.
A method of preparing a sustained release composition comprising:
- combining and mixing:
- a therapeutic agent selected from a (Z)-endoxifen free base, a polymorph of (Z)-endoxifen, a salt of (Z)-endoxifen, and a combination thereof;
- a sustained release agent;
- a binder;
- and
- a lubricant;
- and
- dry compressing the therapeutic agent, the at least one sustained release agent, the at least one binder, and the at least one lubricant to form a core tablet.
A method of administering a sustained release composition comprising to a subject in need thereof, the method comprising orally administering the sustained release composition to the subject in need thereof,
- wherein the sustained release composition comprises a therapeutic agent and a sustained release agent, wherein the therapeutic agent is (Z)-endoxifen free base, a polymorph of (Z)-endoxifen, a salt of (Z)-endoxifen, or a combination thereof, and
- wherein the sustained release composition is formulated such less than 20% of the therapeutic agent dissolves 2 hours after administration and at least 30% of the therapeutic agent dissolves within 12 hours after administration.
A method of administering a sustained release composition comprising to a subject in need thereof, the method comprising orally administering the sustained release composition to the subject in need thereof,
- wherein the sustained release composition comprises a therapeutic agent and a sustained release agent, wherein the therapeutic agent is (Z)-endoxifen free base, a polymorph of (Z)-endoxifen, a salt of (Z)-endoxifen, or a combination thereof, and
- wherein the sustained release composition is formulated such less than 20% of the therapeutic agent dissolves in simulated gastric fluid after 2 hours and at least 30% of the therapeutic agent dissolves after 2 hours in simulated gastric fluid followed by 10 hours in simulated intestinal fluid.
A method of administering a sustained release composition comprising to a subject in need thereof, the method comprising orally administering the sustained release composition to the subject in need thereof,
- wherein the sustained release composition comprises a therapeutic agent and a sustained release agent, wherein the therapeutic agent is (Z)-endoxifen free base, a polymorph of (Z)-endoxifen, a salt of (Z)-endoxifen, or a combination thereof, and
- wherein the therapeutic agent exhibits a time to maximum observed concentration of at least 8 hours, at least 9 hours, at least 10 hours, at least 15 hours, at least 20 hours, or at least 24 hours in a serum of the subject.
A method of treating a subject in need thereof, wherein the subject has a disorder or is at risk of having the disorder, the method comprising administering to the subject a sustained release composition comprising:
- a therapeutic agent, and
- a sustained release agent,
- wherein the therapeutic agent is (Z)-endoxifen free base, a polymorph of (Z)-endoxifen, a salt of (Z)-endoxifen, or a combination thereof, and wherein the sustained release agent is selected from the group consisting of hydroxyalkyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose.
Dependencies are inferred from the claim text.