DE2301896A1 - SOLID PREPARATION - Google Patents

Description

DR. WALTER NIELSCH Patent attorney

2 Hamburg 70 ■ P.O. Box 10914 Telephone: 652970?

Solid preparation

Yamanouchi Pharmaceutical Co. _f Ltd "

5-1 , Nihonbashi-Honchi 2-chome, Chuo-ku, Tokyo (Japan)

The present invention relates to a new solid preparation and, more specifically, it relates to the Invention to a solid preparation which is obtained by mixing 5-4 ° percent by weight calcium lactate, 10-75 percent by weight Saccharide and 20-50 weight percent water and heating the Mixture is obtained.

The solid preparation of this invention is as a suppository base suitable for pharmaceuticals. The solid preparation of this invention is also used as a basid for a preparation for the Oral use, e.g. in the form of lozenges, tablets for buccal use and chewable tablets.

The properties of a suppository depend on the properties the base used. A suppository base should generally have such properties that these has sufficient hardness and is easily softened and dissolved at body temperature and which is easily medicinal releases that have been introduced into body cavities and should only cause the least possible irritation after introduction into the Body cavity occur.

As a suppository base, oily bases such as cocoa butter have hitherto been used and lanolin butter, emulsion bases made by adding an Eraulgator or a surface active agent to the oily

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Base and also water-soluble base substances, such as polyethylene glycol, been used. However, these base materials do not have the aforementioned properties sufficiently, which are required of suppository bases.

Thus, the oily-based masses have the disadvantage that they are not easily dissolved in a body cavity and must or must be stored in a cool place during the summer be cooled just before use for solidification, since they soften at a relatively low temperature and moreover cause irritation when introduced into a body cavity. Some oily-based masses can be used in summer be relatively stable, but such oily-based masses have the disadvantage that they are at body temperature not easily resolved.

These aforementioned disadvantages of these oily base masses have not yet been satisfactorily overcome, if this in emulsion form by adding an emulsifier or of a surfactant were transferred.

On the other hand, the water-soluble base materials have such Disadvantages that the base has hygroscopic properties and insufficient strength and further in one Body cavity is not softened and not-easily dissolved nor does it easily release the drugs in the body cavity.

Recently, a suppository base composed of sorbitol and glycerin and / or alkylenediol has been developed and has a high softening point of 40-6O ⁰ G with sufficient stability and is easily softened and dissolved in body cavities, whereby the drugs, which with

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placed in the body cavity after the suppository can be easily released, as in the United States patent 3 562 3 $ 6 is described. Such a suppository base but is still unsatisfactory, because it has hygroscopic properties and dissolves easily when it is in the atmosphere is exposed.

There is therefore a need for a new suppository base that is quite stable, has no hygroscopic properties, It is considerably softened at body temperature and dissolved in body cavities, making the drug easily accessible to the body cavity submit.

The inventors have now found that a new solid preparation, prepared by mixing 5-40 percent by weight calcium lactate, 10-75 percent by weight saccharide and 20-50 percent by weight water and heating the mixture as required has the properties already explained above to be used as a suppository base and also as a base for.eine preparation for oral administration such as lozenges, buccal tablets and Chewable tray to find use.

Further, the above solid preparation of this invention has advantageous properties, since the preparation has a considerable hardness and almost no hygroscopic properties considering that the base is water soluble. It is noteworthy that when storing the preparation there is no softening or change in the atmosphere and also in summer thanks to its high softening point, at around 50 ° C, remains stable and yet dissolves very quickly when it is inserted into body cavities, in order to make the medicine very good easy to deliver to the body cavity and almost no irritation occurs.

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It is known that an aqueous saccharide solution geliart, when calcium lactate is added to the saccharide solution (see Encyclopädia of Chem. Tech .; 2nd. Ed., 12, 103 (1967)). However, it has never been known that a mixture of calcium lactate, a saccharide and water, when heated, gives a hard solid preparation with poor elasticity as in the present invention and furthermore is completely It has surprisingly been found that the solid preparation thus obtained has the properties explained above, which are required of suppository bases.

As saccharides which can be used according to this invention, there may be mentioned for clarification: sorbitol, mannitol, fructose, Sucrose, glucose, dextrin and the like. As calcium lactate. is usually a hydrate of the same in this invention, such as calcium lactate pentahydrate is used.

The solid preparation of this invention can be prepared by mixing ⁰ !) - 40 percent by weight calcium lactate, 10-75 percent by weight saccharide and 20-50 percent by weight water and heating the mixture, preferably to temperatures above ÖO ° C and cooling the mixture to room temperature and leaving to stand of the mixture at room temperature to solidify within one hour to overnight. The amount of calcium lactate required to obtain the solid preparation of this invention depends on the amounts of saccharide and water used. For example, a suitable amount of calcium lactate is 40 weight percent for 30 weight percent saccharide and 30 weight percent water; furthermore, 5 percent by weight calcium lactate is suitable for 75 percent by weight saccharide and 20 percent by weight water.

Calcium lactate, saccharide and water can be mixed in any order. This means that water becomes one Mixture consisting of calcium lactate and saccharide was added

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or saccharide can be added to an aqueous solution of calcium lactate or, alternatively, calcium lactate be added to an aqueous solution of Zaharid. However, it is preferred to first add calcium lactate V / water dissolve and then dissolve saccharide in the aqueous solution. When the solution is allowed to solidify, the solidification may occur Cooling the solution to temperatures below room temperature are favored.

In practicing this invention in which the calcium lactate and saccharide are dissolved by heating, Add a drug, coloring agent, flavor, fragrance, diluent, surfactant, or the like to the formulation - if necessary - to be added.

In order to use the preparation base of this invention for medical purposes, a drug can be added to the base thereof Invention can be added after their dissolution by heating, or a drug can be added in the dissolution of calcium lactate and saccharide be present in water.

To demonstrate the technical progress achieved, the suppository obtained according to Example 5 of this invention was used the following comparative studies examined in more detail, with a suppository made of polyethylene glycol as Comparative material was used.

After melting a mixture of 20 g of polyethylene glycol with a molecular weight of 4000 and 70 g of polyethylene glycol with a molecular weight of 1500 by heating over 60 C was 14 g of polyethylene sorbitan monolaurate and 10 g of glycerol monostearate added to the melt. Then 10 g of 1- (p-chlorobenzoyl) -5-methoxy-2-methyl4ndole-3-acetic acid became (general name: indomethacin) uniform in that

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Mixture dispersed. The dispersion was poured into a filling machine for the production of rectal suppositories filled in and kept at 60 ° C and then left to stand, to get suppositories.

The hardness and solubility of the suppository in water in this invention, prepared according to Example 5, are shown below and the corresponding values for the comparative suppository using polyethylene glycol Hours, as indicated above, were made at room temperature using a Heberlein tester and a disintegration tester determined according to the USA Pharmacopoeia. The results are summarized below.

Suppository according to the invention

Comparative suppository made of polyethylene glycol

hardness
resolution

4 - 6 kg
12-14 minutes

0.5 - 1 kg

34 - 36 minutes

Examples 1, 4, 6 and 7 illustrate the preparation of the solid preparation by dissolving calcium lactate in hot water and then adding and dissolving the water-soluble one Sac char ids. In example 6 and 7 the filler used is Magne * s ium ilikat co-used.

Examples 2, 3 and 5 illustrate a mode of operation in the calcium lactate is dissolved in hot water and then the water-soluble saccharide is added to the resulting solution and is dissolved. Then polyoxyethylene sorbitan fatty acid ester alone is used as an emulsifier or dispersant or used in combination with glycerol monofatty acid ester.

The example Ö illustrates a manufacturing process in which a uniform mixture of anhydrous calcium lactate and

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water soluble saccharic! spread out and sprayed with water will.

example 1

After heating 250 g of water to over 80 ° C., 16O g Calcium lactate dissolved in the water and then 590 g sucrose in the solution. By standing overnight at room temperature a solid preparation was obtained from the aqueous solution thus prepared,

Example 2

After heating 40 g of water above 80 ° C., 30 g Dissolved calcium lactate. Then, 30 g of sorbitol was dissolved in the resulting solution. Then became the resulting solution 6 g polyoxyethylene sorbitan monolaurate and 6 g glycerol monostearate added and uniformly dispersed in the mixture 8 g of powdery josamycin. By spreading the dispersion A solid preparation was obtained on a flat plate and left standing overnight at room temperature.

Example 3

After 300 g of water had been heated to above 80 ° C., 400 g were obtained therein Dissolved calcium lactate and then added 300 g of sucrose to the solution. The solution thus obtained became uniform with a solution mixed by dissolving 30 g of polyoxyethylene sorbitan monolaurate (Nikkol TL- 10) in 500 g

oC- (p-chlorophenoxy) isobutyric acid ethyl ester (general Designation: Clofibrate) was obtained as a homogeneous dispersion with heating. After allowing the batch to stand as a dispersion A solid preparation was obtained over one hour at room temperature.

Example 4

After heating 200 g of water to temperatures above 80 ° C

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50 g of calcium lactate was dissolved therein and then in the solution 750 g sucrose dissolved. Then 110 g of chloramphenicol was uniformly dispersed in the solution. By leaving the Disperse overnight at room temperature in a suppository mold solid suppositories were obtained.

Example 5

After heating 125 g of water to temperatures above 00 ° C 4 # g of calcium lactate was dissolved in the water and then 177 g of succrose dissolved in the solution. After adding 14 g of polyoxyethylene sorbitan monolaurate and 10 g of monoglycerol stearate became 10 g of powdery 1- (p-chlorobenzoyl) -5-methoxy-2-methylindole-3-acetic acid (general name: indomethacin) dispersed uniformly in the mixture. While holding at 60 ° C the dispersion obtained was poured into a filling device for the production of rectally usable suppositories and then left to stand overnight at room temperature, whereby well usable suppositories were obtained.

Example 6

After heating 200 g of water to above 00 ° C., 50 g of calcium lactate were obtained dissolved in it and then 750 g of sucrose dissolved in the solution. In this solution became a dispersion uniformly of 50 g of magnesium silicate in 700 g of ethyl c6- (p-chlorophenoxy) isobutyrate (general name: Clofibrate) dispersed. The obtained dispersion became spherical Filling device for the preparation of vaginal suppositories filled and then left to stand overnight, making suppositories were obtained.

Example 7

After heating 200 g of water to above 00 ° C., 50 g of calcium lactate were obtained dissolved in water and then 750 g of sucrose dissolved in the solution. The solution thus prepared became uniform

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a dispersion of 50 g of magnesium silicate in 600 g of castor oil dispersed. The obtained dispersion was put into a filling machine for making rectal suppositories and then left to stand overnight at room temperature Obtain suppositories.

Example ß

A uniform mixture of 40 g of anhydrous calcium lactate and 40 g of sorbitol was spread over a flat plate and sprayed with 20 g of water. The batch was left to stand for one hour at room temperature and a solid preparation according to this invention was obtained.

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Claims (6)

- ίο - Patent claims: f \\ Solid preparation, consisting of a mixture of 5-40 percent by weight calcium lactate, 10-75 percent by weight saccharide and 20-50 percent by weight water * 2. Solid preparation according to claim 1, wherein calcium lactate is present as calcium lactate pentahydrate. 3. Solid preparation according to claim 1 or 2, wherein the Saccharide is made up of sucrose. 4. A method for producing a solid preparation, characterized in that 5-40 percent by weight calcium lactate and 10-75 percent by weight of saccharide are mixed with 20-50 percent by weight of water and the batch, optionally after shaping, is made to solidify by allowing it to stand. 5 · The method according to claim 4, characterized in that the components of the mixture in any order or can be added together with the water and dissolved by heating or using heated water and the solution solidifies by allowing it to cool is brought. 6. Use of solid preparations according to any one of claims 1 to 5 for the production of pharmaceutically acceptable Moldings such as suppositories, spheres, troches, tablets, granules and the like, which have good mechanical hardness and Have firmness and which after introduction into the body or a body cavity of warm-blooded animals relatively quickly are dissolvable and easily release the active ingredients contained therein. 309830/1187