US 2014/0179729 A1 · ORAL DOSAGE FORMS FOR OXYGEN-CONTAINING ACTIVE AGENTS AND OXYL-CONTAINING POLYMER

Abstract

The disclosed invention is drawn to pharmaceutical tablets that provide delivery of active agents having at least three oxygen-containing groups, as well as a second active ingredient. Non-limiting examples of three oxygen-containing group active agents include guaifenesin, codeine, hydrocodone, and their pharmaceutically acceptable salts. In one embodiment, a pharmaceutical tablet for oral administration once every 12 hours is provided. The tablet includes a first active agent that is a tri-oxy active agent, a second active agent, and a release rate controlling non-ionic oxyl-containing hydrophilic polymer. The total oxyl content of the hydrophilic polymer in the tablet is about 4×10−4 moles to about 2.0×10−3 moles.

Claims24

Dependent claims

An extended release solid tablet pharmaceutical composition for administration twice-daily comprising:

54 mg of codeine phosphate;
8 mg chlorpheniramine maleate or a pharmaceutically acceptable salt of chlorpheniramine;
and
a release rate controlling non-ionic oxyl-containing hydrophilic polymer, which provides a mean AUCinf of codeine and chlorpheniramine that is 70% to 135% of the respective mean AUCinf provided by an immediate release dosage administered to a subject under fasted conditions every 4 to 6 hours over a 12 hour time period, where the cumulative dosage amount administered over the 12 hour time period of codeine and chlorpheniramine in the immediate release oral dosage is equivalent to the respective amount in said pharmaceutical composition.

1 more element

A pharmaceutical composition comprising:

(a) 54 mg of codeine phosphate;
and
(b) 8 mg chlorpheniramine maleate or a pharmaceutically acceptable salt of chlorpheniramine;
said pharmaceutical composition having two, three, four, or five of the following characteristics:
(i) single-dose administration to a subject under fasted conditions provides a mean Cmax for each of codeine and chlorpheniramine that is 70% to 135% of the respective mean Cmax provided by administering an immediate release oral dosage form to a subject under fasted conditions every 4 to 6 hours over a 12 hour time period, wherein the cumulative dosage amount administered over the 12 hour time period of codeine and chlorpheniramine in the immediate release oral dosage is equivalent to the respective amount of codeine and chlorpheniramine in said pharmaceutical composition;
single-dose administration to a subject under fasted conditions every twelve hours provides a mean Cmax for each of codeine and chlorpheniramine that is 70% to 135% of the respective mean Cmax provided by administering the same oral dosage to the subject under fed conditions every twelve hours;
(iii) single-dose administration to a subject under fed conditions provides a mean Cmax for each of the codeine and the chlorpheniramine that is 70% to 135% of a respective mean Cmax provided by administering an immediate release oral dosage to a subject under fed conditions every 4 to 6 hours over a 12 hour time period, wherein the cumulative dosage amount administered over the 12 hour time period of codeine and chlorpheniramine in the immediate release oral dosage is equivalent to the respective amount of codeine and chlorpheniramine in the pharmaceutical composition;
(iv) when placed in a USP type 2 dissolution apparatus at 50 rpm in 900 mL of 0.1 N hydrochloric acid solution in water at 37° C., the ratio of the amount of codeine released to the chlorpheniramine released at a single time point between 1 hour and 4 hour is from about 0.8:1 and about 1.2:1;
(v) single-dose administration to a subject under fasted conditions, provides a mean Tmax for codeine in the range of about 2.2 hour to about 3.4 hour and a mean Tmax for chlorpheniramine in the range of about 5 hour about 14 hour;
(vi) further comprises a release rate controlling non-ionic oxyl-containing hydrophilic polymer;
and
(vii) the codeine or pharmaceutical composition is resin free.

9 more elements

A pharmaceutical composition for treating cough or cold symptoms said pharmaceutical composition resistant to alcohol dumping, allows a subject to sleep through the night, or a combination thereof, wherein the pharmaceutical composition comprises

54 mg of codeine phosphate;
and
8 mg chlorpheniramine maleate or a pharmaceutically acceptable salt of chlorpheniramine;
said pharmaceutical composition having two, three, four, or five of the following characteristics:
(i) single-dose administration to a subject under fasted conditions provides a mean Cmax for each of codeine and chlorpheniramine that is 70% to 135% of the respective mean Cmax provided by administering an immediate release oral dosage form to a subject under fasted conditions every 4 to 6 hours over a 12 hour time period, wherein the cumulative dosage amount administered over the 12 hour time period of codeine and chlorpheniramine in the immediate release oral dosage is equivalent to the respective amount of codeine and chlorpheniramine in said pharmaceutical composition;
single-dose administration to a subject under fasted conditions every twelve hours provides a mean Cmax for each of codeine and chlorpheniramine that is 70% to 135% of the respective mean Cmax provided by administering the same oral dosage to the subject under fed conditions every twelve hours;
(iii) single-dose administration to a subject under fed conditions provides a mean Cmax for each of the codeine and the chlorpheniramine that is 70% to 135% of a respective mean Cmax provided by administering an immediate release oral dosage to a subject under fed conditions every 4 to 6 hours over a 12 hour time period, wherein the cumulative dosage amount administered over the 12 hour time period of codeine and chlorpheniramine in the immediate release oral dosage is equivalent to the respective amount of codeine and chlorpheniramine in the pharmaceutical composition;
(iv) when placed in a USP type 2 dissolution apparatus at 50 rpm in 900 mL of 0.1 N hydrochloric acid solution in water at 37° C., the ratio of the amount of codeine released to the chlorpheniramine released at a single time point between 1 hour and 4 hour is from about 0.8:1 and about 1.2:1;
(v) single-dose administration to a subject under fasted conditions, provides a mean Tmax for codeine in the range of about 2.2 hour to about 3.4 hour and a mean Tmax for chlorpheniramine in the range of about 5 hour about 14 hour;
(vi) further comprises a release rate controlling non-ionic oxyl-containing hydrophilic polymer;
and
(vii) the codeine or pharmaceutical composition is resin free.

9 more elements

Dependencies are inferred from the claim text.

Oral dosage forms for oxygen-containing active agents and oxyl-containing polymer

Life of this patent

Oral dosage forms for oxygen-containing active agents and oxyl-containing polymer

Life of this patent

Abstract

Claims24