Partially cross-linked esterified cellulose ethers
View Patent ↗A partially cross-linked esterified cellulose ether having A) groups of the formula —C(O)—R—COOA or a combination of aliphatic monovalent acyl groups and groups of the formula —C(O)—R—COOA, wherein R is a divalent aliphatic or aromatic hydrocarbon group and A is hydrogen or a cation, and B) having a molecular weight distribution such that [Wf(>100 k)−Wf(>100 k)XL]/Wf(>100 k)XL is at least 0.20, wherein Wf(>100 k) is the total weight fraction of the esterified cellulose ether that exceeds 100,000 g/mol, and Wf(>100 k)XL is the weight fraction that exceeds 100,000 g/mol of the methylated esterified cellulose ether is useful as enteric polymer for pharmaceutical dosage forms.
1. A partially cross-linked esterified cellulose ether having
A) groups of the formula —C(O)—R—COOA or a combination of aliphatic monovalent acyl groups and groups of the formula —C(O)—R—COOA, wherein R is a divalent aliphatic or aromatic hydrocarbon group and A is hydrogen or a cation, and
B) having a molecular weight distribution such that
[Wf(>100 k)−Wf(>100 k)XL]/Wf(>100 k)XL is at least 0.20,
wherein Wf(>100 k) is the total weight fraction of the esterified cellulose ether that exceeds 100,000 g/mol, and Wf(>100 k)XL is the weight fraction that exceeds 100,000 g/mol of the esterified cellulose ether that has been subjected to methylation after production of the esterified cellulose ether
wherein Wf(>100 k) and Wf(>100 k)XL are determined by Size Exclusion Chromatography using tetrahydrofuran as eluent and polystyrene calibration standards.
2. The esterified cellulose ether of claim 1 wherein the groups of the formula
—C(O)—R—COOA are —C(O)—CH 2 —CH 2 —COOA, —C(O)—CH═CH—COOA, or —C(O)—C 6 H 4 —COOA and the aliphatic monovalent acyl groups are acetyl, propionyl or butyryl groups.
3. The esterified cellulose ether of claim 1 being hydroxypropyl methyl cellulose acetate succinate.
4. The esterified cellulose ether of claim 1 having a viscosity of up to 4.0 mPa·s, measured as a 2.0 wt % solution of the esterified cellulose ether in 0.43 wt % aqueous NaOH at 20° C.
5. The esterified cellulose ether of claim 1 wherein [Wf(>100 k)−Wf(>100 k)XL]/Wf(>100 k)XL is from 0.22 to 3.0.
6. The esterified cellulose ether of claim 1 having a weight average molecular weight Mw of from 80,000 Dalton to 350,000 Dalton, measured by SEC-MALLS using as mobile phase a mixture of 40 parts by volume of acetonitrile and 60 parts by volume of aqueous buffer containing 50 mM NaH 2 PO 4 and 0.1 M NaNO 3 .
7. A composition comprising a liquid diluent and at least one esterified cellulose ether of claim 1 .
8. The composition of claim 7 additionally comprising at least one active ingredient and optionally one or more adjuvants.
9. A solid dispersion comprising at least one active ingredient in at least one esterified cellulose ether of claim 1 .
10. The solid dispersion of claim 9 in the form of strands, pellets, granules, pills, tablets, caplets, microparticles, fillings of capsules or injection molded capsules or in the form of a powder, film, paste, cream, suspension or slurry.
11. A process for producing the solid dispersion of claim 9 comprising the steps of blending a) at least one esterified cellulose ether of claim 1 , b) one or more active ingredients and c) one or more optional additives, and subjecting the blend to extrusion.
12. A process for producing the solid dispersion of claim 9 comprising the steps of blending a) at least one esterified cellulose ether of claim 1 , b) one or more active ingredients, c) one or more optional additives, and d) a liquid diluent to prepare a liquid composition, and removing said liquid diluent.
13. The process of claim 12 wherein the liquid composition is subjected to spray-drying.
14. A dosage form being coated with the esterified cellulose ether of claim 1 .
15. A capsule shell comprising the esterified cellulose ether of claim 1 .