PROCESS FOR RECOVERING AN ESTERIFIED CELLULOSE ETHER FROM A REACTION PRODUCT MIXTURE

Abstract

A process for recovering an esterified cellulose ether from a reaction product mixture obtained from a reaction of (a) a cellulose ether with (b) an aliphatic monocarboxylic acid anhydride or a di- or tricarboxylic acid anhydride or a combination of an aliphatic monocarboxylic acid anhydride and a di- or tricarboxylic acid anhydride, comprises the steps of (i) contacting the reaction product mixture with an aqueous liquid and precipitating the esterified cellulose ether from the reaction product mixture, and (ii) isolating the precipitated esterified cellulose ether from the mixture obtained in step (i), Tackiness of the esterified cellulose ether can be reduced when before or in step (i) a particulate silicon oxide or metal oxide is dispersed or suspended in the reaction product mixture, the aqueous liquid or a combination thereof.

Claims

1. A process for recovering an esterified cellulose ether from a reaction product mixture obtained from a reaction of (a) a cellulose ether with (b) an aliphatic monocarboxylic acid anhydride or a di- or tricarboxylic acid anhydride or a combination of an aliphatic monocarboxylic acid anhydride and a di- or tricarboxylic acid anhydride, wherein the process comprises the steps of (i) contacting the reaction product mixture with an aqueous liquid and precipitating the esterified cellulose ether from the reaction product mixture, and (ii) isolating the precipitated esterified cellulose ether from the mixture obtained in step (i), wherein before or in step (i) a particulate silicon oxide or metal oxide is dispersed or suspended in the reaction product mixture, the aqueous liquid or a combination thereof

2. The process of claim 1 wherein the particulate silicon oxide or metal oxide is dispersed or suspended in the aqueous liquid before contacting the reaction product mixture with the aqueous liquid.

3. The process of claim 1 wherein the reaction product mixture has been obtained from a reaction of (a) a cellulose ether with (b) an aliphatic monocarboxylic acid anhydride or a di- or tricarboxylic acid anhydride or a combination of an aliphatic monocarboxylic acid anhydride and a di- or tricarboxylic acid anhydride in the presence of a combination of (c) an aliphatic carboxylic acid and (d) an alkali metal carboxylate.

4. The process of claim 1 wherein the particulate silicon oxide or metal oxide is silicon dioxide.

5. The process of claim 1 wherein before or in step (i) from 0.003 to 5 weight parts of particulate silicon oxide or metal oxide are dispersed or suspended per weight part of cellulose ether utilized for producing the esterified cellulose ether.

6. The process of claim 5 wherein before or in step (i) from 0.005 to 2 weight parts of particulate silicon oxide or metal oxide are dispersed or suspended per weight part of cellulose ether utilized for producing the esterified cellulose ether.

7. The process of claim 1 wherein the esterified cellulose ether is an esterified alkyl cellulose, a hydroxyalkyl cellulose or a hydroxyalkyl alkylcellulose.

8. The process of claim 1 wherein the cellulose ether has a viscosity of from 1.5 to 50 mPa.Math.s, measured as a 2 weight-% aqueous solution at 20° C.

9. The process of claim 1 wherein the aliphatic monocarboxylic acid anhydride is selected from the group consisting of acetic anhydride, butyric anhydride and propionic anhydride.

10. The process of claim 1 wherein the di- or tricarboxylic acid anhydride is selected from the group consisting of succinic anhydride, maleic anhydride and phthalic anhydride.

11. The process of claim 1 wherein hydroxypropyl methylcellulose is esterified with succinic anhydride and acetic anhydride to produce hydroxypropyl methyl cellulose acetate succinate.

12. The process of claim 11 wherein the hydroxypropyl methylcellulose acetate succinate has a DS.sub.methoxyl of from 1.0 to 2.7 and an MS.sub.hydroxypropoxyl of from 0.40 to 1.30.

13. A process for preparing an esterified cellulose ether wherein (a) a cellulose ether is reacted with (b) an aliphatic monocarboxylic acid anhydride or a di- or tricarboxylic acid anhydride or a combination of an aliphatic monocarboxylic acid anhydride and a di- or tricarboxylic acid anhydride in the presence of (c) an aliphatic carboxylic acid and the esterified cellulose ether is recovered from the produced reaction product mixture according to the process of claim 1.

14. A method of reducing the tackiness of an esterified cellulose ether in a process for recovering the esterified cellulose ether from a reaction product mixture obtained from a reaction of (a) a cellulose ether with (b) an aliphatic monocarboxylic acid anhydride or a di- or tricarboxylic acid anhydride or a combination of an aliphatic monocarboxylic acid anhydride and a di- or tricarboxylic acid anhydride, which method comprises the steps of (i) contacting the reaction product mixture with an aqueous liquid and precipitating the esterified cellulose ether from the reaction mixture, and (ii) isolating the precipitated esterified cellulose ether from the mixture obtained in step (i), wherein before or in step (i) a particulate silicon oxide or metal oxide is dispersed or suspended in the reaction product mixture, the aqueous liquid or a combination thereof.

15. The method of claim 14 wherein the particulate silicon oxide or metal oxide is silicon dioxide.

Description

EXAMPLES

[0051] Unless otherwise mentioned, all parts and percentages are by weight. In the Examples the following test procedures are used.

[0052] Content of Ether and Ester Groups in Hydroxypropyl Methyl Cellulose Acetate Succinate (HPMCAS)

[0053] The content of ether groups in the esterified cellulose ether is determined in the same manner as described for “Hypromellose”, United States Pharmacopeia and National Formulary, USP 35, pp 3467-3469. The ester substitution with acetyl groups (—CO—CH.sub.3) and the ester substitution with succinoyl groups (—CO—CH.sub.2—CH.sub.2—COOH) are determined according to Hypromellose Acetate Succinate, United States Pharmacopeia and National Formulary, NF 29, pp. 1548-1550”. Reported values for ester substitution are corrected for volatiles (determined as described in section “loss on drying” in the above HPMCAS monograph).

[0054] Properties of Hydroxypropyl Methylcellulose (HPMC)

[0055] The content of methoxyl groups and of hydroxypropoxyl groups in HPMC are determined as described for “Hypromellose”, United States Pharmacopeia and National Formulary, USP 35, pp 3467-3469.

[0056] The viscosity of HPMC is determined as a 2% by weight solution in water at 20° C. by Ubbelohde viscosity measurement as described in the United States Pharmacopeia (USP 35, “Hypromellose”, pages 423-424 and 3467-3469 and in ASTM D-445 and ISO 3105 referenced therein).

Example 1

[0057] I. Production of a Reaction Product Mixture Comprising HPMCAS

[0058] 514.07 g of glacial acetic acid, 202.49 g (dry content 98.77%) of a hydroxypropyl methylcellulose (HPMC), and 43.54 g of sodium acetate (water free) were introduced into a glass reactor with an inner diameter of 147 mm and intensively mixed by use of a MIG™ stirrer (two blade axial flow impeller, company EKATO, Schopfheim, Germany) with an outer diameter of 120 mm running at 300 rpm. The HPMC had a viscosity of about 5 mPa.Math.s, measured as a 2% aqueous solution at 20° C., a degree of methoxyl substitution, DS(methoxyl), of 2.0, and a hydroxypropoxyl substitution, MS(hydroxypropoxyl), of 0.86.

[0059] The glass reactor was put in a heated bath and the mixture was heated to 85° C. 33.84 g of succinic anhydride and 147.69 g of acetic anhydride were added. Mixing was continued for 30 minutes, then 130.61 g of sodium acetate (water free) were added. Intense mixing was continued for 3 hours to effect esterification while the bath temperature was kept at 85° C.

[0060] II: Recovering HPMCAS according to the Process of the Present Invention The hot reaction product mixture as obtained in Procedure I above was quenched by addition of 318.46 g of water. The water had room temperature. The reaction product mixture was diluted by quenching and became less viscous. HPMCAS was precipitated from the diluted reaction product mixture by adding a suspension of 25 g of Aerosil® 200 Pharma in 2 L of water having room temperature. Aerosil 200 Pharma is a colloidal silicon dioxide which has a specific surface (BET) of 175-225 m.sup.2/g. It is commercially available from Evonik Industries.

[0061] During the addition of water used for quenching and of the aqueous suspension of Aerosil® 200 Pharma used for precipitation, the content of the glass reactor was stirred using the above described MIG™ stirrer running at 250 rpm.

[0062] HPMCAS was isolated from the resulting suspension via filtration. A filter cake was obtained that displayed some agglomeration but no significant tackiness.

[0063] The filter cake was re-suspended in 3 L of water having room temperature using an Ultra-Turrax stirrer S50-G45 (rotor diameter 36 mm, inner stator diameter 38 mm) running at 5000 rpm. HPMCAS was again isolated from the resulting suspension via filtration. The resulting filter cake was not tacky at all and did not display substantial agglomeration.

[0064] The filter cake was then washed 3 times by re-suspension in 3 L of water having room temperature. Again the Ultra-Turrax stirrer S50-G45 running at 5000 rpm for 60 seconds was used for re-suspension. HPMCAS was isolated from the resulting suspension via filtration. A filter cake of fine particle size was obtained that was not tacky at all and did not display agglomeration.

[0065] The filter cake was washed twice by re-suspension in 3 L of water having room temperature under mild stirring and separation by filtration. After the final filtration HPMCAS was dried at 55° C.

[0066] Silicon dioxide (Aerosil® 200 Pharma) could be removed by the above-mentioned washing steps to a very large degree. A non-tacky filter cake remained. The residue of the remaining silicon dioxide in the final HPMCAS product was determined by centrifugation of a 8 wt. % solution of the HPMCAS in acetone. The 8 wt. % solution of the HPMCAS in acetone was clear. The silicon dioxide residue was only about 0.5 wt. %, based on the total weight of HPMCAS and silicon dioxide.

Example 2

[0067] Example 1 was repeated, except that HPMCAS was precipitated from the diluted reaction product mixture by adding a suspension of 50 g of Aerosil® 200 Pharma in 2 L of water having room temperature. Again a filter cake of fine particle size was obtained that was not tacky at all and did not display agglomeration.

[0068] The residue of the remaining silicon dioxide in the final HPMCAS product was determined by centrifugation of a 8 wt. % solution of the HPMCAS in acetone. The 8 wt. %

[0069] solution of the HPMCAS in acetone was clear. The HPMC residue was only about 0.7 wt. %, based on the total weight of HPMCAS and silicon dioxide.

Example 3

[0070] Example 1 was repeated, except that HPMCAS was precipitated from the diluted reaction product mixture by adding a suspension of 100 g of Aerosil® 200 Pharma in 2 L of water having room temperature. Again a filter cake of fine particle size was obtained that was not tacky at all and did not display agglomeration.

Example 4

[0071] Example 1 was repeated, except that HPMCAS was precipitated from the diluted reaction product mixture by adding a suspension of 5 g of Aerosil® 200 Pharma in 2 L of water having room temperature. Again a filter cake of fine particle size was obtained that was not tacky and did not display agglomeration. No significant increase in tackiness was observed in the filter cake, as compared to the filter cake in Example 1.

Comparative Example A:

[0072] I. Production of a Reaction Product Mixture Comprising HPMCAS

[0073] A reaction product mixture comprising HPMCAS was produced as in Example 1.

[0074] II. Recovering HPMCAS Without Silicon Dioxide Addition

[0075] The hot reaction product mixture as obtained in Procedure I was quenched by addition of 318.46 g of water. The water had room temperature. The reaction product mixture was diluted by quenching and became less viscous.

[0076] HPMCAS was precipitated from the diluted reaction product mixture by adding 2 L of water having room temperature.

[0077] During the addition of water for quenching and precipitation, the content of the glass reactor was stirred using the above described MIG™ stirrer running at 300 rpm. HPMCAS was isolated from the resulting suspension via filtration. An extremely tacky filter cake was obtained that had the appearance of chewing gum.

[0078] The filter cake was re-suspended in 3 L of water having room temperature using an Ultra-Turrax stirrer S50-G45 (rotor diameter 36 mm, inner stator diameter 38 mm) running at 5000 rpm. HPMCAS was again isolated from the resulting suspension via filtration. The resulting filter cake was clearly tacky.

[0079] The filter cake was again re-suspended in 3 L of water having room temperature. Again the Ultra-Turrax stirrer S50-G45 running at 5000 rpm was used for re-suspension. HPMCAS was isolated from the resulting suspension via filtration. The resulting filter cake was still slightly tacky.

[0080] The filter cake was thoroughly washed 5 times by re-suspension at 200 rpm in 3 L of water having room temperature and separation by filtration. The resulting filter cake was still slightly tacky. After the final filtration HPMCAS was dried at 40° C.

Example 5

[0081] Example 1 was repeated, except that HPMCAS was precipitated from the diluted reaction product mixture by adding a suspension of 1 g of Aerosil® 200 Pharma in 2 L of water having room temperature.

[0082] HPMCAS was isolated from the resulting suspension via filtration. A filter cake was obtained that was more tacky than the filter cake obtained in the corresponding step of Examples 1-4, but much less tacky than the filter cake obtained in the corresponding step of Comparative Example A.

[0083] The filter cake was further processed as in Example 1. After the final filtration HPMCAS was dried at 40° C.