Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Wearing apparel – fabric – or cloth
Reexamination Certificate
2000-04-13
2003-11-18
Thibodeau, Paul (Department: 1773)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Wearing apparel, fabric, or cloth
C424S403000, C424S451000, C428S034300, C428S532000
Reexamination Certificate
active
06649180
ABSTRACT:
This invention relates to a cellulose ether film suited for use in forming pharmaceutical and food hard capsules.
BACKGROUND OF THE INVENTION
Hard capsules are commonly used in the pharmaceutical and health food fields. Of the hard capsules, gelatin capsules are most widely used. They are formed from a film of a composition comprising gelatin as a base, a plasticizer (e.g., glycerin or sorbitol), opacifying agent, dye, pigment, and other addenda. Typically, gelatin capsules are manufactured by dipping pins in an aqueous gelatin solution having the above components blended, drawing out the pins with the aqueous gelatin solution adhering to the pins, and drying the gelatin coats.
Flexibility and other properties of gelatin-based film largely depend on the water content of the film. A film with a low water content is too low in impact resistance to withstand the shocks encountered upon filling of medicament. Also, as the water content decreases by drying during storage, the film contracts to undesirably loosen the cap-to-body engagement. To prevent such inconvenience, gelatin capsules must be kept at an optimum water content of about 13 to 15% by weight. Because of the necessity to have such a relatively high water content, it is restricted to apply the gelatin capsules to those medicaments which give rise to a problem upon contact with water. When the gelatin capsules contain a hygroscopic fill, the capsules gradually lose the water content and hence, the strength, inviting the risk of failure.
Under the circumstances, studies have been made on the capsules which can avoid the problems associated with water contents and which are applicable to any type of fill. One exemplary substitute for the gelatin capsules is capsules whose film is formed of a cellulose ether composition comprising a water-soluble cellulose ether as a base in which some of the hydrogen atoms of cellulosic hydroxyl groups are replaced by alkyl and hydroxyalkyl groups or hydroxyalkyl groups, a gelling agent, and a gelling aid, as disclosed in Japanese Patent No. 2,552,937. Some capsules based on hydroxypropyl methyl cellulose (HPMC) have been used in practice. These capsules of cellulose ether film maintain a sufficient strength even at a low water content, and their behaviors such as dissolution are equivalent to those of conventional gelatin capsules. Additionally, they can be manufactured by the so-called dipping method as are conventional gelatin capsules.
However, the capsules of cellulose ether film suffer from the problem that the gelling aid which is blended for assisting in film formation will precipitate out on the film surface during long-term storage.
More particularly, in one appropriate formulation of the cellulose ether film for forming capsules, carrageenan is used as a gelling agent for HPMC, and a potassium or calcium ion is incorporated as a gelling aid in the form of a water-soluble compound such as potassium chloride or calcium chloride. During long-term storage of these cellulose ether film capsules, the water content of the film can be lowered owing to the storage environment or the water absorption of the fill. Then the potassium or calcium ion as the gelling aid will re-form potassium chloride or calcium chloride which precipitates out on the film surface.
The precipitates of the gelling aid give rise to no problem to the practical usage, but are unpleasant to look at. Especially in the case of colorless clear film, the precipitates develop as cloud and sometimes, cloud spots rather than uniform cloud, exacerbating the outer appearance of capsules noticeably.
SUMMARY OF THE INVENTION
An object of the invention is to provide a novel and improved cellulose ether film of a composition comprising a cellulose ether as a base, a gelling agent, and a gelling aid, which prevents the gelling aid from precipitating out and maintains a favorable outer appearance during long-term storage.
It has been found that when a film, typically a capsule film is formed of a composition comprising a cellulose ether as a base in which some of the hydrogen atoms of cellulosic hydroxyl groups are replaced by alkyl groups and/or hydroxyalkyl groups, a gelling agent, and a gelling aid, the use of the cellulose ether having an alkoxyl and hydroxyalkoxyl content of up to 37.6% by weight is effective for preventing precipitation of the gelling aid, thereby maintaining a favorable outer appearance even after long-term storage.
Accordingly, the invention provides a cellulose ether film formed of a composition comprising a cellulose ether as a base in which some of the hydrogen atoms of cellulosic hydroxyl groups are replaced by alkyl groups and/or hydroxyalkyl groups, a gelling agent, and a gelling aid, wherein the total content of alkoxyl and hydroxyalkoxyl groups in the cellulose ether is up to 37.6% by weight.
Although the reason why precipitation of the gelling aid can be restrained by limiting the total content of alkoxyl and hydroxyalkoxyl groups in the cellulose ether to 37.6% by weight or lower is not well understood, the following mechanism is inferred. In the cellulose ether used as the film base, some of the hydrogen atoms of cellulosic hydroxyl groups are replaced by alkyl groups and/or hydroxyalkyl groups whereby the hydroxyl groups are converted into alkoxyl or hydroxyalkoxyl groups. By limiting the total content of alkoxyl and hydroxyalkoxyl groups to 37.6% by weight or lower, the proportion of (remaining) hydroxyl groups having high affinity to water becomes relatively high so that the water-holding force of the film is effectively improved. This ensures that potassium or calcium as the gelling aid is retained in ion form within the water held in the film, effectively restraining precipitation of the gelling aid.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Briefly stated, the cellulose ether film of the invention is manufactured by using a cellulose ether as a base, blending a gelling agent and a gelling aid therein, and forming the composition into a film.
The cellulose ether used as the base is one in which some of the hydrogen atoms of cellulosic hydroxyl groups are replaced by alkyl groups and/or hydroxyalkyl groups whereby alkoxyl and/or hydroxyalkoxyl groups are created.
Though not critical, the cellulose ether is preferably one in which some of the hydrogen atoms of cellulosic hydroxyl groups are replaced by alkyl groups and hydroxyalkyl groups or by only hydroxyalkoxyl groups. Of the alkyl groups, methyl is preferred. Of the hydroxyalkyl groups, hydroxypropyl or hydroxyethyl is preferred. Illustrative examples of the cellulose ether substituted with these groups include hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl methyl cellulose (HEMC), and methyl cellulose (MC). Of these, HPMC is best suited for capsule film application because of effective film formation and mechanical strength at low water contents.
According to the invention, the total content of alkoxyl and hydroxyalkoxyl groups created in the cellulose ether by introducing the above substituents is limited to 37.6% by weight or lower. More particularly, the total content corresponds to the total content of methoxyl groups (abbreviated as “MO groups”) and hydroxypropoxyl groups (abbreviated as “HPO groups”) in the case of HPMC, the content of HPO groups in the case of HPC, the total content of MO groups and hydroxyethoxyl groups in the case of HEMC, and the content of MO groups in the case of MC. A cellulose ether having a total content of such substituents of up to 37.6% by weight is used.
The lower the total content of alkoxyl and hydroxyalkoxyl groups, the better becomes the effect of preventing precipitation of the gelling aid. However, if the total content of alkoxyl and hydroxyalkoxyl groups is too low, the resulting film may lose flexibility, strength or other performance, which is inconvenient in some applications. Therefore, the total content of alkoxyl and hydroxyalkoxyl groups is preferably in the range of 23 to 37.6% by weight though not limited thereto. Especially when the film is used as ca
Matsuura Seinosuke
Tanjoh Masaru
Bernatz Kevin M.
Birch & Stewart Kolasch & Birch, LLP
Shionogi Qualicaps Co., Ltd.
Thibodeau Paul
LandOfFree
Hard capsule formed of cellulose ether film with a specific... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Hard capsule formed of cellulose ether film with a specific..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Hard capsule formed of cellulose ether film with a specific... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3181863