JPS6013719A - Coated solid rrug - Google Patents

Abstract

PURPOSE:A coated solid drug not dissolved in saliva in the mouth but rapidly collapsing independent of pH in the stomach, obtained by coating a solid drug, especially one having bitterness with methyl cellulose having specific substitution amount of methoxy group and viscosity of aqueous solution. CONSTITUTION:A solid drug is coated with methyl cellulose having 24-33wt% methoxy group content, and 3-15 centipoise viscosity at 2wt% aqueous solution at 20 deg.C. Especially a solid drug (e.g., fine granule, granule, pill, tablet, etc.) having bitterness is coated. An amount of methyl cellulose coated is preferably 2- 30wt% based on the solid drug. It is not starched, has almost no slimeness, is collapsed rapidly independent of pH in the stomach, and shows medicinal effects. Consequently, it is usable for patients of anacidity. Since the methyl cellulose has low viscosity (low polymerization degree), coating is carried out uniformly.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an improved coated solid drug C2, in particular a coated solid drug with a bitter taste, which does not dissolve in the saliva in the mouth and remains in the stomach while being swallowed. The purpose of the present invention is to provide a coated solid drug that is rapidly disintegrated.

Conventionally, solid drugs with a bitter taste have been coated with acrylic or vinyl polymers that are soluble at a specific pH. In other words, this coating takes advantage of the property that it does not dissolve in oral saliva (neutral) but dissolves in gastric juice (acidic).However, this conventionally used coating is pH-dependent. If the pH range in the stomach is not suitable for the coating because it has solubility properties, for example in patients with achlorhydria, the coating may pass through without being disintegrated on the back. was there.

On the other hand, coating materials used for solid drugs include hydroxypropyl cellulose and hydroxypropyl methylcellulose, but since these coating materials are soluble in all pH ranges, drugs coated with them are difficult to swallow in the mouth. The dissolution rate is fast, and the effect of bitterness is insufficient. Furthermore, if the thickness of the coating film is increased in order to extend the dissolution suppression time, although it is effective, it becomes pasty, and as a result of research on oral health, it was found that the amount of methoxy group substitution and the viscosity of the aqueous solution were within a specific range ≦2. The present invention was completed by discovering that a certain methylcellulose exhibits extremely excellent performance for the purpose of the present invention.

That is, the present invention provides solid drugs with methoxy group-containing
This relates to a coated solid drug coated with methylcellulose, which has a concentration of ~33% by weight and a 2% aqueous solution having a viscosity of 3 to 15 cm at 20°C, and has an excellent effect of eliminating bitterness in the mouth. At that time, it does not gelatinize and has almost no slimy feeling, and the pH in the stomach is low.
Regardless of the value of degree of polymerization], it also has the advantage that solid drug coating can be easily and uniformly carried out.

The solid drugs targeted by the present invention include fine granules, granules, pills, tablets, etc., but they have a particularly bitter taste, and the bitter taste is counteracted by coating.

Methyl cellulose is prepared in advance into a coating solution and subjected to the coating process, and the coating solution is prepared using water, a mixed solvent of water and alcohol, a mixed solvent of alcohol and chlorinated hydrocarbons, or even a mixed solvent of alcohol and chlorinated hydrocarbons. A method may be used in which methylcellulose is dissolved in a solution containing water at a concentration of approximately 2 to 15% by weight. In addition, this coating liquid contains inorganic or organic lightning strength agents, plasticizers, colorants, colorants,
There is no problem in adding lubricants and other auxiliary agents.

The coating operation may be performed by conventionally known methods such as pan coating, fluidized bed coating, aerated rotary drum coating, etc. A coating film is formed by spraying a methylcellulose coating solution onto the solid drug using a spray gun and drying it. Ru.

The amount of film coated on the solid drug surface by such coating operation depends on the type, shape, size, and
Furthermore, it varies depending on the surface condition of the solid drug to be coated, but approximately 2 to 3
It may be set to 0%. Further, the coated preparation may be subjected to a polishing operation by a conventionally known method.

Next, examples of the present invention will be shown.

Example 1 ((1) Preparation of tablets: 71 parts by weight of lactose (hereinafter referred to simply as parts), 3 parts of provantyline bromide (bitter component), 18 parts of corn starch,
Low substituted hydroxypropyl cellulose (LH-11:
5 parts of hydroxypropyl cellulose (Eya: trade name of Shin-Etsu Chemical Co., Ltd.) and 2 parts of hydroxypropyl cellulose (Eya: trade name of Shin-Etsu Chemical Co., Ltd.) were mixed for 20 minutes in a V-type mixer, and then 1 part of magnesium ζ-nistearate was added and mixed for 2 minutes. The mixture was formed into tablets with a diameter of 9 mm and a weight of 280 liters each using a rotary tablet press. The obtained tablet had a hardness of about 12 (ERWEKA) and a disintegration time of about 8 minutes and 33 seconds (Japanese Pharmaceutical Law, 10th Amendment).

(2) Preparation of coating liquid 6 parts of the coating base shown in Table 1 1-2 was dissolved in a mixed solvent consisting of 75 parts of ethanol and 19 parts of water to prepare a coating liquid.

(3) Coating operation One tablet prepared in the above (1) was placed in a Freund industrial pan coating machine [FM-2], and coated thereon with the coating solution prepared in (2) under the following conditions.

Spray speed: 18d/min Spray interval:
...10 seconds spray 15 seconds drying Tablet temperature...38-40°C Drying air temperature...80°C Various tests were conducted on the coated tablets as above. The results were as shown in Table 1.

(a) Disintegration time: Measured according to the Japanese Pharmacopoeia 10th revised disintegration test method. (b) Bitter taste absorption time: Put two coated tablets in the mouth and measure the time until bitterness is felt (measured by a panel of 4 people and averaged). ).

()9 Slimy feeling: (B) When measuring bitterness time C
The sliminess inside Nilo was also investigated.

Note that the abbreviations in the fE1 table have the following meanings.

MC: Methylcellulose HPMC: Hydroxypropyl methylcellulose HPC
:Hydroxypropyl cellulose On the other hand, as a control example, a 6% coated tablet and the tablet of Experiment 162 in Table 1 were coated using the above coating method (:acrylic) and copolymer (which dissolves at pH 5 or less). When a disintegration test was carried out using liquid water with liquid C2, it was found that Aku IJ)
However, the copolymer coniting did not disintegrate at all, whereas the one with 1L showed a rapid disintegration property that was completely the same as when using the first liquid.

Example 2 (1) Preparation of granules 72.8 parts of lactose, 1 part of provantyline bromide, 18.2 parts of corn starch, 5 parts of low-substituted hydroxypropylcellulose (LH-11), hydroxypropylcellulose (EF( )) After mixing 3 parts in a Henschel mixer for 30 seconds.

To this mixed rice, 20 parts of water was added and the rice was combined for an additional 3 minutes. This kneaded product was granulated in a cylindrical granulator using a 0.8 am screen and dried.

, particle size 16-32 mesh depending on Jt, friability (48 after operating for 10 minutes using a Roche type fly ablator)
mesh bath rate) 0.5%, collapse time (Japanese station 10 method) 2
Granules of 0 seconds were obtained.

(2) Preparation of coating liquid 5 parts of the coating base shown in Table 2 was dissolved in a mixed solvent consisting of 75 parts of ethanol and 20 parts of water to prepare a coating liquid.

(3) Coating operation I kg of the granules obtained in step 11 above were loaded into a fluid coating device GLATT We G-11 manufactured by Okawara Seisakusho, and coated with the coating solution prepared in step (2) under the following conditions.

Spray gun... Nozzle diameter 0.8 txm Spray gust pressure... 2.5 Ky/cr/1 spray speed... 30/47 minutes Damper...
・As shown in Inlet 5 and Kawaguchi 2 and above, various tests were conducted on the granules coated with water, and the results were as shown in Table 2.As can be seen from these results, in the case of the present invention (2 is It was found that the disintegration in the mouth was sufficient, and that the disintegration properties were excellent, and there was no adverse effect on the dissolution rate, which is a particular problem.

(a) Disintegration time 2 Measured according to the Japanese Pharmacopoeia 10th revised disintegration test method (b) Bitter taste absorption time: Put approximately 200 kg of coated granules in the mouth and measure the time until bitterness is felt (measured by 4 panelists and averaged) did).

(/9 Slimy feeling: When measuring the bitterness absorption time in (B), the slimy feeling in the mouth was also investigated.

(d) Dissolution test: The test solution contains 1 part of the 1st solution (Japanese Pharmacopoeia method 10).
000-, and a disintegration tester was used as the apparatus. First, sample 2? The sample was precisely weighed and placed in a basket for granule disintegration test, and the operation was carried out. 1O- was sampled every 10 minutes, and the dissolution rate was measured from the absorbance at 282 mμ. The crude drug content in the granules was determined from the absorbance of the granules ground in a mortar and dispersed in the first liquid.

Claims (1)

[Scope of Claims] 1. A coated solid drug obtained by coating a solid drug with methylcellulose having a methoxy group content of 24 to 33% by weight and a 2% aqueous solution having a viscosity of 3 to 15 centiboise at 20°C g2. The coated solid drug 3 according to claim 1, wherein the solid drug is a bitter-tasting fine granule, granule, pill, or tablet, wherein the amount of methylcellulose coated on the solid drug is 2 to 2.
The coated solid road side according to claim 1, which is 30% by weight.