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 a cellulose ether is added before or in step (i) to the reaction product mixture, to 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 a cellulose ether is added before or in step (i) to the reaction product mixture, to the aqueous liquid or a combination thereof.

2. The process of claim 1 wherein in step (i) the reaction product mixture is first diluted with a first amount of aqueous liquid without precipitating the esterified cellulose ether from the reaction product mixture, the diluted reaction product mixture is then contacted with a second amount of aqueous liquid to precipitate the esterified cellulose ether from the diluted reaction product mixture, and the cellulose ether is added while diluting the reaction product mixture with the first amount of aqueous liquid, and/or after dilution of the reaction product mixture with the first amount of aqueous liquid and before contacting the diluted reaction product mixture with a second amount of aqueous liquid, and/or while contacting the diluted reaction product mixture with a second amount of aqueous liquid.

3. The process of claim 1 or 2, wherein the cellulose ether is dissolved or dispersed in the aqueous liquid, in the first amount of liquid, or in the second amount of liquid before addition to the reaction product mixture.

4. The process of any one of claims 1 to 3 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.

5. The process of any one of claims 1 to 4 wherein the weight ratio between the cellulose ether added to the reaction product mixture before or in step (i) and the cellulose ether utilized for producing the esterified cellulose ether is from 0.05:1 to 5:1.

6. The process of claim 5 wherein the weight ratio between the cellulose ether added to the reaction product mixture before or in step (i) and the cellulose ether utilized for producing the esterified cellulose ether is from 0.25:1 to 1:1.

7. The process of any one of claims 1 to 6 wherein each cellulose ether independently is an alkyl cellulose, a hydroxyalkyl cellulose or a hydroxyalkyl alkylcellulose.

8. The process of any one of claims 1 to 7 wherein each cellulose ether independently has a viscosity of from 1.5 to 50 mP.Math.s, measured as a 2 weight-% aqueous solution at 20 C.

9. The process of any one of claims 1 to 8 wherein the aliphatic monocarboxylic acid anhydride is selected from the group consisting of acetic anhydride, butyric anhydride and propionic anhydride.

10. The process of any one of claims 1 to 9 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 any one of claims 1 to 10 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. The process of any one of claims 1 to 12 wherein the cellulose ether added before or in step (i) to the reaction product mixture, to the aqueous liquid or a combination thereof is hydroxypropyl methyl cellulose.

14. 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 any one of claims 1 to 13.

15. 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 product mixture, and (ii) isolating the precipitated esterified cellulose ether from the mixture obtained in step (i), wherein a cellulose ether is added before or in step (i) to the reaction product mixture, to the aqueous liquid or a combination thereof.

Description

EXAMPLES

[0052] Unless otherwise mentioned, all parts and percentages are by weight. In the Examples the following test procedures are used.

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.

[0054] The ester substitution with acetyl groups (COCH.sub.3) and the ester substitution with succinoyl groups (COCH.sub.2CH.sub.2COOH) 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).

[0055] Properties of Hydroxypropyl Methylcellulose (HPMC)

[0056] 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.

[0057] 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

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.

II: Recovering HPMCAS according to the Process of the Present Invention

[0060] 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.

[0061] HPMCAS was precipitated from the diluted reaction product mixture by adding a solution of 100 g of HPCM in 2 L of water having room temperature. The HPMC had a methoxyl substitution (DS.sub.M) of 1.92, a hydroxypropoxyl substitution (MS.sub.HP) of 0.24 and a viscosity of 3.0 mPa.Math.s, measured as a 2% solution in water at 20 C. The HPMC is commercially available from The Dow Chemical Company as Methocel E3 LV Premium cellulose ether.

[0062] During the addition of water for quenching and of the HPMC solution for precipitation, the content of the glass reactor was stirred using the above described MIG stirrer running at 300 rpm.

[0063] HPMCAS was isolated from the resulting suspension via filtration. A modestly tacky filter cake was obtained.

[0064] The filter cake was re-suspended in 3 L of boiling water 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 only slightly tacky.

[0065] The filter cake was re-suspended in 3 Lof water having room temperature. Again the Ultra-Turrax stirrer S50-G45 running at 5000 rpm was used for re-suspension. PMCAS was isolated from the resulting suspension via filtration. The resulting filter cake was not tacky at all.

[0066] The filter cake was thoroughly washed 5 times by re-suspension at 200 rpm in 3 Lof water having room temperature and separation by filtration. After the final filtration HPMCAS was dried at 40 C. HPMC could be removed by these washing steps to a very large degree. A non-tacky filter cake remained. The residue of the remaining HPMC in the final HPMCAS product was determined by centrifugation of a 5 wt. % solution of the HPMCAS in acetone. The HPMC residue was only about 0.2 wt. %, based on the total weight of HPMCAS and HPMC.

Comparative Example A

I. Production of a Reaction Product Mixture Comprising HPMCAS

[0067] A reaction product mixture comprising HPMCAS was produced as in Example 1.

II. Recovering HPMCAS without Cellulose Ether Addition

[0068] 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.

[0069] HPMCAS was precipitated from the diluted reaction product mixture by adding 2 L of water having room temperature.

[0070] 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.

[0071] HPMCAS was isolated from the resulting suspension via filtration. An extremely tacky filter cake was obtained that had the appearance of chewing gum.

[0072] The filter cake was re-suspended in 3 Lof 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.

[0073] The filter cake was again re-suspended in 3 Lof 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.

[0074] The filter cake was thoroughly washed 5 times by re-suspension at 200 rpm in 3 Lof 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.

Comparative Example B

[0075] Comparative Example A was repeated, except that after precipitation of the HPMCAS from the diluted reaction product mixture, isolating HPMCAS from the resulting suspension and recovering an extremely tacky filter cake that had the appearance of chewing gum, the filter cake was re-suspended in 3 Lof boiling water using an Ultra-Turrax stirrer S50-G45 (rotor diameter 36 mm, inner stator diameter 38 mm) running at 5000 rpm.

[0076] The filter cake was re-suspended in 3 Lof water having room temperature. Again the Ultra-Turrax stirrer S50-G45 running at5000 rpm was used for re-suspension. HPMCAS was isolated from the resulting suspension via filtration. The resulting filter cake was even tackier than in Comparative Example A.

Example 2

I. Production of a Reaction Product Mixture comprising HPMCAS

[0077] A reaction product mixture comprising HPMCAS was produced as in Example 1.

II: Recovering HPMCAS according to the Process of the Present Invention

[0078] 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. 100 g of the same type of HPMC as in Example 1 was added as a solid to the diluted reaction product mixture. After 10 min HPMCAS was precipitated from the diluted reaction product mixture by addition of 2L of water having 21 C.

[0079] HPMCAS was isolated from the resulting suspension via filtration. The filter cake was even less tacky than in Example 1.

[0080] The filter cake was then re-suspended in 3 L of boiling water using an Ultra-Turrax stirrer S50-G45 and again isolated from the resulting suspension via filtration, as described in Example 1. The resulting filter cake was again even less tacky than in Example 1.

[0081] The filter cake was re-suspended in 3 L of water having room temperature and again isolated from the resulting suspension via filtration, as described in Example 1. The resulting filter cake was not tacky at all. It was further processed as in Example 1.