Fibrous support comprising particles containing a partially water-soluble active agent, particles, and methods for producing said particles

Abstract

The invention relates to a support consisting of natural and/or synthetic fibers which particles are held, which are preferably water-soluble, comprising at least one active agent, said particles at least partially releasing the active agent(s) under the effect of an external stress, characterized in the active agent has a water-solubility of between 0.1 and 60 wt. %, preferably between 0.1 and 30 wt. %.

Claims

1. A process for the manufacture of a particle provided in the form of: a) a microcapsule comprising a solid casing including a fluid or solid phase in which at least one active agent is present; or b) a microsphere comprising a solid matrix in which at least one active agent is present; said active agent having a solubility in water of 0.1% to 60% by weight, wherein the process comprises the steps of: (A)(i) forming an emulsion from an oily phase comprising fluorinated oil and containing at least one active agent having a solubility in water of 0.1% to 60% by weight, and from an aqueous phase containing silane monomers capable of being condensed for the formation of polysiloxanes; and (ii) forming a membrane defining a microcapsule by polycondensation of the silane monomers by modifying the pH or the temperature, the oily phase comprising a fluorinated oil being chosen so that the active agent exhibits a high partition coefficient between this oily phase and the aqueous phase, the partition coefficient being defined as the ratio of the concentration of the active agent in the oily phase to the concentration of the active agent in the aqueous phase; and (B)(i) forming particles by the method (A); (ii) forming a dispersion of the particles in an aqueous phase containing a water-soluble polymer; (iii) rendering the initially water-soluble polymer insoluble in order to form polymer condensates which migrate to particle interfaces; and (iv) treating the polymer condensates thermally or chemically in order to form a casing on the particles.

2. The process of claim 1, wherein said active agent has a solubility in water of 0.1% to 30% by weight.

3. The process of claim 1, wherein the casing of the particles is a melamine-formaldehyde polymer.

4. The process of claim 1, wherein the manufactured particle is resistant to thermal degradation at a temperature of up to and including 120 C.

Description

DESCRIPTION OF THE FIGURES

(1) The appended figures respectively represent:

(2) FIG. 1A, 1B SEM and optical photographs of the microspheres obtained in A2 Test 1;

(3) FIG. 1C, 1D SEM and optical photographs of the microspheres obtained in A3 Test 2;

(4) FIG. 1E SEM and optical photograph A4 Test 3;

(5) FIG. 1F optical microscopy A5 Test 4;

(6) FIG. 2 is a particle size distribution curve of the microspheres of A5 Test 4;

(7) FIG. 3 optical microscopy observation B Test 1 (IR3535 in Dynasan 118);

(8) FIG. 4 optical photograph of an untreated wipe and of a wipe impregnated with microspheres;

(9) FIG. 5 an optical photograph of the microcapsules of C2 Test 1.

METHODS OF MANUFACTURE OF THE PARTICLES

(10) Generally, in the present invention, the particles are obtained according to the following methods: (A) Encapsulation by phase separation (microspheres) (i)forming an aqueous mixture of a matrix material, which is preferably insoluble in water, and of at least one active agent having a solubility in water of 0.1% to 60% by weight, preferably of 0.1% to 30% by weight; and (ii)forming fine droplets of the emulsion by atomization in order to obtain microspheres, the formulation of the emulsion being optimized by means of a ternary diagram model which takes into account the solubilities in water of the different constituents so that, during the evaporation of the water during the atomization, a phase separation takes place within the droplets, resulting in the appearance of a matrix-rich phase at their periphery. (B) Encapsulation by polycondensation (microcapsules) i)forming an emulsion from an oily phase containing at least one active agent having a solubility in water of 0.1% to 60% by weight, preferably of 0.1% to 30% by weight, and from an aqueous phase containing monomers capable of being condensed, and (ii)carrying out the polycondensation of the monomers in order to form a membrane defining a microcapsule, the active agent having a measurable partition coefficient between the oily phase and the aqueous phase. The partition coefficient is defined as being the ratio of the concentration of the active agent in the oily phase to the concentration of the active agent in the aqueous phase. Preferably, the partition coefficient is greater than or equal to 1, better still greater than or equal to 1.5 and better still greater than or equal to 2. (C) Encapsulation by modification of the Creaspher process (patent FR 2 995 222) (microspheres) (i)forming an oily phase of a water-insoluble wax, which is solid at ambient temperature, containing at least one active agent having a solubility in water of 0.1% to 60% by weight, preferably of 0.1% to 30% by weight, by heating the wax above its melting point, (ii)forming a primary aqueous phase containing at least one surfactant and optionally a protective colloid, this primary aqueous phase being heated to a temperature similar to that of the oily phase, (iii)forming a primary oil-in-water emulsion from the preceding phases, (iv)forming a secondary aqueous phase containing a surfactant and optionally a protective colloid, this secondary aqueous phase also containing the active agent at a concentration which limits the extraction of the active agent present in the primary emulsion toward the secondary aqueous phase, preferably at a concentration close to saturation, (v)adding the hot primary emulsion dropwise to the cold secondary aqueous phase in order to form, by solidification, wax droplets (microspheres) containing the active agent; and (D) Encapsulation on preformed particles (microcapsules) (i)forming a particle according to the invention by one of the methods (A), (B) or (C), (ii)forming a dispersion of the particles in an aqueous phase containing a water-soluble polymer, (iii)rendering the initially water-soluble polymer insoluble in order to form polymer condensates which migrate to the interface of the particles, and (iv)treating the polymer condensates thermally or chemically in order to form a casing on the particles (forming microcapsules).

(11) The technology by phase separation, method (A), is known in its general principle.

(12) However, as a result of the difference in solubility in water of the constituents of the starting formulation, the least soluble constituent will form solid particles or insoluble domains before the constituent exhibiting a greater solubility. The order of appearance and the amplitude of these phase separations will have an impact on the structure of the final microspheres. As the active agent of the invention is partially soluble in water, in order to be able to keep the agent at the core of the microsphere, it is necessary to determine the formulation of the initial preparation (solution or emulsion) so that, in the process of formation of the microspheres, the active agent does not precipitate before the constituent material of the matrix. In order to do this, according to the invention, the formulation of the emulsion is optimized by referring to a ternary diagram which takes into account the solubilities in water of the different constituents. This diagram makes it possible to define, for a desired final composition of the microcapsules, the composition ranges accessible for the initial formulations.

(13) The first case is the case where a person skilled in the art has access to the empirical ternary diagram of the water/agent/matrix system at the given operating temperature (atomization temperature), that is to say that he has available a diagram which describes, for each given composition of the water/matrix/agent system, the number and the type of phases present at thermodynamic equilibrium.

(14) Data present on the empirical phase diagram can be:

(15) presence of a homogeneous liquid phase in which the agent and the matrix are soluble

(16) or

(17) coexistence of two phases, one liquid, containing x % of dissolved agent and y % of dissolved matrix, and the other solid, consisting of pure matrix

(18) or

(19) coexistence of 3 phases, one liquid, containing water and x % of agent, another solid, consisting of pure matrix, and a third liquid, consisting of pure agent.

(20) In this case,

(21) 1/ A person skilled in the art determines the final composition of the microspheres which is desired once all the water has evaporated, that is to say the agent/matrix ratio (or the desired composition range).

(22) 2/ For these final compositions, a person skilled in the art determines, from the ternary diagram, the compositions of corresponding formulations (zones on the diagram) containing the 3 constituents, water/agent/matrix, which correspond to the agent/matrix ratio (or to the range) set.

(23) 3/ For these compositions of initial formulations, a person skilled in the art observes the phase separations liable to take place during the evaporation of the water. For this, it is sufficient to plot a straight line starting from the initial composition point toward the final composition point where all the water has evaporated and to observe the different phases and phase separations encountered.

(24) In a typical case, the system is homogeneous (a single liquid phase) at the starting point (composition of the initial formulation) and then, when a percentage % of the water present has been removed, a phase separation takes place between a liquid phase containing water and agent and a solid phase consisting of pure matrix. When the amount of water decreases further, the coexistence of these two phases with an enriching of the liquid phase in agent is observed. Finally, when all the water has evaporated, the presence of two solid phases, respectively of pure agent and of pure matrix, is observed.

(25) During the atomization process, the droplets exhibit a water concentration gradient. In the above case, the phase separation involving the appearance of a pure matrix phase takes place before that involving the appearance of a pure agent phase; it can therefore be predicted that the microspheres thus formed will preferably have matrix at the periphery and agent at the core.

(26) 4/ A person skilled in the art can thus, in view of the above information, prepare initial formulations such that, during evaporation, the phase separations involving the formation of matrix-rich phases take place before those involving the formation of agent-rich phases and can confirm, by tests, the structure of the microspheres.

(27) Kinetic parameters, such as the input and output temperatures, can have an impact on the structures of the microspheres.

(28) In the second case, where a person skilled in the art does not have available the theoretical ternary diagram, he will have to determine himself, by experimentation, by the cloud point method, for example, the zones of existences and of coexistences of the different liquid and/or solid phases of the three constituents, this indicating to him in the end the zones of phase separation.

(29) Preferably, in the atomization method (A), use will be made of matrices which are insoluble or only slightly soluble in water, such as cellulose acetate phthalate or ethylcellulose.

(30) The size of the microspheres obtained generally varies from 1 to 30 m.

(31) According to the material of the matrix, the atomization takes place at temperatures greater than the glass transition temperature of the material of the matrix, for example ethylcellulose.

(32) The fact that the matrix is insoluble in water contributes resistance to washing by limiting the erosion of the microspheres.

(33) The method (B) of encapsulation by polycondensation, which relates to the preparation of microcapsules, is also known in its most general aspect, in particular for encapsulation by means of silicones. Such a method is described in particular in the patent EP 2 080 552.

(34) Typically, in this method, an emulsion is formed from an oily phase containing the active agent and from an aqueous phase containing polycondensable monomers (in particular monomers for the formation of polysiloxanes). During the process, the monomers migrate to the interface of the droplets (as a result of the pH or of the ionic strength) and their polycondensation is initiated by modifying the pH or the temperature in order to form the membrane of the microcapsules which traps the oily phase containing the active agent.

(35) According to the invention, this method is modified by the choice of the oily phase, in particular a fluorinated oil, which is chosen so that the agent exhibits a high partition coefficient between the oily phase and the aqueous phase (and thus that the concentration of agent in the aqueous phase at equilibrium is minimal). As indicated above, the partition coefficient is defined as being the ratio of the concentration of the agent in the oily phase to the concentration of the agent in the aqueous phase. Preferably, the partition coefficient is greater than or equal to 1, better still greater than or equal to 1.5 and better still greater than or equal to 2 (measured at 25 C.).

(36) By way of example, for the preparation of antifogging capsules, the active agent can be Zonyl FSO100 and the fluorinated oil can be the oil HFE 7300.

(37) Apart from the fact that the microcapsules obtained contain the active agent at their core, they have the advantage of making possible easy release of the active agent and of having a high resistance to the temperature, of the order of 120 C.

(38) The method (C) is a modification of the process by encapsulation by the Creaspher process relating to the preparation of microspheres which is described in particular in the patent FR 2 995 222.

(39) The problem associated with this technology lies in the fact that, as soon as the active agent of the primary aqueous phase is partially soluble in water, there exists a high risk of the active agent being extracted from the primary aqueous phase to pass into the secondary phase before the solidification has taken place.

(40) According to the process of the invention, the following stages are carried out: (i) forming an oily phase of a water-insoluble wax containing at least one active agent having a solubility in water of 0.1% to 60% by weight, preferably of 0.1% to 30% by weight, by heating the wax above its melting point; (ii) forming a primary aqueous phase containing at least one surfactant and optionally a protective colloid, this primary aqueous phase being heated to a temperature similar to that of the oily phase; (iii) forming a primary oil-in-water emulsion from the preceding phases; (iv) forming a secondary aqueous phase containing a surfactant and optionally a protective colloid, this secondary aqueous phase also containing the active agent at a concentration which limits the extraction of the active agent present in the primary emulsion toward the secondary aqueous phase, preferably at a concentration close to saturation with active agent and better still at a concentration corresponding to saturation with active agent at the temperature of implementation of the process; (v) adding the hot primary emulsion to the cold secondary aqueous phase in order to form, by solidification, wax droplets (microspheres) containing the active agent. A concentration close to saturation with active agent is understood to mean a concentration corresponding to the concentration of saturation with active agent +/10% maximum of the saturation value.

(41) The temperature required by the secondary aqueous phase for the implementation of the process preferably varies from 15 to 35 C.

(42) The waxes of the oily phase are insoluble in water and generally have a melting point of greater than 35 C., preferably from 50 C. to 75 C.

(43) Waxes which can be used are described in the patent application FR 2 995 222.

(44) The surface-active agents used in the primary and secondary aqueous phases are generally chosen from those mentioned above.

(45) The object of the protective colloids is to prevent the coalescence of the droplets and they are generally chosen from gum arabic, gelatin, cellulose derivatives, polyvinylpyrrolidones or polyvinyl alcohols.

(46) The microspheres obtained by this method generally have a size of the order of 0.5 to 50 m.

(47) The method (D) of encapsulation is known in its general aspect and is described in particular in the patent EP 1 533 415. According to one embodiment, the method (D) is implemented and the casing of the particles is a melamine-formaldehyde polymer.

(48) However, the method (D) cannot be applied directly to the formation of microcapsules containing a partially water-soluble active agent. Thus, according to the invention, this method is carried out starting from water-insoluble particles containing an active agent as defined.

(49) The particles are dispersed in an aqueous phase containing an initially water-soluble polymer. The polymer is subsequently rendered insoluble, for example by modifying the pH or adding salts. Small solid polymer particles (condensates) are then formed, which particles migrate to the interface of the droplets and subsequently form, under the action of a heat or chemical treatment, a membrane over the particles.

(50) This technology is particularly suitable for conferring, on the particles of the invention, a casing capable of being grafted by a covalent bond to the support.

(51) The process (D) is described more specifically but nonlimiting below.

(52) The process (D) comprises the following stage or preferably consists in again encapsulating microcapsules obtained using the processes (A), (B) or (C) in a membrane.

(53) The new microcapsules can subsequently be attached to fibers (via a binder, for example), can be released by rubbing actions and can exhibit a resistance to washing operations.

(54) The main stages of the process are as follows: Preparation of an aqueous solution containing a water-soluble polymer (or prepolymer). The polymer can be chosen from the products, the solubility of which can be controlled by the pH. The products can be chosen from aminoplast resins, such as urea-formaldehyde resins and melamine-formaldehyde resins, or copolymers of acrylic acid and methyl methacrylate (such as the Eudragit poly(methacrylic acid-co-methyl methacrylate) 1:2 range), such as Eudragit L100; Mixing the polymer solution with the microcapsules to be coated; Modifying the solubility of the polymer by lowering the pH. For the aminoplast resins, the pH can be adjusted within the range from 3.5 to 4.5, preferably within the range from 3.7 to 4.2, typically 4, by addition of formic acid, for example. The desolvation of the polymer brings about the formation of condensates. For the Eudragit copolymers of acrylic acid and methyl methacrylate, the pH can be lowered to 5 or less by addition of a strong acid, such as PTSA (para-toluenesulfonic acid) or by a weak acid, such as acetic acid; Typically, Eudragit L100 is soluble for pH values above 5.5 and insoluble below; Migration of the condensates to the water/microcapsules interface, making possible the formation of a polymer membrane around the microcapsules in order to form novel microcapsules. Curing the membrane by increasing the temperature above the crosslinking temperature for aminoplast resins or by increasing the temperature above the temperature which makes possible the formation of a polymer film around the microcapsules. In the case of aminoplast membranes, the microcapsules can be applied to the textile via known textile processes and chemically attached (by covalent bonds or via a binder). In the case of Eudragit L100 membranes, the microcapsules can be applied to the textile from the known processes of the textile industry, generally at a pH of less than or equal to 5.

(55) The invention also relates to the use of a support as presented above for conferring or reactivating a functional group on a surface of a substrate, in which the support is applied to the substrate under the effect of an external stress in order to release the active agent(s).

(56) The external stress can be, without limitation, a mechanical, thermal or chemical stress.

(57) In one embodiment, the substrate is an ophthalmic lens, such as a spectacle lens.

(58) In another embodiment, the substrate is human or animal skin. In this case, the use of the support can in particular be a therapeutic (for example dermatological), cosmetic, cosmetic and nontherapeutic or nontherapeutic use, according to the nature of the active agent or agents.

(59) The invention is illustrated in a nonlimiting way by the following examples.

EXAMPLES

(60) Equipment and Methods

(61) The particles obtained were characterized visually by optical and electron microscopy

(62) optical microscope

(63) scanning electron microscope

(64) The size distribution of the water-insoluble particles was measured with a Malvern Mastersizer 2000 laser particle size analyser.

(65) The atomization is carried out on an SD1 tower equipped with a cocurrent internal mixing nozzle, supplied by TechniProcess.

(66) The D1 pilot plant is a tower for drying by atomization which was designed to have an evaporative capacity of between 1 and 3 kg/h and a drying air flow rate in the vicinity of 100 kg/h.

(67) A. Description of the Tests of Encapsulation by Phase Separation Carried Out (Microspheres)

(68) 1. Procedure for Carrying Out the Tests

(69) Preparation of the solution to be atomized containing: the matrix, the active agent to be encapsulated and the additives, if necessary, in an aqueous medium.

(70) Atomization of the solution on a drying tower and recovery of the particles in the powder form.

(71) 2. Test 1: Ethyl Butylacetylaminopropionate/Acacia Gum:

(72) Formulation at pH 2 and at 50 C.:

(73) 500 g of solution, the formulation of which is favorable to the encapsulation by phase separation for placing the active agent at the center of the capsules:

(74) TABLE-US-00001 Designation Content Acacia gum 24% Ethyl butylacetylaminopropionate 8% para-Toluenesulfonic acid (PTSA) 4% Water 64%
Estimated content of active agent in the powder 25% [8/(24+8)]
NB: The addition of PTSA makes it possible to increase the solubility of the ethyl butylacetylaminopropionate.

(75) Spraying Parameters:

(76) Inlet temperature 180 C.

(77) Outlet temperature 85-90 C.

(78) Nozzle pressure 2 bar

(79) 3. Test 2: Xylitol/Acacia Gum:

(80) Formulation at ambient temperature and neutral pH:

(81) 500 g of solution, the formulation of which is favorable to the encapsulation by phase separation for placing the active agent at the center of the capsules

(82) Xylitol has a solubility in water at 25 C. of 30% by weight.

(83) TABLE-US-00002 Designation Content Acacia gum 21% Xylitol 9% Water 70%
Estimated content of active agent in the powder 30%

(84) Atomization Parameters:

(85) Inlet temperature 180 C.

(86) Outlet temperature 85.5 C.

(87) Pressure of the nozzle 3 bar

(88) Grayish powder (ground acacia), normal appearance of ground acacia, acacia odor, no water uptake

(89) 4. Test 3: NaCl/Acacia Gum

(90) Formulation at ambient temperature and neutral pH:

(91) 500 g of solution, the formulation of which is favorable to the encapsulation by phase separation for placing the active agent at the center of the capsules

(92) TABLE-US-00003 Designation Content Acacia gum 21% NaCl 9% Water 70%
Estimated content of active agent in the powder 30%

(93) NaCl has a solubility in water of 26% by weight at 25 C.

(94) Atomization Conditions:

(95) Inlet temperature 180 C.

(96) Outlet temperature 80 C.

(97) Pressure of the nozzle 3 bar

(98) As the crystal structure of the salt is cubic, the 3E photograph makes it possible to observe that the salt crystals are located inside the capsule (desired location).

(99) 5. Test 4: Zonyl FSO100/Ethylcellulose SD_1023.066

(100) Formulation under cold conditions and neutral pH

(101) 300 g of solution favorable to the encapsulation by phase separation for placing the active agent at the center of the capsules.

(102) Ethylcellulose commercially available as a 30% suspension in water (Aquacoat ECD)

(103) TABLE-US-00004 Designation Content Aquacoat ECD as suspension (30% 50% (15% dry) solids content) Zonyl 9% Triacetin 3% Water q.s. for 100%
Estimated content of active agent in the powder 33%
Atomization Conditions:
Inlet temperature 180 C.
Outlet temperature 80 C.
Pressure of the nozzle 3 bar

(104) B. Description of the Encapsulation of IR3535 by the Adapted Creaspher Process (Microspheres)

(105) 1. Procedure

(106) The slurry of microspheres is prepared in the following way:

(107) 1. Preparation of the fatty phase containing the wax and the active principle to be encapsulated, at 10 C. above the melting point of the wax used

(108) 2. Preparation of the aqueous phase 1 containing a surfactant, a protective colloid, such as acacia gum, and heating to the same temperature as the fatty phase

(109) 3. Addition of the molten fatty phase to the aqueous phase 1 and preparation of an emulsion for 10 minutes with stirring (IKA deflocculating paddle, 1200 rev/min)

(110) 4. Preparation of the aqueous phase 2 containing a surfactant and a protective colloid, such as acacia gum, cooling of the solution to 4 C.

(111) 5. Dropwise transfer of the first emulsion into the second aqueous phase with stirring (mixing paddle, 1000 rev/min)

(112) The particles are recovered in suspension in water.

(113) Test 1: Ethyl Butylacetylaminopropionate (IR3535) in Dynasan 118 (FIG. 3)

(114) TABLE-US-00005 Phase Products/Stages W (g) Fatty phase Oil: Dynasan 118 84.00 Cosmetic wax. Melting point 70-74 C. Active agent: Ethyl 56.00 butylacetylaminopropionate Aqueous phase 1 Water 129.2 Brij 721P 0.72 Fibregum Bio 10.08 Aqueous phase 2 Water 103.56 Ethyl 7.2 butylacetylaminopropionate Fibregum Bio 8.64 Brij 721P 0.60

(115) IR3535 has a solubility in water at 20 C. of approximately 7% by weight.

(116) Beyond, two phases are observed: an aqueous phase containing 7% of IR3535 and a liquid phase of IR3535 alone.

(117) The particles obtained have the following characteristics:

(118) TABLE-US-00006 Particle size determination 12.6 m Concentration of encapsulated active agent 12.6% in the slurry (estimated) 37% in the dry slurry 40% in the capsule Theoretical solids content 41.8%

(119) Application: Deposition of the Capsules by Padding on CEMOI Textile

(120) The bath for impregnating the wipes is composed of ethyl butylacetylaminopropionate/Dynasan 118 microspheres prepared in the preceding example and diluted in water, the concentration of microspheres in the bath being 24.5%. The padding parameters (concentration of the bath and adjustments of the apparatus) are defined in order to optimize the amount deposited as a function of the level of residue.

(121) $\mathrm{Calculation}\mathrm{of}\mathrm{the}\mathrm{level}\mathrm{of}\mathrm{residue}\left(\mathrm{in}\%\right)\text{:}\frac{\left({\mathrm{weight}}_{\mathrm{textile}+\mathrm{deposit}}-{\mathrm{weight}}_{\mathrm{textile}}\right)}{{\mathrm{weight}}_{\mathrm{textile}}}100$

(122) After having defined the level of residue of the textile, the concentration of microspheres in the bath is adjusted so as to deposit a predetermined amount of microspheres on the textile.

(123) The padding parameters thus chosen make possible a deposit of microspheres of 15 m, while keeping them intact (spherical shape), equivalent to approximately 130 mg of active agent per wipe.

(124) The wipes are dried flat and at ambient temperature in order to limit the evaporation of the active agent related to drying in an oven.

(125) C. Description of the Encapsulation by Polycondensation (Microcapsules)

(126) 1. Procedure 1. Production of an acidic aqueous phase containing a cationic surfactant and stabilizers 2. Preparation of the fatty phase containing the dissolved active agent In order to prevent the amphiphilic active principle from migrating into the aqueous phase during the preparation of the emulsion, it is dissolved in a solvent such that the partition coefficient of the active compound in the aqueous phase is as low as possible. 3. Preparation of an oil-in-water emulsion 4. Addition of the silane monomers to the emulsion. Stationary phase of two hours during which the acid hydrolysis of the silanes to give silanols and the migration of the monomers to the interface of the emulsion take place. 5. Increase in the pH by addition of a base and formation of the membrane by a polycondensation reaction of the silanols located at the interface. 6. Neutralization of the medium The particles are recovered in the slurry form.

(127) 2. Test 1: Zonyl FSO100 in Silicone

(128) TABLE-US-00007 Phases Products W (g) Acidic aqueous Water 53.02 phase Tylose H15YG4 0.57 hydroxyethylcellulose CMC 7LC 0.12 carboxymethylcellulose Cationic surfactant: 1.13 Crodacel QM Volpo L3 Special 0.38 Acetic acid 3.79 Formic acid 1.13 Fatty phase Active agent: 3.89 Zonyl FSO 100 Solvent: HFE 7300 34.91 Silicone Dynasylan A 7.91 membrane Dynasylan MTES 7.91 Basic medium for NaOH 8.99 (q.s. for pH 5.5) polycondensation NaOH amount sufficient for pH 7.5 Antimicrobial Symdiol 68T 1.25
Role of the Tylose and CMC: Rheology Modifiers

(129) The particles obtained have the following characteristics:

(130) TABLE-US-00008 Particle size determination: 8.38 m Estimated content of active agent: 33.1% Solids content (65 C.): 18.3% pH: 7.75

(131) D. Description of the Encapsulation by Melamine Around Preformed Capsules (Microcapsules) 1. Dissolution of the water-soluble polymer (melamine) with a surfactant at 35 C. 2. Mixing the polymer solution with the washed and dried capsules to be coated 3. Addition of formic acid: the polymer reacts with the formaldehyde and condenses at the surface of the capsules to begin to form the membrane 4. Increase in the temperature to 80 C. (1 C./min over 45 min): the membrane becomes rigid 5. Addition of melamine and formic acid (continuously over 90 min), crosslinking of the wall and neutralization of the excess formaldehyde. During this stage, the pH has to be kept below 4.5 6. Cooling and increase in the pH with a diethanolamine solution (the addition of DEA makes it possible to consume the residual formaldehyde). 7. The capsules are recovered in the slurry form.