DE2010116A1 - Process for the production of micro-granules - Google Patents

Description

FARBENFABRIKEN BAYER AG

LEVERICUS EN-Bayerwerk patent department

G / O.

March -2! 970

■ Process for the production of micro-granules ..

Microcapsules made of hydrophobic or hydrophilic core substances and shells made of polymers have recently been of great interest found because they enable the encapsulated substances to be released under defined conditions.

Gelatin coacervates, which are made from aqueous Medium are applied, can be used. In this case, hydrophilic shells are provided.

Microcapsules with hydrophobic shells are more difficult to manufacture. Such shells are particularly interesting for water-soluble core substances. Such capsules can be obtained if the core material is optionally dispersed as a solution in the solution of a capsule-forming polymer and a second solvent is added which reduces the solubility of the polymer so that a polymer-rich phase (coacervate) is formed. This coacervate can envelop the dispersed particles or drops so that, after isolation and drying, capsules with hydrophobic envelopes and, for example, hydrophilic contents are present. In British Patent Specification 931,148 appropriate solvent pairs are combined with various polymers described. However, working with such solvent mixtures is very inefficient and causes high costs. In addition, this process is only applicable to a limited extent, since the solvents must be matched to the core material.

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In a further known method for producing capsules with hydrophobic casings, the substances to be encased are in the solution of a polymer, which is intended for the shell formation, dispersed and this dispersion in a second Liquid distributed. The first liquid (solvent for the polymer) should be miscible with the second liquid be, but the polymer should not dissolve in the second liquid, so that when distributing the polymer solution that the Contains dispersed core material, in the second liquid the polymer precipitates and settles on the surface of the envelope Particle precipitates (Dutch interpretation 68 11852).

Practically mix, as can easily be shown experimentally can - the two solvents so quickly that the polymer precipitates in the form of threads, lumps or cakes and for one Envelopment of the dispersed particles is no longer available. Like the examples in the Dutch exposition 6 811 852 show, this can be partially prevented if a substance, e.g. also a polymer, is included in the second liquid dissolves, which can enter into an interface reaction with the shell-forming polymers in the first liquid. Then mix the two solvents react more slowly and usable capsule formation becomes possible. In this procedure, as By-products to solvent mixtures which are contaminated by the shell-forming polymers. Your work-up is difficult.

The invention relates to a process for the production of solid, free-flowing, spherical microgranules from synthetic organic polymers that contain embedded solid or liquid particles of a core material.

The method is characterized in that the solid or liquid core material in a solution of a cellulose ester in a glycol ether disperses or dissolves, the dispersion or solution

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solution in the form of discrete drops in water, whereby the Drops through. Withdrawal of the glycol ether solidify and.the Granulate separates solidified drops.

For the process according to the invention suitable water-miscible glycol ethers are, for example. Mono- and dialkyl ethers of aliphatic glycols such as ethylene glycol, propylene glycol, butylene glycol with 1 - 6 carbon atoms in the ether alkyl group, ethylene glycol monomethyl ether CH ₃ O-CH ₂ CH OH, diethylene glycol ether HOCH ₂ Ch-OCH ₂ CH ₂ OH and ethylene glycol monoethylene.

Suitable cellulose esters are, for example, esters of cellulose with monovalent aliphatic carboxylic acids with preferably 1-6 carbon atoms, such as cellulose acetate, cellulose propionate and mixed esters such as cellulose propionate acetate or cellulose butyrate acetate. The acyl contents of the cellulose esters preferably correspond to degrees of substitution of 2.2-2.6 acyl residues per anhydroglucose unit,

It was surprising that in the procedure according to the invention, Generally speaking, when the organic phase is introduced, in the form of preformed particles, into the aqueous phase, round Microgranulate particles are formed with a solid shell.

The procedure according to the invention is based on the glycol ether / cellulose ester system limited. For example, if you replace the cellulose ester by ethyl cellulose, - so are also when entering dispersions prepared therefrom in water in the form of preformed Particles do not receive spherical particles, but rather the particles entering the water spread and split up fibrous. The same applies if other solvents such as ketones are used instead of the glycol ethers mentioned.

The process according to the invention can be carried out as follows: One starts from a 2% by weight, preferably 3–15% by weight. % By weight solution of the cellulose ester in the glycol ether.

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The KeiTimaterial to be enveloped or embedded is in this

Solution dispersed or dissolved, using the usual mixing devices Vibromixers, high-speed stirrers and other homogenizing devices are also used in the production of dispersions will. The amount of core material that is dispersed or dissolved can be between 20 and 90% by weight, based on the polymer solution, lie. In general, the proportions are chosen according to the desired ratio between cellulose esters and coated core material, since in the present process there is practically no loss of polymer or core material enter. Amounts of cellulose ester are sufficient for most purposes from 5-70% by weight, based on the microgranules.

With the method according to the invention, the following substances encased or embedded: solid or liquid, hydrophobic or hydrophilic, inorganic or organic substances The following groups of substances may be mentioned from the large number of these: Pharmaceuticals and pesticides, foodstuffs and luxury foods (e.g. flavorings, spices), fragrances, dyes (e.g. inorganic or organic pigments, dye solutions or Pastes), chemicals, lubricants and lubricants such as oils, adhesives, adhesives, etc. Mixtures of such substances are enveloped.

The dispersions or solutions of the substances in the core Äthy- Wk lenglykoläther-Celluloseester solution are then introduced in the form of preformed particles in water, with known for mildly mixing with aid (stirrer, recirculating pump) is provided. The dispersions or solutions are preferably first atomized in air with the aid of one- or two-component nozzles, so that preformed particles with a certain particle diameter are formed, which are then introduced into the optionally stirred or mixed aqueous phase, the aqueous phase also being part of one flowing system can be.

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In the simplest case, atomization by means of a single-fluid nozzle the water surface, care must be taken to choose the best distance between the nozzle outlet and the water surface at which spherical particles are formed. If the distance is too small large, partly coherent droplets, which break easily when they hit the surface, so that the particle size distribution the resulting particle becomes very wide. If the distance is too great, the result is not spherical but deformed Particles.

The size of the primary particles depends on the viscosity of the solution or dispersion from which they are generated (i.e. Amount and type of solvent of the cellulose ester and the Shell substance) and how it is produced. (When spraying e.g. from the nozzle diameter and the spray pressure)

The particles entering the aqueous phase lose their solvent extremely quickly, with the diameter of the primary particles decreasing. In general, residence times in pure are sufficient Water 5-10 minutes out to allow most of the solvent passed into the aqueous phase and the shell solidification has occurred. In the case of aqueous phases which already contain solvents, the solvent transition occurs a little slower.

The processes described can in principle be carried out at temperatures between 5 and 90 ^° C.
one in the range of 15 - 40 ⁰ C.

between 5 and 90 ⁰ C are carried out, usually works

After sufficient solidification of the shell, the spherical particles be separated from the water, if necessary you can wash them with more water, possibly to remove any remaining Solvent.

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The separated particles are then dried, e.g. in a stream of air or in a vacuum at temperatures of 50 - 100 ° C, The drying conditions must be adapted to the capsule content (boiling point, melting point) so that the particles are not destroyed and the core substance emerges.

The spherical particles obtained contain the core material in the form of small droplets or particles embedded in the polymer, or z. T. solved. The size of the enveloped droplets or particles can be determined by the dispersing process vary.

Core substances that were dissolved in the glycol ether are usually finely divided when the solvent escapes.

The size of the spherical particles, ie the microgranulate, depends on the parameters already described. Particle sizes of 50 αχ up to several millimeters can be achieved easily.

The microgranulates have a complete outer skin, which at small .polymer and high solvent quantities also made porous can be.

The microgranulates produced according to the invention are of considerable importance for the administration or use of substances whose release is to be delayed (eg pharmaceuticals, pesticides) or for which the release is to take place under special conditions such as eg pressure, temperature increase, addition of solvents, etc.

example 1

In a solution of 5 parts of acetyl cellulose (molecular weight 9'io \ degree of substitution 2.5 acetyl groups per anhydroglucose unit) and 95 parts of ethylene glycol monomethyl ether 20 parts of acetylsalicylic acid were dissolved. This solution was

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de with the aid of a nozzle with an inner diameter of 0.2 mm at a driving pressure of 1.5 atü in 300 parts of water, which were kept gently in motion with a stirrer, the nozzle outlet was 15 cm above the water surface. The drops entering the water (diameter approx. -Ifi - 2 mm) were immediately covered with a skin, and the solvent emerged in the form of streaks. After a residence time of 30 ', the spherical particles were sieved off and dried at 40 ° C. in a stream of air.

25 parts of microgranules with a particle diameter of 0.8 mm were obtained, those with a solid, tight casing were coated and the inside fine acetylsalicylic acid crystals, which were separated from each other by the polymer, contained. -

With a nozzle diameter of 0.15 ram and a propulsion pressure of ~ $ atm, microgranules with an average particle diameter of 0.2 ram were obtained. "'. -

Example 2 ';

The same solution as in Example 1 was not dripped into water with the help of a nozzle, but with vigorous stirring poured into the water. Amorphous lumps, threads and cakes formed. The acetylsalicylic acid 'went partly in the aqueous phase over.

example

In a solution of 8 parts of cellulose propionate acetate (molecular weight approx. 10, propionate residues calculated as propionic acid 57%, acetyl residues calculated as acetic acid 5 %) in

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92 parts of ethylene glycol monomethyl ether: 8 parts of paraffin oil were emulsified with a high-speed stirrer (drop size 10 20 / u) . This emulsion was introduced with the aid of a nozzle (inner diameter 0.2, propulsion pressure 4 atmospheres) at a height of fall of 20 cm into 35O parts of water, which was thoroughly mixed. After 30 ' , the spherical particles were separated off and dried at 40 ° C. in a stream of air. 16 parts of a microgranulate with an average ball diameter of 0.4 mm were obtained. The particles contained the oil droplets inside, separated from one another by polymer walls.

Example 4

In a solution of 6 parts of cellulose butyrate acetate (molecular weight 7-8-10, butyrate groups calculated as butyric acid 45 %, acetyl groups calculated as acetic acid 20 %) in 96 parts of diethylene glycol (2,2'-dihydroxyethyl ether), 12 parts of titanium dioxide (particle size 20-40 / u) dispersed using a high-speed stirrer. This dispersion was introduced into 200 parts of water with the aid of a nozzle of 0.5 mm at a driving pressure of 3 atmospheres and a height of fall of 15 cm. After a residence time of 20 minutes, the spherical particles were separated off and dried at 30 ° C. in a vacuum.

18 parts of microgranules with a particle diameter of 0.5-0.7 mm were obtained, which _{contained the individual TiO 2} particles encased in the polymer matrix.

Example 5

Example 1 was repeated, but instead of acetyl cellulose as the polymer, ethyl cellulose (molecular weight 5'Iu ³ ) was used under the same atomization conditions, could no microgranules be obtained? the drops entering the water split up and the polymer precipitated out in the form of fibers and patties.

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Example 6 i β

Example ~ $ was repeated, but butanone was used as the solvent. When injecting the corresponding emulsion under the same conditions, however, no spherical particles with a solid shell were obtained, but the. Drops entering in water spread, the polymer separated in flatbreads and threads. .. "

Example 7

In a solution of 4-0 parts of acetyl cellulose (molecular weight "3-10->, acetyl groups calculated as acetic acid 5J5 %) in 700 parts of ethylene glycol monomethyl ether, 20 parts of the phosphorus compound (CH ₃ O) ₂ POCCHOh-CCI ₃ ) were dissolved and brought to 0 ° C This solution was introduced with a nozzle (internal diameter 1 mm, driving pressure 1 atm) at a height of fall of 20 cm into 2000 parts of water, which was mixed and the temperature was 0 ° C. The spherical particles were after a residence time of 25 Minutes and dried in vacuo at 355 ° C. 98 parts of microgranulate with a particle diameter of 1.5 mm were obtained.

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Claims (1)

ClaimsJf \ 1. Process for the production of solid, free-flowing, spherical. Micro-granules made from synthetic, organic polymers that are embedded in solid or liquid particles of a core material contain, characterized in that the solid or liquid core material is in a solution of a cellulose ester dispersed or dissolved in a glycol ether, brings the dispersion or solution in the form of discrete drops in water, whereby the drops solidify by withdrawing the glycol ether and the drops which have solidified to form granules are separated. Le A 12 873 - 10 - M39838 / 0929