DE2237483C3 - Process for the encapsulation of water-insoluble or poorly water-soluble substances or mixtures of substances in microcapsules - Google Patents

Description

The invention relates to a method for encapsulating water-insoluble or sparingly water-soluble substances or mixtures of substances in microcapsules, in which a macromolecular wall material dissolved in water, the The substance to be encapsulated or the mixture of substances to be encapsulated is dispersed or emulsified in the solution and then by precipitation, temperature change, addition of further macromolecular components and / or pi I-value change brought about a phase separation will.

As is well known, microcapsules consist of a liquid or solid core that extends from a wall macromolecular material is surrounded. The diameter of microcapsules is between 2 and 4000 μm.

As the core, ie as substances or mixtures of substances to be encapsulated - hereinafter also referred to as "internal phase" - come e.g. B. solvents, fragrances and * o aromatic substances, dyes and pigments, drugs, pesticides and fertilizers, catalysts, inhibitors, fuels, adhesives and magnetic particles, in short, all kinds of active ingredients. The encapsulation of active ingredients is carried out ⁴ ', for example, in order to let their effect occur gradually or suddenly, ie at a desired point in time. With gradual decomposition of the wall material, the release of the active ingredient is distributed over a longer period of time, i.e. delayed. This is important, for example, with pesticides and fertilizers B. by pressing the type lever of a writing or calculating machine on microcapsules that are filled with dyes or pigments.

In microencapsulation, a distinction is made between encapsulation in an aqueous medium and encapsulation in organic solvents (USA- ^M patents 28 00 457 and 28 00 458). When encapsulating in an aqueous medium, gellable hydrophilic colloids, e.g. B. polyvinyl alcohol and gelatin, used as wall material. As already mentioned in the introduction, the process according to the invention is carried out in an aqueous medium.

Certain changes in liquid solutions of film-forming polymeric substances cause phase separation of the solution, creating a relatively viscous, polymer-rich liquid phase and a polymer-poor liquid phase. This appearance of the Phase separation is referred to as "coacervation", the relatively viscous phase as "coacervate" or "coacervate solution" and the polymer-poor phase as "equilibrium liquid". Coacervation can can be introduced into polymer solutions in various ways. With simple coacervation, a homogeneous polymer solution containing only one polymer, by adding a microionic agent or by a change caused by a physical means, for example a change in temperature, causes itself into the viscous coacervate phase and the non-viscous equilibrium phase, which for the most part of the solvent contains, to separate. In complex coacervation, polymers with opposite electrical charges act under corresponding ones Conditions so together that they allow the formation of a relatively viscous complex of the polymers cause. The phase separation in a homogeneous solution of a polymer and the formation of a viscous one Coacerval phases can also be achieved by introducing a second polymer that is incompatible with the first polymer Polymer or a nonsolvent for the polymer are effected, thereby reducing the solubility of the dissolved polymer is reduced and this causes its deposition (German Auslegeschrift 1546 271).

When using gelatin as a wall material, the phase separation or coacervation is achieved by adding caused by one or more of the following substances: Gum arabic. Copolymers of ethylene or Vinyl ethers with maleic anhydride, carrageenan or salt solutions, e.g. B. sodium sulfate, polyphosphates Polysilicate, sodium tungstate and polymolybdate solutions.

The end products of microencapsulation are either dry microcapsules or a capsule slurry in which the Microcapsules are present in dispersion. The following requirements are placed on dry microcapsules:

a) The wall material must form a stable wall around the internal phase.

b) The capsules must be so stable when wet at room temperature that they can Let it filter off without being damaged.

c) The capsules must filtered can be dried by the fluidized bed method or a similar method, without / u agglomerate (ie, without that the surface is so tacky that the individual capsules sticking to each other).

d) The capsules must form a free flowing powder.

e) The finished capsules must have sufficient retention capacity for the inner phase.

An end product in the form of a capsule slurry need only meet conditions a and e.

The retention capacity ("time release") of the microcapsules is largely determined by the quality of the used wall material. When using gelatine as a wall material, the Permeability of the capsule wall (with parameters kept constant according to the law of diffusion) with increasing gel strength.

In addition to viscosity, gel strength is a characteristic for grading the quality of glue and gelatine. It depends on the concentration of the jelly that

Gelatinization time and gelatinization temperature away. It is a measure of the mechanical quality properties of glue or gelatin and increases with the same Concentration and temperature with the quality (Ulimanns Encyklopadie der technischen Chemie, 11. Volume (1960). Page 638).

The gel strength is measured in the Bloomgelometer from Amer. Nat Assoc. of Glue Manufacturers. The measure (1 bloomgram) for the gel strength is the force that is required to press an ebonite stamp (plastic) with a diameter of 12.7 mm and an even lower surface into a gel of the glue to be tested 4 mm deep. In the case of bone, hide and leather glue and technical gelatine, jellies of 12.5% by weight are tested, and of 6.67% by weight of food and photo gelatine. For glue, weigh 15 ± 0.03 g of the test sample with 105 ± 0.25 g of distilled water into Bloomtesl glasses (7.5 g weight for gelatine) and melt after swelling at 60 ° C in a water bath. The sealed with a pierced rubber stopper glasses stay in front of the measurement in the Bloom test apparatus 16-18 h in a water bath at 10 + 0.1 ⁰ C (Ullmann, supra, page 640).

The gel strength is also called gel strength, gel strength or bloom strength. For the measure of the Gelatinous strength can be found next to the abovementioned term "Bloomgram" and terms such as "Grams measured with or after the Bloomgelometer" and "Bloom strength ... grams". Hereinafter the term »bloom number« (without »gram«) or »bloom« is used here, whereby the Information always relate to jellies with a water content of 6.67% by weight.

It is known for microencapsulation gelatin to be used with Bloom numbers between 275 and 305 (DE-PS 8 55 998 and 8 7 J 556, DE-AS 16 19 791, DE-OS 21 03 298 and AT-PS 2 79 556). Such gelatin is referred to as high quality gelatin (US-PS 35 33 958).

In DE-OS 21 03 528 it is mentioned that gelatin, inter alia. therefore very often for production water-soluble capsules are used and preferred to other substances because they are cheap. This advice but apparently only refers to the cheapness of a comparison with other polymeric substances, e.g. B. with the Polyvinyl alcohol mentioned in this context, because on the other hand it is known from DE-AS 19 48 626, that in most cases where gelatin is used, it must have a high degree of purity. A however, a higher degree of purity results in a higher price.

It is also known from DE-OS 21 03 528 that in the production of microcapsules with a capsule wall of two layers of each chemical Various types of gelatin, including chemically modified materials such as succinylated gelatin, can be used for various hydrophilic polymeric materials can. However, nothing is said about the quality and degree of purity of these types of gelatin.

In summary, it can therefore be stated that for the microencapsulation so far consistently high quality and pure gelatin, in particular pig skin gelatin of the first and second bouillon, is used. These Gelatin is quite expensive as it is only available in limited quantities in the manufacture of gelatin. this affects the economy of microencapsulation very strongly, since the price of gelatin is 50 to 80% of the Raw material cost (excluding the cost of the internal phase to be encapsulated, of course).

The invention is based on the object that

Encapsulating water-insoluble or poorly water-soluble substances or mixtures of substances in microcapsules cheaper without affecting the quality of the microcapsules or the capsule babe will.

According to the invention, this object is achieved by that as macromolecular wall material gelatin or gelaline mixtures, which are used as waste in the production of Push-fit or hard capsules and / or soft capsules and a gel strength greater than 80 blooms can be used without prior cleaning.

There is no upper limit to the bloom number of the usable gelatin waste. It can do both Gelatin waste, the starting gelatine of which has been digested in an acidic manner, as well as those whose starting gelatin has been digested in an alkaline manner, are used will. Mixtures of the aforementioned gelatin tablets can also be used.

The gelatins or gelatin mixes that are considered waste incurred in the gelatine processing industry, remain in the manufacture of push-fit or hard capsules and of soft capsules z. B. left in the form of gelatin tapes with punched holes.

Such gelatin waste contains gelatin z. B. still sorbitol and / or glycerine, flavorings, Dyes, pigments and water.

In principle, gelatin waste in solid or dissolved form which contains at least 2% by weight of gelatin can be used. For example, the gelatin waste from Weichkapselherstelliing i0 contain up to 60 wt ° / o gelatin (Bloom number from 100 to 200), 10 to 30 wt .-% of glycerol and / or sorbitol, to tu 2% impurities, such as dyes, pigments and flavorings , and traces of active ingredients in the soft capsules, the rest water.

Gelatin waste from hard capsule production contains, for example, 0 to 4% by weight of dyes and pigments and flavorings, 5 to 15% by weight water (depending on storage), the remainder gelatin (Bloom number 200).

The gelatin scraps and gelatin scrap mixtures which can be used in the process according to the invention are preferably coacervated or precipitated with one or more of the substances listed below: Gum arabic, vinyl ether-maleic anhydride copolymers, ethylene-maleic anhydride copolymers, carageenan, high and low molecular weight Polyphosphates, polysilicates and polymolybdates as well as salt solutions such as sodium sulfate and sodium tungstate solutions. Of course, it is also possible to Coacervation or precipitation to use other substances with an analogous effect. The in the invention Process used internal phase can be thin, viscous or solid.

The advantages achieved by the invention are in particular that it is due to the cheaper Wall material is possible to carry out the microencapsulation of those active ingredients in which the so far because of the price relation wall material: inner phase not worthwhile.

Gelatin waste is used directly, i.e. without cleaning. This is particularly beneficial because it has been so far It was not worthwhile or impossible to separate gelatin waste from its additives in order to regenerate Reuse gelatin. So there are no costs for the gelatin regeneration, the impurities are removed during the encapsulation without anyone additional work step eliminated. A part of

Additives from macrocapsule production even have a positive effect on the quality of the process products off, ζ. B. the plasticizers that are used in the material Wcichkapselproduction are included, in particular glycerin and / or sorbitol.

When creating the capsule wall, ζ, Β. by Coacervation or precipitation is removed from the mixture only the gelatine, the impurities remain in solution or sediment. The whole mix of capsules and impurities is filtered that Capsules stay on the filter and most of the impurities drain through the filter. Of the The process is similar to purification by recrystallization.

In some known encapsulation processes, to improve the final quality of the capsule wall, ζ. Β. to increase the impermeability, added sorbitol and / or glycerine during encapsulation. This Sorbitol or glycerine is new for each batch uses and burns the microencapsulation considerably. Those preferably used according to the invention Gclatin waste already contain sorbitol and / or glycerine as an impurity.

In gelatin waste, which contains considerable amounts of water, the gelatin is already swollen and therefore swollen dissolves very quickly. The usual swelling of the gelatine is no longer necessary. This results in a time saving.

The invention is explained in more detail below on the basis of a few exemplary embodiments.

Examples 1 and 2 demonstrate the possibility of using gelatin waste mixing small capsules up to 20 μm to produce in suspension.

Examples 3 and 4 show that with gelatin waste mixtures also larger capsules up to 500 μίτι to free-flowing »powders« can be dried.

example 1

Raw material:

Gclatin waste of the composition 20 g

46% by weight gelatin (gelatin mixture with 130 to
170 Bloom)

33% by weight water

20% by weight glycerin

1% by weight of dye and pigment
Gum arabic 10 g

Water 1040 g

Vinyl ether-maleic anhydride copolymer 5% 12 g

Internal phase: tetrachlorethylene 100 g

Sulfuric acid 10% 10 g

Glutaraldehyde 25% 5 g

Vinyl ether-maleic anhydride copolymer 10 g

NaOH 20% q.s.

The gelatin waste is dissolved in about 500 ml of water, the internal phase is dispersed in this solution until the particles of the internal phase are about 2 µm in size (during this work the temperature of the solutions is kept between 50 and 60 ° C). The gum arabic solution, the vinyl ether-maleic anhydride copolymer solution and the remaining water are added to this dispersion. As long as the temperature is still above 50 ° C, the pH value is set to 9.0. Ditnn is contacted with sulfuric acid of pH to 4.40 and rapidly cooled to about 10 ⁰ C. It is cured with glutaraldehyde and warehousing vinyl ether-maleic anhydride copolymer was added and reacted with NaOH to a pH value of about 10 degrees.

result

Durable capsule pulp. Single drop about 2 μm. Agglomerates about 15 μm.

ίο

Example 2 Raw material: 20 g 10g 1040 g Gelatin waste of the composition as in example 1 12g Gum arabic JOOg water 10g Vinyl ether maleic anhydride 5g Copolymer 5% Internal phase: tetrachlorethylene 10g Acetic acid 10% q.s. Glutaraldehyde 25% Vinyl ether maleic anhydride Copolymer NaOH 20%

The gelatin waste is dissolved in about 500 ml of water, the internal phase is dispersed in this solution until the particles about 4 (50 Temp. ⁰ to 60 C) μπι large.

The gum arabic solution is added to this dispersion, the vinyl ether-maleic anhydride copolymer solution and the remaining water are added.

As long as the temperature is still above 50 ^° C., the pH is adjusted to 9.0.

The pH is then brought to 4.5 with sulfuric acid and the mixture is rapidly cooled ^{to about 10 ° C.}

It is hardened with glutaraldehyde and vinyl ether-maleic anhydride copolymer for storage added and brought to a pH of about 10 with NaOH.

result

Durable capsule pulp.
Agglomerates about 20 μm.

Single drops about 4 μιτι.

Example 3

Raw materials:

Gelatin waste of the composition

as in example 1

Polymethaphosphate 25% strength by weight

water
Internal phase: toluene

Caustic soda 10%

Hydrochloric acid 10%

Silicone-based antifoam agents

Glutaraldehyde
Tallow trimethyl ammonium chloride

(quaternary ammonium compounds)

White, powdery, highly porous,

very light silica gel,

Particle size 0.5 to 3 μm

100 g
830 g
1000g
440 g
qs
qs
0.1g
50 g

Ig

5g

procedure

The gelatin waste is dissolved in the water (temp, about 50 to 60 ^° C.). The internal phase is dispersed in this solution to the desired drop size (60 to 200 μm). The polymethaphosphate 7.u is added at 45 "C, then the mixture has about 38" C and the pH is adjusted to 6.3. It is cooled to 10 ^° C. in 90 minutes while stirring. During this time

the wall forms. The glutaraldehyde is then added, the pH is adjusted to 4.5 to 4.7 and the mixture is stirred at room temperature (18 to 28 ^° C.) for 12 hours. The capsules are then separated from the "mother liquor" by filtration. The impurities remain in the mother liquor. The capsules are washed three times with about 1 liter of water, mixed with tallow trimethylammonium chloride and silica gel and dried in a fluidized bed dryer.

result

Dry capsules, free-flowing powder, size 60 to 200 μm.

Example 4 Raw materials: 100 g 860 g 920 g Gelatin waste of the composition 710g as in example 1 q.s. Polymethaphosphate 25% by weight q.s. water 0.1g Internal phase: tetrachlorethylene 50 g Caustic soda 10% Hydrochloric acid 10% ig Antifoam agent (as in example 3) 5g Glutaraldehyde Tallow trimethyl ammonium chloride (as in example 3) Silica gel (as in example 3) procedure

water 150 g Internal phase: tetrachlorethylene 100 ml Polymetaphosphate 25% strength by weight 90 ml Caustic soda 10% q.s. Hydrochloric acid 10% q.s. Antifoam agent (as in example 3) 0.1g Glutaraldehyde 5g Tallow trimethyl ammonium chloride (as in example 3) ig Silica gel (as in example 3) 5g

10

result

Dry, free-flowing individual capsules, size 50 to 150 μm.

Example 5 raw materials:

Gelatin waste of the composition 10 g 88% by weight gelatin (BJoom number 280) 10% by weight water
2% by weight of dye and pigment

60

65

procedure

20th

25th

30th

The gelatin waste is dissolved in the water (temp, about 50 to 60 ^° C.). In this solution, the internal phase is dispersed to the desired drop size (50 to 150 μm). The polymetaphosphate is added at 45.degree. C., then the mixture is about 38.degree. C. and the pH is adjusted to 7.5. In 90 minutes, the mixture is cooled to 10 ° C. while stirring. During this time, the wall is formed. The glutaraldehyde is then added, the pH is adjusted to 4.5 to 4.7 and the mixture is stirred for 12 hours at room temperature (18 to 28 ° C.). The capsules are then separated from the "mother liquor" by filtration. The impurities remain in the mother liquor. The capsules are washed three times with about 1 liter of water, mixed with tallow trimethylammonium chloride and silica gel and dried in a fluidized bed

The gelatin waste is dissolved in water (Temp, about 50 to 6O ⁰ C. In this solution, the internal phase to desired drop size dispersed (50 to 200 μπι). At 45 ° C one adds the polymetaphosphate to, then the mixture has about 38 ^° C. and the pH value is adjusted to 6.3. In 90 minutes, the mixture is cooled to 10 ^° C. while stirring. During this time, the wall is formed. The glutaraldehyde is then added and the pH value is adjusted to 4 , 5 to 4.7 and stir at room temperature (18 to 28 ° C) for 12 hours. Then the capsules are separated from the "mother liquor" by filtration washed, mixed with tallow trimethylammonium chloride and silica gel and dried in a fluidized bed dryer

result

Dry capsules, free flowing powder. Size 50 to 200 μm.

Example 6

Raw materials:

Gelatin waste of the composition 10 g

88% by weight gelatin (Bloom number 280)

10 wt% water
2% by weight of dye and pigment
Water 500 g

Gum arabic 10 g

Internal phase: tetrachlorethylene 100 ml
Caustic soda 10%
Acetic acid 10%
Glutaraldehyde

Tallow trimethyl ammonium chloride
(as in example 3)
Silica gel (as in example 3)

qs
qs
5g

Ig
5g

procedure

The gelatin waste and the gum arabic are dissolved separately in water and poured together at 40 to 50 ° C. The internal phase is dispersed in this solution to the desired droplet size. The mixture is then about 40 ^° C. and the pH is adjusted to 3.95 to 4.00. In 90 minutes ^{, the mixture is cooled to 10 °} C. while stirring the wall forms. The pH is adjusted to 4.1 to 43, the glutaraldehyde is added and the mixture is stirred at room temperature for 12 hours. The capsules are then separated from the "mother liquor" by filtration. The impurities remain in the mother liquor. The capsules are washed three times with about 1 liter of water, mixed with tallow trimethylammonium chloride and silica gel and dried in a fluidized bed dryer

result

Dry capsules, free flowing powder, size 50 to 200 um.

Measurements of the weight loss of the capsules produced in this way showed a change after 3 months which is equal to that of microcapsules produced from pure or fresh gelatin. The dry capsules have the same retention capacity as those made from high-quality gelatine.

Claims (1)

Patent claims: 1. A method for encapsulating water-insoluble diluents of poorly water-soluble substances or substance mixtures in microcapsules, in which a macromolecular wall material is dissolved in water, the substance to be encapsulated or the substance mixture to be encapsulated dispersed or emulsified in the solution and then by precipitation, cooling, adding more of macromolecular components and / or a change in pH value, a phase separation is brought about, characterized in that as macromolecular wall material gelatin or gelatin mixtures that are used as waste during manufacture from push-fit or hard capsules and / or from soft capsules, and a gel strength greater than 80 Bloom can be used without prior cleaning. 20th