Melt-processed imatinib dosage form
View Patent ↗The invention provides a dosage form, comprising a melt-processed mixture of (a) a pharmaceutically effective amount of imatinib or a salt thereof, (b) at least one polymeric binder, and (c) at least one pharmaceutically acceptable non-ionic surfactant. The invention provides imatinib dosage forms with high drug loading which can be prepared in a simple and efficient manner, imatinib dosage forms from which the active principle is released in an essentially pH-independent fashion, and extended release imatinib dosage forms.
1. A dosage form, comprising a melt-processed mixture of
(a) a pharmaceutically effective amount of imatinib or a salt thereof,
(b) at least one polymeric binder, and
(c) at least one pharmaceutically acceptable non-ionic surfactant having an HLB of 3.5 or less, wherein the non-ionic surfactant is a polyol fatty acid ester, a polyalkoxylated polyol fatty acid ester, a polyalkoxylated fatty alcohol ether or a mixture thereof.
2. The dosage form of claim 1 , wherein imatinib or a salt thereof is present in an amount of at least 50% by weight based on the total weight of the melt-processed mixture.
3. The dosage form of claim 1 , which is direct-shaped.
4. The dosage form of claim 3 , wherein direct-shaping is carried out by calendering, injection-moulding, or thermoforming.
5. The dosage form of claim 1 , wherein the drug release from the dosage form is essentially independent of pH.
6. The dosage form of claim 1 , wherein the drug release at 8 hours results in a ratio of a release value at pH 6.8 relative to a release value at pH 1.0 of at least 0.6.
7. The dosage form of claim 1 , wherein the non-ionic surfactant is a propyleneglycol fatty acid mono- or diester or a mixture thereof.
8. The dosage form of claim 1 , wherein the non-ionic surfactant has an HLB of 2.5 or less.
9. The dosage form of claim 1 , wherein the polymeric binder is selected from the group consisting of cellulose esters, cellulose ethers and homo- or copolymers of vinylpyrrolidone, and mixtures thereof.
10. A method for preparing the dosage form of claim 1 , the method comprising
(a) mixing and heating imatinib or a salt thereof, at least one polymeric binder, and at least one pharmaceutically acceptable non-ionic surfactant having an HLB of 3.5 or less, and optionally further ingredients to obtain a cohesive mouldable mass, wherein the non-ionic surfactant is a polyol fatty acid ester, a polyalkoxylated polyol fatty acid ester, a polyalkoxylated fatty alcohol ether or a mixture thereof; and
(b) forcing the mass through a die.
11. The method of claim 10 , comprising bringing the cohesive mouldable mass directly into the desired shape of the dosage form.
12. The dosage form of claim 9 , wherein the cellulose ether is methylcellulose, ethyl cellulose, hydroxyalkylcellulose or hydroxyalkylalkylcellulose.
13. The dosage form of claim 12 , wherein the hydroxyalkylcellulose is hydroxyproplylcellulose.
14. The dosage form of claim 12 , wherein the hydroxyalkylalkylcellulose is hydroxyproplymethylcellulose.
15. The dosage form of claim 9 , wherein the cellulose ester is selected from the group consisting of cellulose phthalates and cellulose succinates.
16. The dosage form of claim 15 , wherein the cellulose phthalate is cellulose acetate phthalate, hydroxyproplylmethlycellulose phthalate or hydroxyproplylmethylcellulose acetate phthalate.
17. The dosage form of claim 15 , wherein the cellulose succinate is hydroxyproplylmethlycellulose succinate or hydroxyproplylmethylcellulose acetate succinate.