EP2144697A2 - Procédé servant à encapsuler des substances chimiquement actives et produit encapsulé - Google Patents

Procédé servant à encapsuler des substances chimiquement actives et produit encapsulé

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Publication number
EP2144697A2
EP2144697A2 EP08748062A EP08748062A EP2144697A2 EP 2144697 A2 EP2144697 A2 EP 2144697A2 EP 08748062 A EP08748062 A EP 08748062A EP 08748062 A EP08748062 A EP 08748062A EP 2144697 A2 EP2144697 A2 EP 2144697A2
Authority
EP
European Patent Office
Prior art keywords
water
sulphate
encapsulating material
active substance
product
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.)
Withdrawn
Application number
EP08748062A
Other languages
German (de)
English (en)
Inventor
Fernando César FERNANDES
Maria Inês RÉ
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Instituto de Pesquisa Tecnologicas do Estado Sao Paulo S/A (IPT)
Fermavi Eletroquimica Ltda
Original Assignee
Instituto de Pesquisa Tecnologicas do Estado Sao Paulo S/A (IPT)
Fermavi Eletroquimica Ltda
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Instituto de Pesquisa Tecnologicas do Estado Sao Paulo S/A (IPT), Fermavi Eletroquimica Ltda filed Critical Instituto de Pesquisa Tecnologicas do Estado Sao Paulo S/A (IPT)
Publication of EP2144697A2 publication Critical patent/EP2144697A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • B01J13/06—Making microcapsules or microballoons by phase separation
    • B01J13/14—Polymerisation; cross-linking
    • C—CHEMISTRY; METALLURGY
    • C05—FERTILISERS; MANUFACTURE THEREOF
    • C05D—INORGANIC FERTILISERS NOT COVERED BY SUBCLASSES C05B, C05C; FERTILISERS PRODUCING CARBON DIOXIDE
    • C05D9/00—Other inorganic fertilisers
    • C05D9/02—Other inorganic fertilisers containing trace elements
    • C—CHEMISTRY; METALLURGY
    • C05—FERTILISERS; MANUFACTURE THEREOF
    • C05G—MIXTURES OF FERTILISERS COVERED INDIVIDUALLY BY DIFFERENT SUBCLASSES OF CLASS C05; MIXTURES OF ONE OR MORE FERTILISERS WITH MATERIALS NOT HAVING A SPECIFIC FERTILISING ACTIVITY, e.g. PESTICIDES, SOIL-CONDITIONERS, WETTING AGENTS; FERTILISERS CHARACTERISED BY THEIR FORM
    • C05G5/00—Fertilisers characterised by their form
    • C05G5/30—Layered or coated, e.g. dust-preventing coatings
    • C—CHEMISTRY; METALLURGY
    • C05—FERTILISERS; MANUFACTURE THEREOF
    • C05G—MIXTURES OF FERTILISERS COVERED INDIVIDUALLY BY DIFFERENT SUBCLASSES OF CLASS C05; MIXTURES OF ONE OR MORE FERTILISERS WITH MATERIALS NOT HAVING A SPECIFIC FERTILISING ACTIVITY, e.g. PESTICIDES, SOIL-CONDITIONERS, WETTING AGENTS; FERTILISERS CHARACTERISED BY THEIR FORM
    • C05G5/00—Fertilisers characterised by their form
    • C05G5/30—Layered or coated, e.g. dust-preventing coatings
    • C05G5/37—Layered or coated, e.g. dust-preventing coatings layered or coated with a polymer
    • 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
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5052—Proteins, e.g. albumin
    • 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
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5052—Proteins, e.g. albumin
    • A61K9/5057—Gelatin
    • 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
    • A61K9/5094—Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K9/00—Use of pretreated ingredients
    • C08K9/10—Encapsulated ingredients

Definitions

  • the present invention refers to an encapsulated system that comprises a core containing an active material and a coating layer formed by a water-soluble or hydrophilic material, and to the process for the preparation thereof.
  • the proposed system can be applied to pharmaceutical, food, veterinary or human products, or other technical applications (pigment industry, accelerating or retarding agents, fillers, crystallization inhibitors, flame retarding substances, etc.).
  • the coating layer maintains the core isolated under a solid formulation, isolating it from the contact with other components, and protects the core from the action of factors such as humidity, pH, temperature and oxygen presence, and it delays the solubilization of the core when the system is introduced into aqueous medium.
  • the core comprises a chemically active substance, organic or inorganic, under a solid and hydrated form.
  • the encapsulated system to which the present invention refers, can be applied for encapsulating or coating active organic or inorganic substances, existing under different hydration forms, which exhibit instability under the action of factors like humidity, temperature, pH, reactivity with other components or ingredients of formulations in which they are introduced.
  • solid, liquids and/or gases substances can be formulated with other materials, said encapsulating materials, for various reasons: to protect additives sensitive to the contact with the surrounding medium and action of external factors like humidity, heat, pH and oxygen presence; to make it compatible and to stabilize sensitive additives in a formulation by limiting their physical contact with other components, to transform easy to handle and able to be incorporated liquids into solid ingredients, to mask taste and flavors, and to modify and control the release profile of the active material to obtain a prolonged or immediate effect of its action.
  • substances sensitive to oxygen and/or humidity are incorporated into certain products, among which, vitamins and minerals such as iron for food fortification. If these additives are not protected against the surrounding medium, which is rich in oxygen or humidity, they will be oxidized, thus altering the color, flavor and the nutritive value of the products to which they have been added.
  • the coating or encapsulation of these additives aims at decreasing such reactivity with the surrounding medium and assuring the durability of the product.
  • a set of techniques allows the preparation of individual particles, constituted by an encapsulating material containing an active substance.
  • the formulated particles present a size ranging from about 1 ⁇ m to 1 mm, containing typically between 5 to 90% (in mass) of the active substance.
  • the active substances can be varied: pharmaceutical active principles, cosmetic actives, food additives, phytosanitary products, essential oils, fragrances, microorganisms, cells, chemical catalysts, pigments, etc.
  • the encapsulating materials are natural or synthetic polymers, or lipids.
  • microparticles present different morphologies: 1) a capsule, i.e., a particle constituted by a core containing the active substance, surrounded by a solid continuous layer of encapsulating material; 2) a matrix, when the particle is constituted by a macromolecular or lipid continuous network wherein the active substance is finely dispersed, or under a molecular state, or in the form of fine solid particles, or also like liquid droplets.
  • the techniques known in the specialized literature mainly differ for the nature of the process used for the association of the active material with the encapsulating material, which can be either physically (spray drying, coating bed fluidization, extrusion), or physicochemically (coacervation or phase separation, among others), or chemically (molecular inclusion, interfacial or emulsion polymerization).
  • the physicochemical processes are based in the following:
  • control of solubility variations and precipitation conditions of the encapsulating material refers, for instance, to the controlled precipitation of a polymer in solution, due to the addition of a non- solvent (emulsification and evaporation or extraction of the solvent), or of another incompatible polymer (simple coacervation), or also the temperature or pH variation of the solution (complex coacervation).
  • the formulation of the particles allows the use of a wide range of encapsulating materials.
  • the composition of the encapsulating material, the effect of its association with a given active substance, and the resulting product, or the form under which this association is performed have been the subject of patents.
  • inorganic salts are used, which are rather sensitive to humidity, thus leading to caking during storage. Encapsulation of these salts limits this type of problem, as described in patent US 4,659,557, where heptahydrated ferrous (II) sulphate is coated with brown coal dust capable of absorbing a substantial amount of moisture, thus avoiding caking and improving fluidity of the product during handling and storage.
  • the process consists in physically mixing the powders (ferrous sulphate and brown coal) under intense stirring in conventional equipment for solids mixing (rotating drums, centrifugal mixers, etc).
  • document US 2004/0069033 describes a formulation of a water-soluble fertilizer capable of extending their dissolution time by the control of its water permeability and the releasing of encapsulated nutrients, wherein the encapsulation is also made through conventional physical methods like rotating drums, fluidized beds, or Wurster process (which principle is similar to a fluidized bed).
  • document US 2006/0249707 describes a process and a product referring to sodium percarbonate particles coated with at least two layers of encapsulating material, the external layer of the chemical composition being different from the internal one, with the aim of increasing the chemical stability of the substance in the presence of the other detergent components.
  • the layers are deposited over the particles in a fluidized bed, with drying of the first layer before deposition of the second layer.
  • Encapsulating physical processes are also widely used in the pharmaceutical field, as described by the patent documents mentioned above.
  • the document US 2002/0192285 describes a heterogeneous coating for drugs comprising an insoluble polymer presented as a latex dispersion in water, an enteric polymer, which is added to the latex and a water- soluble polymer dissolved in an aqueous medium.
  • This composition of dispersed and dissolved polymers is nebulized over the solid particles (medicine) by conventional nebulizing and drying processes, preferably in a fluidized bed.
  • the polymeric film deposited over the pharmaceutical active principle particles has a controlled porosity with the objective to control the core dissolution rate.
  • the known physical process for encapsulating solid particles involves a first step for the preparation of a dispersion of these particles in a solution of the coating encapsulating. Then, the dispersion is dried to eliminate the solvent (generally water), and to form a solid layer of the encapsulating material over the particles.
  • the solvent generally water
  • the particles in suspension in the encapsulating material solution are undergo a simultaneous process of drying and coating described in several patents, which innovate for the encapsulating material composition to obtain a programmed effect (controlled-release, flavor masking, etc) as exemplified in the prior art already described herein.
  • some of the limitations are the size of the particles to be coated (preferably of no more than 250 ⁇ m), the quality of the coating film which tends to be porous due to the rapid solvent evaporation, and the agglomeration tendency of the particles during the process.
  • the coating and encapsulation processes which involves the nebulization of the encapsulating material over the solid particles maintained under mixing and stirring, are exclusively applied to solid active materials and are very used as evidenced by innumerous patent documents found in the specialized literature.
  • the particles are maintained in suspension in a heated gaseous vehicle (hot air), which can be performed in a fluidized bed, pan coating, or any other equipment of mixing and stirring which maintains the particles in motion, dispersed by a gaseous flux, and able to be aspersed by the coating material solution.
  • the solvent evaporation generally water is necessary for the deposition of the solid layer over the particles.
  • control parameters and process adjustment in order to assure a uniform coating of the particles. They are linked either to the nebulization step (concentration of the formulation, feed rate and size of the droplets formed), or to the film drying (air temperature, fluidization gas flow or mixing).
  • the concentration and the flow of the solution must be rigorously adjusted to avoid aggregation of the particles when they collide in the mixer; the process requires a rigid control of the nebulization step to have liquid drops smaller than the particles to be encapsulated in order to control the liquid deposition rate over the particles; the particles to be coated must be heated when the liquid layer is deposited on their surface to allow drying and to avoid agglomeration; nebulized drops of the encapsulating solution can dry before making contact with the particles, providing fine particles and reducing the coating process due to the material loss.
  • Another object of the present invention is to provide a new process where the hardening of the coating layer is independent from the simple or complex coacervation steps.
  • said encapsulation occurs by the simple mixing of said solution with the particles of the active compound, at room temperature.
  • the process can be carried out in a batch or as a continuous operation.
  • the hardening of the encapsulating material occurs due to the water reincorporation of the hydrating or crystallizing water to the active compounds molecules and, thereby, reverts to its original composition.
  • the process does not require the heating or drying of the encapsulated particles.
  • the physical process for coating and encapsulating solid particles described in the present invention presents several advantages compared to the existing processes conventionally used, which comprises several steps including drying after deposition of the liquid film over the particles for solvent elimination, and solidification of the encapsulating material, namely: -
  • the contact between the encapsulating material solution and the solid particles to be encapsulated occurs through a simple mixture of the encapsulating solution with the active material at room temperature.
  • the deposition occurs through the re-hydration of the substance with the water of the encapsulating material solution.
  • the solid layer of the encapsulating material is formed over the particles due to the incorporation of water by the substance being hydrated, which means that a later or simultaneous drying of the mixture as occurs in the other physical processes known until then is not necessary.
  • the process is adapted to a wide granulometry range (from about 1 ⁇ m to 1 mm) and allows the reduction of particles size naturally imposed by their dehydration during the first step of the process.
  • the particles size distribution of the substance to be encapsulated is adjusted by and additional milling step when starting from a higher granulometry.
  • Figure 1 shows, in a schematic way, the process for producing chemically active substances encapsulated in a hydrated form.
  • Figure 2 shows optical micrograph images illustrating, after immersion of the samples in water, the effect of gelling during the hydration and swelling of the gelatin layer formed around the iron (II) sulphate encapsulated with 2% gelatin, which is not observed with the non-encapsulated which dissolves in less than 1 minute.
  • Figure 3 exhibits physical characteristics of the encapsulated and non-encapsulated material after 70 hours of exposure to a load of 1 kg/cm 2 , simulating the loading of a 10 to 15 meters silo.
  • the process for preparing chemically active substances, in hydrated form and coated with an encapsulating material, which is the object of this invention, is performed through the steps described hereafter.
  • the chemically active substance containing crystallization water must firstly be partially or totally dehydrated.
  • crystallization water is meant the water present in crystalline compounds, within determined proportions.
  • Many crystalline salts forms hydrated compounds containing 1, 2, 3, or more water molecules for each molecule of compound, and the water can be trapped within the crystal under various forms. Thus, the water molecules can simply occupy positions in the crystal network, or to form links with the anions or cations.
  • the complete or partial removal of the crystallization water from the chemically active substance can be performed through any drying or precipitation process that allows its removal.
  • this operation can be done by evaporation through conventional drying processes.
  • Convective methods are indicated for this operation, such as rotating dryers equipped or not with agitating pallets, pneumatic transport or fluidized bed with temperature control, wherein the particles are maintained in ascending-descending movement through an air stream that permeates the particle bed.
  • the important factor is the control of the process temperature for controlling the dehydration (kinetic of the process and amount of removed water), and the composition of the drying gas (control of the oxygen content) to avoid the oxidation of the active substance if it is easily oxidize.
  • the removal of crystallization water can be equally done, by an alternative step, by precipitation of the substance under anhydrous form by varying the temperature of a saturated solution (precipitation by temperature increase or decrease, depending upon the effect of this parameter on the substance solubility).
  • the amount of the water used for the preparation of the aqueous solution of the encapsulating material must be equivalent to the amount of the hydration water removed from the chemically active substance in the previous step of the process, or equivalent to the amount of the hydrated substance in the encapsulated form.
  • the specified amount of the encapsulating material preferably under controlled temperature between 15 and 60 0 C, and more preferably between 40 and 50 0 C.
  • the encapsulating material can be any water-soluble or hydrophilic substance, with film formation properties like proteins, raw materials derived from the collagen hydrolysis such as food gelatin, technical gelatin, animal glue, polyvinyl alcohol, polyvinylpirrolidone, alginate, chitosan, cellulose derivatives such as hydroxypropylmethylcellulose or sodium carboxymethylcellulose, acrylic acids and similar compounds. Water absorbing compounds but not soluble in water at the temperature between 15 to 25°C, and, which can be treated by crosslinking or hardening agents to decrease the coating solubility are particularly desired to increase the applicability of the product in aqueous media.
  • a protein more specifically a gelatin, which is a protein derived from the partial hydrolysis of the collagen, which is the main constituent of animal skins, bones, tendons and connective tissues.
  • Gelatin is obtained from the collagen purification, which is separated and processed, being converted in the final product. This process can be carried out under acid conditions, resulting in type A gelatin, or in alkaline conditions, resulting in type B gelatin.
  • the production encompasses as basic steps the treatment of the collagen tissue, extraction, purification, concentration, sterilization, cooling, drying, milling and packaging.
  • animal source glue The technical gelatin produced from raw bovine leather or bones through alkaline process, known as animal source glue, also can be used; it can also be used vegetal source proteins, such as the ones disclosed in US 2002/0187185, which has good physical property in place of the animal gelatin, in a great range of applications, especially in the manufacture of gelatin capsules.
  • gelatin is sold in several classifications corresponding to these specific properties. Commercially, gelatin is classified in function of the mechanical resistance to gel (Bloom value) measured under standard test conditions. Usually, gelatin having gel strength of 80 to 520 g bloom can be selected, preferably between 200 and 380 g bloom.
  • the present invention is not limited to the use of some gelatin with specific properties. It can be used, for example, gelatins extracted from raw material of bovine, swine, poultry, fish origin and the like, and which has the property of changing the sol-gel condition in function of the temperature.
  • the process of the present invention allows the use of conventional gelatins used in the manufacture of capsules, such as acid, alkali and amphoterically-treated gelatins, or chemically modified gelatins, pure or in combination, food grade gelatins, pharmaceutical grade, technical gelatin or animal glue, besides vegetal source gelatins.
  • conventional gelatins used in the manufacture of capsules such as acid, alkali and amphoterically-treated gelatins, or chemically modified gelatins, pure or in combination, food grade gelatins, pharmaceutical grade, technical gelatin or animal glue, besides vegetal source gelatins.
  • it can be used gelatins with gel strength between 80 and 520 g bloom and, preferably, between 200 and 38Og bloom. It is recommended that the amount of the encapsulating material
  • the active substance in its hydrated form to be encapsulated, preferably between 0.2 and 4%.
  • the encapsulating material solution can be added to the active substance that will be encapsulated (partially hydrated or in anhydrous form) in one single step (batch) or gradually (continuous process), in the desired proportion of the encapsulating material to the substance to be encapsulated.
  • This step can be performed in conventional stirring and mixing equipments such as intense stirring mechanical mixers, for example, those having pallets or stirring pins. Due to the possibility of the presence of fine particles of the active substance and, consequently, powder formation in the materials mixture, it is recommended to perform this operation in closed equipments.
  • the obtained material (generally under paste form) is maintained at rest to cool at room temperature, preferably in the form of a small thickness layer, for a period sufficient for the active substance re-hydration by the water of the encapsulating material solution.
  • This operation results in an increase of the temperature of the material, due to the hydration heat of the active substance.
  • the water is then incorporated to the active substance as crystallization water and the encapsulating material solidifies at its surface.
  • the obtained material can be submitted to a mechanical disintegration process of the aggregated particles of the coated and hydrated active substance.
  • the disintegration of this material does not require milling and is easily obtained by any process that promotes the contact and mechanical stirring of these aggregates, like contact mills (roll), fluidized bed, or even pneumatic transport.
  • the disaggregated product can be submitted to a final granulometric classification, if necessary.
  • a variation of the process of the present invention consists in a fifth optional step for the reinforcement of the resistance of the encapsulating material deposited over the surface of solid re-hydrated particles by means of stable reactions of ionic complexation chemical crosslinking or by the action of hardening agents.
  • gelling hydrophilic compounds especially hydrophilic compounds able to expand in water but not soluble in water in the application temperature, that is, between 15 and 25 0 C, such as proteins, polyvinyl alcohol and similar compounds, which can be treated by crosslinking and hardening agents to avoid dissolution of the coating, are particularly adequate as coating forming substances for use in aqueous medium.
  • Proteins like gelatin are preferred, this being a material able to form gel and to form stable complexes of the polyelectrolyte source (polycation-polyanion) or chemical reticulation with aldehydes, tannic acid and others.
  • Polyelectric complexes are formed by the interaction of a polyanion with polycations.
  • polyanion it is advantageous to use water- soluble cellulose derivatives such as, for instance, carboxymethylcellulose, cellulose sulphate, or also pectins, alginates, Arabic gum, but also synthetic polymers such as polyacrylic or polymetacrylic acids, etc.
  • polycations it can be applied mainly natural substances, such as chitosan, gelatin, etc.
  • the reinforcement can be performed through the deposition of an additional layer of a cross-linking material solution (e.g. glutaraldehyde solution) or of a complexing agent (polyanion such as sodium alginate or sodium carboxymethylcellulose).
  • a cross-linking material solution e.g. glutaraldehyde solution
  • a complexing agent polyanion such as sodium alginate or sodium carboxymethylcellulose.
  • the process involves the deposition of the complexing or crosslinking solution over the already formed layer on the re-hydrated particles, followed by drying of the chemically modified layer.
  • the variation of the process is done by the aspersion of a crosslinking solution layer over layer already deposited in the particle surfaces.
  • a subsequent drying step is carried out by any known technique reported in the specialized literature (fluidized bed, liophylization, rotating drum, etc).
  • the solid material to be re-hydrated and coated by the encapsulating material is fed through a screw conveyor (1) into a vertical fluidized bed (2).
  • the drier is fed by a hot gas stream (3) that maintains the solid mass under stirring and mixing.
  • the material is dehydrated during its permanence time in the drying chamber due to its contact with the hot gas (3).
  • the fluidization speed control is done so that the dehydrated particles are transported to a cyclone (4), from which a fine fraction is recovered from a filter (5), and the thicker fraction, through a screw conveyor (6), feeds the mixer/encapsulator (7).
  • the encapsulating material solution (8) is added to the mixer (7) where the encapsulating process as schematized in (11) occurs. After a period of mixture for re-hydration of the water present in the system by the solid particles, the product is discharged in the conveying belt.
  • the encapsulating material (12) is contacted with the active substance granules (13), recovering their surface.
  • the compound absorbs water from the encapsulating solution, as indicated by the arrows.
  • the encapsulating material contained in the solution solidifies by forming a film wall (15), which coats the re-hydrated compound (14).
  • the process described in this invention can be applied to the production of heptahydrated FeSO 4 encapsulated with gelatin.
  • the iron sulphate (II) can be in different hydrated forms (heptahydrate, tetrahydrate, and monohydrate).
  • the most common type is the heptahydrate one (FeSO 4 * 7 H 2 O), which is not thermally stable. At 60-70 0 C, it dehydrates to tetrahydrate (FeSO 4 * 4 H 2 O), and at 115 0 C to monohydrate (FeSO 4 * 1 H 2 O).
  • Heptahydrated FeSO 4 particles have been used in this process, as an example of its applicability.
  • Step 1 Partial dehydration of heptahydrated iron sulphate
  • the initial step of material dehydration has been performed in a dryer/fluidized bed dehydrator working with 1 ton of FeSO 4 .7H 2 O feed per hour.
  • the solid material to be dehydrated is placed in contact with a heated drying gas stream, capable of providing the energy necessary for the evaporation of the water incorporated into the product, in this case, FeSO 4 JH 2 O.
  • LPG combustion gas Liquefied Petroleum Gas
  • GLP Gas of Petroleum
  • the dryer was provided with GLP (Liquefied Gas of Petroleum) combustion gas with a volumetric flow of 7000 m 3 per hour at a temperature of 250-300 0 C, and the temperature of the gas at the output of the dryer was maintained at 9O 0 C to control the residence time of the active substance in the dryer (about 6 min., with a mass of 100 kg in permanence in the dryer) and the amount of the hydration water to be eliminated (about 60- 70% of the crystallization water of the heptahydrate form).
  • Step 2 Preparation of the coating material solution
  • Non-edible type B gelatin with 210-230 g bloom and viscosity 30- 41mps is used as the encapsulating material.
  • ferrous sulphate previously dehydrated (after lost of 60% of its crystallization water, i.e., 27 kg of water/100kg of initial heptahydrate ferrous
  • Step 4 Encapsulation of the chemically active substance
  • the obtained mixture was discharged and maintained at rest for 30 minutes, which is the period necessary for the absorption of the water of the gelatin solution by the iron (II) sulphate, and for the deposition of the gelatin on the re-hydrated particles. After this period, the material, already under solid form, was disintegrated in a rubber roll mill, in order to obtain the product with the desired granulometry (less than 200 ⁇ m).
  • Tables 1 , 2 and 3 show some characteristics of the products at different steps of the process.
  • Example 1 The above-described process (Example 1) was used to obtain a product with higher type B gelatin content used as encapsulating material.
  • the material used was type B non-edible industrial gelatin with 210-230 g bloom and viscosity of 30-41 mps.
  • An aqueous solution containing 74 grams of gelatin per liter of water was obtained.
  • Steps (3) and (4) were similar to the ones used in the preparation process described in Example 1.
  • Table 4 shows the granulometry and the physical characteristics of the product obtained comparable to the particles coated with 1% gelatin solution presented in Example 1.
  • Example 1 The above-described process (Example 1) was used to obtain a product using, as encapsulating material, gelatin hydrolyzed from collagen, known as animal glue, with 250 g bloom and viscosity of 90 mps). The same proportions used in Example 1 , as well as the same variables, were maintained. An amount of animal glue equivalent to 1 % in mass of the amount of FeSO 4 JH 2 O, was dissolved in a volume of water equivalent to 60% of the crystallization water of FeSO 4 JH 2 O 1 at a temperature of 4O 0 C. An aqueous solution containing 37 grams of animal glue per liter of water was obtained.
  • Steps (3) and (4) were similar to the ones used in the process described in Example 1.
  • Table 5 shows the granulometry and the physical characteristics of the product obtained comparable to the particles coated with 1 % gelatin solution presented in Example 1.
  • the encapsulated products produced in Examples 1 and 2 were submitted to a dissolution test in water, to verify the presence of a gelatin film covering the surface of the heptahydrated ferrous (II) sulphate crystals.
  • Example 2 heptahydrated ferrous (II) sulphate encapsulated with 2% type B non-edible gelatin
  • Example 3 heptahydrated ferrous (II) sulphate encapsulated with 1% of animal glue
  • Table 7 shows the obtained results, showing that the coating layer on the surface of the product obtained in Example 2 restricted the absorption of humidity of the medium by the product from 6.3% (heptahydrated product) to
  • Figure 3 shows pictures that illustrate the material physical state after application of the load for 70 hours.
  • the gelatin encapsulation changes the physical characteristics of the material, preventing the caking observed on Figure 3 (a), which has occurred with the non-encapsulated material ( Figure 3b).
  • the results presented in Table 8 show that the particles coating assured a lower alteration of the product during storage (compressibility index of 17% for the encapsulated product compared to 26.7% for the non- encapsulated one), the encapsulated material being able to be stored in silos for a longer time, with less risks for the frequent caking problem encountered with the heptahydrated ferrous (II) sulphate.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • General Preparation And Processing Of Foods (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

La présente invention concerne : un système encapsulé lequel comprend un cœur contenant la substance active et une couche d'enrobage formée par une matière soluble dans l'eau ou hydrophile; et le procédé de préparation de celui-ci. Selon un mode de réalisation de l'invention, le procédé pour la préparation de substances chimiquement actives comprend les étapes consistant à : éliminer partiellement ou totalement l'eau de cristallisation de la substance active; préparer la solution de matière d'encapsulation avec l'équivalent de la quantité d'eau de cristallisation requise pour parvenir au degré d'hydratation souhaité pour la substance encapsulée; mélanger la substance active partiellement hydratée, ou sous forme anhydre, avec la solution d'enrobage; et enrober la substance active par la réhydratation de ladite substance avec l'eau provenant de la composition d'enrobage liquide et solidifier simultanément la matière d'enrobage sur la substance active.
EP08748062A 2007-05-10 2008-05-09 Procédé servant à encapsuler des substances chimiquement actives et produit encapsulé Withdrawn EP2144697A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
BRPI0701693-0A BRPI0701693A2 (pt) 2007-05-10 2007-05-10 processo de encapsulaÇço de substÂncias quÍmicamente ativas e produto encapsulado resultante
PCT/BR2008/000137 WO2008138085A2 (fr) 2007-05-10 2008-05-09 Procédé servant à encapsuler des substances chimiquement actives et produit encapsulé

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EP2144697A2 true EP2144697A2 (fr) 2010-01-20

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EP (1) EP2144697A2 (fr)
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WO (1) WO2008138085A2 (fr)

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CN108451976A (zh) * 2018-07-02 2018-08-28 上海应用技术大学 一种硫酸亚铁微丸及其制备方法
CN118748045B (zh) * 2024-06-13 2025-04-01 武汉理工大学 一种硅酸盐水泥缓凝性能预测模型的构建方法及其计算分析仪

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DE4200821A1 (de) * 1992-01-15 1993-07-22 Bayer Ag Geschmacksmaskierte pharmazeutische mittel
DE19954771A1 (de) * 1999-11-15 2001-05-17 Remmers Bauchemie Gmbh Mikrokapseln umschließend einen wasserlöslichen Feststoff
AUPR590701A0 (en) * 2001-06-25 2001-07-19 Colocaps Pty Ltd Laxative preparation

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See references of WO2008138085A2 *

Also Published As

Publication number Publication date
WO2008138085A2 (fr) 2008-11-20
BRPI0701693A2 (pt) 2008-12-23
WO2008138085A3 (fr) 2009-03-12

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