NOVEL ESTERIFIED CELLULOSE ETHERS OF HIGH MOLECULAR WEIGHT AND HOMOGENEITY
A process for making esterified cellulose ethers which have i) 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, ii) a weight average molecular weight M w of from 80,000 Dalton to 350,000 Dalton, iii) a Polydispersity M w /M n of from 1.3 to 4.1, and iv) 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., are useful as enteric polymers for pharmaceutical dosage forms.
1 .- 15 . (canceled)
16 . A process for producing a comprising the step of reacting a cellulose ether with a combination of an aliphatic monocarboxylic acid anhydride and a dicarboxylic acid anhydride in an aliphatic carboxylic acid as a reaction diluent and in the presence of an esterification catalyst at a molar ratio [aliphatic carboxylic acid/anhydroglucose units of cellulose ether] of from [4.9/1.0] to [11.5/1.0], a molar ratio [alkali metal carboxylate/anhydroglucose units of cellulose ether] of from [0.4/1.0] to [3.3/1.0], a molar ratio [anhydride of aliphatic monocarboxylic acid/anhydroglucose units of cellulose ether] of from [0.9/1] to [3.0/1] and a molar ratio [anhydride of a dicarboxylic acid/anhydroglucose units of cellulose ether] of from [0.1/1] to [0.6/1],
thereby producing an esterified cellulose ether having:
i) as ester groups 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,
ii) a weight average molecular weight M w of from 80,000 Dalton to 350,000 Dalton,
iii) a Polydispersity M w /M n of from 1.5 to 3.4, and
iv) 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. according to an Ubbelohde measurement according to DIN 51562-1:1999-01, and
wherein M w and M n are 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 .
17 . The process of claim 16 , wherein the aliphatic monovalent acyl groups are acetyl, propionyl or butyryl groups and 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.
18 . The process of claim 16 , wherein the esterified cellulose ether is an esterified hydroxyalkyl methyl cellulose.
19 . The process of claim 16 , wherein the esterified cellulose ether is hydroxypropyl methyl cellulose acetate succinate.
20 . The process of claim 16 , wherein the esterified cellulose ether has a weight average molecular weight M w of from 110,000 Dalton to 200,000 Dalton.
21 . The process of claim 16 , wherein the esterified cellulose ether has a Polydispersity M w /M n of from 2.0 to 3.4.
22 . The process of claim 16 , further comprising the steps of blending a) the produced esterified cellulose ether, b) one or more active ingredients and c) one or more optional additives, and subjecting the blend to extrusion, thereby producing a solid dispersion comprising at least one active ingredient in the at least one esterified cellulose ether.
23 . The process of claim 16 , further comprising the steps of blending a) the produced esterified cellulose ether, 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, thereby producing a solid dispersion comprising at least one active ingredient in the at least one esterified cellulose ether.
24 . The process of claim 23 , wherein the liquid composition is subjected to spray-drying.
25 . The process of claim 19 , wherein the hydroxypropyl methyl cellulose acetate succinate has a weight average molecular weight M w of from 110,000 Dalton to 200,000 Dalton and a Polydispersity M w /M n of from 2.0 to 3.3.