Plastic and nonmetallic article shaping or treating: processes – Mechanical shaping or molding to form or reform shaped article – Forming plural articles
Reexamination Certificate
1999-10-13
2001-10-23
Tentoni, Leo B. (Department: 1732)
Plastic and nonmetallic article shaping or treating: processes
Mechanical shaping or molding to form or reform shaped article
Forming plural articles
C264S301000
Reexamination Certificate
active
06306333
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to an improved process for making low molecular weight cellulose ethers. The process employs partial neutralization of acid following an acid-catalyzed depolymerization step.
BACKGROUND OF THE INVENTION
Low molecular weight cellulose ethers are commonly employed commercially in pharmaceutical and food. Preferred cellulose ethers for such applications are methylcellulose and hydroxypropylmethylcellulose.
A problem frequently observed in low molecular cellulose ether is yellowing or discoloration. Such yellowing or discoloration can be observed in products into which the compositions are formulated. Yellowing or discoloration is easily observed in transparent pharmaceutical capsules and light-colored food compositions.
It would be desirable to have a process for manufacturing low molecular weight cellulose ethers wherein yellowing or discoloration is reduced or diminished. It would be desirable to reduce or diminish yellowing or discoloration in pharmaceutical capsules and food compositions.
SUMMARY OF THE INVENTION
According to the present invention, there is a process for making a low molecular weight cellulose ether. The process comprises the following: a) providing a high molecular weight cellulose ether of a viscosity of about 200 centipoise or more in a two percent aqueous solution at 20° C.; b) contacting the high molecular weight cellulose ether with an amount of an acid sufficient to partially depolymerize it to a low molecular weight cellulose ether of a viscosity of about 100 cP or less at 20° C. in a two percent aqueous solution; c) partially or substantially neutralizing the acid by contacting the low molecular weight cellulose ether with a basic compound; d) repeating steps a)-c) to produce two or more discrete product batches of low molecular weight cellulose ether; and e) blending the two or more discrete product batches to form a combined product batch of low molecular weight cellulose ether of a pH of 4 to 6.8.
Further according to the present invention, there is a process for making pharmaceutical capsules. The combined product batch of low molecular weight cellulose ether referenced above is dissolved in water to form a dip coating solution. Metal pins are dipped into the coating solution. The solution is allowed to thermally gel and subsequently dry on the pins to form thin films of dried cellulose ether composition around the pins. The thin films take the form of caps and/or bodies of two-piece hard shell capsules 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 are possible.
DETAILED DESCRIPTION
In the present invention, it was discovered that control of acid content of a low molecular weight cellulose ether to certain pH levels significantly reduced yellowing and discoloration in the end product. Acidic pH is maintained by retaining a portion of the catalyzing acid following an acid-catalyzed depolymerization step in the manufacture of the low molecular weight cellulose ether. An observed problem of effective pH control in the end product low molecular weight cellulose ether is addressed by blending of two or more discrete product batches to form a combined batch.
In conventional manufacturing processes for making low molecular weight cellulose ethers, a higher molecular weight cellulose ether is depolymerized to the lower molecular weight cellulose ether by acid-catalyzed hydrolysis, usually by exposure to a strong inorganic acid such as hydrogen chloride or hydrochloric acid. After the desired degree of depolymerization is achieved, hydrolysis is halted by neutralization of the acid with an alkaline or basic compound such as sodium bicarbonate. The cellulose ether is typically neutralized to a neutral pH of about 7.
In the present invention, some degree of acidity is retained in the end product cellulose ether by neutralizing only a portion of the catalyzing acid. Physical and chemical stability problems in the end product associated with substantial retention of acid content, such as continued depolymerization, are diminished by partial neutralization of the acid and control of the resulting pH to within 4-6.8.
Useful low molecular weight cellulose ethers typically have molecular weights such that a two percent aqueous solution at 20° C. has a viscosity of about 100 cP or less, preferably about 3 to about 100 cP, and most preferably about 3 to about 15 cP in a two percent aqueous solution at 20° C.
Useful cellulose ethers include the following: methylcellulose (MC), hydroxyethylmethylcellulose (HEMC), hydroxypropylmethylcellulose (HPMC), hydroxyethylmethylcellulose (HEMC), ethylhydroxyethylcellulose (EHEC) and hydroxybutylmethylcellulose (HBMC). A particularly useful cellulose ether in making pharmaceutical capsules is hydroxypropylmethylcellulose. Particularly useful cellulose ethers in making food compositions are methylcellulose and hydroxypropylmethylcellulose.
Low molecular weight cellulose ethers are formed by acid-catalyzed depolymerization of high molecular weight cellulose ethers. High molecular weight cellulose ethers typically have viscosities of about 200 centipoise or more in a two percent aqueous solution at 20° C.
Depolymerization is typically carried out by contacting the high molecular weight cellulose ether with a strong acid, preferably anhydrous hydrogen chloride. The acid can be added to the headspace of the reactor or directly into the cellulose ether powder. The headspace of the reactor may be purged with an inert gas to prevent combustion or ignition of the powder.
Following depolymerization, the cellulose ether is contacted with a basic compound, preferably a substantially anhydrous compound such as sodium bicarbonate, with the aim or goal of partially neutralizing the residual acid to retain some degree of acidic content. While the aim of the neutralization step is to partially neutralize rather than substantially or completely neutralize the residual acid, control of the neutralization process, particularly on an industrial scale, is difficult. Some end product batches may be underneutralized or overneutralized. This control problem is discussed below. A preferred method of neutralizing is blowing the compound into the headspace or interior of the depolymerization reactor or other vessel where the depolymerized particulate cellulose ether may be situated. The depolymerization reactor or other vessel is preferably agitated or tumbled during neutralization to ensure uniform contact with the internal surfaces of the reactor.
Targeting a specific end product pH or end product pH within a relatively narrow range, i.e. 4 to 6.8, is difficult as a practical matter. The pH can be impacted demonstrably by relatively small differences in the amount of basic compound used to neutralize acid content. Targeting within still narrower pH ranges is commensurately more difficult. Depending upon the extent of neutralization actually effected, some end product batches may have a pH of less than four. Others may have a pH of 4 to 6.8. Still others may have a pH of greater than 6.8.
In the present invention, pH control is maintained within the desired 4 to 6.8 pH range in the end product by producing two or more discrete product batches of the low molecular weight cellulose ether and subsequently blending them to form a combined product batch having a pH of 4 to 6.8 on a conventional pH logarithmic scale of 0 to 14. At least one of the discrete product batches will have been partially neutralized to a pH of 6.8 or less. Blending of two or more discrete product batches allows pH to be much more accurately targeted and ensures excellent product quality control. Discrete product batches that fall above and below the desired 4 to 6.8 range can be blended to form combined product batches that fall within the desired range or can be blended with discrete product batches that already fall within the desired 4 to 6.8 range to produce combined product batches that still fall with
Rosenberg Steven
Schulz Gary J.
Spencer Michael V.
Tentoni Leo B.
The Dow Chemical Company
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