JPH0460624B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing effervescent tablets containing dipeptide sweeteners with excellent preservability and solubility. α-L-Aspartyl-L-phenylalanine methyl ester (hereinafter referred to as aspartame) is a low-calorie sweetener with a refreshing sweetness similar to sucrose. When considering its practical use as a sweetener, its low solubility and dispersibility pose a problem. Furthermore, since aspartame has a sweetness level approximately 200 times that of sugar, it is difficult to control the sweetness level during use. To address these issues, attempts have been made to granulate the product with highly soluble excipients, to form disintegrating tablets using excipients, and to form effervescent tablets that foam upon dissolution. Among these, effervescent tablets contain aspartame and additives (excipients, binders, disintegrants, lubricants, etc.) as well as effervescent agents (carbonates, bicarbonates, etc.) and neutralizing agents (acidic substances). However, when placed in water, both substances are neutralized and gases such as carbon dioxide are generated to quickly dissolve them, but this method has had problems with its shelf life. That is, the effervescent agent and the neutralizing agent start to react with a small amount of moisture contained in the tablet or with moisture absorbed during storage, and the effervescence after storage decreases, resulting in a marked deterioration of solubility. If the excipient contains sugar, it may react with aspartame, causing browning or loss of the sweetness of aspartame, and may also cause tablets to bond to each other due to moisture generated or absorbed by the reaction between the blowing agent and the neutralizing agent. Adhesion of tablets and containers occurs. The present inventors have conducted intensive studies to resolve the problems faced by effervescent tablets composed of conventional ingredients and to obtain effervescent tablets containing dipeptide sweeteners with excellent storage stability. The present invention was completed based on the finding that by incorporating cyclodextrin as an excipient, effervescent tablets containing a dipeptide sweetener that do not deteriorate in quality even after long-term storage can be obtained. That is, the present invention provides at least aspartame,
When manufacturing effervescent tablets containing an effervescent agent, a neutralizing agent, and an excipient, cyclodextrin may be blended in an amount of 110 to 800% by weight based on the weight of aspartame as all or part of the excipient. The present invention relates to an effervescent tablet containing a dipeptide sweetener, characterized by: The cyclodextrin added as part or all of the excipient may be α-, β- or γ-cyclodextrin, and two of these may be used.
Although more than one species may be used in combination, β-cyclodextrin is generally used. If the amount of cyclodextrin added is less than 100% of aspartame on a weight basis, a sufficient effect will not be obtained, and furthermore, if it is added in mixture with other excipients, the effect will be greatly reduced. Since the dissolution time and other factors increase with the storage period, it is desirable that the ratio of cyclodextrin to aspartame be large, and should be at least 110%, and usually about 150% is most desirable. Although there is no upper limit for the content, it is considered to be around 800% in terms of calories and other factors. In addition, when this amount of cyclodextrin was added, even a disintegrating tablet without effervescence had good disintegration and solubility, and the liquid after dissolution had good clarity. As the excipient, cyclodextrin may be used alone, but it is also possible to use it in combination with dextrin, sucrose, glucose, lactose, sorbitol, etc., or inorganic substances such as calcium phosphate, calcium sulfate, etc. As the foaming agent and neutralizing agent, a suitable combination of foaming agents such as sodium hydrogen carbonate, malic acid, citric acid, fumaric acid, tartaric acid, and other neutralizing agents may be added. In addition to the above ingredients, leucine,
Isoleucine, L-valine, sugar ester,
Magnesium stearate and the like may be blended in consideration of the relationship with the base agent and the tablet manufacturing method, or taste and flavor components other than sweeteners may be blended as necessary. In addition, sweeteners other than aspartame, for example,
Needless to say, this does not preclude the use of saccharin, stevioside, glycyrrhizin, etc., or a suitable disintegrant. When producing effervescent tablets, known production methods can be applied, such as mixing the above-mentioned tablet components and producing by direct powder compression method, dry granule compression method, etc. Next, the present invention will be further explained by examples. Example 1 Effervescent tablets containing a dipeptide sweetener were manufactured from a tablet composition having the composition shown in Table 1 by a dry granule compression method or the like. Table 1 Ingredients Aspartame 22% β-cyclodextrin* 33% Sodium hydrogen carbonate 24% Citric acid 20% Sugar ester 1% *Product name: RINGDEX-B (manufactured by Sanraku Osyan Co., Ltd.) Table 2 Average tablet physical properties Weight mg 70 〃 Hardness * ¹ Kg 2.3 〃 Dissolution time * ² seconds 17 Appearance Good Functionality Good Tabletability Good *1; Breaking hardness by Kiya type hardness tester (5Kg) *2; 150ml of warm water at 60℃±1℃ and dissolved it. The shelf life of the above tablet was compared with that of an effervescent tablet containing a dipeptide sweetener manufactured with the same weight and hardness by changing the excipient from β-cyclodextrin to another excipient of the same weight category. Storage conditions were 44°C and RH78% as acceleration conditions. The excipients used are shown in Table 3, and the storage results are shown in Tables 4 and 5. Table 3 Excipients “Pinedex #100” (Matsuya Chemical Co., Ltd.) “Amicol 7H” (Nippon Chemical Co., Ltd.) “Glister P” (Matsuya Chemical Co., Ltd.) “Sandex #100 (Sanwa) Starch Co., Ltd.) Maltitol (Towa Kasei Kogyo Co., Ltd.)

【table】

[Table] Furthermore, in the experimental groups other than β-cyclodextrin, a phenomenon in which the tablets stuck together was observed, but with β-cyclodextrin,
-This phenomenon did not occur with cyclodextrin. Example 2 The amount of cyclodextrin relative to aspartame is 10%, 50%, 100%, 110%, 150% or 200%
Effervescent tablets containing a dipeptide sweetener were manufactured by direct powder compression method according to the following formulation. After each raw material was pulverized, the mixture was mixed in a V-type mixer and then directly compressed into tablets. Table 6 shows the ingredients, and Table 7 shows the physical properties of the tablets.

[Table] Table 7 Physical properties of tablets Average hardness* Kg 2.3 Appearance Good Functionality Good Compressibility Good *Fracture hardness determined by Kiya type hardness tester (5Kg) Tablets with the above properties were compared for storage stability under the same conditions.
Storage conditions were 44°C and RH78% as acceleration conditions. The storage results are shown in Tables 8 and 9.

【table】

【table】

【table】

[Table] As shown above, β
- It can be confirmed that when the amount of cyclodextrin increases, the dissolution time increases, the progress of browning is small, and the storage stability is significantly improved. In particular, a large improvement in storage stability was observed between experimental plots 3 and 4. The correlation between acceleration experiments and actual storage stability is quite clear, and from the above results, sufficient storage stability can be obtained when the amount of β-cyclodextrin is 110% or more compared to aspartame.

Claims (1)

[Claims] 1. When manufacturing effervescent tablets containing at least α-L-aspartyl-L-phenylalanine methyl ester, a blowing agent, a neutralizing agent, and an excipient, α -L-
A method for producing an effervescent tablet containing a dipeptide sweetener, which comprises blending cyclodextrin in an amount of 110 to 800% by weight based on the weight of aspartyl-L-phenylalanine methyl ester.