WO2000063254A1 - Haze-free cellulose ether capsules and process for making - Google Patents

Haze-free cellulose ether capsules and process for making Download PDF

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Publication number
WO2000063254A1
WO2000063254A1 PCT/US2000/009787 US0009787W WO0063254A1 WO 2000063254 A1 WO2000063254 A1 WO 2000063254A1 US 0009787 W US0009787 W US 0009787W WO 0063254 A1 WO0063254 A1 WO 0063254A1
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WO
WIPO (PCT)
Prior art keywords
ceuulose
ether
composition
weight
depolymerized
Prior art date
Application number
PCT/US2000/009787
Other languages
French (fr)
Inventor
Colin M. Keary
Gary J. Schulz
Original Assignee
The Dow Chemical Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Dow Chemical Company filed Critical The Dow Chemical Company
Priority to JP2000612340A priority Critical patent/JP2002541945A/en
Priority to DE60030425T priority patent/DE60030425T2/en
Priority to AU44558/00A priority patent/AU759877B2/en
Priority to BRPI0011141-4A priority patent/BR0011141B1/en
Priority to CA002370294A priority patent/CA2370294C/en
Priority to EP00925943A priority patent/EP1173487B1/en
Publication of WO2000063254A1 publication Critical patent/WO2000063254A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B11/00—Preparation of cellulose ethers
    • C08B11/20—Post-etherification treatments of chemical or physical type, e.g. mixed etherification in two steps, including purification
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
    • C08L1/08—Cellulose derivatives
    • C08L1/26—Cellulose ethers
    • C08L1/28—Alkyl ethers

Definitions

  • the present invention relates to haze-free cellulose ether capsules and a process for making.
  • the capsules are useful in pharmaceutical applications.
  • Cellulose ethers are commonly employed commercially to form capsules which are adapted to contain and orally deliver pharmaceutical agents and medicaments.
  • Preferred cellulose ethers for such applications are methylceUulose and hydroxypropylmethylcellulose.
  • Cellulose ether capsules are typically manufactured by dipping hot pins in a cold, aqueous cellulose ether dip coating solution.
  • the solution gels on the pins and water evaporates during a drying step to form thin film layers of dried cellulose ether around the hot pins.
  • the thin films take the form of caps and bodies, which are then removed from the pins.
  • Caps are mated with bodies to form capsules.
  • Analogous processes exist wherein cold pins are dipped in a hot, aqueous cellulose ether solution. Processes for making capsules are seen in U.S. Patent Nos. 3,617,588; 4.001,211 ; 4,917,885; and 5,756,036.
  • a problem commonly encountered in manufacturing cellulose ether capsules is haze formation at their inner surfaces. Haze formation is most noticeable in transparent capsules.
  • Haze causes cellulose ether capsules to exhibit less luster and gloss than they would otherwise. Due to haze, cellulose ether capsules typically do not have the same level of luster as gelatin capsules. This difference in appearance is discussed in "HPMC Capsules - An Alternative to Gelatin," Pharmaceutical Technology Europe 10(11)(1998).
  • cellulose ether capsules which are substantially free of haze formation at their interior surfaces and a process for making such capsules. It would also be desirable to have a process for making a cellulose ether composition useful in such capsules.
  • a cellulose ether composition comprising a low molecular weight cellulose ether.
  • the composition has a sodium chloride content of about 0.3 weight percent or less based upon the weight of the cellulose ether.
  • the composition exhibits significantly reduced haze formation when in capsule form.
  • Useful embodiments also include aqueous and capsule forms of the composition.
  • a process for making a cellulose ether composition comprises a) alkalyzing a cellulose pulp by contacting it with sodium hydroxide; b) ether ⁇ ying the cellulose pulp to form a cellulose ether; c) washing the cellulose ether to reduce sodium chloride content; d) drying the cellulose ether to a reduced moisture content; e) milling the cellulose ether to a paniculate form; 1) contacting the 0 paniculate cellulose ether with an amount of hydrogen chloride sufficient to partially depolymerize it such that a two percent aqueous solution of it has a viscosity of 200 cP or less at 20°C; g) partially or substantially neutralizing the acid by contacting with a sodium compound.
  • the cellulose ether is washed to a sufficient extent and the amount of hydrogen chloride employed is adjusted to a sufficient extent to limit the sodium chloride content of the 5 depolymerized cellulose ether to about 0.3 weight percent or less based upon the weight of the depolymerized cellulose ether.
  • cellulose ether capsules from the cellulose ether composition having low sodium chloride content.
  • the o cellulose ether is dissolved in water to form a dip coating solution.
  • Metal pins are dipped into the coating solution.
  • the solution is allowed to gel and subsequently dry on the pins to form thin films of dried cellulose ether around the pins.
  • the thin films takes the form of caps and/or bodies which are then removed from the pins.
  • the caps and/or bodies can subsequently be mated to form whole capsules.
  • Both hot pin/cold solution and cold pin hot solution processes 5 are contemplated.
  • haze formation in cellulose ether capsules can be significantly reduced by limiting the amount of sodium chloride remaining in the depolymerized end product from which the capsules are formed.
  • the amount of sodium o chloride remaining in the end product can be controlled by the following two methods: i) washing the cellulose ether following etherif ⁇ cation and prior to milling to reduce sodium chloride content and ⁇ ) limiting the amount of hydrogen chloride employed in the depolymer- zation reactor to limit and preferably miiiimize the amount of sodium chloride byproduct produced.
  • Substeps i) and ii) are employed to an extent sufficient to reduce the sodium chloride content of the depolymerized cellulose ether end product to about 0.3 weight percent or less and most preferably about 0.15 weight percent or less based upon the weight of the depolymerized cellulose ether.
  • low molecular weight cellulose ethers are produced by alkalyzing or causticizing a cellulose pulp and etherifying it to form a high molecular weight cellulose ether, which is then depolymerized to form a low molecular weight ceUulose ether.
  • High molecular weight ceUulose ethers have viscosities of up to about 100,000 ccntipoise (cP) in a 2 percent aqueous solution at 20°C.
  • Low molecular weight ceUulose ethers have viscosities of about 200 cP or less in a 2 percent aqueous solution at 20°C. Viscosities are determined according to ASTM D1347 and D2363.
  • CeUulose pulp is alkalyzed or causticized in a reactor with an alkaline hydroxide, preferably sodium hydroxide.
  • the pulp may be alkalyzed by any means known in the art such as steeping in a bath or stirred tank or by spraying directly on dry pulp.
  • the headspace of the reactor may be evacuated or purged with an inert gas to control depolymerization of the ceUulose ether product.
  • ceUulose ethers preferably up to about 100,000 cP in a 2 percent aqueous solution at 20°C.
  • Typical etherifying agents include the lower alkyl haUdes such as methyl chloride and ethyl chloride and epoxides such as ethylene oxide, propylene oxide, and butylene oxide.
  • methyl chloride may be used to make methylceUulose and a mixture of methyl chloride and propylene oxide may be used to make hydroxypropylmethylceUulose.
  • the use of methyl chloride with sodium hydroxide as an alkalyzing agent results in the by-product formation of sodium chloride (salt).
  • a dUuent such as dimethyl ether may be employed during etherification.
  • the ceUulose ether is washed to remove salt and other reaction by-products. Washing is employed in conjunction with control of the amount of hydrogen chloride used in the depolymerization reaction (see below) to rrimimize residual salt content in the depolymerized ceUulose ether end product. Any solvent in which salt is soluble may be employed, but water is highly preferred.
  • the ceUulose ether may be washed in the etherification reactor but is preferably washed in a separate washer located downstream of that reactor. Process washing variables which impact residual salt content in the ceUulose ether include washing residence time, salt content of wash solvent (water), and multiple washings. Residual salt content is most effectively controUed by multiple washings, with two separate washings usuaUy being sufficient. Before or after washing, the ceUulose ether may be stripped by exposure to steam to further reduce residual organic content. 0
  • the washed ceUulose ether is then dried to a reduced moisture content of 0.5 to 5.0 weight percent water and preferably 0.8 to 3.0 weight percent water based upon the weight of ceUulose ether.
  • Useful dryers include tray dryers, fluid bed dryers, flash dryers, agitation dryers, and tube dryers. 5
  • the ceUulose ether is miUed to particulates of desired size. If desired, the ceUulose ether may be milled and dried simultaneously. Milling may be accomplished by any means known in the art such as a baU miU or an impact pulverizer.
  • the milled particulates of high molecular weight ceUulose ether are depolymerized to form particulate low molecular weight ceUulose ethers.
  • Depolymerized low molecular weight ceUulose ethers typicaUy have molecular weights such that a two percent aqueous solution at 20°C has a viscosity of about 200 cP or less, preferably 1 to 100 cP, and more preferably 3 to 100 cP.
  • CeUulose ethers usuaUy employed in making pharmaceutical capsules and coatings 5 have viscosities of 3 to 15 cP in a two percent aqueous solution at 20°C.
  • the ceUulose ether particulates are heated to a temperature of 50°C to 130°C and preferably 60°C to 100°C. The heating may be accomplished in the depolymerization reactor or by a separate heater upstream of such reactor. o The moisture content of the particulates can be restored, if necessary, to a higher level prior to depolymerization by blending the particulates with water in the depolymerization reactor or a separate mixer upstream of such reactor.
  • the miUed ceUulose ether particulates are depolymerized by contacting or treating them with a strong acid, preferably anhydrous hydrogen chloride. The acid can be added to the headspace of the reactor or directly into the ceUulose ether powder. The headspace of the 5 reactor may be purged with an inert gas to prevent combustion or ignition of the powder.
  • the paniculate ceUulose ether is contacted with a basic sodium compound, preferably a substantiaUy anhydrous compound such as sodium bicarbonate, to partiaUy or substantiaUy neutralize any remaining acid.
  • a preferred method of 0 neutralizing is blowing the compound into the headspace or interior of the depolymerization reactor or other vessel where the depolymerized paniculate ceUulose ether may be situated.
  • the depolymerization reactor or other vessel is preferably tumbled during neutralization to ensure uniform contact with the internal surfaces of the reactor.
  • the amount (concentration) of hydrogen chloride employed to catalyze the depolymerization reaction is set at relatively low levels and is preferably rrnr ⁇ nized.
  • Amount (concentration) of hydrogen chloride and reaction temperature substantiaUy govern reaction rate. Losses in reaction rate due to reduction in the amount of hydrogen chloride employed o can be compensated for by increasing reaction temperature or by increasing reaction time. Given that increases in reaction time reduce production efficiencies and raise economic costs, it is most desirable to increase reaction temperatures to make up for relatively lesser amounts of hydrogen chloride.
  • ConventionaUy, depolymerization reaction temperatures have ranged from 50°C to 130°C and more typicaUy from 60°C to 100°C.
  • reaction temperatures 80°C to 110°C are most preferred in the present invention.
  • hydrogen chloride is added to the depolymerization reactor at 0.10 to 0.19 weight percent based upon the weight of the ceUulose ether to be depolymerized.
  • ceUulose ethers Useful teachings relating to making low molecular weight ceUulose ethers are seen in o U.S. Serial No. 09/203,324, filed December 1, 1998.
  • the present process is useful for making the foUowing ceUulose ethers: methylceUulose, hydroxyethylmethylceUulose, hydroxypropylmethylceUulose. and hydroxybutylmethylceUulose.
  • the process is particularly useful in making methylceUulose and hydroxypropylmethylceUulose.
  • the low molecular weight ceUulose ethers are useful in other pharmaceutical apphcations such as tablet coatings and as exipients for pharmaceutical agents and medicaments in capsules and tablets.
  • Other useful apphcations include buUding products and food apphcations.

Abstract

Disclosed is a cellulose ether composition having a low molecular weight cellulose ether of a viscosity of about 200 mPas or less in a two percent aqueous solution at 20°C. The composition has a sodium chloride content of about 0.3 weight percent or less based upon the weight of the cellulose ether. The composition exhibits significantly reduced haze formation when in capsule form. Also disclosed is a process for making the composition.

Description

HAZE-FREE CELLULOSE ETHER CAPSULES AND PROCESS FOR MAKING
The present invention relates to haze-free cellulose ether capsules and a process for making. The capsules are useful in pharmaceutical applications.
Cellulose ethers are commonly employed commercially to form capsules which are adapted to contain and orally deliver pharmaceutical agents and medicaments. Preferred cellulose ethers for such applications are methylceUulose and hydroxypropylmethylcellulose.
Cellulose ether capsules are typically manufactured by dipping hot pins in a cold, aqueous cellulose ether dip coating solution. The solution gels on the pins and water evaporates during a drying step to form thin film layers of dried cellulose ether around the hot pins. The thin films take the form of caps and bodies, which are then removed from the pins. Caps are mated with bodies to form capsules. Analogous processes exist wherein cold pins are dipped in a hot, aqueous cellulose ether solution. Processes for making capsules are seen in U.S. Patent Nos. 3,617,588; 4.001,211 ; 4,917,885; and 5,756,036.
A problem commonly encountered in manufacturing cellulose ether capsules is haze formation at their inner surfaces. Haze formation is most noticeable in transparent capsules.
Haze causes cellulose ether capsules to exhibit less luster and gloss than they would otherwise. Due to haze, cellulose ether capsules typically do not have the same level of luster as gelatin capsules. This difference in appearance is discussed in "HPMC Capsules - An Alternative to Gelatin," Pharmaceutical Technology Europe 10(11)(1998).
It would be desirable to have cellulose ether capsules which are substantially free of haze formation at their interior surfaces and a process for making such capsules. It would also be desirable to have a process for making a cellulose ether composition useful in such capsules.
According to the present invention, there is a cellulose ether composition comprising a low molecular weight cellulose ether. The composition has a sodium chloride content of about 0.3 weight percent or less based upon the weight of the cellulose ether. The composition exhibits significantly reduced haze formation when in capsule form. Useful embodiments also include aqueous and capsule forms of the composition.
5 Further according to the present invention, there is a process for making a cellulose ether composition. The process comprises a) alkalyzing a cellulose pulp by contacting it with sodium hydroxide; b) etherϋying the cellulose pulp to form a cellulose ether; c) washing the cellulose ether to reduce sodium chloride content; d) drying the cellulose ether to a reduced moisture content; e) milling the cellulose ether to a paniculate form; 1) contacting the 0 paniculate cellulose ether with an amount of hydrogen chloride sufficient to partially depolymerize it such that a two percent aqueous solution of it has a viscosity of 200 cP or less at 20°C; g) partially or substantially neutralizing the acid by contacting with a sodium compound. The cellulose ether is washed to a sufficient extent and the amount of hydrogen chloride employed is adjusted to a sufficient extent to limit the sodium chloride content of the 5 depolymerized cellulose ether to about 0.3 weight percent or less based upon the weight of the depolymerized cellulose ether.
Further according to the present invention, there is a process for making cellulose ether capsules from the cellulose ether composition having low sodium chloride content. The o cellulose ether is dissolved in water to form a dip coating solution. Metal pins are dipped into the coating solution. The solution is allowed to gel and subsequently dry on the pins to form thin films of dried cellulose ether around the pins. The thin films takes the form of caps and/or bodies which are then removed from the pins. The caps and/or bodies can subsequently be mated to form whole capsules. Both hot pin/cold solution and cold pin hot solution processes 5 are contemplated.
In the present invention, it was discovered that haze formation in cellulose ether capsules can be significantly reduced by limiting the amount of sodium chloride remaining in the depolymerized end product from which the capsules are formed. The amount of sodium o chloride remaining in the end product can be controlled by the following two methods: i) washing the cellulose ether following etherifϊcation and prior to milling to reduce sodium chloride content and ϋ) limiting the amount of hydrogen chloride employed in the depolymer- zation reactor to limit and preferably miiiimize the amount of sodium chloride byproduct produced. Substeps i) and ii) are employed to an extent sufficient to reduce the sodium chloride content of the depolymerized cellulose ether end product to about 0.3 weight percent or less and most preferably about 0.15 weight percent or less based upon the weight of the depolymerized cellulose ether.
Generally, low molecular weight cellulose ethers are produced by alkalyzing or causticizing a cellulose pulp and etherifying it to form a high molecular weight cellulose ether, which is then depolymerized to form a low molecular weight ceUulose ether. High molecular weight ceUulose ethers have viscosities of up to about 100,000 ccntipoise (cP) in a 2 percent aqueous solution at 20°C. Low molecular weight ceUulose ethers have viscosities of about 200 cP or less in a 2 percent aqueous solution at 20°C. Viscosities are determined according to ASTM D1347 and D2363.
CeUulose pulp is alkalyzed or causticized in a reactor with an alkaline hydroxide, preferably sodium hydroxide. The pulp may be alkalyzed by any means known in the art such as steeping in a bath or stirred tank or by spraying directly on dry pulp. The headspace of the reactor may be evacuated or purged with an inert gas to control depolymerization of the ceUulose ether product.
The alkylated ceUulose pulp is then etherified to form ceUulose ethers of preferably up to about 100,000 cP in a 2 percent aqueous solution at 20°C. Typical etherifying agents include the lower alkyl haUdes such as methyl chloride and ethyl chloride and epoxides such as ethylene oxide, propylene oxide, and butylene oxide. For instance, methyl chloride may be used to make methylceUulose and a mixture of methyl chloride and propylene oxide may be used to make hydroxypropylmethylceUulose. The use of methyl chloride with sodium hydroxide as an alkalyzing agent results in the by-product formation of sodium chloride (salt). If desired, a dUuent such as dimethyl ether may be employed during etherification.
The ceUulose ether is washed to remove salt and other reaction by-products. Washing is employed in conjunction with control of the amount of hydrogen chloride used in the depolymerization reaction (see below) to rrimimize residual salt content in the depolymerized ceUulose ether end product. Any solvent in which salt is soluble may be employed, but water is highly preferred. The ceUulose ether may be washed in the etherification reactor but is preferably washed in a separate washer located downstream of that reactor. Process washing variables which impact residual salt content in the ceUulose ether include washing residence time, salt content of wash solvent (water), and multiple washings. Residual salt content is most effectively controUed by multiple washings, with two separate washings usuaUy being sufficient. Before or after washing, the ceUulose ether may be stripped by exposure to steam to further reduce residual organic content. 0
The washed ceUulose ether is then dried to a reduced moisture content of 0.5 to 5.0 weight percent water and preferably 0.8 to 3.0 weight percent water based upon the weight of ceUulose ether. Useful dryers include tray dryers, fluid bed dryers, flash dryers, agitation dryers, and tube dryers. 5
The ceUulose ether is miUed to particulates of desired size. If desired, the ceUulose ether may be milled and dried simultaneously. Milling may be accomplished by any means known in the art such as a baU miU or an impact pulverizer.
o The milled particulates of high molecular weight ceUulose ether are depolymerized to form particulate low molecular weight ceUulose ethers. Depolymerized low molecular weight ceUulose ethers typicaUy have molecular weights such that a two percent aqueous solution at 20°C has a viscosity of about 200 cP or less, preferably 1 to 100 cP, and more preferably 3 to 100 cP. CeUulose ethers usuaUy employed in making pharmaceutical capsules and coatings 5 have viscosities of 3 to 15 cP in a two percent aqueous solution at 20°C.
In preparation for depolymerization, the ceUulose ether particulates are heated to a temperature of 50°C to 130°C and preferably 60°C to 100°C. The heating may be accomplished in the depolymerization reactor or by a separate heater upstream of such reactor. o The moisture content of the particulates can be restored, if necessary, to a higher level prior to depolymerization by blending the particulates with water in the depolymerization reactor or a separate mixer upstream of such reactor. The miUed ceUulose ether particulates are depolymerized by contacting or treating them with a strong acid, preferably anhydrous hydrogen chloride. The acid can be added to the headspace of the reactor or directly into the ceUulose ether powder. The headspace of the 5 reactor may be purged with an inert gas to prevent combustion or ignition of the powder.
FoUowing depolymerization, the paniculate ceUulose ether is contacted with a basic sodium compound, preferably a substantiaUy anhydrous compound such as sodium bicarbonate, to partiaUy or substantiaUy neutralize any remaining acid. A preferred method of 0 neutralizing is blowing the compound into the headspace or interior of the depolymerization reactor or other vessel where the depolymerized paniculate ceUulose ether may be situated. The depolymerization reactor or other vessel is preferably tumbled during neutralization to ensure uniform contact with the internal surfaces of the reactor.
5 To minimize or limit the amount of sodium chloride by-product produced during neutralization, the amount (concentration) of hydrogen chloride employed to catalyze the depolymerization reaction is set at relatively low levels and is preferably rrnrώnized. Amount (concentration) of hydrogen chloride and reaction temperature substantiaUy govern reaction rate. Losses in reaction rate due to reduction in the amount of hydrogen chloride employed o can be compensated for by increasing reaction temperature or by increasing reaction time. Given that increases in reaction time reduce production efficiencies and raise economic costs, it is most desirable to increase reaction temperatures to make up for relatively lesser amounts of hydrogen chloride. ConventionaUy, depolymerization reaction temperatures have ranged from 50°C to 130°C and more typicaUy from 60°C to 100°C. To increase reaction time, 5 higher reaction temperatures of 80°C to 110°C are most preferred in the present invention. In a preferred embodiment, hydrogen chloride is added to the depolymerization reactor at 0.10 to 0.19 weight percent based upon the weight of the ceUulose ether to be depolymerized.
Useful teachings relating to making low molecular weight ceUulose ethers are seen in o U.S. Serial No. 09/203,324, filed December 1, 1998. The present process is useful for making the foUowing ceUulose ethers: methylceUulose, hydroxyethylmethylceUulose, hydroxypropylmethylceUulose. and hydroxybutylmethylceUulose. The process is particularly useful in making methylceUulose and hydroxypropylmethylceUulose.
The low molecular weight ceUulose ethers are useful in other pharmaceutical apphcations such as tablet coatings and as exipients for pharmaceutical agents and medicaments in capsules and tablets. Other useful apphcations include buUding products and food apphcations.
WhUe embodiments of the capsule process and process of the present invention have been shown with regard to specific detaUs. it wiU be appreciated that the present invention may be modified while still being fairly within the scope of the novel teachings and principles set forth herein.

Claims

WHAT IS CLAIMED IS:
1. A ceUulose ether composition, the composition comprising a low molecular weight ceUulose ether having a viscosity of 200 centipoise or less in a two percent aqueous solution at 20°C, the composition having a sodium chloride content of about 0.3 weight percent or less based upon the weight of the ceUulose ether.
2. The composition of Claim 1, the composition having a sodium chloride content of about 0.15 weight percent or less based upon the weight of the ceUulose ether.
3. The composition of Claim 1 , the ceUulose ether comprising methylceUulose or hydroxypropylmethylceUulose.
4. The composition of Claim 1, the composition taking the form of an aqueous composition.
5. The composition of Claim 1, the composition taking the form of a capsule.
6. The composition of Claim 1, wherein the viscosity is 3 to 100 cP.
7. The composition of Claim 1, wherein the viscosity is 3 to 15 cP.
8. The composition of Claim 3, wherein the viscosity is 3 to 15 cP, the composition taking the form of a capsule.
9. The composition of Claim 8, wherein the composition has a content of about
0.15 weight percent sodium chloride or less based upon the weight of the ceUulose ether.
10. A process for making a ceUulose ether composition, the process comprising: a) alkalyzing a ceUulose pulp by contacting it with sodium hydroxide; b) etherifying the ceUulose pulp to form a ceUulose ether; c) washing the ceUulose ether to reduce sodium chloride content; d) drying the ceUulose ether to a reduced moisture content: e) milling the ceUulose ether to a paniculate form; f) contacting the paniculate ceUulose ether with an amount of hydrogen chloride sufficient to partially depolymerize it such that a two percent aqueous solution of it has a viscosity of 200 cP or less at 20°C; g) partiaUy or substantiaUy neutralizing the hydrogen chloride by contacting the paniculate ceUulose ether with a basic sodium compound, the ceUulose ether being washed in step c) to an extent and the amount of hydrogen chloride being adjusted in step f) to an extent sufficient to limit the sodium chloride content of the depolymerized ceUulose ether to about 0.3 weight percent or less based upon the weight of the depolymerized ceUulose ether.
11. The process of Claim 1 , wherein the depolymerized ceUulose ether is dissolved in water to form a dip coating solution, metal pins being dipped into the coating solution, the metal pins being removed from the coating solution, the solution being aUowed to gel and subsequently dry on the surface of the pins to form caps and/or bodies, and the caps and/or bodies being removed from the pins.
12. The process of Claim 10, wherein the sodium compound is sodium bicarbonate.
13. The process of Claim 11 , wherein the sodium compound is sodium bicarbonate.
14. The process of Claim 10, wherein the ceUulose ether is a methylceUulose or a hydroxypropylmethylceUulose.
15. The process of Claim 11 , wherein the ceUulose ether is a methylceUulose or a hydroxypropylmethylceUulose.
16. The process of Claim 10, wherein the paniculate ceUulose ether is depolymerized at a temperature of 50°C to 130°C.
17. The process of Claim 10. wherein the particulate ceUulose ether is depolymerized at a temperature of about 80°C to about 110°C.
18. The process of Claim 10. wherein the amount of hydrogen chloride employed is 5 0.10 to 0.19 weight percent based upon the weight of the ceUulose ether.
19. The process of Claim 17, wherein the amount of hydrogen chloride employed is 0.10 to 0.19 weight percent based upon the weight of the ceUulose ether.
l o 20. The process of Claim 10, wherein the sodium compound is sodium bicarbonate, the ceUulose ether being a methylceUulose or a hydroxypropylmethylceUulose, the particulate ceUulose ether being depolymerized at a temperature of 80°C to 110°C. the amount of hydrogen chloride employed being 0.10 to 0.19 weight percent based upon the weight of the particulate ceUulose ether to be depolymerized.
15
PCT/US2000/009787 1999-04-21 2000-04-12 Haze-free cellulose ether capsules and process for making WO2000063254A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP2000612340A JP2002541945A (en) 1999-04-21 2000-04-12 Haze-free cellulose ether capsule and method of making
DE60030425T DE60030425T2 (en) 1999-04-21 2000-04-12 TURBINE-FREE CELLULOSE ETHER CAPSULES AND MANUFACTURING PROCESS
AU44558/00A AU759877B2 (en) 1999-04-21 2000-04-12 Haze-free cellulose ether capsules and process for making
BRPI0011141-4A BR0011141B1 (en) 1999-04-21 2000-04-12 cellulose ether composition in the form of a turbidity-free capsule and process for preparing a cellulose ether composition.
CA002370294A CA2370294C (en) 1999-04-21 2000-04-12 Haze-free cellulose ether capsules and process for making
EP00925943A EP1173487B1 (en) 1999-04-21 2000-04-12 Haze-free cellulose ether capsules and process for making

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US09/295,692 US6294008B1 (en) 1999-04-21 1999-04-21 Haze-free cellulose ether capsules and process for making
US09/295,692 1999-04-21

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AR (1) AR028147A1 (en)
AT (1) ATE338066T1 (en)
AU (1) AU759877B2 (en)
BR (1) BR0011141B1 (en)
CA (1) CA2370294C (en)
CO (1) CO5170467A1 (en)
DE (1) DE60030425T2 (en)
ES (1) ES2265937T3 (en)
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FR2953217A1 (en) * 2009-11-27 2011-06-03 Ifremer PROCESS FOR DEPOLYMERIZATION OF POLYSACCHARIDES BY MECHANICAL MILLING
WO2013157702A1 (en) * 2012-04-18 2013-10-24 삼성정밀화학(주) Film and preparation method thereof
US9156919B2 (en) 2011-07-27 2015-10-13 Dow Global Technologies Llc Method of removing alkylene halogenohydrin from cellulose ether
EP3988578A1 (en) * 2020-10-22 2022-04-27 Shin-Etsu Chemical Co., Ltd. Method for producing depolymerized cellulose ether
US11407842B2 (en) 2017-08-16 2022-08-09 Nutrition & Biosciences Usa 1, Llc Method for controlled preparation of low molecular weight cellulose ether
US11879022B2 (en) 2020-10-22 2024-01-23 Shin-Etsu Chemical Co., Ltd. Method for producing depolymerized cellulose ether

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CA2370294C (en) 2008-12-02
EP1173487B1 (en) 2006-08-30
AU4455800A (en) 2000-11-02
EP1173487A1 (en) 2002-01-23
CO5170467A1 (en) 2002-06-27
BR0011141A (en) 2002-02-26
US6294008B1 (en) 2001-09-25
BR0011141B1 (en) 2010-12-28
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AU759877B2 (en) 2003-05-01
CA2370294A1 (en) 2000-10-26
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DE60030425D1 (en) 2006-10-12
JP2010222585A (en) 2010-10-07

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