JPH0584288B2 - - Google Patents

Description

[Detailed description of the invention]

INDUSTRIAL APPLICATION FIELD The present invention relates to a bitter taste suppressing pharmaceutical composition obtained by adding lecithin to a bitter-tasting drug. The composition of the present invention is a composition that suppresses the bitter taste of a drug and does not affect the absorbability of the drug itself in the living body. It was done. In order to orally administer bitter-tasting drugs, it is most common to pack them into capsules, but it is difficult for infants and children to take capsules. Since the bitter taste suppressing pharmaceutical composition obtained according to the present invention is obtained in powder or fine granule form, it can be administered as it is or after being suspended and mixed in a drink, so it is suitable for infants and children. There is no difficulty in taking it. The manufacturing method does not require any special manufacturing equipment, and is not only simple and can be mass-produced, but also can be manufactured in an aqueous solution (wet method) or as a powder (dry method) by devising the composition and changing the operating method. Therefore, the present invention can be applied regardless of the physicochemical properties of drugs that exhibit bitter taste. BACKGROUND TECHNOLOGY Medical compositions containing strongly bitter drugs are difficult to administer as they are, so they are generally administered in dosage forms such as sugar-coated tablets, film-coated tablets, and capsules that mask the bitter taste. However, it is difficult to administer these solid preparations to children, especially infants, so there is a strong demand for preparations that are convenient for administration, such as powders, fine granules, and granules. Efforts are being made to block this. Generally, to suppress the bitter taste of powdered drugs, sweeteners and/or flavoring agents are added, and other formulation methods include microencapsulation, powder coating with a gastric soluble coating agent, or combination with a low-melting waxy solid. Examples include a method in which after eutectic melting, the material is ejected from a nozzle using a spray method, cooled, solidified, and powdered. However, none of these methods can completely mask the bitter taste, do not take bioabsorbability of the drug into consideration beyond masking, require special equipment for manufacturing, and are difficult to produce at low cost and in large quantities. It has disadvantages such as being difficult. Problems to be Solved by the Invention When trying to obtain a powder preparation that masks the bitter taste of a liquid or powdered drug that exhibits a bitter taste, the process or method described in the "Prior Art" section mainly produces a drug that exhibits a bitter taste. It is important to minimize the elution by saliva in the oral cavity, and for this purpose, the surface of the powder is mainly coated with a coating agent that is insoluble in water. As the coating agent, an acid-soluble gastric soluble coating agent or a coating agent made of a water-insoluble waxy substance is used. The former gastric soluble coating agent is generally a basic substance. On the other hand, many drugs have a bitter taste and are chemically unstable in their free state, so hydrochloric acid, sulfuric acid, phosphorous powder,
It is chemically stabilized by forming a salt with an organic acid and crystallizing it. However, the crystals obtained in this way taste bitter as they are, so they must be coated with a coating agent, but as mentioned above, if the coating agent is basic, it will neutralize the acid bound to the bitter drug. The drug becomes free and chemically unstable. For this reason, talampicillin hydrochloride (an antibiotic) and the like are extremely unstable in a basic environment. Therefore, the above-mentioned gastric soluble coating agent cannot be used, and its scope of use is limited. Originally, the main purpose of the gastric soluble coating agent is to coat tablets, so the effective amount to suppress the bitter taste of powdered drugs is large compared to the main agent, and the coating layer on the surface of the drug is thick. Therefore, it has the disadvantage of extremely poor biological absorption. Furthermore, powder coating of bitter-tasting drugs with waxy substances must be carried out by melting at the melting point of the waxy substance, which is unsuitable for coating substances that are unstable with respect to temperature. Note that drugs coated with waxy substances also have extremely poor biological absorption. Therefore, in order to improve these drawbacks, a production method with a good dissolution rate by combining a low-melting point wax and a water-swellable polymer substance has been devised, but this method requires a special method called the spray consolidating method. Therefore, it is industrially difficult to produce large quantities of bitter taste suppressing preparations. Therefore, the present invention provides a bitter taste suppressing pharmaceutical composition that is safe for living organisms, stable for drugs, and that can be mass-produced easily and quickly without impairing its biological absorption, and a method for producing the same. The inventors have studied the following and invented a pharmaceutical composition and a method for producing the same that satisfy the above conditions. Means for Solving the Problems The drugs used in the composition of the present invention are those that exhibit a strong bitter taste, and there is no particular restriction on the scope of the drugs, but since children generally avoid bitter drugs, they are frequently used in children. The main targets are drugs that can be used to treat cancer.
Examples include the antibiotic talampicillin hydrochloride, the antipyretic analgesic acetaminophen, and the sedative phenobarbital. The bitterness suppressant used in the present invention is lecithin, also called phosphatidylcholine, diacyl-L-3-
Corresponds to glycerylphosphorylcholine. In the body, it is abundantly contained in the brain spinal cord, nerves, blood cells, and egg yolk. It also exists in plant seeds, and egg yolk lecithin derived from egg yolk and soybean lecithin derived from soybeans are widely used industrially. Lecithin has an acyl group of C ₁₄ ~
It is commonly C ₂₂ and is a waxy substance that is easily oxidized and colored. Soluble in chloroform, ether, and alcohol, slightly soluble in acetone, and almost insoluble in water. Because it exists as a zwitterion at any pH and has surface activity,
Soybean lecithin, which is available at low cost, is highly safe and is therefore used in large quantities as an emulsifier in foods and medicines. In the present invention, the safety and water-insoluble property of lecithin and the ability to form liposomes (closed vesicles) are utilized to apply lecithin to suppress the bitter taste of a drug that exhibits a bitter taste. In addition, there are no particular restrictions on the powder filler (excipient) for powdering, but since it is preferable to keep the total dosage of the preparation as small as possible for pediatric use, lecithin can be powdered with a small amount of excipient. What you get is good;
For example, magnesium aluminate metasilicate, synthetic aluminum silicate, anhydrous silicic acid, magnesium stearate, etc. are effective. There are two methods for producing the pharmaceutical composition of the present invention. In the first method, after the drug is dissolved or dispersed in water, a solution of lecithin in an amount equal to or more than the drug is dissolved in an organic solvent (preferably chloroform, which is more than 1/4 the amount of water used) is mixed. Emulsify. Further, excipients in an amount equal to or more than the drug are added, mixed, dried under reduced pressure, and then pulverized. If necessary, flavoring, coloring and/or sweetening agents may be added to the product. In the second method, 1 part of the drug, 1 part or more of lecithin, and 1 part or more of an excipient are added and mixed in a solvent such as chloroform that dissolves lecithin without using water. This mixture is dried under reduced pressure as in the first method, and then pulverized. If necessary, flavoring, coloring and/or sweetening agents may be added to the product. Generally, the first method is a method in which liposomes are formed by drug inclusion of retitin, and the second method is a so-called powder coating method. Effects In order to demonstrate the bitter taste suppressing effect and drug biological absorption effect of the pharmaceutical composition of the present invention, a sensory test regarding bitterness and a drug biological absorption test using experimental animals (rats) were conducted and the results were obtained. are shown in Tables 1 and 2.

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[Table] As is clear from Tables 1 and 2, the pharmaceutical composition of the present invention did not taste bitter at all in the sensory test, and its biological absorption was higher than that of the bulk drug used as a control. It shows the same absorbency. This fact shows that the bitter taste suppressing effect of the composition of the present invention is extremely good. The reason why the composition of the present invention suppresses bitterness is not necessarily clear, but it is thought that the main reason is that the mixture of lecithin and excipient physically covers the surface of the drug powder to form a coating film. . That is, it is thought that the physical coating of lecithin and the physical and chemical effects of the excipient cooperate with each other. Next, the bitter taste suppressing pharmaceutical composition of the present invention and its manufacturing method will be explained with reference to Examples. Example 1 Talampicillin hydrochloride 100g Soybean lecithin 200g Magnesium aluminate metasilicate 150g Lactose 50g Talampicillin hydrochloride was dissolved in 1000ml of purified water.
Separately, add soybean lecithin to 250ml of chloroform.
dissolved in. Both solutions were mixed and stirred at room temperature.
Magnesium metasilicate aluminate and lactose were added to this, and the mixture was thoroughly mixed and dried under reduced pressure.Then, the mixture was pulverized and passed through a No. 32 sieve. Example 2 Talampicillin hydrochloride 100g Soybean lecithin 200g Magnesium aluminate metasilicate 100g Mannite 100g Talampicillin hydrochloride and soybean lecithin 500g
ml of chloroform, magnesium aluminate metasilicate and mannite were added thereto, mixed well and dried under reduced pressure, then ground and passed through a No. 32 sieve. Example 3 Acetaminophen 100g Soybean lecithin 100g Synthetic aluminum silicate 150g Mannite 50g A composition having the above components was prepared in the same manner as in Example 1. Example 4 Acetaminophene 100g Soy lecithin 100g Synthetic aluminum silicate 100g Magnesium stearate 100g A composition having the above components was prepared in the same manner as in Example 2. Example 5 Phenobarbital 100g Soy lecithin 100g Magnesium aluminate metasilicate 150g Lactose 50g A composition having the above components was prepared in the same manner as in Example 1. Example 6 Phenobarbital 100g Soybean lecithin 100g Synthetic aluminum silicate 150g Mannite 50g A composition having the above components was prepared in the same manner as in Example 2. Effects of the Invention As shown in Tables 1 and 2, the composition of the present invention is a pharmaceutical composition that significantly suppresses the bitter taste of bitter-tasting drugs and is comparable in terms of biological absorption of drugs. It is. Regardless of whether the bitter drug is water-soluble or water-insoluble, it can be produced by either dry or wet methods, and the method for producing this composition is simple and easy to mass-produce. It has the advantage of being suitable for

Claims (1)

[Claims] 1. A powdered or granular bitter taste suppressing pharmaceutical composition comprising a bitter drug, an excipient, and lecithin,
the excipient is magnesium aluminate metasilicate;
A composition selected from the group consisting of synthetic aluminum silicate, anhydrous silicic acid, and magnesium stearate, and wherein the blending ratio of a bitter drug, lecithin, and excipient is 1:1 or more: 1 or more on a weight basis.