MXPA00012482A - Method for manufacturing a laminate consisting of individual layers - Google Patents

Abstract

The invention relates to a method for manufacturing a laminate consisting of individual layers and comprising the following steps:initially preparing a substrate serving as a support and applying a flowable material as a layer under processing conditions. The invention is characterized in that at least one flowable material is subsequently applied under processing conditions as additional layer and in that at least one layer contains at least one pharmaceutical or cosmetic active substance and/or adjuvant.

Description

PROCEDURE FOR THE MANUFACTURE OF A LAMINATE COMPOSED OF DIFFERENT LAYERS DESCRIPTION OF THE INVENTION The invention relates to a process for the manufacture of a laminate composed of different layers, consisting of a succession of operations in which a support substrate is prepared on which is applied, in the form of a layer, a mass that under production conditions, at least one additional layer is fluid and then on this layer, which under production conditions is also fluid. Laminates are multilayer materials in the form of a band. Laminates in the form of dressings for cutaneous application usually encompass at least one sheet and at least one adherent layer. For the purposes of the invention, "laminate" is understood as a structure composed of different layers, none of which necessarily consists of a sheet. According to the state of the art, multilayer laminates are usually manufactured by joining different layers. A layer of this type is manufactured in such a way that a support substrate is first prepared, usually in Ref: 125898 adhesive sheet form, which is then coated with a "liquid" polymer mass, that is, containing solvent. Subsequent drying of the coated substrate causes evaporation of the solvent and, consequently, crosslinking of the polymer chains of the applied layer. The dried polymer layer can then be covered with a removable sheet. After the indicated operations, the manufacture of a multilayer laminate takes place by joining several layers, eliminating the cover sheet of each layer. The known manufacturing process presents drawbacks from several points of view. In a succession of operations, different layers have to be worked out and then joined together. Since the cover sheets of each layer are removed, the process also consumes a lot of material. On the other hand, the incorporation of active substances and volatile auxiliaries in solids-containing masses causes in the drying process of each layer and / or laminate the evaporation of a possibly considerable fraction of the substances incorporated.

Overall, the conventional coating process used in the manufacture of a multilayer laminate is expensive and uneconomical, sometimes even unsuitable for the vast majority of active substances and auxiliaries of this kind. The invention aims to describe a method of manufacturing a laminate composed of different layers of the type indicated in the generic part of the claim, which, avoiding the above mentioned disadvantages and difficulties, serves to profitably manufacture laminates with pharmaceutical and / or cosmetic ingredients. and at the same time minimize evaporation losses during drying and consumption of cover sheets. The solution of this task is achieved according to the invention by a method of manufacturing a laminate composed of different layers according to the generic part of claim 1, following the operations specified in the specific part of the claim For this, a mass in the fluid state is applied in the form of an initial layer on the solid substrate that serves as support and at least one other mass, also in the fluid state, is applied in the form of an additional layer on the existing initial mass in the form of layer in the fluid state. Next, the multilayer laminate manufactured by this process can be freed from the solvent residues by careful drying. In this way, the different masses arranged in the form of a layer in the fluid state pass to a non-fluid state, for example solid. In addition to drying, this can also be achieved by chemical crosslinking of the individual components of the masses arranged in the form of a layer or by solidification by cooling a fluid mass substantially free of solvents. By flowed state, equivalent to the concept of "liquid" for the purposes of the invention, is understood as the state in which the dough has a consistency such that it allows it to change shape. In this sense, therefore, fusions, solutions, dispersions, suspensions, conglomerates, etc., can exist in a fluid state. of macromolecular substances, for example. This state, which describes the fluidity of a system, is described by the expert by the degree of viscosity. The different masses used in the manufacturing process described are characterized by a dynamic viscosity [mPa s] in a range from 1 to 500,000, preferably from 50 to 10,000 for substances with solvents and from 500 to 250,000 for fusions (hotmelts), and from particularly preferred are between 500 and 5,000 for solvent-based substances, and between 800 and 15,000 for hotmelts. At the end of the process of the invention, the masses of the different layers are in a non-fluid state, for example solid. This means that, in spite of still exhibiting a certain degree of elasticity, the masses have lost the ability to be able to permanently modify the shape of the layer. The method of the invention allows to manufacture multilayer laminates in a single operation per layer without the need to use a support and / or cover sheet, which allows to significantly reduce the working times of the machines and the material costs. By dispensing with intermediate drying, the use of solvents and drying energy is reduced at least to a large extent, two concepts that increase the cost, and the time required for manufacturing is minimized. On the other hand, the use of suitable recipes of the different coating masses, together with the reduction of the operations required for each layer, also makes it possible to manufacture laminates with special properties. The first layer may contain for example a volatile active / auxiliary substance, while the recipe for the next layer, which during the drying process acts as a barrier for the active substance of the previous layer, does not contain active substances. This facilitates the manufacture of laminates with active substances and volatile auxiliaries. In this sense, the different layers can be superimposed advantageously, without intermediate drying, in the "liquid-on-liquid" state. Other variants of the process, described in the subclaims, are provided. One of the variants envisages using a mass containing solvents for a layer. In spite of this, a mass with at least one crosslinkable component can also be used to apply a layer. A variant of the method also provides for the laminate to dry after applying a final layer. For different layers to be applied on the substrate, masses with similar components can be used.

For the application of layers on the substrate can also be used masses whose composition resembles in all but one of the ingredients. For the purposes of the invention, it is not excluded that a layer with 10% minimum solvent content is coated with a second layer. For this, masses differing in thickness and / or viscosity and / or crosslinkability and / or solids content and / or solvent content and / or pH can be used. It is also possible to apply layers of different thicknesses or to choose the same or different coating widths for each layer. The invention also contemplates the possibility of using a monolayer or multilayer substrate as a support for the laminate. The multiple coating of the substrate can be carried out by means of different application and dosing procedures, such as by means of doctor blade, cylinders, distributor sprayer. hotmelt coating processes, or by a combination thereof. According to the method of the invention, the manufacture of the layers can also be provided by printing processes, inking buffer or screen printing. In principle, the thickness of the layers that can be manufactured from the stated fluid masses is not limited. In the process according to the invention, it is basically between 1 and 500 μm, preferably between 10 and 200 μm. However, in certain circumstances, the thickness of the layer may have an upper limit that will depend on the degree of fluidity of the masses in the fluid state. In masses with a good degree of fluidity (low viscosity, that is, relatively liquid, a small external force suffices to be deformed), the thickness of the layer may eventually exhibit an upper limit of this type. Experts, however, know how to influence the fluidity of the dough. A reduction of the melting temperature and / or solvent fraction of the solution (or suspension or dispersion) and / or a greater degree of crosslinking of a polymeric material usually reduce the degree of fluidity. This kind of measures have to be applied eventually to vary the fluidity of the masses so that they serve for the manufacture of layers of the desired thickness. However, if the degree of fluidity of a dough is very low (high viscosity, ie, relatively thick), it must be improved by increasing the melting temperature and / or solvent fraction of the solution and / or reducing the degree of crosslinking of a polymeric material and / or by applying a greater external force (for example, pressure) in the laminate. The process according to the invention is particularly suitable for the manufacture of laminates carrying active substances for topical application in the form of a dressing, in particular in the field of transcutaneous medication. Furthermore, according to the process, laminates carrying active substances not intended for topical use, such as, for example, administration forms in the form of a film or sheet, can also be manufactured. The polymeric material containing the coating masses of the different layers may consist of rubber, homopolymers, copolymers and synthetic block polymers of rubber substitutes, silicones, polyacrylises and copolymers thereof, polyurethane, ethylene polymers, polysiloxanes, etc. They may also contain auxiliary substances that perform the usual functions of plasticizers, binders, absorbents, stabilizers and fillers. The chemical crosslinking of a macromolecular substance, ie a polymer, is carried out by crosslinking agents known to those skilled in the art. These substances usually have at least two functional groups and confer, in the framework of chemical crosslinking, a three-dimensional structure to the chained polymeric molecules. The specific substances for each case depend on the nature of the polymer. By laminates such as those used according to the invention, for example, for cutaneous application, those monolayer and multilayer laminates are understood whose materials are, by virtue of their nature, suitable for prolonged application on the skin. This includes the known "strips", such as Hansaplast®, Leukosilk®, Leukoplast®, as well as dressing materials that also carry active substances, such as the transdermal therapeutic systems (STT) described in K. Heilmann "Therapeutische Syste - Konzept und Realization programmierter Arzneiverabreichung "(4 * edition, 1984). As a rule they include a dorsal layer, a matrix composed of one or more layers and a removable protective layer. The dorsal layer may be composed of a flexible or rigid material. The substances used for their manufacture are of polymeric nature, such as polyethylene, polypropylene, polyethylene terephthalate, polyurethane and polyamide. Other materials to consider are polyvinyl alcohol, styrene-diene block polymers, polyvinyl chloride and polymethacrylates, to name a few examples. Combinations of the indicated materials can also be used. Likewise. As supplementary materials, for example, aluminum vaporized sheets isolated or coated with a polymeric substrate can be used. For the removable protective sheets, in principle they are the same materials, although they must also have adhesion properties, which can be achieved by siliconizing. In addition to one or more active substances, the reservoir, that is, the matrix, which may consist of one or more layers, contains as a rule other auxiliary substances as additives. The substances in question are polymers, such as, for example, polyisobutylene, polyvinyl alcohol ester, polyacrylic acid ester and polymethacrylic acid, natural rubber, styrene polymer, isoprene and styrene-butadiene polymer, silicone polymers, resinous components such as, for example, saturated and unsaturated hydrocarbons, derived from abietinic alcohol and ß-pinene, plasticizers such as phthalic acid ester, triglycerides and fatty acids. The polymeric material of the matrix can also be synthesized from polymers such as rubber, synthetic homopolymers, copolymers and block polymers of rubber substitutes, polyurethanes, ethylene copolymers and polysiloxanes. The mentioned additives, also called auxiliary substances, are classified according to their function in plasticizers, binders, absorbents, stabilizers and fillers. Substances of this type, which must be physiologically safe, are known to the person skilled in the art. For the laminates used in the process according to the invention, and especially for the laminates from which STTs are manufactured, preferably topical pharmaceutical active substances can be used, such as those belonging to the groups of active substances of the parasympatholytics (as for example scopolamine, atropine, benacticine), cholinergic agents (such as physostigmine, nicotine), neuroleptics (such as chloropromazine, haloperidol), monoamine oxidase inhibitors (such as trancylcypromine, salagiline), of sympathomimetics (such as ephedrine, D-norseudoephedrine, salbuta ol, fenflura ina), sympatholytics and anti-Totonic antibodies (such as propanolol, timolol, bupranolol, clonidine, dihydroergotamine, naphazoline), anxiolytics ( such as diazepam, triazolam), local anesthetics (such as lidocaine), central analgesics (such as fentanyl, sufentanil), antirheumatics (such as indometasin, piroxicam, lornoxicam), coronary drugs (such as glyceroltrinitrate, isosorbitoldinitrate), estrogen, androgen, antihistamines (such as diphenhydramine, clemastine, terfenadine), of the prostaglandin derivatives, of vitamins (such as vitamin E, cholecalciferol) and cytostatics. By means of the process according to the invention, in particular of the "liquid-on-liquid" coating of mass carrying active substances and auxiliaries, multilayer laminates can be produced in a closed sequence of highly profitable production operations. It is very advantageous, in particular, to manufacture laminates containing active substances and volatile auxiliaries. In this sense, the invention solves optimally the initially proposed purpose. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (17)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1.
2. Method of manufacturing a laminate composed of different layers, in which in a succession of operations a support substrate is prepared and, on the same, it is applied in the form of a layer at least one mass that under fluid production conditions, characterized by subsequently applying at least one mass, which under fluid production conditions, as an additional layer, and containing at least one layer with at least one active substance and / or pharmaceutical or cosmetic auxiliary, 2.
3. Method according to claim 1, characterized by applying at least one layer without active or auxiliary substance, preferably as a barrier layer, on a substance-containing layer active Method according to claim 1 or 2, characterized in that the layers are applied one on top of the other "liquid on liquid", without intermediate drying.
4. 4. Process according to one or more of claims 1 to 3, characterized in that a mass is used with at least one solvent for the application of a layer.
5. Method according to one or more of claims 1 to 4, characterized in that an emulsion of two immiscible solvents is used as coating material.
6. Method according to one or more of claims 1 to 5, characterized in that an adhesive layer is used.
7. Method according to one or more of claims 1 to 6, characterized in that a mass is used with at least one crosslinkable component for bonding a layer, 8.
8. Method according to one or more of claims 1 to 7, characterized in that the laminate is dried after the application of the last layer.
9. Method according to one or more of claims 1 to 8, characterized in that it is used, for at least two of the layers to be applied on the substrate, to cover masses of similar composition.
10. 10. Process according to one or more of claims 1 to 9, characterized in that, for at least two of the layers to be applied to the substrate, use coating masses of similar composition in all but one of the ingredients.
11. Method according to one or more of claims 1 to 10, characterized in that a layer, with a minimum solvent content of 10%, is coated with a second layer.
12. Method according to one or more of claims 1 to 11, characterized in that coating compositions are used which differ in thickness and / or viscosity, crosslinkability, solids content, solvent content and pH.
13. Method according to one or more of claims 1 to 12, characterized by the application of layers of different thicknesses.
14. Method according to one or more of claims 1 to 13, characterized in that equal or different coating widths are chosen for the different layers.
15. 15. Process according to one or more of claims 1 to 14, characterized in that a monolayer or multilayer substrate is used. Method according to one or more of claims 1 to 15, characterized in that multiple coating of the substrate is applied by different application and dosing methods. Method according to one or more of Claims 1 to 16, characterized by the production of layers by printing, inking or screen printing processes or by the hot-melt application process. PROCEDURE FOR THE MANUFACTURE OF A LAMINATE COMPOSED OF DIFFERENT LAYERS SUMMARY OF THE INVENTION Process of manufacturing a laminate composed of different layers, in which in a succession of operations a support substrate is prepared and, on it, is applied in a at least one mass which is fluid under production conditions, characterized by subsequently applying at least one mass, which under fluid production conditions, as an additional layer, and containing at least one layer with at least one substance active and / or pharmaceutical or cosmetic auxiliary.