Sustained release dosage forms
View Patent ↗A sustained release dosage form comprises an active ingredient blended with a polymeric matrix. At least a portion of the polymeric matrix is formed by a cellulose ether having an onset dissolution temperature of at least 40° C., having anhydroglucose units joined by 1-4 linkages and having methyl groups, hydroxyalkyl groups, and optionally alkyl groups being different from methyl as substituents such that the cellulose ether has an MS (hydroxyalkyl) of 0.05 to 1.00, and hydroxyl groups of anhydroglucose units are substituted with methyl groups such that [s23/s26−0.2*MS(hydroxyalkyl)] is 0.31 or less, wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 3-positions of the anhydroglucose unit are substituted with a methyl group and wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 6-positions of the anhydroglucose unit are substituted with a methyl group.
1. A sustained release dosage form comprising at least one active ingredient blended with a polymeric matrix, wherein at least a portion of the polymeric matrix is formed by at least one cellulose ether having an onset dissolution temperature of at least 40° C., having anhydroglucose units joined by 1-4 linkages and having methyl groups, hydroxyalkyl groups, and optionally alkyl groups being different from methyl as substituents such that
said at least one cellulose ether has an MS (hydroxyalkyl) of 0.05 to 1.00, and
hydroxyl groups of anhydroglucose units are substituted with methyl groups such that s23/s26−0.2*MS(hydroxyalkyl) is 0.31 or less,
wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 3-positions of the anhydroglucose unit are substituted with a methyl group and
wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 6-positions of the anhydroglucose unit are substituted with a methyl group, and
wherein said at least one cellulose ether has an onset dissolution temperature of at least 40° C., measured at a concentration of 2 weight percent in water and
wherein the amount of said at least one cellulose ether is at least 10 percent, based on the total weight of the dosage form.
2. The sustained release dosage form of claim 1 wherein said at least one cellulose ether has an onset dissolution temperature of at least 45° C.
3. The sustained release dosage form of claim 1 wherein said at least one cellulose ether is a hydroxyalkyl methyl cellulose.
4. The sustained release dosage form of claim 3 wherein said at least one cellulose ether is a hydroxypropyl methyl cellulose.
5. The sustained release dosage form of claim 1 wherein said at least one cellulose ether has a DS(methyl) of 1.2 to 2.2.
6. The sustained release dosage form of claim 5 wherein said at least one cellulose ether has a DS(methyl) of 1.60 to 2.05.
7. The sustained release dosage form of claim 1 wherein said at least one cellulose ether has an MS (hydroxyalkyl) of 0.20 to 0.40.
8. The sustained release dosage form of claim 1 wherein said at least one cellulose ether has a viscosity of at least 50 mPa·s, determined as a 1.5% by weight solution in water in a Haake rheometer at 20° C. and at a shear rate of 2.55 s −1 .
9. A process for preparing a sustained release dosage form comprising the steps of
I.) blending one or more cellulose ethers, one or more active ingredients, and one or more optional adjuvants, and
II.) compressing the blend to a dosage form,
wherein at least one cellulose ether has anhydroglucose units joined by 1-4 linkages wherein
the ether substituents are methyl groups, hydroxyalkyl groups, and optionally alkyl groups being different from methyl,
the cellulose ether has an MS (hydroxyalkyl) of 0.05 to 1.00, and
hydroxyl groups of anhydroglucose units are substituted with methyl groups such that s23/s26−0.2*MS(hydroxyalkyl) is 0.31 or less,
wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 3-positions of the anhydroglucose unit are substituted with a methyl group and
wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 6-positions of the anhydroglucose unit are substituted with a methyl group, and
wherein said at least one cellulose ether has an onset dissolution temperature of at least 40° C., measured at a concentration of 2 weight percent in water and
wherein the amount of said at least one cellulose ether is at least 10 percent, based on the total weight of the dosage form.
10. The process of claim 9 wherein said at least one cellulose ether has an onset dissolution temperature of at least 45° C.
11. The process of claim 9 wherein said at least one cellulose ether is a hydroxyalkyl methyl cellulose.
12. The process of claim 9 wherein said at least one cellulose ether is a hydroxypropyl methyl cellulose.
13. The process of claim 9 wherein said at least one cellulose ether has a DS(methyl) of 1.60 to 2.05.
14. The process of claim 9 wherein said at least one cellulose ether has an MS (hydroxyalkyl) of 0.20 to 0.40.
15. The process of claim 9 wherein said at least one cellulose ether has a viscosity of at least 50 mPa·s, determined as a 1.5% by weight solution in water in a Haake rheometer at 20° C. and at a shear rate of 2.55 s −1 .