JPS62258327A - Production of coated powdery agent and coated granular agent - Google Patents

Abstract

PURPOSE:To produce a solid preparation having excellent moistureproofing property, free from pinhole and resistant to agglomeration, by using a coating composition produced by compounding a hardened oil and a water-soluble coating base at a specific ratio. CONSTITUTION:A coated powdery agent or coated granular agent is produced by coating powder, etc., with a coating composition composed of a hardened oil (e.g. paraffin wax, spermaceti, etc.) and a water-soluble coating base (e.g. methylcellulose) at a weight ratio of (4-9):1. The coating composition is used usually as a solution or dispersion in a proper solvent (e.g. methylene chloride) optionally in combination with various ajuvant (e.g. food dye, flavor, etc.). The coated powdery agent and coated granular agent produced by the above process is free from pinhole, resistant to agglomeration, capable of effectively preventing the compositional variation with small amount of coating material and releases the active component at a high rate.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention provides a method in which the hydrogenated oil and the water-soluble coating base are 4:
The present invention relates to a method for producing coated powders and coated granules, which comprises coating using a coating composition having a ratio of 1 to 9:1 (weight ratio). An object of the present invention is to provide coated powders and coated granules with improved blendability of solid preparations having small particle diameters and improved taste.

[Prior art] Conventionally, when administering a combination of two or more types of solid pharmaceutical preparations with small particle sizes, interactions between the different types of pharmaceutical ingredients can cause changes in color tone, denaturation, decomposition, etc., resulting in decreased efficacy. There were some undesirable things that happened. Therefore, in order to prevent these interactions and make the preparations stable and effective, as well as to hide the unpleasant taste of various solid preparations and make them easier to take, various film-forming agents have been added to them. coating with a substance that

It is well known that water-soluble cellulose derivatives are generally used as film-forming substances used as coating bases.

Furthermore, hydrogenated oils are also used as coating materials for pharmaceuticals (for example, Japanese Patent Application Laid-Open No. 9713/1993).

[Problems to be solved by the invention] Solid preparations with small particle diameters, such as powders and granules, are easily handled and are administered by combining them with a herbal medicine. If the efficacy is reduced due to denaturation or decomposition, the above-mentioned coating is necessary.

However, when coating solid drugs with small particle sizes, such as powders and granules, with water-soluble cellulose derivatives, the amount of coating is larger than when coating tablets because these have a large surface area per unit weight. It is necessary to increase the number of

Furthermore, coating pans, fluidized bed coating devices, centrifugal fluidized coating devices, and the like are usually used for these coatings, but in that case, particles tend to bond with each other and grow into large particles, which is the so-called agglomeration phenomenon.

Furthermore, this agglomeration phenomenon is more likely to occur as the amount of coating increases and as the particles become smaller.

As a method to suppress this agglomeration phenomenon, attempts have been made to add, for example, talc, sugar, and a powdered tablet disintegrant to the coating composition and spray a dispersed liquid. The reality is that there are many problems such as this, and that sufficient effects are not always recognized.

When hardened oil is used alone as a coating base to coat solid agents with small particle sizes, such as powders and granules, pinholes occur, which poses safety problems, and tends to result in roughness and delayed dissolution time. It is not desirable because it is in

[Means for Solving the Problems] In order to solve the above problems, the present inventors have developed a method for coating solid agents with small particle sizes, such as powders and granules, with as little coating amount as possible and during the coating operation. We have conducted intensive research on coating methods that do not cause grains or aggregates and provide sufficient coating effects, such as enabling combination with prohibited items, improving taste, and improving moisture resistance.

As a result, the hydrogenated oil and water-soluble coating base are 4=
When solid agents with small particle sizes, such as powders and granules, especially fine granules, are coated with a coating composition consisting of a ratio of 1 to 9:1 (heavy ffi ratio), they have excellent moisture resistance and are free from pinholes. The present invention was completed based on the discovery that it is possible to formulate an excellent solid preparation that does not cause any agglomeration or agglomeration.

The present invention will be explained in detail below.

The hardened oil used in the present invention may be either vegetable or animal as long as it is pharmaceutically acceptable, such as paraffin wax, carp wax, spermaceti, beeswax, and caster wax. , hydrogenated beef oil, hydrogenated vegetable oil 1. Examples include hydrogenated castor oil, hydrogenated rapeseed oil, and hydrogenated peanut oil.

Examples of water-soluble coating bases include methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, and hydroxybutylcellulose.

A preferred combination of hydrogenated oil and water-soluble coating base is a combination of hydrogenated rapeseed oil and hydroxypropyl methylcellulose.

The mixing ratio of hardened oil and water-soluble coating base in the coating composition is 4:1 to 9:1 (weight ratio).

In addition, the coating amount is mff of the target uncoated agent.
1 to 20% by weight, preferably 3 to 10% by weight based on 1
It is.

The coating composition composed of a hardened oil and a water-soluble coating base used in the present invention is usually dissolved and dispersed in a suitable solvent (coating liquid). In this case, the solvent may be methylene chloride, chloroform, etc. halogenated hydrocarbons; alcohols such as methanol and ethanol; halogenated hydrocarbons; acetone/halogenated hydrocarbons; single solvents or mixed solvents such as water/alcohols/halogenated hydrocarbons. .

Moreover, it is preferable to dissolve it at an appropriate humidity as necessary.

The concentration of the hardened oil and the water-soluble coating base in the coating liquid is such that the total solid component is 1 to 10% by weight, preferably 2 to 5% by weight.

The coating solution obtained in this way may contain various auxiliary agents, such as coloring agents such as food dyes, food lakes, and titanium oxide, glycerin fatty acid esters, polyethylene glycols, and propylene glycols. Examples include plasticizers, silicone oils, surfactants, and fragrances.

Although a centrifugal fluid coating device is usually used in the method of the present invention, a fluidized bed coating device can also be used.

By the way, any commonly used spray gun will suffice.

[Effects of the invention] (1) Formulations of blend change test examples and reference examples and magnesium oxide at a ratio of 3:2
(weight ratio) and left under the conditions of 40'C and 75% relative humidity. The quantitative value of acladonium napadisylate in the compounded product after standing with respect to the constant m value of disulfonate (generic name: acradonium napadisylate, hereinafter referred to as acradonium napadisylate) was calculated as a relative percentage and was defined as the residual rate. The results are shown in Table-1.

The determination of acradonium napadisylate was carried out using the bromcresol green colorimetric method, that is, acladonium napadisylate and bromcresol green were combined, extracted with chloroform, and then a sodium hydroxide solution was added, shaken, and then added to the aqueous layer. This was done by quantifying the back-extracted bromcresol green by spectrophotometry.

(Left below) (2) Dissolution test Japanese Pharmacopoeia (10th revision) Dissolution test method (paddle method, 11
The elution amount of acladonium napadisylate was measured by spectrophotometry according to the method (using the first liquid 800d used in the disintegration test method), and the time (T75) until the elution rate reached 75% was calculated.

The results are shown in Table-2.

Table 2 From the above results, the coated powders and coated granules produced by the coating method of the present invention do not produce pinholes (
(Refer to Figures 1 and 2), it is possible to effectively prevent changes in the formulation with a small amount of coating without causing agglomeration, and the coating agent thus removed exhibits good dissolution. I can understand.

In addition, the unpleasant texture felt by coated powders and coated granules coated with hydrogenated oil alone is also eliminated.
Moreover, the taste of the medicine inside is hidden.

[Examples] Next, the present invention will be described with reference to Examples and Reference Examples, but the present invention is not limited thereto.

In addition, in Examples and Reference Examples, granulated sugar, centrifugal fluid coating machine, 5% hydroxypropyl methylcellulose, lactose, hydrogenated rapeseed oil, hydroxypropyl methylcellulose, mannitol, cornstarch, and ethylene oxide/propylene oxide copolymer are as follows. I used something.

0 Granulated sugar [60-80 mesh: manufactured by Shiomiko Sugar Co., Ltd.] 0 Centrifugal fluid coating machine [CF-360: manufactured by Freund Sangyo Co., Ltd.] 05% hydroxypropyl methylcellulose [HPC-
L: manufactured by Nippon Soda Co., Ltd.] 0 lactose [MiCrOtO3e: manufactured by Megre Co., Ltd.] 0 hydrogenated rapeseed oil [Love Relax 102; Freund Sangyo (
Co., Ltd.] 0 hydroxypropyl methylcellulose [TC-5RW
; Manufactured by Shin-Etsu Chemical Co., Ltd.] O Mannit [manufactured by Noriwa Kasei Co., Ltd.] O Cornstarch [manufactured by Hokuriku Sugar Co., Ltd.] 0r! I-ized ethylene/propylene oxide copolymer [PEP-
101: Manufactured by Freund Sangyo Co., Ltd.] Example 1 (1) 1400 g of granulated sugar was charged into a centrifugal flow coating machine, and a 5% hydroxypropyl methyl cellulose water-containing ethanol solution [water:ethanol = 1:3.25] was prepared.
(Weight ratio)] Powder coat a mixture of Navadicil Yoshi Acladonium 302.1 and lactose 625.6 g while spraying 1040 g. Subsequently, 420 g of lactose is powder coated in a continuous operation. If the generated particles are dried overnight at 40°C, fine particles 275 for coating can be obtained.
Get 29.

(2) Coating fine particles 5009 obtained in (1)
into a centrifugal fluid coating machine, hardened rapeseed oil 48
．． 6g and hydroxypropyl methylcellulose5.
4 g of methylene chloride 1674 cJ and ethanol 43
A solution (hereinafter referred to as coating solution A) dissolved in 2 g of the mixed solution is sprayed to coat. Drying the resulting particles at 40'C overnight yields 545 g of fine granules.

Example 2 30.19 g of hardened rapeseed oil and 7.59 hydroxypropyl methylcellulose were added to 1164.89 g of methylene chloride for 500 g of coating fine particles of Example 1 (1).
and a solution dissolved in a mixture of ethanol 300.69 (
Hereinafter, it will be referred to as coating liquid B. ) and coat. Fine granules 5333 are obtained by drying the produced particles at 40° C. overnight.

Example 3 (1) Granules 1!11400y were charged into a centrifugal flow coating machine, and a 5% hydroxypropyl methyl cellulose water-containing ethanol solution [water: ethanol = 1 nia, 5
A mixture of 280 g of acladonium napadisylate and Mannitol 4203 is powder coated while spraying 1823y (weight ratio).

Subsequently, a mixture of Mannitol 2803 and Cornstarch 4203 is powder coated in a continuous operation. Drying the resulting particles at 40° C. overnight provides fine particles 2781 for coating.

(2) Fine particles for coating 600 obtained by 1q in (1)
9, spray coating liquid A1247cJ,
Coat. Fine granules 6209 are obtained by drying the produced particles at 40'C overnight.

Example 4 406 g of fine particles for coating obtained in Example 3 (1)
Coating liquid B8869 is sprayed onto the sample to coat it. Fine granules 4229 are obtained by drying the resulting particles at 40° C. overnight.

Reference Example 1 Coating fine particles 5009 obtained in Example 3 (1)
For hydrogenated rapeseed oil 34.1 to methylene chloride 113
Spray and coat with a mixture of 1.9 g and 205.89 g of ethanol. The generated particles are 4
Drying overnight at 0'C yields 524 g of fine granules.

Reference Example 2 Fine particles for coating 5003 obtained in Example 3 (1)
against hydroxypropyl methylcellulose 19.
8g and ethylene oxide/propylene oxide copolymer2.
O12 was mixed with 612.1% of medilene chloride and 158.1% of ethanol.
1 and water 10.3! ? Spray the solution dissolved in the mixture to coat. Drying the produced particles at 40°C overnight yields 509 g of fine granules.

[Brief explanation of drawings]

The photographs in Figures 1 and 2 (scanning electron microscope, near 0x magnification) show the fine granules of Reference Example 1 and Example 1, respectively.

Claims (2)

[Claims] (1) Hydrogenated oil and water-soluble coating base of 4:1 or more
A method for producing coated powders and coated granules, which comprises coating using a coating composition having a weight ratio of 9:1. (2) Claim No. 2, wherein the coated powder is a coated fine granule (
1) The method for producing the coated powder described in section 1).