CA2050599A1 - Encapsulation of active substances in starch - Google Patents
Encapsulation of active substances in starchInfo
- Publication number
- CA2050599A1 CA2050599A1 CA002050599A CA2050599A CA2050599A1 CA 2050599 A1 CA2050599 A1 CA 2050599A1 CA 002050599 A CA002050599 A CA 002050599A CA 2050599 A CA2050599 A CA 2050599A CA 2050599 A1 CA2050599 A1 CA 2050599A1
- Authority
- CA
- Canada
- Prior art keywords
- starch
- coating
- active compound
- essentially
- encapsulation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/70—Fixation, conservation, or encapsulation of flavouring agents
- A23L27/72—Encapsulation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
Abstract
Abstract:
The encapsulating or coating carrier substance used for the encapsulation or coating of one or more active compounds in a or with a carrier substance is a mixture of essentially native starch and at least one agent at least partially swelling the starch and is mixed, for encapsulation or for coating, with the active compound and at least one emulsifier. During mixing, preferably at least one oily substance is additionally added to the swollen starch with the active compound, which substance is essentially unable to form a homogeneous mixture with the starch or whereby no phase mixing between the oil and the swollen starch takes place. The mixture of the swelling agent, the emulsifier, the oily substance and the native starch with the active compound is preferably carried out at elevated temperature in a mixing apparatus, such as a mixer, kneader or extruder.
The encapsulating or coating carrier substance used for the encapsulation or coating of one or more active compounds in a or with a carrier substance is a mixture of essentially native starch and at least one agent at least partially swelling the starch and is mixed, for encapsulation or for coating, with the active compound and at least one emulsifier. During mixing, preferably at least one oily substance is additionally added to the swollen starch with the active compound, which substance is essentially unable to form a homogeneous mixture with the starch or whereby no phase mixing between the oil and the swollen starch takes place. The mixture of the swelling agent, the emulsifier, the oily substance and the native starch with the active compound is preferably carried out at elevated temperature in a mixing apparatus, such as a mixer, kneader or extruder.
Description
PT r, ~/9'2 Encapsulation of Active Substances with Starch The present invention relates to a method for encapsulating or S coating one or more active compounds in a or with a carrier substance, to an encapsulated or coated actiYe compound which is coated by a carrier substance and to uses of the methods according to the invention.
The presence of active compounds, such as, for example, pharmaceuticals, adhesives, fragrances, detergent additives, dyes, concrete additives, pesticides etc., in a reprocessible, reusable, transportable, marketable etc. form has been a central problem for a long time. In particular, active compounds must be protected from 15 environmental influences, such as moisture7 I JV radiation, mechanical stress etc., and at the same time should be easy to meter and practical to handle.
A large number of processes, methods and techniques is known 20 to present active compounds in a handleable form, as is necessary in accordance with the abovementioned statement of the problem.
;
For example, the production of tablets, where essentially solid active compounds are compressed into table~ form by a consolidating 2s means, is known. This form of handling is unsuitable, in particular, for moisture- sensitive active compounds or for fine metering.
Paclcing in small bags, for example composed of plastic, has the disadvantage that the packaging, i.e. the bag, must first be opened 3 o when using the active compounds, which, in particular with small bags, is very impracticable. Moreover waste results if the bag is not additionally usable.
Of particular interest is the coating or encapsulation of active 3 5 compounds, for which purpose in the latter case capsules or microcapsules are prepared which are filled with the active ` :
, - 2 ~ 3 ~
compound. The methods customary for the production of these capsules or for their filling, however, are very complicated and expensive, so that in particular with relatively inexpensive active compounds they are hardly viable or not viable at all. The principle of S this encapsulation has until now been essentially restricted to pharmaceutical active compounds, as these active compounds are relatively expensive and the costs of the encapsulation process are not so crucial. This technique has previously been described in many different ways, for which purpose, for example, reference is made to 10 the following specifications.
In EP-A-0,092,908, EP-PS-0,090,600, EP-A-0,118,240 and EP-A-0,304,401 the production of capsules by injection moulding or deep drawing is described, hydrophilic polymers, such as gelatin or starch, 5 being proposed for the production of the capsules, which can be brought at least partially into thermoplastically processible form for the processing and production of the capsules by means of suitable processes. What is concerned here is exclusively the production of capsules of the larger type, which are only filled with active 20 compounds or sealed after their production.
In the Encyclopedia of Polymer Science and Engineering, Vol. 9, John Wiley & Sons, pp. 724 ff., various methods and applications and a large number of literature citations about production methods for the 25 production of microcapsules are described. In these methods, an active compound, such as, for example, an active agent, a core material, a filler, a nuclide etc., is encapsulated by a carrier material, a coating or a membrane etc. The size of these microcapsules is between 1 and 1000 ,um. The most important areas of application are in the 30 production of carbon-free copying papers and in the microencapsulation of pharmaceutical active compounds.
In particular, the use of the rnethods used until now for microencapsulation is described in detail in the Encyclopedia of 3~ Chemical Technology by Kirk-Othmer, 3rd Edition, Vol. 15, on pp. 487 ff. In this literature citation, reference may in particular be made to the literature index on pp. 492 and 493.
3 2 ~ .3 ~
As the production of microcapsules per se has been described adequately in the two literature citations mentioned and the various production methods are varied and extensive, a detailed description of the latter is dispensed with, the contents of these two literature S citations herewith being considered all-embracing as a part of the present introduction.
All the methods or techniques proposed above for producing capsules or microcapsules have the important disadvantage that they 10 are very expensive and thus are only worth considering at all in connection with expensive active compounds, such as, for example, pharmaceutical products. This statement is further corroborated in the literature citation of Kirk-Othmer on p. 491 in the last section in that it is mentioned here that so-called "large scale" industrial use of 15 the production of microcapsules is limited as a result of high costs and thus only has future prospects in the pharmaceutical area, medicine and some special markets.
It is therefore an object of the present invention to develop a 20 method according to which active compounds and active substances can be encapsulated or coated in a simple and inexpensive manner, the carrier substance used for the encapsulation or coating preferably including a material which can be additionally used in the reuse of the active substance or the active compound, such that waste products are 2~ not formed nor is the further use of the active substance negatively influenced by the carrier substance.
This object is achieved by a method, preferably according to at least one of the claims, such as in particular according to one of Claims 30 1 or 18.
A method for encapsulating or for coating one or more active compounds in a or with a carrier substance is proposed in which a mixture of essentially native starch and at least one agent at least 35 partially swelling the starch is used as the encapsulating or coating carrier substance and is mixed together with the active compound and at least one emulsi~ler for encapsula~ion or for coating.
I~ is proposed in this case that the swelling agent includes at least one substance such as is described in the characterising part of one of Claims 2 to 5 or 9.
The agent which initiates swelling or which swells the starch is preferably chosen in such a way that the active substance to be encapsulated is poorly or sparingly soluble in the swelling agent.
Correspondingly, in the case of active substances highly soluble 10 in water, it is further proposed that on mixing the essentially native starch with the agent swelling the starch moisture is at least partially removed from the starch.
It may be preferable here that the at least partially swollen 15 starch contains less than 12% by weight of water during the encapsulation or coating of the active compound, it being possible for this to lead in a further preferred çmbodiment of the method according to the invention to the rnost extensive freedom from water of the swollen starch.
In addition, it is also possible that the active compound itself is at least partially the agent swelling the starch or else is soluble in the swelling agent.
2s Suitable swelling agents or agents which initiate the dissolution of the starch which have in particular emerged are glycerol and aminoalcohols, as are claimed in the characterising part of Claim 5. In the case of the aminoalcohols, monomers and also oligomers of the aminoalcohols mentioned can come into consideration here.
30 Triethanolamine, for example, has proved particularly suitable.
As is proposed according to the invention, an emulsifier is additionally added to the mixture of native starch and the swelling agent. Owing to the boundary surface activity, this emulsifier 35 concentrates on the surface of the swollen starch and influences the wetting be~ween the active compound and the swollen starch. The complete wetting of the swollen starch is assisted by the emulsifier, as a result of which the absorption of the active substance by the starch .
` .
- 5 - ~ `3.~
or the coating of the active substance is favoured. Preferably, it is proposed that up to about 4% by weight, relative to the total mixture, of the emulsifier be used.
. . .
In order further to ensure that the swelling agent/starch phase does not form a coherent homogeneous material, it is further proposed that on mixing the swollen starch with the active substance at least one oily substance is additionally added, which is essentially unable to form a homogeneous mixture with the starch, or in which 10 the oil and the swollen starch form two separate phases and the swollen starch grains are coated with a film of oil or dispersed in the oil.
Preferably, it is proposed that on mixing the swollen starch with 1S the active compound up to 10% by weight, preferably 5 to 10% by weight, relative to the total mixture, of an oily substance is admixed, ` which does not allow hornogeneous mixing with the swollen starch. Itis essential here that the active compound, on the one hand, is not soluble in this oily phase, and moreover it must be more wettable by 20 the swelling agent/starch phase than by the oil phase, as a result of which it is ensured that the starch/swelling agent phase encloses the active compound.
Likewise, in order to prevent the formation of a coherent 25 homogeneous material, it is further proposed that the native starch is at least partially swollen and mixed with the swelling agent in such a way that a grain structure is essentially retained. This means, for example, that the temperature chosen is not so high that the grains are melted and form a homogeneous amorphous starch phase. On the 30 other hand, the mechanical stress on the grains (shearing, kneading, mixing) may only be so large that the active compound is incorporated into the grains, but the grains are not destroyed. The structural viscosity of the starch grains must not fall below a lower limit which, for example, is about 20 Pa/sec at a shear rate of 100 35 sec~l. The swollen starch grairis in this case can already exhibit ` increased amorphous structure, but the individual grains still do not coagulate, i.e. a homogeneous melt is still not formed. The so-called particulate phase of the swollen starch must be retained.
t . ` ` ' . ' ' ' :' , .
- 6 - ~ s3 Thus, for example, the temperature must not be above 170C on mixing the individual components when using 40% glycerol as the swelling agent.
s It is further proposed in the process according to the invention that up to 60% by weight, preferably 30 to 50% by weight, of the swelling agent is added. It is ensured by this that the formerly hard native grains of the starch are adequately swollen up and thus form o elastic grains into which the various active compounds can be easily kneaded. The choice of the amount of added swelling agent added here is strongly dependent on the swelling agent chosen, by which of course active substances can also be effectively encapsulated with less than 30% of added swelling agent, such as, for example, of water.
15 However, if more than 60% of a swelling agent is added, the grains become too soft, so that they burst even under slight mechanical stress and the granular, pulverulent material can agglutinate to give a compact mass.
Depending on the required properties of the final product, and also owing $o possible toxic properties of the swelling agent, it may possibly be advantageous to at least partially remove the swelling agent again after encapsulation or coating.
2~ In particular when using up to lO~o by weight addition of an oily substance, the added amount of the ernulsifier used is preferably 1 to 2% by weight, relative to the total mixture.
The method according to the invention for encapsulating or for 30 coating one or more active compounds in a or with a carrier substance in particular includes mixing a mixture of 2~ to 60% by weight of a swelling agent to start to swell the native starch, preferably 30 to ~0%
by weight, 0.1 to 4% by weight of an emulsifier, 0 to 10% by weight of an oily substance, and the remainder of native starch in a mixing 35 apparatus, such as a mixer, kneader or extruder, the mixing taking place together with the active compound, preferably at elevated temperature, in order to produce an essentially homogeneous powder which contains the encapsulated or coated ac~ive compound.
., - ;
- 7 - ~ 3 0-,~ z~
The mechanical agitation in the mixer, kneader or extruder is carried out at elevated temperature because the wetting and sorption process of the swollen starch by the active substance takes place only very slowly without these additional measures as a result of the high 5 viscosity of the starch/swelling agent phase. The swelling process can also be carried out at roonn temperature, the following problems emerging:
- Dependin~, on the content of swelling agent, it takes up to 24 hours for all the swelling agent to be absorbed.
o - Because of poor mixing, the homogeneity of the product is not ensured (variously sized grains~.
In this case, the mixture is first heated to a temperature which is below the melting temperature of the starch/swelling agent 15 mixture. The starch is then at least partially swollen by means of the swelling agent, whereupon under the action of the mechanical agitation the swollen starch coats the active compound or takes this up by sorption, the emulsifier and possibly the oil causing an essentially homogeneous powder to be formed instead of a coherent 20 material.
The following substances inter alia, for example, have proved suitable as emulsifiers:
- lecithin, 25 - a polyoxyethylene derivative of a sorbitan ester, such as, for example, Tween ~rom the company ICI, - an ethylene oxide derivative of a sugar or sugar ester, sugar alcohol and/or sugar alcohol ester.
A triglyceride can be used, for example, as the oily substance.
The metering of the carrier substance with the active compound(s) is carried out by the choice of the mean particle size of the native starch used and/or the degree of swelling of the starch or 35 the ratio of starch content to swelling agent. If, for example, the starting material used is a native starch grain from maize whose mean ;~ particle size is in the range of about 14 llm, a starch grain of this type can be essentially more poorly "filled" with an active substance than, :`
- 8 - ~ ~eJ c 7 ~
for example, a native starch grain of the potato, whose mean particle size is in the range of about 35 llm. As a generalisation, it can be said that the larger the mean particle size of the native starch which is used as a starting material, the more active compound can be coated S with the same protective action. However, it has to be considered here that larger grains probably have greater protective action, but the total mixture of the encapsulated active substances is less homogeneous.
o As the active substances once encapsulated cannot be ground, it is therefore also important to control the particle size of the finally encapsulated active compound via the particle size of the native starch which is used as a starting material.
By means of the process according to the invention described above, an encapsulated or coated active compound is prepared which is covered by a carrier substance, the carTier substance for the encapsulation or coating being essentially composed of at least partially swollen starch.
The encapsulated or coated active compound is distinguished in particular by the fact that a mixture of essentially native starch and at least one agent at least partially swelling the starch is used as an encapsulating or coating carrier substance for its preparation and, for 25 encapsulation or coating, is mixed together with the active compound and at least one emulsifier.
The methods according to the invention described above are in particular suitable for encapsulating or coating pharmace~ltical active 30 compounds and/or for the production of medicaments or medicinal indications .
The method according to the inveniion is moreover of particular interest for encapsulating water-soluble or water-miscible substances, 35 in particular water-soluble vitamins and citric acid.
The methods are additionally suitable for the encapsulation or coating of adhesives, flavourings, fragrances, detergents, pesticides, .
herbicides, dyes, synthetic resin additives, building material additives, concrete additives and/or reactants for the coating of carbon-free copying papers.
As representative of these areas of application, specific reference may be made to the use of the method according to the invention for ~he encapsulation of concrete additives, such as wetting agents, hardening regulators, synthetic resin additives etc., whose use is difficult as a result of their existence as highly viscous or viscous 0 liquids. They carmot be added, or cannot be added in metered form, to the dry cement, and on adding to the wet cement their reaction is immediately started.
In contrast, the dry, pulverulent starch/active compound l S mixture can easily be admixed with the dry cement, both metering and also subsequent storage of the cement duTing a relatively long period of time being unproblematic. The additives become in each case active on adding water.
At this point reference may be made to the literature citations with respect to the production and use of microcapsules which have been mentioned as prior art in the introduction and in which extensive applications of microcapsules are mentioned. In this connection, reference may additionally be made to Ullmann's 2s Encyclopedia of Industrial Chemistry, 5th Edition, Vol. A S, where on pp. 518 ff. reference is made in detail to possible additives for the preparation of concrete, for whose encapsulation the methods according to the invention mentioned above are also suitable.
3 0 The invention described above will now be illnstrated in greater detail with reference to the appended S exarnples of the encapsulation of vitamin C.
,~
- 10 - ~ ~ J ~ 3 Encapsulation of vitamill C:
Example l:
The presence of active compounds, such as, for example, pharmaceuticals, adhesives, fragrances, detergent additives, dyes, concrete additives, pesticides etc., in a reprocessible, reusable, transportable, marketable etc. form has been a central problem for a long time. In particular, active compounds must be protected from 15 environmental influences, such as moisture7 I JV radiation, mechanical stress etc., and at the same time should be easy to meter and practical to handle.
A large number of processes, methods and techniques is known 20 to present active compounds in a handleable form, as is necessary in accordance with the abovementioned statement of the problem.
;
For example, the production of tablets, where essentially solid active compounds are compressed into table~ form by a consolidating 2s means, is known. This form of handling is unsuitable, in particular, for moisture- sensitive active compounds or for fine metering.
Paclcing in small bags, for example composed of plastic, has the disadvantage that the packaging, i.e. the bag, must first be opened 3 o when using the active compounds, which, in particular with small bags, is very impracticable. Moreover waste results if the bag is not additionally usable.
Of particular interest is the coating or encapsulation of active 3 5 compounds, for which purpose in the latter case capsules or microcapsules are prepared which are filled with the active ` :
, - 2 ~ 3 ~
compound. The methods customary for the production of these capsules or for their filling, however, are very complicated and expensive, so that in particular with relatively inexpensive active compounds they are hardly viable or not viable at all. The principle of S this encapsulation has until now been essentially restricted to pharmaceutical active compounds, as these active compounds are relatively expensive and the costs of the encapsulation process are not so crucial. This technique has previously been described in many different ways, for which purpose, for example, reference is made to 10 the following specifications.
In EP-A-0,092,908, EP-PS-0,090,600, EP-A-0,118,240 and EP-A-0,304,401 the production of capsules by injection moulding or deep drawing is described, hydrophilic polymers, such as gelatin or starch, 5 being proposed for the production of the capsules, which can be brought at least partially into thermoplastically processible form for the processing and production of the capsules by means of suitable processes. What is concerned here is exclusively the production of capsules of the larger type, which are only filled with active 20 compounds or sealed after their production.
In the Encyclopedia of Polymer Science and Engineering, Vol. 9, John Wiley & Sons, pp. 724 ff., various methods and applications and a large number of literature citations about production methods for the 25 production of microcapsules are described. In these methods, an active compound, such as, for example, an active agent, a core material, a filler, a nuclide etc., is encapsulated by a carrier material, a coating or a membrane etc. The size of these microcapsules is between 1 and 1000 ,um. The most important areas of application are in the 30 production of carbon-free copying papers and in the microencapsulation of pharmaceutical active compounds.
In particular, the use of the rnethods used until now for microencapsulation is described in detail in the Encyclopedia of 3~ Chemical Technology by Kirk-Othmer, 3rd Edition, Vol. 15, on pp. 487 ff. In this literature citation, reference may in particular be made to the literature index on pp. 492 and 493.
3 2 ~ .3 ~
As the production of microcapsules per se has been described adequately in the two literature citations mentioned and the various production methods are varied and extensive, a detailed description of the latter is dispensed with, the contents of these two literature S citations herewith being considered all-embracing as a part of the present introduction.
All the methods or techniques proposed above for producing capsules or microcapsules have the important disadvantage that they 10 are very expensive and thus are only worth considering at all in connection with expensive active compounds, such as, for example, pharmaceutical products. This statement is further corroborated in the literature citation of Kirk-Othmer on p. 491 in the last section in that it is mentioned here that so-called "large scale" industrial use of 15 the production of microcapsules is limited as a result of high costs and thus only has future prospects in the pharmaceutical area, medicine and some special markets.
It is therefore an object of the present invention to develop a 20 method according to which active compounds and active substances can be encapsulated or coated in a simple and inexpensive manner, the carrier substance used for the encapsulation or coating preferably including a material which can be additionally used in the reuse of the active substance or the active compound, such that waste products are 2~ not formed nor is the further use of the active substance negatively influenced by the carrier substance.
This object is achieved by a method, preferably according to at least one of the claims, such as in particular according to one of Claims 30 1 or 18.
A method for encapsulating or for coating one or more active compounds in a or with a carrier substance is proposed in which a mixture of essentially native starch and at least one agent at least 35 partially swelling the starch is used as the encapsulating or coating carrier substance and is mixed together with the active compound and at least one emulsi~ler for encapsula~ion or for coating.
I~ is proposed in this case that the swelling agent includes at least one substance such as is described in the characterising part of one of Claims 2 to 5 or 9.
The agent which initiates swelling or which swells the starch is preferably chosen in such a way that the active substance to be encapsulated is poorly or sparingly soluble in the swelling agent.
Correspondingly, in the case of active substances highly soluble 10 in water, it is further proposed that on mixing the essentially native starch with the agent swelling the starch moisture is at least partially removed from the starch.
It may be preferable here that the at least partially swollen 15 starch contains less than 12% by weight of water during the encapsulation or coating of the active compound, it being possible for this to lead in a further preferred çmbodiment of the method according to the invention to the rnost extensive freedom from water of the swollen starch.
In addition, it is also possible that the active compound itself is at least partially the agent swelling the starch or else is soluble in the swelling agent.
2s Suitable swelling agents or agents which initiate the dissolution of the starch which have in particular emerged are glycerol and aminoalcohols, as are claimed in the characterising part of Claim 5. In the case of the aminoalcohols, monomers and also oligomers of the aminoalcohols mentioned can come into consideration here.
30 Triethanolamine, for example, has proved particularly suitable.
As is proposed according to the invention, an emulsifier is additionally added to the mixture of native starch and the swelling agent. Owing to the boundary surface activity, this emulsifier 35 concentrates on the surface of the swollen starch and influences the wetting be~ween the active compound and the swollen starch. The complete wetting of the swollen starch is assisted by the emulsifier, as a result of which the absorption of the active substance by the starch .
` .
- 5 - ~ `3.~
or the coating of the active substance is favoured. Preferably, it is proposed that up to about 4% by weight, relative to the total mixture, of the emulsifier be used.
. . .
In order further to ensure that the swelling agent/starch phase does not form a coherent homogeneous material, it is further proposed that on mixing the swollen starch with the active substance at least one oily substance is additionally added, which is essentially unable to form a homogeneous mixture with the starch, or in which 10 the oil and the swollen starch form two separate phases and the swollen starch grains are coated with a film of oil or dispersed in the oil.
Preferably, it is proposed that on mixing the swollen starch with 1S the active compound up to 10% by weight, preferably 5 to 10% by weight, relative to the total mixture, of an oily substance is admixed, ` which does not allow hornogeneous mixing with the swollen starch. Itis essential here that the active compound, on the one hand, is not soluble in this oily phase, and moreover it must be more wettable by 20 the swelling agent/starch phase than by the oil phase, as a result of which it is ensured that the starch/swelling agent phase encloses the active compound.
Likewise, in order to prevent the formation of a coherent 25 homogeneous material, it is further proposed that the native starch is at least partially swollen and mixed with the swelling agent in such a way that a grain structure is essentially retained. This means, for example, that the temperature chosen is not so high that the grains are melted and form a homogeneous amorphous starch phase. On the 30 other hand, the mechanical stress on the grains (shearing, kneading, mixing) may only be so large that the active compound is incorporated into the grains, but the grains are not destroyed. The structural viscosity of the starch grains must not fall below a lower limit which, for example, is about 20 Pa/sec at a shear rate of 100 35 sec~l. The swollen starch grairis in this case can already exhibit ` increased amorphous structure, but the individual grains still do not coagulate, i.e. a homogeneous melt is still not formed. The so-called particulate phase of the swollen starch must be retained.
t . ` ` ' . ' ' ' :' , .
- 6 - ~ s3 Thus, for example, the temperature must not be above 170C on mixing the individual components when using 40% glycerol as the swelling agent.
s It is further proposed in the process according to the invention that up to 60% by weight, preferably 30 to 50% by weight, of the swelling agent is added. It is ensured by this that the formerly hard native grains of the starch are adequately swollen up and thus form o elastic grains into which the various active compounds can be easily kneaded. The choice of the amount of added swelling agent added here is strongly dependent on the swelling agent chosen, by which of course active substances can also be effectively encapsulated with less than 30% of added swelling agent, such as, for example, of water.
15 However, if more than 60% of a swelling agent is added, the grains become too soft, so that they burst even under slight mechanical stress and the granular, pulverulent material can agglutinate to give a compact mass.
Depending on the required properties of the final product, and also owing $o possible toxic properties of the swelling agent, it may possibly be advantageous to at least partially remove the swelling agent again after encapsulation or coating.
2~ In particular when using up to lO~o by weight addition of an oily substance, the added amount of the ernulsifier used is preferably 1 to 2% by weight, relative to the total mixture.
The method according to the invention for encapsulating or for 30 coating one or more active compounds in a or with a carrier substance in particular includes mixing a mixture of 2~ to 60% by weight of a swelling agent to start to swell the native starch, preferably 30 to ~0%
by weight, 0.1 to 4% by weight of an emulsifier, 0 to 10% by weight of an oily substance, and the remainder of native starch in a mixing 35 apparatus, such as a mixer, kneader or extruder, the mixing taking place together with the active compound, preferably at elevated temperature, in order to produce an essentially homogeneous powder which contains the encapsulated or coated ac~ive compound.
., - ;
- 7 - ~ 3 0-,~ z~
The mechanical agitation in the mixer, kneader or extruder is carried out at elevated temperature because the wetting and sorption process of the swollen starch by the active substance takes place only very slowly without these additional measures as a result of the high 5 viscosity of the starch/swelling agent phase. The swelling process can also be carried out at roonn temperature, the following problems emerging:
- Dependin~, on the content of swelling agent, it takes up to 24 hours for all the swelling agent to be absorbed.
o - Because of poor mixing, the homogeneity of the product is not ensured (variously sized grains~.
In this case, the mixture is first heated to a temperature which is below the melting temperature of the starch/swelling agent 15 mixture. The starch is then at least partially swollen by means of the swelling agent, whereupon under the action of the mechanical agitation the swollen starch coats the active compound or takes this up by sorption, the emulsifier and possibly the oil causing an essentially homogeneous powder to be formed instead of a coherent 20 material.
The following substances inter alia, for example, have proved suitable as emulsifiers:
- lecithin, 25 - a polyoxyethylene derivative of a sorbitan ester, such as, for example, Tween ~rom the company ICI, - an ethylene oxide derivative of a sugar or sugar ester, sugar alcohol and/or sugar alcohol ester.
A triglyceride can be used, for example, as the oily substance.
The metering of the carrier substance with the active compound(s) is carried out by the choice of the mean particle size of the native starch used and/or the degree of swelling of the starch or 35 the ratio of starch content to swelling agent. If, for example, the starting material used is a native starch grain from maize whose mean ;~ particle size is in the range of about 14 llm, a starch grain of this type can be essentially more poorly "filled" with an active substance than, :`
- 8 - ~ ~eJ c 7 ~
for example, a native starch grain of the potato, whose mean particle size is in the range of about 35 llm. As a generalisation, it can be said that the larger the mean particle size of the native starch which is used as a starting material, the more active compound can be coated S with the same protective action. However, it has to be considered here that larger grains probably have greater protective action, but the total mixture of the encapsulated active substances is less homogeneous.
o As the active substances once encapsulated cannot be ground, it is therefore also important to control the particle size of the finally encapsulated active compound via the particle size of the native starch which is used as a starting material.
By means of the process according to the invention described above, an encapsulated or coated active compound is prepared which is covered by a carrier substance, the carTier substance for the encapsulation or coating being essentially composed of at least partially swollen starch.
The encapsulated or coated active compound is distinguished in particular by the fact that a mixture of essentially native starch and at least one agent at least partially swelling the starch is used as an encapsulating or coating carrier substance for its preparation and, for 25 encapsulation or coating, is mixed together with the active compound and at least one emulsifier.
The methods according to the invention described above are in particular suitable for encapsulating or coating pharmace~ltical active 30 compounds and/or for the production of medicaments or medicinal indications .
The method according to the inveniion is moreover of particular interest for encapsulating water-soluble or water-miscible substances, 35 in particular water-soluble vitamins and citric acid.
The methods are additionally suitable for the encapsulation or coating of adhesives, flavourings, fragrances, detergents, pesticides, .
herbicides, dyes, synthetic resin additives, building material additives, concrete additives and/or reactants for the coating of carbon-free copying papers.
As representative of these areas of application, specific reference may be made to the use of the method according to the invention for ~he encapsulation of concrete additives, such as wetting agents, hardening regulators, synthetic resin additives etc., whose use is difficult as a result of their existence as highly viscous or viscous 0 liquids. They carmot be added, or cannot be added in metered form, to the dry cement, and on adding to the wet cement their reaction is immediately started.
In contrast, the dry, pulverulent starch/active compound l S mixture can easily be admixed with the dry cement, both metering and also subsequent storage of the cement duTing a relatively long period of time being unproblematic. The additives become in each case active on adding water.
At this point reference may be made to the literature citations with respect to the production and use of microcapsules which have been mentioned as prior art in the introduction and in which extensive applications of microcapsules are mentioned. In this connection, reference may additionally be made to Ullmann's 2s Encyclopedia of Industrial Chemistry, 5th Edition, Vol. A S, where on pp. 518 ff. reference is made in detail to possible additives for the preparation of concrete, for whose encapsulation the methods according to the invention mentioned above are also suitable.
3 0 The invention described above will now be illnstrated in greater detail with reference to the appended S exarnples of the encapsulation of vitamin C.
,~
- 10 - ~ ~ J ~ 3 Encapsulation of vitamill C:
Example l:
4 kg of native potato starch are extruded with 2.5 kg of a mixture composed of the following components:
- 77.6% of glycerol, - 15.5% of triglycerol (Miglyol 812), - 6.9% of emulsifier (Tween 80 from ICI)~
10 using a kneading extruder (Buss, Pratteln, Switzerland) during the course of one hour. The water content of the starch in this case was about 12%. The following process conditions were chosen in the kneading extruder: -- Spindle temperature 110C, lS - Heating zone 1: 113C, - Heating zone 2: 116C, - Heating zone 3: 122C, - Speed: 140 revolutions/min., - Power consumption: 0.6 kw.
A flaky white powder was formed as the product, individual grains, which are swollen with glycerol, being clearly detectable under the microscope.
A mean particle size of about 100 ,um is achieved by homogenising in the kneader. Due to the oil used, aglommeration of the starch polymer spheres is prevented. Other starches can of course also be used as the polymer, which in the present example is potato starch.
20% of vitamin C was added to the powder obtained in the above manner and kneaded in with the same parameters during a 3 second passage through the kneader. The result can likewise be clearly seen under the microscope. The largest part of the vitamin C
35 crystals is embedded in the élastic bodies. If, for example, the grains are pressed flat, the embedded vitamin C crystals can be detected therein under the polarising microscope.
3 ~i ~J ~
Other active compounds can also be incorporated into these elastic grains. The only condition is that a certain affinity of the active compound for the polar glycerol starch must be present, i.e. the active compound must be wettable by the glycerol starch mass.
Example 2:
The same composition as under 1), but allowed to stand overnight (not extruded). 12 hours later, a swollen powder is likewise 10 obtained, into which vitamin C is kneaded. This experiment shows that the increase in the temperature only accelerates swelling, but is not a condition that swelling takes place. The vitamin C is incorporated as in the fiTst example using the Buss kneader.
15 Exam~le 3:
40 g of starch (water content: 12%) and 25 g of the mixture from Example 1 ) are kneaded for about 2 minutes in a Brabender laboratory kneader (70 g batches) and 16 g (20%) of vitamin C are 20 then added and the mixture is kneaded for a further 2 minutes. The vitamin C is kneaded into the starch grains to more than 90%. Further experiments with 30% or 40% of vitamin C also give po~itive results, and the percentage of non- encapsulated vitamin C only rises slowly.
2s Example 4:
16 kg of native potato starch (water content: 5%) are swollen with 10.8 kg of the same mixture as above in a synchronised double spindle extruder at 150C. 20% of vitamin C is added to this powder in ` 30 a tumbler mixer and the mixture is then extruded again at 140C in order to knead in the vitamin C.
Example 5:
- 35 The same conditions as under l~xample 4), only ca~ried out in one step. The screw configuration of the extruder is modified in such a way that during entry starch and emulsion are mixed and swollen to give powder and vitamin C is added directly to the centre of the - 12- ~ 3~
extruder. At the end, a fine powder of encapsulated vitamin C is obtained which does not additionally have to be subsequently treated (grinding, sieving, etc.).
The abovementioned examples of the encapsulation of vitamin C
by glycerol/starch are only used to explain the method according to the invention, which of course can be modified in all sorts of ways, as disclosed in detail in the description.
Thus, the method is also suitable for encapsulating other vitamins, pharmaceutical or cosmetic active compounds, o-f particular interest being encapsulation or coating of or with water-soluble or with water-miscible substances, such as7 in particular, water- soluble vitamins and, inter alia, with citric acid. As representatives, some 15 active substances have been processed according to the method according to the invention in the following Example 6, it being possible, of course, to extend the list of possible active substances in the most varied manner.
20 Example 6:
As mentioned above, various active compounds were incorporated into swollen or thermoplastically processible starch, comprising about 27% to 30% of glycerol. The practical procedure was 2s carried out at 140C in a so-called Brabender kneader, 70 g batches being employed analogously to the examples described above.
Riboflavine (vitamin B2), pyridoxine (vitamin B6), nicotinic acid, methionine, citric acid, thia~nine NO3 (nitrate) and lysine HCl were 3 0 used as active compounds.
Basically, the active compounds described can be incorporated into the swollen starch analogously to vitamin C, as described in Example 5, in order to form a fine powder of encapsulated active 3s compound.
As the active compounds mentioned behave like fillers in industrial polymers, extrusion of these active compounds into a .
swollen starch mel~ is also possible, the colTesponding melt, the fluidity of the melt and the subsequent cuttability being investigated or listed in Table I which follows.
Table I
Substance % bv ~. hlelt Dec~m~o- Tacki- Extrusion of active sition ness çs~m p .
- Riboflavine(B2) 20% ~+,yellow none d,h,b Pyridoxine(B6) 30% ~ possible gummy +
Nlcotinic acid 20% ++,viscous none d,~
Me~hionine 20% ++,brown possible d,~
Citric acid 2û% ~ n o n e d,+~
Thiamine NO3 20% ++,yellow possible d,~ +
Lysine HCI 20% rubbcr none t,~
~: ~ good very good ' 20 d dry . h hard b brittle t tacky . .
The results presented in Table I have only rest~icted validity in this respect, as when using additional additives in the melt the statements can appear completely different.
~s already mèntioned above in the description, the method according to the invention is not only suitable for the coating of ` medicinal, cosmetic or pharmaceutical active compounds, but also for the encapsulation and coating of dye additives, foodstuff additives, concrete additives, detergent additives etc.
3 s As representatives of this almost unrestricted glOUp of : possible additives, the invention will be explained in greater detail in the following, for example, with reference to a foodstuff additive and concrete additives.
:
. :
- ' ~ , ' ~ , ..
.
.
- 1 4 ~ ~ ~3 Example 7: Lemon flavour Up to 40% by weight of lemon flavour are kneaded in cold 5 form with dry starch. The lemon flavour emulsion contains very volatile components, which would evaporate on increasing the temperature. The emulsion is absorbed into the starch within 2 min., and a yellow powder is formed which smells less intensively of lemon than the emulsion itself. If the powder is heated, it O immediately begins to adhere and forms pearl grey lumps.
The advantage of the powder prepared in this way compared to the emulsion itself is that the powder can be very simply reprocessed and in particular can be very easily metered. The 15 emulsion used hitherto, on the other hand, is not stable and it must be stirred again and again. Moreover, the emulsion dries out rapidly - and loses the flavour if it is allowed to stand in the open. In contrast, the powder hardly loses the lemon flavour.
20 Example 8: Concrete additives The concrete additives are usually highly viscous or viscous substances which can be metered only poorly and in particular cannot be admixed homogeneously to the dry cement. If the concrete 25 additives are only added to the already made-up aqueous cement, their activity is immediately initiated and the cement must be processed immediately.
The concrete additives investigated in connection with the 30 method according to the invention are - Rheobuild 1000, a naphthalene sulphonate (Na salt), SO4-Na, - Rheobuild 2000~ a melamine derivative of the following - formula:
N~2 I
c~
N N
11 l C C
/\ ~\
where 1 or 2 -NH2 can be replaced by -Cl or -OH or alkyl, - Rheobuild SV 87056, a polycarboxyl compound based on polyacrylic acid Na salt or a copolymer of acrylic acid esters and free acrylic acids and their Na salt, 15 - Beclcopox EH 623, an amine epoxide hardener, and - Rutapox EH 4000, an epoxy resin.
All the concrete additive active compounds mentioned are commercial products and can be obtained from Masterbuilders Technologies Europe AG, Ifangstrasse 11 in 8952 Schlieren/
Switzerland .
These liquid concrete additives can be easily kneaded Y.rith dry starch withou~ additional swelling agent, such as glycerol or aminoethanol. Glycerol in addi~ion could not be used because of its incompatibility with concrete. Obviously, in the present cases the active compound itself also still forms the swelling agent for the swelling of the starch. After at most 2 min. with heating if necessary, the liquids are absorbed in the starch, this occasionally taking place ~` 3 0 with evolution of heat.
If aminopropanol or ethanol is additionally employed as the swelling agent, the swelling should be started in the cold in order `~ that the starch does not form a paste, or else an emulsifying oil must :` 35 be added as in the examples described above with respect, for example, to vitamin C.
.
, , ~ , , ,~
. . , , ~ , - .
, ., , -, , - 1 6 - 2 ~ c~ ~Ç; ~
The active compounds according to Examples 7 and 8 are represented in tabular form in the followingTable II, in which their behaviour on swelling or absorption into the starch has likewise been more closely investigated.
Table II
Tyge Swell_ng Soluble Mixin~ Process agent for in aminQ~ ratio Description starch ethanol Lemon yes, only 30 40% only flavour cold (20C) cold kneaded Rheobuild no yes max.30% hot 1000 kneaded Rheobuild yes, but cold max.30% hot 2000 kneaded Rheobuild SV 87056 yes, heat yes max.30% hot (140C) kneaded Beckopox yes, good yes 20% hot EH 6~3 kneaded Rutapox yes yes 20% hot EH 4000 kneaded 2s The active compounds described in Examples 1 to 8 are representative of a nearly unlimited list of possible active compounds and substances which can be encapsulated or coated by the method according to the invention. The encapsulation and coating method itself can also be changed or modi~led in any desired ways.
It is essential for ~he method according to the invention to use ~` native starch, a swelling agent at least partially swelling the native starch and, under certain circumstances, an emulsifier, where the active substance must be wettable by the swelling agent/starch ` 35 phase. It is thoroughly possible here that the active compound itself`~ serves as the swelling agent. An oily substance is preferably additionally used :
~''`
,;` - '
- 77.6% of glycerol, - 15.5% of triglycerol (Miglyol 812), - 6.9% of emulsifier (Tween 80 from ICI)~
10 using a kneading extruder (Buss, Pratteln, Switzerland) during the course of one hour. The water content of the starch in this case was about 12%. The following process conditions were chosen in the kneading extruder: -- Spindle temperature 110C, lS - Heating zone 1: 113C, - Heating zone 2: 116C, - Heating zone 3: 122C, - Speed: 140 revolutions/min., - Power consumption: 0.6 kw.
A flaky white powder was formed as the product, individual grains, which are swollen with glycerol, being clearly detectable under the microscope.
A mean particle size of about 100 ,um is achieved by homogenising in the kneader. Due to the oil used, aglommeration of the starch polymer spheres is prevented. Other starches can of course also be used as the polymer, which in the present example is potato starch.
20% of vitamin C was added to the powder obtained in the above manner and kneaded in with the same parameters during a 3 second passage through the kneader. The result can likewise be clearly seen under the microscope. The largest part of the vitamin C
35 crystals is embedded in the élastic bodies. If, for example, the grains are pressed flat, the embedded vitamin C crystals can be detected therein under the polarising microscope.
3 ~i ~J ~
Other active compounds can also be incorporated into these elastic grains. The only condition is that a certain affinity of the active compound for the polar glycerol starch must be present, i.e. the active compound must be wettable by the glycerol starch mass.
Example 2:
The same composition as under 1), but allowed to stand overnight (not extruded). 12 hours later, a swollen powder is likewise 10 obtained, into which vitamin C is kneaded. This experiment shows that the increase in the temperature only accelerates swelling, but is not a condition that swelling takes place. The vitamin C is incorporated as in the fiTst example using the Buss kneader.
15 Exam~le 3:
40 g of starch (water content: 12%) and 25 g of the mixture from Example 1 ) are kneaded for about 2 minutes in a Brabender laboratory kneader (70 g batches) and 16 g (20%) of vitamin C are 20 then added and the mixture is kneaded for a further 2 minutes. The vitamin C is kneaded into the starch grains to more than 90%. Further experiments with 30% or 40% of vitamin C also give po~itive results, and the percentage of non- encapsulated vitamin C only rises slowly.
2s Example 4:
16 kg of native potato starch (water content: 5%) are swollen with 10.8 kg of the same mixture as above in a synchronised double spindle extruder at 150C. 20% of vitamin C is added to this powder in ` 30 a tumbler mixer and the mixture is then extruded again at 140C in order to knead in the vitamin C.
Example 5:
- 35 The same conditions as under l~xample 4), only ca~ried out in one step. The screw configuration of the extruder is modified in such a way that during entry starch and emulsion are mixed and swollen to give powder and vitamin C is added directly to the centre of the - 12- ~ 3~
extruder. At the end, a fine powder of encapsulated vitamin C is obtained which does not additionally have to be subsequently treated (grinding, sieving, etc.).
The abovementioned examples of the encapsulation of vitamin C
by glycerol/starch are only used to explain the method according to the invention, which of course can be modified in all sorts of ways, as disclosed in detail in the description.
Thus, the method is also suitable for encapsulating other vitamins, pharmaceutical or cosmetic active compounds, o-f particular interest being encapsulation or coating of or with water-soluble or with water-miscible substances, such as7 in particular, water- soluble vitamins and, inter alia, with citric acid. As representatives, some 15 active substances have been processed according to the method according to the invention in the following Example 6, it being possible, of course, to extend the list of possible active substances in the most varied manner.
20 Example 6:
As mentioned above, various active compounds were incorporated into swollen or thermoplastically processible starch, comprising about 27% to 30% of glycerol. The practical procedure was 2s carried out at 140C in a so-called Brabender kneader, 70 g batches being employed analogously to the examples described above.
Riboflavine (vitamin B2), pyridoxine (vitamin B6), nicotinic acid, methionine, citric acid, thia~nine NO3 (nitrate) and lysine HCl were 3 0 used as active compounds.
Basically, the active compounds described can be incorporated into the swollen starch analogously to vitamin C, as described in Example 5, in order to form a fine powder of encapsulated active 3s compound.
As the active compounds mentioned behave like fillers in industrial polymers, extrusion of these active compounds into a .
swollen starch mel~ is also possible, the colTesponding melt, the fluidity of the melt and the subsequent cuttability being investigated or listed in Table I which follows.
Table I
Substance % bv ~. hlelt Dec~m~o- Tacki- Extrusion of active sition ness çs~m p .
- Riboflavine(B2) 20% ~+,yellow none d,h,b Pyridoxine(B6) 30% ~ possible gummy +
Nlcotinic acid 20% ++,viscous none d,~
Me~hionine 20% ++,brown possible d,~
Citric acid 2û% ~ n o n e d,+~
Thiamine NO3 20% ++,yellow possible d,~ +
Lysine HCI 20% rubbcr none t,~
~: ~ good very good ' 20 d dry . h hard b brittle t tacky . .
The results presented in Table I have only rest~icted validity in this respect, as when using additional additives in the melt the statements can appear completely different.
~s already mèntioned above in the description, the method according to the invention is not only suitable for the coating of ` medicinal, cosmetic or pharmaceutical active compounds, but also for the encapsulation and coating of dye additives, foodstuff additives, concrete additives, detergent additives etc.
3 s As representatives of this almost unrestricted glOUp of : possible additives, the invention will be explained in greater detail in the following, for example, with reference to a foodstuff additive and concrete additives.
:
. :
- ' ~ , ' ~ , ..
.
.
- 1 4 ~ ~ ~3 Example 7: Lemon flavour Up to 40% by weight of lemon flavour are kneaded in cold 5 form with dry starch. The lemon flavour emulsion contains very volatile components, which would evaporate on increasing the temperature. The emulsion is absorbed into the starch within 2 min., and a yellow powder is formed which smells less intensively of lemon than the emulsion itself. If the powder is heated, it O immediately begins to adhere and forms pearl grey lumps.
The advantage of the powder prepared in this way compared to the emulsion itself is that the powder can be very simply reprocessed and in particular can be very easily metered. The 15 emulsion used hitherto, on the other hand, is not stable and it must be stirred again and again. Moreover, the emulsion dries out rapidly - and loses the flavour if it is allowed to stand in the open. In contrast, the powder hardly loses the lemon flavour.
20 Example 8: Concrete additives The concrete additives are usually highly viscous or viscous substances which can be metered only poorly and in particular cannot be admixed homogeneously to the dry cement. If the concrete 25 additives are only added to the already made-up aqueous cement, their activity is immediately initiated and the cement must be processed immediately.
The concrete additives investigated in connection with the 30 method according to the invention are - Rheobuild 1000, a naphthalene sulphonate (Na salt), SO4-Na, - Rheobuild 2000~ a melamine derivative of the following - formula:
N~2 I
c~
N N
11 l C C
/\ ~\
where 1 or 2 -NH2 can be replaced by -Cl or -OH or alkyl, - Rheobuild SV 87056, a polycarboxyl compound based on polyacrylic acid Na salt or a copolymer of acrylic acid esters and free acrylic acids and their Na salt, 15 - Beclcopox EH 623, an amine epoxide hardener, and - Rutapox EH 4000, an epoxy resin.
All the concrete additive active compounds mentioned are commercial products and can be obtained from Masterbuilders Technologies Europe AG, Ifangstrasse 11 in 8952 Schlieren/
Switzerland .
These liquid concrete additives can be easily kneaded Y.rith dry starch withou~ additional swelling agent, such as glycerol or aminoethanol. Glycerol in addi~ion could not be used because of its incompatibility with concrete. Obviously, in the present cases the active compound itself also still forms the swelling agent for the swelling of the starch. After at most 2 min. with heating if necessary, the liquids are absorbed in the starch, this occasionally taking place ~` 3 0 with evolution of heat.
If aminopropanol or ethanol is additionally employed as the swelling agent, the swelling should be started in the cold in order `~ that the starch does not form a paste, or else an emulsifying oil must :` 35 be added as in the examples described above with respect, for example, to vitamin C.
.
, , ~ , , ,~
. . , , ~ , - .
, ., , -, , - 1 6 - 2 ~ c~ ~Ç; ~
The active compounds according to Examples 7 and 8 are represented in tabular form in the followingTable II, in which their behaviour on swelling or absorption into the starch has likewise been more closely investigated.
Table II
Tyge Swell_ng Soluble Mixin~ Process agent for in aminQ~ ratio Description starch ethanol Lemon yes, only 30 40% only flavour cold (20C) cold kneaded Rheobuild no yes max.30% hot 1000 kneaded Rheobuild yes, but cold max.30% hot 2000 kneaded Rheobuild SV 87056 yes, heat yes max.30% hot (140C) kneaded Beckopox yes, good yes 20% hot EH 6~3 kneaded Rutapox yes yes 20% hot EH 4000 kneaded 2s The active compounds described in Examples 1 to 8 are representative of a nearly unlimited list of possible active compounds and substances which can be encapsulated or coated by the method according to the invention. The encapsulation and coating method itself can also be changed or modi~led in any desired ways.
It is essential for ~he method according to the invention to use ~` native starch, a swelling agent at least partially swelling the native starch and, under certain circumstances, an emulsifier, where the active substance must be wettable by the swelling agent/starch ` 35 phase. It is thoroughly possible here that the active compound itself`~ serves as the swelling agent. An oily substance is preferably additionally used :
~''`
,;` - '
Claims (30)
1. Method for encapsulating or for coating one or more active compounds in a or with a carrier substance, characterised in that the encapsulating or coating carrier substance used is a mixture of essentially native starch and at least one agent at least partially swelling the starch and which, for encapsulation or for coating, is mixed together with the active compound and at least one emulsifier.
2. Process, preferably according to at least one of the claims, such as according to Claim 1, characterised in that the swelling agent includes at least one substance whose solubility parameter is greater than 15 [cal 1/2cm -3/2] and which on mixing with the starch reduces its melting point in such a way that the melting temperature of the starch together with the substance is below the decomposition temperature of the starch.
3. Method, preferably according to at least one of the claims, such as according to one of Claims 1 or 2, characterised in that the swelling agent in the mixture together with the starch has a vapour pressure of less than 1 bar at temperatures in the range closely below the melting point of the mixture.
4. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 3, characterised in that the swelling agent is essentially formed from glycerol.
5. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 3, characterised in that the swelling agent is essentially formed from at least one aminoalcohol of the following formula:
[NHXR3-X]Y
where: X=0,1 or 2 at least one R = R1OH, R2OH and/or R3OH, where R1, R2 or R3 is aliphatic or cycloaliphatic, but not aromatic, and where Y = 1, 2, 3 ... 100 with a molar mass <2000.
[NHXR3-X]Y
where: X=0,1 or 2 at least one R = R1OH, R2OH and/or R3OH, where R1, R2 or R3 is aliphatic or cycloaliphatic, but not aromatic, and where Y = 1, 2, 3 ... 100 with a molar mass <2000.
6. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 5, characterised in that on mixing the essentially native starch with the agent swelling the starch moisture is at least partially removed from the starch.
7. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 6, characterised in that the at least partially swollen starch contains less than 12% by weight of water during the encapsulation or coating of the active compound.
8. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 7, characterised in that the at least partially swollen starch is essentially anhydrous.
9. Method, preferably according to at least one of the claims, such as according to one of Claims 1, 2, 6 or 7, characterised in that the swelling agent is essentially water.
10. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 9, characterised in that the active compound(s) at least partially forms or form the agent swelling the starch.
11. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 10, characterised in that up to about 4% by weight, relative to the total mixture, of the emulsifier is used.
12. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 11, characterised in that on mixing the swollen starch with the active compound additionally at least one oily substance is added, which is essentially unable to form a homogeneous mixture with the starch, or in which the oil and the swollen starch form two separate phases and the swollen starch particles are covered individually with at least one oil film or are dispersed in the oil phase.
13. Process, preferably according to at least one of the claims, such as according to one of Claims 1 to 12, characterised in that on mixing the swollen starch with the active compound up to 10% by weight, preferably 5 to 10% by weight, relative to the total mixture, of an oily substance is admixed, which does not allow itself to be homogeneously mixed with the swollen starch.
14. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 13, characterised in that the native starch is at least partially swollen and mixed with the swelling agent in such a way that a grain structure is essentially retained.
15. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 14, characterised in that up to 60%
by weight, preferably 30 to 50% by weight, of the swelling agent is added.
by weight, preferably 30 to 50% by weight, of the swelling agent is added.
16. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 15, characterised in that the swelling agent is removed at least partially again after encapsulation or coating.
17. Method, preferably according to at least one of the claims, such as according to one of Claims 11 to 16, characterised in that 1 to 2%
by weight, relative to the total mixture, of the emulsifier is used.
by weight, relative to the total mixture, of the emulsifier is used.
18. Method for encapsulating or for coating one or more active compounds in a or with a carrier substance, preferably according to at least one of the claims, characterised in that a mixture of:
- 20 to 60% by weight of a swelling agent for initiating the swelling of the native starch, preferably 30 to 50% by weight, - 0.1 to 4% by weight of an emulsifier, - 0 to 10% by weight of an oily substance and - the remainder of native starch is mixed in a mixing apparatus, such as a mixer, kneader or extruder, together with the active compound, preferably at elevated temperature, in order to produce an essentially homogeneous powder which contains the encapsulated or coated active compound.
- 20 to 60% by weight of a swelling agent for initiating the swelling of the native starch, preferably 30 to 50% by weight, - 0.1 to 4% by weight of an emulsifier, - 0 to 10% by weight of an oily substance and - the remainder of native starch is mixed in a mixing apparatus, such as a mixer, kneader or extruder, together with the active compound, preferably at elevated temperature, in order to produce an essentially homogeneous powder which contains the encapsulated or coated active compound.
19. Method, preferably according to at least one of the claims, such as according to Claim 18, characterised in that the mixture is first heated to a temperature which is below the melting temperature of the starch/ swelling agent mixture, then the starch is swollen at least partially by the swelling agent, whereupon under the action of the mechanical agitation the swollen starch coats the active compound or takes this up by sorption, the emulsifier and possibly the oil causing an essentially homogeneous powder to be formed instead of a coherent material.
20. Method, preferably according to at least one of the claims, such as according to one of Claims 11 to 19, characterised in that the emulsifier chosen is at least one of the following substances:
- lecithin, - a polyoxyethylene derivative of a sorbitan ester (Tween = ?
from ICI), - an ethylene oxide derivative of a sugar or sugar ester, sugar alcohol and/or sugar alcohol ester.
- lecithin, - a polyoxyethylene derivative of a sorbitan ester (Tween = ?
from ICI), - an ethylene oxide derivative of a sugar or sugar ester, sugar alcohol and/or sugar alcohol ester.
21. Method, preferably according to at least one of the claims, such as according to one of Claims 12 to 20, characterised in that essentially at least one triglyceride is used as the oily substance.
22. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 21, characterised in that the metering of the carrier substance with the active compound(s) is adjusted by the choice of the mean particle size of the native starch used and/or the degree of swelling of the starch or the ratio of starch contents to swelling agent in the mixture.
23. Method, preferably according to at least one of the claims, such as according to one of Claims 1 to 22, characterised in that the mean particle size of the encapsulated active compounds is adjusted by the choice of the mean particle size of the native starch used.
24. Encapsulated or coated active compound, which is covered by means of a carrier substance, characterised in that the carrier substance for the encapsulation or coating is essentially composed of at least partially swollen starch.
25. Encapsulated or coated active compound, preferably according to at least one of the claims, such as according to Claim 24, characterised in that the encapsulating or coating carrier substance used for its preparation is a mixture of essentially native starch and at least one agent at least partially swelling the starch and which, for encapsulation or for coating, is mixed together with the active compound and at least one emulsifier.
26. Encapsulated or coated active compound, preferably- according to at least one of the claims, such as according to one of Claims 24 or 25, characterised in that the active compound is a water-soluble or water- miscible substance, such as, in particular, a water- soluble vitamin or citric acid.
27. Use of the method according to one of Claims 1 to 23 for encapsulation or coating of pharmaceutical or cosmetic active compounds and/or for the production of medicaments or medicinal indications.
28. Use of the method according to one of Claims 1 to 23 for the encapsulation or coating of water-soluble or water-miscible substances, such as, in particular, water- soluble vitamins and/or citric acid.
29. Use of the method according to one of Claims 1 to 23 for the encapsulation or coating of adhesives, flavourings, fragrances, detergents, pesticides, herbicides, dyes, synthetic resin additives, building material additives, concrete additives and/or reactants for the coating of carbon-free copying papers.
30. Use of the method according to one of Claims 1 to 23 for the encapsulation or coating of viscous and highly viscous liquids and/or emulsions, such as flavourings, dye additives, synthetic resin additives, building material additives, concrete additives etc., in particular for improving their processibility or meterability.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4002257A DE4002257A1 (en) | 1990-01-26 | 1990-01-26 | ENCLOSURE OF ACTIVE SUBSTANCES BY MEANS OF STRENGTH |
| DEP4002257.9 | 1990-01-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2050599A1 true CA2050599A1 (en) | 1991-07-27 |
Family
ID=6398819
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002050599A Abandoned CA2050599A1 (en) | 1990-01-26 | 1991-01-24 | Encapsulation of active substances in starch |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0468003B1 (en) |
| JP (1) | JPH04505418A (en) |
| KR (1) | KR920700622A (en) |
| CN (1) | CN1055294A (en) |
| AT (1) | ATE112164T1 (en) |
| AU (1) | AU633685B2 (en) |
| CA (1) | CA2050599A1 (en) |
| DE (2) | DE4002257A1 (en) |
| DK (1) | DK0468003T3 (en) |
| ES (1) | ES2064078T3 (en) |
| WO (1) | WO1991011178A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2586523A1 (en) * | 2010-06-23 | 2013-05-01 | Kanagawa University | Process for producing emulsifier-producing material, process for producing emulsifier, emulsifier for orally administered composition, and orally administered composition |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5061697A (en) * | 1989-08-03 | 1991-10-29 | The United States Of America As Represented By The Secretary Of Agriculture | Adherent, autoencapsulating spray formulations of biocontrol agents |
| FR2686320B1 (en) * | 1991-11-21 | 1996-12-13 | Rhone Poulenc Agrochimie | AGROCHEMICAL COMPOSITION EFFERVESCENT IN THE PULVERULENT STATE IN A WATER-SOLUBLE OR WATER-DISPERSABLE BAG. |
| DE4233625C2 (en) * | 1992-10-06 | 1995-08-03 | Altrogge Holding S A | Animal baits and methods of making same |
| US6056971A (en) * | 1996-07-24 | 2000-05-02 | Biosytes Usa, Inc. | Method for enhancing dissolution properties of relatively insoluble dietary supplements and product incorporating same |
| EP1116515A3 (en) * | 2000-01-11 | 2002-08-21 | Givaudan SA | Encapsulated liquid |
| US20040202632A1 (en) * | 2003-04-10 | 2004-10-14 | Unilever Home & Personal Care Usa, Division Of Conocpo, Inc. | Fragranced solid cosmetic compositions based on a starch delivery system |
| FR2913353B1 (en) | 2007-03-09 | 2010-05-21 | Inst Francais Du Petrole | HIGH PERFORMANCE STRUCTURE TRIM FOR FLUID CONTACT COLUMN AND METHOD OF MANUFACTURE. |
| CN102228061B (en) * | 2011-04-27 | 2013-08-07 | 董书法 | Plant source pesticides, its preparation method, its use method and its application |
| KR101763947B1 (en) * | 2011-05-04 | 2017-08-01 | 주식회사 두산 | Method of microcapsulating phosphatidylserine |
| WO2019177727A1 (en) * | 2018-03-16 | 2019-09-19 | Dow Global Technologies Llc | Foam control |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3582361A (en) * | 1963-10-12 | 1971-06-01 | Dragoco Gerberding Co Gmbh | Food flavoring compositions and process of making and using same |
| BE793650A (en) * | 1972-11-06 | 1973-07-03 | Union Carbide Corp | FURNISHABLE, INSOLUBLE AND INFLATABLE PARTICULAR POLYMERS AND PROCESS FOR PREPARING THEM |
| DE2708513C3 (en) * | 1977-02-26 | 1981-01-08 | C.H. Boehringer Sohn, 6507 Ingelheim | Water-insoluble, physiologically harmless mass, process for their production and their use |
| ES478736A1 (en) * | 1978-03-23 | 1979-06-01 | Hoechst Ag | Polyvinyl alcohol pellets containing a plasticizer, and method for their preparation. |
| GB2021948A (en) * | 1978-05-30 | 1979-12-12 | Speywood Lab Ltd | Water miscible gum composition and its preparation and use |
| US4382813A (en) * | 1980-10-30 | 1983-05-10 | The United States Of America As Represented By The Secretary Of Agriculture | Encapsulation by entrapment within starch adduct matrix |
| PH18554A (en) * | 1981-07-21 | 1985-08-09 | Unilever Nv | Encapsulation of volatile liquids |
| DE3235189A1 (en) * | 1982-09-23 | 1984-03-29 | Hoechst Ag, 6230 Frankfurt | POLYMER GRANULES, METHOD FOR THE PRODUCTION AND USE THEREOF |
| US4707367A (en) * | 1984-07-16 | 1987-11-17 | Sunkist Growers, Inc. | Solid essential oil flavor composition |
| US4755397A (en) * | 1986-12-24 | 1988-07-05 | National Starch And Chemical Corporation | Starch based particulate encapsulation process |
| GB8702411D0 (en) * | 1987-02-03 | 1987-03-11 | Zyma Sa | Swellable pellets |
| CH675966A5 (en) * | 1987-02-20 | 1990-11-30 | Firmenich & Cie | |
| GB2214918B (en) * | 1988-02-03 | 1992-10-07 | Warner Lambert Co | Polymeric materials made from starch and at least one synthetic thermoplastic polymeric material |
-
1990
- 1990-01-26 DE DE4002257A patent/DE4002257A1/en active Granted
-
1991
- 1991-01-24 DE DE59103092T patent/DE59103092D1/en not_active Revoked
- 1991-01-24 JP JP3502181A patent/JPH04505418A/en active Pending
- 1991-01-24 AT AT91901671T patent/ATE112164T1/en not_active IP Right Cessation
- 1991-01-24 CA CA002050599A patent/CA2050599A1/en not_active Abandoned
- 1991-01-24 DK DK91901671.7T patent/DK0468003T3/en active
- 1991-01-24 EP EP91901671A patent/EP0468003B1/en not_active Revoked
- 1991-01-24 KR KR1019910701195A patent/KR920700622A/en not_active Application Discontinuation
- 1991-01-24 ES ES91901671T patent/ES2064078T3/en not_active Expired - Lifetime
- 1991-01-24 AU AU70531/91A patent/AU633685B2/en not_active Ceased
- 1991-01-24 WO PCT/CH1991/000020 patent/WO1991011178A1/en not_active Application Discontinuation
- 1991-01-26 CN CN91101244A patent/CN1055294A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2586523A1 (en) * | 2010-06-23 | 2013-05-01 | Kanagawa University | Process for producing emulsifier-producing material, process for producing emulsifier, emulsifier for orally administered composition, and orally administered composition |
| EP2586523A4 (en) * | 2010-06-23 | 2014-12-17 | Univ Kanagawa | Process for producing emulsifier-producing material, process for producing emulsifier, emulsifier for orally administered composition, and orally administered composition |
Also Published As
| Publication number | Publication date |
|---|---|
| DE59103092D1 (en) | 1994-11-03 |
| KR920700622A (en) | 1992-08-10 |
| ATE112164T1 (en) | 1994-10-15 |
| DK0468003T3 (en) | 1995-03-13 |
| AU7053191A (en) | 1991-08-21 |
| AU633685B2 (en) | 1993-02-04 |
| DE4002257A1 (en) | 1991-08-01 |
| DE4002257C2 (en) | 1992-02-13 |
| WO1991011178A1 (en) | 1991-08-08 |
| CN1055294A (en) | 1991-10-16 |
| EP0468003A1 (en) | 1992-01-29 |
| ES2064078T3 (en) | 1995-01-16 |
| JPH04505418A (en) | 1992-09-24 |
| EP0468003B1 (en) | 1994-09-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |