JPS62249935A - Cyclodextrin-containing gelatin substrate for drug preparation - Google Patents

Abstract

PURPOSE:To obtain the titled gelatin substrate for drug preparation giving an encapsulation film having suppressed hardening phenomenon and delay of disintegration time, by adding a specific amount of cyclodextrin to gelatin. CONSTITUTION:A gelatin substrate produced by adding 10-2wt% cyclodextrin to gelatin. Although various drug preparations prepared by using a gelatin substrate have excellent advantages, they are inferior in stability and disintegrability, etc. Cyclodextrin is a malto-oligosaccharide wherein glucose molecules are linked with each other with alpha-1,4-glycoside bond in the form of a ring. It is composed mainly of 6-8 glucose units corresponding to cyclohexa-, cyclohepta- and cycloocta-dextrin each of which has alpha-, beta- and gamma-isomers. The problems of hardening phenomenon and delay of disintegration time have been solved by the addition of cyclodextrin to gelatin.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention is applicable to pharmaceuticals, confectionery, certain types of foods, and other foods that are ingested orally by coating them with a gelatin film.
The present invention relates to adding cyclodextrin to the gelatin matrix to improve its performance.

[Prior art and problems to be improved by the present invention]

Generally, when something with a unique taste or odor is ingested through the oral route, it is covered or coated with a gelatin coating, and in the case of pharmaceuticals in particular, it is used to dissolve in the intestines without dissolving in the stomach. Capsules coated with gelatin membrane are widely used. These capsule preparations include hard capsules, soft capsules, and microcapsules, and are widely applied to liquid or emulsion-like substances and solid substances such as granules and powders.

However, it is an undeniable fact that although various products using these gelatin bases have excellent advantages, they also have disadvantages.

In other words, to give a few examples, capsules made using a gelatin base treated with formalin are stabilized and enteric-coated, but the insolubilization phenomenon becomes noticeable when stored for a long time under high temperature reflux or when exposed to ultraviolet rays. However, problems arise in terms of physiological activity.

In addition, capsules made using gelatin bases obtained by adding so-called hydrophilic substances such as ethylene glycol polymers and sugars are known to have higher disintegration properties, but to have problems with moisture resistance. ing. Furthermore, gelatin bases made by thiolating the amine groups present in the chemical structure of gelatin with thionyl halide or acylating them with acid anhydrides such as succinic acid or maleic acid have increased stability in terms of moisture resistance and moisture resistance. There are concerns about disintegration in the human gastrointestinal tract.

In addition, in the case of enteric preparations, acidic succinyl or aliphatic monoacyl of cellulose derivatives such as cellulose acetate phthalate, hydroxypropyl cellulose phthalate, cellulose acetate succinate, methylcellulose phthalate, and cellulose ethers substituted with alkyl groups, hydroxyalkyl groups, etc. Products made using mixed esters undergo a hydrolysis reaction due to moisture, resulting in the release of acids and the use of ethyl acetate, methyl alcohol, acetone, etc., which are harmful to the human body, in preparing the immersion liquid, so they are difficult to use from a physical and medical standpoint. This is not necessarily desirable.

As described above, several methods proposed for the purpose of stabilizing and entericizing various preparations using gelatin bases have been pointed out to have shortcomings.

[Means for Solving the Problems] The present invention has been achieved in order to overcome the drawbacks of the conventional methods described above and to develop a more satisfactory gelatin base.
It is characterized by the addition of a compound called cyclodextrin.

The cyclodextrin used in the present invention is a maltooligosaccharide in which glucose molecules are linked in a cyclic manner through α-1,4-glycosidic bonds, and is mainly composed of α-1β- and γ-types composed of 6 to 8 glucose molecules. It is said that there are cyclohexa-, cyclohepta-, and cycloocta-dextrins, respectively. It has been known that cycloocta) IJ has the effect of incorporating other organic compounds into the molecular cavity formed by its unique molecular structure to form inclusion compounds.

In the present invention, gelatin and clodextrin are
Either knead with or without adding water, or mix gelatin and macrodextrin with a plasticizer such as D-sorbitol or glycerin, dissolve and stir in a conventional manner to form gelatin capsules or coated tablets. In these cases, it is desirable that the amount of cyclodextrin be 10 parts by weight or less, preferably 5 parts by weight, per 100 parts by weight of gelatin. If the amount of cyclodextrin added is too large, hardening of the gelatin matrix will occur, and if too little is added, the desired effect will not be obtained.

Addition of the above-mentioned plasticizer is particularly important when producing soft capsules, but it is not so necessary for other capsule preparations.

Below, several examples of implementation of the present invention will be given, together with a detailed explanation of the present invention: Example 1 100 parts by weight of gelatin, 5 parts by weight of β-cyclodextrin, 25 parts by weight of glycerin, and 4 parts by weight of D-sorbitol.
Mix parts by weight, add an appropriate amount of purified water, and knead at room temperature to obtain a gelatin base.

Using this gelatin base, a capsule formulation of the desired drug is manufactured by a conventional method.

Example 2 A soft capsule preparation was prepared in the same manner as in Example 1 with the following formulation per capsule: Contents: Macrogol 400 300tIIy Film gelatin 100 parts by weight Glycerin
25 D-Sorbitol 3.5 Titanium oxide
0.6〃Cyclodextrin
5 Purified water Appropriate amount [Effects of the invention] The following experiments were conducted on the soft capsules and coated tablets produced in Example 1 in comparison with products without cyclodextrin additives.

Experimental method: In accordance with the disintegration test method of the Japanese Pharmacopoeia, a disintegration tester manufactured by Toyama Sangyo Co., Ltd. was used to measure the time (in units of 2 minutes) from when the sample was placed in the test liquid until a hole opened in the sample film and the content began to be released. Shida: Table 1 (Note 20D is an abbreviation for cyclodextrin) According to the results in the above table, the gelatin capsules or coated tablets of the present invention do not extend the disintegration time compared to the control product even after 12 months have passed since manufacture. It has been proven that there are far fewer

The complete dissolution time (hr) of the gelatin film in this disintegration test was as follows: The content release time for the same product under the conditions of 40 ± 1 ° C, relative humidity 75 ± 5 dI) (hr,') was as follows: Next, for the soft capsule formulation of Example 2, 40 ± 1 °C
1 The results of the hardness test and disintegration test conducted under accelerated conditions of relative humidity 75 ± 5°C are shown below: Disintegration to observe the release time (hF', ) of the contents (1 day "Macrogol 400") In the test: (CD is cyclodextrin) In the hardness test for the same specimen, expressed as kq number under pressure when the film is broken and the contents are released: From the test results for the product of Example 2 described above, it is generally found that the film ( coating)
When titanium oxide as an opacifier or a high molecular weight polymer such as polyalkylene glycol (Macrogol 400) is added to the filling liquid, the hardening of the film and the delay in disintegration time are unavoidable. It was proved that these difficulties were solved at once by adding cyclodextrin.

(Patent applicant: Toyo Capsule Co., Ltd.) (Representative: Yasu Kasuya, patent attorney)

Claims (1)

[Claims] 1. 10-2% by weight of cyclodextrin in gelatin
Gelatin substrate for pharmaceutical preparations characterized by the addition of