JP3672008B2 - Hard capsule and method for producing the same - Google Patents

Description

＊１：ゼラチンカプセル
＊２：ＨＰＭＣカプセル
：変化なし
△：外観はほとんど変化しないが、強度が低下する
×：皮膜表面からＰＥＧ＃４００がにじみでる
【００４０】
【発明の効果】
本発明によれば、厳密な温度コントロール等の必要なく簡単に非ゼラチンカプセルを製造でき、得られたカプセルはポリエチレングリコール＃２００〜＃６００の充填が可能なものである。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a non-gelatin hard capsule used for pharmaceuticals, quasi drugs, foods and the like.
[0002]
[Prior art and problems to be solved by the invention]
Conventionally, gelatin hard capsules are mainly used as hard capsules used in pharmaceuticals, quasi drugs, foods, etc. Recently, non-gelatin hard capsules have been demanded.
[0003]
As a non-gelatin hard capsule, a hard capsule based on a water-soluble cellulose derivative such as hydroxypropylmethylcellulose (HPMC) has been conventionally known (Japanese Patent Laid-Open No. 3-279325).
[0004]
However, this hard capsule is based on a cellulose ether substituted with an alkyl group or a hydroxyalkyl group, but this type of cellulose derivative dissolves in low-temperature water, but does not dissolve at high temperature. Also, the viscosity of the cellulose derivative dissolution / dispersion solution is easily affected by temperature, and when the temperature of the cellulose derivative solution dispersed in water at a high temperature is gradually lowered, the viscosity increases rapidly at around 50 ° C.
[0005]
Therefore, when manufacturing a hard capsule using the said cellulose derivative, exact | strict temperature control of a capsule preparation liquid is required.
[0006]
Moreover, when the hard capsule shape | molded with the said cellulose derivative is filled with polyethyleneglycol # 200- # 600 (PEG # 200- # 600) in this, it has been observed that a polyethylene glycol oozes out on the capsule surface. On the other hand, as is well known, in recent years, capsules in which a liquid drug is filled into a hard capsule have been put into practical use by the development of a capsule filling machine and a sealing machine for liquids. By the way, polyethylene glycol (PEG # 200 to # 600) which is liquid at room temperature has an excellent dissolving action for hardly soluble drugs and is preferably used as an excipient. It has been observed that when the molded hard capsule is filled with PEG # 200 to # 600, PEG oozes out on the surface of the capsule film. For this reason, it is difficult to fill the hard capsules of the cellulose derivative with the contents containing polyethylene glycol # 200 to # 600.
[0007]
The present invention has been made in view of the above circumstances, and is a non-gelatin hard capsule that does not bleed even when filled with polyethylene glycol # 200 to # 600 and can be easily produced without requiring strict temperature control. And it aims at providing the manufacturing method.
[0008]
Means for Solving the Problem and Embodiment of the Invention
As a result of intensive studies to achieve the above object, the present inventor has found that it is effective to produce hard capsules based on hemicellulose. That is, polysaccharides such as hemicellulose are known to form a good film. When these aqueous solutions are coated on a plate-like substance or a spherical substance and dried, a film is formed. However, when capsules are to be produced with these aqueous solutions by the so-called dipping method, the polymer solution drips down before drying, and the film cannot be homogenized, making it impossible to mold capsules well. . However, it was found that capsules can be manufactured satisfactorily by blending a substance that easily gels with a change in temperature as a gelling agent into the polymer aqueous solution and gelling the polymer liquid on the pin. . Further, it has been found that even when a hard capsule formed of the above polymer gel is filled with polyethylene glycol # 200 to # 600, no bleeding occurs.
[0009]
Therefore, this invention provides the hard capsule characterized by consisting of the gel which mix | blended the gelatinizer with hemicellulose and gelatinized. In this case, the hard capsule is effectively filled with a filler containing polyethylene glycol # 200 to # 600.
[0010]
Further, the present invention is characterized in that a capsule forming pin is immersed in a capsule preparation solution containing hemicellulose and a gelling agent, and then the pin is pulled up to gel and dry the capsule preparation solution attached to the pin. A method for producing a hard capsule is provided.
[0011]
Since polysaccharides such as hemicellulose dissolve in aqueous solutions at a wide range of temperatures, the relationship between temperature and viscosity is different from that of the previous cellulose derivative, and the viscosity does not change as rapidly as the previous cellulose in the normal temperature range. However, by adding a gelling agent to an aqueous solution of these polymers, the polymer adhering to the pins rapidly gels when cooled, and thus the capsule can be easily molded. As described above, as a result of examining the moldability of capsules and the filling properties of polyethylene glycol # 200 to # 600 with respect to various polymers, by adding a substance that easily gels to hemicellulose as a gelling agent, It has been found that the moldability of the capsule is improved, and that polyethylene glycol # 200 to # 600 can be filled.
[0012]
Hereinafter, the present invention will be described in more detail. The non-gelatin hard capsule of the present invention uses hemicellulose as a base and is obtained by gelling with a gelling agent.
[0013]
Here, as hemicellulose, for example, “hemylose” made from soybeans manufactured by Fuji Oil Co., Ltd. is preferably used.
[0014]
The manufacturing method of the hard capsule based on the hemicellulose of the present invention will be described in more detail. The capsule forming pin is immersed in a capsule preparation solution in which the hemicellulose and the gelling agent are dissolved. The capsule preparation liquid adhering to the pin is gelled and dried.
[0015]
Here, the concentration of hemicellulose in the capsule preparation liquid is preferably 5 to 30% (% by weight, the same applies hereinafter), particularly 10 to 20%.
[0016]
The gelling agent is preferably a substance that easily gels due to temperature changes. Specific examples include xanthan gum, locust bean gum, gellan gum, carrageenan, tamarind seed polysaccharide, pectin, curdlan, gelatin, farseleran, and agar. In addition, two or more of these substances can be mixed and used.
[0017]
The concentration of the gelling agent is preferably 0.01 to 10%, particularly 0.1 to 1.0% in the capsule preparation solution.
[0018]
When kappa carrageenan is used as the gelling agent, a water-soluble compound that gives potassium ions, ammonium ions, calcium ions, such as potassium chloride, ammonium chloride, ammonium acetate, calcium chloride, etc., may be used as the gelling aid. In the case of using iota carrageenan, a water-soluble compound that gives calcium ions such as calcium chloride can be used.
[0019]
When gellan gum is used as a gelling agent, water-soluble compounds that give sodium ions, potassium ions, calcium ions, magnesium ions, such as sodium chloride, potassium chloride, calcium chloride, magnesium sulfate, etc., are used as gelling aids. Further, organic acids and water-soluble salts thereof such as citric acid or sodium citrate can be used.
[0020]
When using the said gelatinization adjuvant, it is 0.05-0.6% in a capsule preparation liquid, and the use of 0.06-0.2% of a gelatinization adjuvant is preferable.
[0021]
In the present invention, an appropriate amount of additives usually used for hard capsules such as dyes and pigments may be added.
[0022]
In the present invention, the above-mentioned hemicellulose, gelling agent, and other desired components are dissolved in water to obtain a capsule preparation solution. However, there is no particular limitation on the dissolution order of the components in water, and hemicellulose is first dissolved. Alternatively, the gelling agent may be dissolved. The melting temperature is not particularly limited, but it is recommended that the melting temperature be 40 to 100 ° C, more preferably 50 to 95 ° C.
[0023]
The temperature at which the capsule forming pin is immersed is also selected as appropriate, but is preferably 30 to 80 ° C, particularly 40 to 60 ° C.
[0024]
In addition, it is preferable that the viscosity of the capsule preparation liquid at the time of this pin immersion is 100-10,000 mPa * s, especially 1,000-8,000 mPa * s.
[0025]
Gelation after the pins are pulled up is preferably performed by allowing to cool, but may be dried by heating to 40 to 80 ° C. after gelation.
[0026]
The hard capsule of the present invention obtained as described above is based on the above hemicellulose, but preferably has the following composition.
Hemicellulose: 70% or more, more preferably 80% or more,
Gelling agent: 0.01-30%, more preferably 0.1-10%,
Gelling aid: 0-30%, more preferably 5% or less,
Moisture: 1-20%, more preferably 5-15%,
Total 100%
[0027]
The capsules according to the present invention can be applied to drugs or fertilizers for animals or plants, including pharmaceuticals or foods. In particular, as a pharmaceutical, it can be applied as a container for orally administered drugs, a container for inhalation, or a suppository. Furthermore, it can also be applied as a so-called quasi-drug for the purpose of disinfecting and cleaning dentures, glasses, contact lenses and the like.
[0028]
In this case, since the capsule of the present invention does not ooze out when filled with polyethylene glycol # 200 to # 600, it is effective for filling various fillers containing polyethylene glycol # 200 to # 600.
[0029]
As other components that can be filled in the capsule of the present invention, stearyl alcohol, cetanol, polyethylene glycol, or an ester thereof can be cited as alcohol / polyhydric alcohol, in addition to generally known powders, granules, and tablets. As fats and oils, sesame oil, soybean oil, peanut oil, corn oil, hydrogenated oil, paraffin oil, beeswax, etc., other fatty acids such as triethyl citrate, triacetin, stearic acid, palmitic acid, myristic acid and derivatives thereof, For example, triglyceride can be mentioned, and it is suitable for filling liquid and semi-solid substances.
[0030]
【Example】
Hereinafter, a detailed explanation of the present invention through examples, the present invention is not intended to be limited to the following examples.
[0036]
〔Example〕
20 g of hemirose was dissolved in 179 g of water at 80 ° C. This was cooled to 50 ° C. to dissolve 0.4 g of carrageenan and 0.4 g of potassium chloride. This was continuously kept at 50 ° C., and a capsule-forming pin was put in and then taken out and dried to produce a capsule.
The obtained capsules were subjected to a solution test using 50 ml of purified water heated to 37 ± 2 ° C. in accordance with the solution test method stipulated by the Japanese Pharmacopoeia (3 capsules to be tested). As a result, the dissolution time was 5.93 ± 0.39 minutes.
[0038]
[Experimental example]
The capsules of the examples were filled with PEG # 400 and stored at 60 ° C. for 3 days, and then the appearance of the capsules was visually inspected, and the results shown in Table 1 were obtained (number of test capsules: 3).
[0039]
[Table 1]

* 1: Gelatin capsule * 2: HPMC capsule: No change Δ: Almost no change in appearance, but the strength decreases ×: PEG # 400 oozes from the coating surface
【The invention's effect】
According to the present invention, non-gelatin capsules can be easily produced without the need for strict temperature control or the like, and the obtained capsules can be filled with polyethylene glycol # 200 to # 600.

Claims (8)

  A hard capsule comprising a gel formed by mixing a gelling agent with hemicellulose.   The hard capsule according to claim 1, wherein one or more selected from xanthan gum, locust bean gum, gellan gum, carrageenan, tamarind seed polysaccharide, pectin, curdlan, gelatin, farseleran and agar are used as a gelling agent.   The hard capsule according to claim 2, comprising a gel formed by mixing carrageenan as a gelling agent in hemicellulose and gelling.   The hard capsule according to any one of claims 1 to 3, which is filled with a filler containing polyethylene glycol # 200 to # 600.   Production of a hard capsule characterized by immersing a capsule forming pin in a capsule preparation liquid containing hemicellulose and a gelling agent, then pulling up the pin, and gelling and drying the capsule preparation liquid attached to the pin Method.   6. The method according to claim 5, wherein the concentration of hemicellulose in the capsule preparation liquid is 5 to 30% by weight and the concentration of the gelling agent is 0.01 to 10% by weight.   The method according to claim 5 or 6, wherein the gelling agent is one or more selected from xanthan gum, locust bean gum, gellan gum, carrageenan, tamarind seed polysaccharide, pectin, curdlan, gelatin, fur celerane and agar. .   The manufacturing method according to claim 7, wherein the capsule preparation liquid contains hemicellulose and carrageenan as a gelling agent thereof.