JPS5824409B2 - The best way to get started - Google Patents

Description

[Detailed description of the invention] Original invention (Patent No. 893583 (Japanese Patent Publication No. 52-1824)
No. 8)) is a volatile liquid and active substance-containing powder (
in which one of these components contains a binder soluble in the liquid) are applied alternately to the seed material moving in a dragee;
The present invention relates to a process for the production of medicaments in the form of small spheres, by adjusting the amount of liquid added in each case to the critical liquid uptake of the amount of powder to be subsequently added.

In this case, the term ``critical liquid quantity'' refers to the liquid quantity such that the powder quantity to which it belongs forms a compound that is neither sticky nor disintegrating.

A large number of test methods are described in the original patent specification which make it possible to simply and accurately determine the "critical liquid quantity" in every respective case.

Generally, the critical liquid uptake is about 10 to 30 grams of liquid per 100 y' of powder.

A typical example of a liquid to be used according to the invention is an alcoholic aqueous solution of polyvinylpyrrolidone or polyvinylalcohol.

The compound formed from the two components in the proportions described above has such strength that it can be formed into drug spherules on conventional seed materials without intermediate drying.

Only when the desired final particle size is reached is a drying step carried out.

However, it has been found that for the process according to the invention it is not of fundamental importance that the binder is soluble in the volatile liquid used.

According to another embodiment described in the original specification, the binder is present in the form of particles that are dispersed in water.

The liquid used together with the powder component for layering is therefore a plastic aqueous dispersion.

Preferably, plastic dispersions with a solids content of 5 to 50% by weight are used.

In this case, the critical liquid uptake, as in the binder solution, is of the order of magnitude of 100 to 30 g of dispersion per 100 Pa of powder.

The structure of the plastic dispersed in the dispersion is determined by the desired behavior of the globular drug in vivo, rather than by the globule manufacturing method.

Globular drugs whose active substances are to be released primarily by diffusion include completely non-containing agents which may be composed solely of esters of acrylic or methacrylic acid, vinyl esters, styrene, vinyl chloride or other water-insoluble monomers. Dispersions of water-soluble plastics are suitable.

On the other hand, if the small spherical drug should dissolve in the acidic atmosphere of the stomach or in the slightly alkaline atmosphere of the intestine or swell slightly (but strongly), dispersions of plastics with hydrophilic groups are used. .

Preference is given to using plastic dispersions of the type described in German Patent Specification No. 21 35 073.

These plastics are composed of 10 to 55% by weight of monomers having carboxyl groups and/or monoalkyl- or dialkylamine ester groups.

Preferred monomers from this group are acrylic acid and methacrylic acid and their diethylamino-, dimethylamino- or butylaminoethyl esters.

The remaining 45-90% by weight of the copolymer comprises other vinyl monomers, such as esters of acrylic or methacrylic acid with aliphatic alcohols, glycols or glycerin, as well as nitriles or amides, vinyl esters, chlorides of the aforementioned acids. Vinyl, vinylidene chloride, olefin, styrene, etc.

The high solids content and at the same time low viscosity of the aqueous plastic dispersion makes it possible to produce small spherical drugs with a significantly higher binder content than is possible using binder solutions.

This plastic content can be up to 10% of the weight of the finished drug pellets.

This makes it possible to delay the release of the active substance.

Another advantage of the invention is that when using the binder organic solution, no organic solvents are used together, the recovery of which is already unavoidable for reasons of environmental protection.

The drug spherules can be filled in gelatin capsules in a manner known per se, optionally with an additional coating that can influence the release of the active substance.

The present invention will be explained in detail below using examples.

Example 1 Hotaka 2 with particle size 0.5-0.8 mm into sugar coating pot
Charge 0 kg.

22 kg of the pulverized lactose mixture are used as dusting powder.

As a binder, 50% of acrylic resin whose main component is a copolymer of methacrylic acid ester and acrylic acid ester is used.
% dispersion is used.

In preliminary tests, the critical liquid absorption capacity was 14m1/1.
00g was obtained.

Using a spray gun, add 0.281 each of the dispersions,
Spray onto the rotating charge in the kettle.

Immediately thereafter, 2 kg of the powder mixture are sprinkled onto the wet charge.

After the powder has been contained in the crystals or granules, the charge is allowed to rotate freely again and the process is repeated until the entire amount of the spreading mixture has been used for coating.

After coating has taken place, the pellets thus produced are screened on a sieve and dried in a drying mold.

In this case, the amount of binder is 7%, based on the amount of powder to be spread.

The yield of finished pellets is approximately 42 kg.

Example 2 Hotaka 20 with particle size 0.5-0.8 mm into sugar coating pot
Charge kg.

Lactose, hydroxymethylnitrofurantoin (61%)
and Koliton-25 are used as the dusting powder.

A 30% aqueous plastic dispersion based on methacrylic acid and ethyl acrylate is used as a binder.

In a preliminary test, the required amount 21 as the critical liquid absorption amount
■/100P was obtained.

Using a spray gun, first add 0.32 kg of the dispersion.
Spray onto the rotating charge in the kettle.

Immediately thereafter, 1.5 ky of the powder mixture described above is sprinkled onto the wet charge.

After the powder has been contained in the crystals or granules, the charge is allowed to rotate freely again and the process is repeated until the entire amount of the spreading mixture has been used for coating.

After 5 coatings, the amount of liquid to be added each time is 0.63
1 and the powder amount increases to 3ky.

After coating has taken place, the pellets thus produced are screened on a sieve and dried in a drying mold.

In this case, the amount of binder is 4.8% of the amount of powder to be spread.
%.

The yield of finished pellets is approximately 42 kg.

Example 3 The procedure according to Example 2 is repeated, except that instead of Hotaka as charge, each particle, obtained by a suitable granulation method, has a particle size of 0.
Active substance granules as seed material are used with a diameter of 5 to 0.8 mm.

Critical liquid absorption amount is 20rrLl/100g (solid material)
It is.

Embodiments of the invention are described below.

(1) The binder to be dispersed in water is 10 to 55% by weight.
2. A method according to claim 1, characterized in that the vinyl polymer is composed of monomers having carboxyl groups and/or monoalkyl- or dialkylaminoalkyl ester groups.

Additional related original invention (Patent No. 893583 (Japanese Patent Publication No. 52-1824)
No. 8)) is a volatile liquid and active substance-containing powder (
The present invention relates to a method for producing drug spherules by alternately applying medicaments (one of which contains a binder soluble in the liquid) to a seed material moving in a dragee. is an invention of a method for producing a small spherical drug, which is the target substance of the original invention, by using a binder in the form of water-dispersible particles instead of the volatile liquid-soluble binder in the original invention. Therefore, it falls under Article 31, Item 1 of the Patent Act.

Claims (1)

[Claims] 1 a volatile liquid and an active substance-containing powder, in which case one of these components contains a binder soluble in said liquid,
In the production of medicaments in the form of small spheres by applying them alternately to a seed material moving in a dragee, the amount of liquid added in each case being matched to the critical liquid uptake of the amount of powder to be subsequently added, A process for the preparation of small spherical drugs, characterized in that water is used as volatile liquid and the binder is used in the form of particles dispersed in the water.