SLOW-RELEASE MEDICAL PLASTER

Abstract

A slow-release medical plaster is described, based on diclofenac, specifically a medical plaster based on diclofenac sodium salt, whose formulation allows the release of the active ingredient continuously and at locally therapeutically active concentrations over 24 hours, and also the polymer adhesive matrix (PSA) for use in a medical plaster based on diclofenac sodium salt.

Claims

1. A medical plaster comprising a base layer (backing), a “Pressure Sensitive Adhesive” (PSA) matrix, a protective coating layer (liner), wherein the PSA matrix comprises or consists of: a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio, in a concentration ranging from 40 to 49% by dry weight with respect to the dry weight of the matrix; a plasticizing agent selected from esters of citric acid, in a concentration ranging from 40 to 49% by weight with respect to the dry weight of the matrix; butylhydroxyanisole (BHA) in a concentration ranging from 0.10 to 0.20% by weight with respect to the dry weight of the matrix; there being dispersed in said PSA matrix an active ingredient, which is diclofenac sodium, in a concentration ranging from 1 to 20% by weight with respect to the dry weight of the matrix.

2. The medical plaster according to claim 1, wherein the esters of citric acid are selected from triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, preferably the ester is tributyl citrate.

3. The medical plaster according to claim 1, wherein the PSA matrix comprises or consists of: a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio in an aqueous dispersion at 40% by weight, in a concentration ranging from 45 to 48% by dry weight with respect to the dry weight of the matrix; a plasticizing agent which is tributyl citrate, in a concentration ranging from 45 to 48% by weight with respect to the dry weight of the matrix; BHA in a concentration ranging from 0.13 to 0.18% by weight with respect to the dry weight of the matrix; diclofenac sodium being dispersed in said PSA matrix, in a concentration ranging from 5 to 10% by weight with respect to the dry weight of the matrix.

4. The medical plaster according to claim 1, wherein the PSA matrix comprises or consists of: a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio in an aqueous dispersion at 40% by weight, in a concentration equal to 46.3% by dry weight with respect to the dry weight of the matrix; tributyl citrate, in a concentration equal to 46.3% by weight with respect to the dry weight of the matrix; BHA in a concentration equal to 0.15% by weight with respect to the dry weight of the matrix; diclofenac sodium being dispersed in said PSA matrix, in a concentration equal to 7.25% by weight with respect to the dry weight of the matrix.

5. The medical plaster according to claim 1, wherein the base layer (backing) consists of a non-perforated 100% polyester non-woven fabric.

6. The medical plaster according to claim 1, wherein the protective coating layer (liner) is a protective sheet of monosilicone paper.

7. A medical plaster according to claim 1, for use in the once-a-day treatment of painful and inflammatory conditions affecting the musculoskeletal system and of traumas.

8. An adhesive polymeric matrix (PSA) comprising or consisting of: a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio, in a concentration ranging from 40 to 49% by dry weight with respect to the dry weight of the matrix; a plasticizing agent selected from esters of citric acid, in a concentration ranging from 40 to 49% by weight with respect to the dry weight of the matrix; butylhydroxyanisole (BHA) in a concentration ranging from 0.10 to 0.20% by weight with respect to the dry weight of the matrix; there being dispersed in said PSA matrix an active ingredient, which is diclofenac sodium, in a concentration ranging from 1 to 20% by weight with respect to the dry weight of the matrix.

9. The adhesive polymeric matrix (PSA) according to claim 8, wherein the esters are selected from triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, preferably the ester is tributyl citrate.

10. The adhesive polymeric matrix (PSA) according to claim 8, comprising or consisting of: a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio in an aqueous dispersion at 40% by weight, in a concentration ranging from 45 to 48% by dry weight with respect to the dry weight of the matrix; a plasticizing agent which is tributyl citrate, in a concentration ranging from 45 to 48% by weight with respect to the dry weight of the matrix; BHA in a concentration ranging from 0.13 to 0.18% by weight with respect to the dry weight of the matrix; diclofenac sodium being dispersed in said PSA matrix, in a concentration ranging from 5 to 10% by weight with respect to the dry weight of the matrix.

11. The adhesive polymeric matrix (PSA) according to claim 8, comprising or consisting of: a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio in an aqueous dispersion at 40% by weight, in a concentration equal to 46.3% by dry weight with respect to the dry weight of the matrix; tributyl citrate, in a concentration equal to 46.3% by weight with respect to the dry weight of the matrix; BHA in a concentration equal to 0.15% by weight with respect to the dry weight of the matrix; diclofenac sodium being dispersed in said PSA matrix, in a concentration equal to 7.25% by weight with respect to the dry weight of the matrix.

12. The medical plaster according to claim 7, wherein painful and inflammatory conditions affecting the musculoskeletal system and traumas are selected from osteoarthritis, sprains, muscle tears, bruises with intact skin.

13. The medical plaster according to claim 1, wherein the PSA matrix comprises or consists of: a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio in an aqueous dispersion at 40% by weight, in a concentration ranging from 45 to 48% by dry weight with respect to the dry weight of the matrix; a plasticizing agent which is tributyl citrate, in a concentration ranging from 45 to 48% by weight with respect to the dry weight of the matrix; BHA in a concentration ranging from 0.13 to 0.18% by weight with respect to the dry weight of the matrix; diclofenac sodium being dispersed in said PSA matrix, in a concentration ranging from 5 to 10% by weight with respect to the dry weight of the matrix.

14. The medical plaster according to claim 2, wherein the PSA matrix comprises or consists of: a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio in an aqueous dispersion at 40% by weight, in a concentration equal to 46.3% by dry weight with respect to the dry weight of the matrix; tributyl citrate, in a concentration equal to 46.3% by weight with respect to the dry weight of the matrix; BHA in a concentration equal to 0.15% by weight with respect to the dry weight of the matrix; diclofenac sodium being dispersed in said PSA matrix, in a concentration equal to 7.25% by weight with respect to the dry weight of the matrix.

15. The medical plaster according to claim 3, wherein the PSA matrix comprises or consists of: a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio in an aqueous dispersion at 40% by weight, in a concentration equal to 46.3% by dry weight with respect to the dry weight of the matrix; tributyl citrate, in a concentration equal to 46.3% by weight with respect to the dry weight of the matrix; BHA in a concentration equal to 0.15% by weight with respect to the dry weight of the matrix; diclofenac sodium being dispersed in said PSA matrix, in a concentration equal to 7.25% by weight with respect to the dry weight of the matrix.

16. The medical plaster according to claim 2, wherein the base layer (backing) consists of a non-perforated 100% polyester non-woven fabric.

17. The medical plaster according to claim 3, wherein the base layer (backing) consists of a non-perforated 100% polyester non-woven fabric.

18. The medical plaster according to claim 4, wherein the base layer (backing) consists of a non-perforated 100% polyester non-woven fabric.

19. The medical plaster according to claim 2, wherein the protective coating layer (liner) is a protective sheet of monosilicone paper.

20. The medical plaster according to claim 3, wherein the protective coating layer (liner) is a protective sheet of monosilicone paper.

Description

DESCRIPTION OF THE INVENTION

[0015] The present invention relates to a medical plaster comprising [0016] a base layer (backing), [0017] a “Pressure Sensitive Adhesive” (PSA) matrix, [0018] a protective coating layer (liner),
wherein the PSA matrix comprises [0019] a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio, in a concentration ranging from 40 to 49% by dry weight with respect to the dry weight of the matrix; [0020] a plasticizing agent selected from esters of citric acid, in a concentration ranging from 40 to 49% by weight with respect to the dry weight of the matrix; [0021] butylhydroxyanisole (BHA) in a concentration ranging from 0.10 to 0.20% by weight with respect to the dry weight of the matrix;
there being dispersed in said PSA matrix [0022] an active ingredient, which is diclofenac sodium, in a concentration ranging from 1 to 20% by weight with respect to the dry weight of the matrix.

[0023] It is specified that the neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio is available on the market in an aqueous dispersion at 30% or 40% by weight of dry product (respectively Eudragit® NE30D and Eudragit® NE40D, Evonik Industries AG Technical Information).

According to the present invention, the Applicant claims a medical plaster comprising a PSA matrix, and the PSA matrix itself, comprising [0024] a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio, in a concentration ranging from 40 to 49% by dry weight with respect to the dry weight of the matrix
the range from 40 to 49% by dry weight of said copolymer thus referring to the weight of the dry product contained in the aqueous dispersion as above disclosed. It is preferred the neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio, in an aqueous dispersion at 40% by weight (Eudragit® NE40D).

[0025] In the medical plaster according to the present invention, the “Pressure Sensitive Adhesive” (PSA) matrix is applied by spreading on the base layer (backing), said matrix then being coated by the protective coating layer (liner), to be removed before application.

[0026] The main advantage of the medical plaster containing diclofenac sodium salt according to the present invention consists in the fact that, after local application, it releases the active ingredient for the following 24 hours at therapeutically active concentrations on the site of application. The plaster is soft, flexible, adheres perfectly to the skin, is removed without causing pain or irritation, maintains the stability of the active ingredient over time and, ensuring its pharmacological effect for 24 hours, significantly improves the compliance of the patient, who will have to replace the plaster only once, and not two or more, times a day.

[0027] The present invention further relates to said medical plaster for use in the once-a-day treatment of painful and inflammatory conditions affecting the musculoskeletal system, such as for example osteoarthritis, and also traumas such as sprains, muscle tears, bruises with intact skin, more specifically when a localized effect is desired and it is preferable or necessary to avoid the administration of painkillers/anti-inflammatory drugs orally or by injection.

[0028] The present invention also relates to a polymeric adhesive matrix (PSA) comprising or consisting of: [0029] a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio, in a concentration ranging from 40 to 49% by dry weight with respect to the dry weight of the matrix; [0030] a plasticizing agent selected from esters of citric acid, in a concentration ranging from 40 to 49% by weight with respect to the dry weight of the matrix, as above defined; [0031] butylhydroxyanisole (BHA) in a concentration ranging from 0.10 to 0.20% by weight with respect to the dry weight of the matrix;
there being dispersed in said PSA matrix [0032] an active ingredient, which is diclofenac sodium, in a concentration ranging from 1 to 20% by weight with respect to the dry weight of the matrix.

[0033] The medical plaster according to the present invention comprises or consists in its entirety of: [0034] a layer that acts as a base (backing), on which it is uniformly spread [0035] a “Pressure Sensitive Adhesive” matrix in which it is dispersed [0036] the active ingredient, this matrix being coated by [0037] a protective layer that acts as a liner, to be removed before application.

[0038] The backing is made of a soft and flexible material, shapeable in any form and size: in general a polymer base is used, in particular polyester is used. In the plaster described herein, the backing is anon-perforated 100% polyester non-woven fabric, which improves adhesion to the skin and prevents the adhesive matrix, and with it the dispersed drug, from leaking out.

[0039] The liner is a protective sheet of monosilicone paper, which can be easily removed.

[0040] The active principle used in the medical plaster according to the present invention is diclofenac sodium salt (DicloNa); as already mentioned, the choice of salifying diclofenac is necessary, considering the chemical-physical properties of this active ingredient. With respect to the choice of salt, it is known in the state of the art that the nature of the counter-ion with which diclofenac is salified is extremely important: in particular, it is essential for the salt to maintain sufficient hydrophobicity as to be able to pass through the corneum stratum of the skin but to be sufficiently hydrophilic as to be able to be diffused in the underlying layers, reaching locally therapeutically active concentrations, as required for a medical plaster. The diclofenac salts that have shown the best performance in this sense are organic salts with aliphatic amines, both linear and cyclic. Diclofenac salts with inorganic bases, in particular with potassium or sodium, on the contrary, are less suitable for this type of application as they have very low partition coefficients, up to 3,000 times lower than those of acid diclofenac; their very high hydrophilicity therefore strongly limits their passage through the corneum stratum of the skin (Fini et al., 2012, Pharmaceutics, 4, 413-429).

[0041] In confirmation of this, there are products on the market based on diclofenac for topical application in the form of emulgel, in which the active ingredient is salified with diethylamine, which is a linear amine (e.g., Voltaren Emulgel®), or in the form of a medical plaster, more interesting for the purposes of the present invention, in which the salification takes place with hydroxyethylpyrrolidine, which is a cyclic amine (for example the medical plaster Flector®).

[0042] The possibility of using the sodium salt of diclofenac represents a marked improvement with respect to the state of the art in terms of industrial processing and potential side-effects of the final product. With respect to the industrial aspect, the synthesis of the sodium salt is effected very simply and economically, without 5 the use of toxic reagents, without the need for the controlled disposal of processing waste. As regards the potential side-effects of the final product, it is known that aliphatic amines, especially cyclic amines, can be toxic or at least very frequently give rise to irritative phenomena, due to the release of the amine as such or of its metabolites (Myers et al, 1997, J Tox Subst Mech, 16, 2; Greim et al., 1998, Chemosphere, 36, 271-295).

[0043] The use of the sodium salt of diclofenac therefore eliminates these problems and makes the plaster object of the invention also applicable to sensitive and easily irritable skin, such as that, for example, of an elderly patient or potentially allergic or atopic subjects.

[0044] The PSA matrix is composed of an aqueous dispersion of copolymers deriving from esters of acrylic and methacrylic acids, preferably it is composed of Eudragit® NE40D (Evonik Industries), i.e. a poly(ethyl-acrylate, methyl-methacrylate) copolymer in a ratio of 2:1 in an aqueous dispersion at 40% by weight. A plasticizing agent selected from esters of citric acid is added to this copolymer, preferably a plasticizing agent which is tributyl citrate; a matrix similar to that described for example in WO2012089256 is thus obtained, already tested, unsuccessfully, for the release of diclofenac in the form of sodium salt.

[0045] The Applicant has however surprisingly discovered that the addition to the matrix described above of minimal quantities of butylhydroxyanisole (BHA) significantly modifies its properties, allowing the DicloNa dispersed therein to be released in a constant, continuous, prolonged manner, at locally therapeutically active doses for a duration of 24 hours.

[0046] The release profile is completely comparable to that of a commercial product widely used as a once-a-day plaster (Flector®), containing diclofenac salt of hydroxyethylpyrrolidine, therefore a salt with a cyclic amine, and a completely different PSA matrix (based on gelatin, polyvinylpyrrolidone, carboxymethylcellulose and other polymers).

[0047] BHA is an ingredient with an antioxidant and preservative action, widely used 5 in the food, cosmetic, and animal feed industries for avoiding rancidity of the fats contained therein. It is also used in pharmaceuticals, as an excipient in solid formulations of active ingredients of a lipid nature, specifically for avoiding oxidation and therefore the loss, or at least the reduction, of pharmacological activity: they are formulated with BHA, for example, isotretinoin, some statins and ketoconazole (Braz J Pharm Sci, 2012, 48, 405-4015). BHA is also used in liquid pharmaceutical formulations, for example, injections, in the presence of unstable active ingredients.

[0048] Within the scope of the present invention, BHA is used for the first time in a solid composition for topical use devoid of lipid components and which therefore does not require an antioxidant, thus ensuring that, as will be demonstrated hereunder, the diclofenac sodium dispersed in the PSA matrix of the medical plaster object of the invention is released in a constant and continuous manner over 24 hours, possibly reaching the circulatory stream only in traces, thus respecting the definition of medical plaster.

[0049] This result is completely contrary and unexpected with respect to the teachings of the state of the art.

[0050] The evaluation of the release of diclofenac is effected through the Dissolution Test described in the Official Pharmacopoeias, more specifically in the present application through the Dissolution Test described in the European Pharmacopoeia (Ph. Eur. 5.0, 2.9.4). In relation to the different pharmaceutical forms to be tested, the devices for carrying out the Dissolution Test differ from each other in the type of support in which the material to be analyzed is placed. The general methods for carrying out the test are the same: briefly, the sample to be analyzed is positioned in a suitable support, in turn inserted in a larger container in which a medium (Dissolution Medium) heated to a specific temperature is placed, which comes into contact with the sample. The drug is progressively transferred from the sample to the dissolution medium; at regular intervals fractions of the dissolution medium are collected and analyzed in order to calculate the quantity of drug present therein. The analysis is generally effected with a spectroscope or with high-pressure liquid chromatography (HPLC), more frequently with HPLC. In the Dissolution Test it is essential to operate under sink condition, i.e. with large volumes of dissolution medium: only in this way it is possible, in fact, to avoid that the extent of dissolution of the active ingredient be lower than the actual dissolution, due to the progressive increase in concentration in the receiving medium which, if in small volumes, rapidly approaches saturation.

[0051] The PSA matrix of the medical plaster according to the present invention comprises or consists of: [0052] a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio, in a concentration ranging from 40 to 49% by dry weight with respect to the dry weight of the matrix, as defined above; [0053] a plasticizing agent selected from esters of citric acid, in a concentration ranging from 40 to 49% by weight with respect to the dry weight of the matrix; [0054] butylhydroxyanisole (BHA) in a concentration ranging from 0.10 to 0.20% by weight with respect to the dry weight of the matrix;
there being dispersed in said PSA matrix [0055] an active ingredient, which is diclofenac sodium, in a concentration ranging from 1 to 20% by weight with respect to the dry weight of the matrix.

[0056] Preferably the esters of citric acid are selected from triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, more preferably the ester is tributyl citrate.

[0057] The composition of the PSA matrix of the medical plaster according to the present invention preferably comprises or consists of: [0058] a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio in an aqueous dispersion at 40% by weight, in a concentration ranging from 45 to 48% by dry weight with respect to the dry weight of the matrix, as above defined; [0059] the plasticizing agent is tributyl citrate, in a concentration ranging from 45 to 48% by weight with respect to the dry weight of the matrix; [0060] BHA in a concentration ranging from 0.13 to 0.18% by weight with respect to the dry weight of the matrix;
diclofenac sodium being dispersed in said PSA matrix in a concentration ranging from 5 to 10% by weight with respect to the dry weight of the matrix.

[0061] The concentrations are always expressed by weight in relation to the dry weight of the matrix; as the pharmacological effect is exerted by diclofenac sodium alone dispersed in the PSA matrix, as the concentration of the latter varies in relation to the amount of active ingredient to be inserted in the plaster, the quantities of the copolymer and plasticizer will consequently also vary, to complete 100% of the final composition.

[0062] The composition of the PSA matrix of the medical plaster according to the present invention even more preferably comprises or consists of: [0063] a neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio in an aqueous dispersion at 40% by weight, in a concentration equal to 46.3% by dry weight with respect to the dry weight of the matrix, as above defined; [0064] tributyl citrate, in a concentration equal to 46.3% by weight with respect to the dry weight of the matrix; [0065] BHA in a concentration equal to 0.15% by weight with respect to the dry weight of the matrix;
diclofenac sodium being dispersed in said PSA matrix in a concentration equal to 7.25% by weight with respect to the dry weight of the matrix.

[0066] The process for the preparation of the medical plaster object of the invention, containing diclofenac sodium (DicloNa) dispersed in the PSA matrix described above, consists of various phases which can be summarized as follows: [0067] mixing the plasticising agent selected and BHA until dissolved; [0068] addition of DicloNa and mixing until dissolved; [0069] addition of the selected neutral copolymer based on ethyl acrylate and methyl methacrylate in a 2:1 ratio in an aqueous dispersion and mixing until total dispersion; [0070] pouring the PSA/DicloNa matrix mass on a temporary liner; [0071] drying of the mass and its coupling with the backing; [0072] replacement of the provisional liner with the definitive liner; [0073] cutting the plasters to the desired size; [0074] insertion of each plaster in its primary packaging.

[0075] Some examples are provided for better illustrating the purposes and advantages of the present invention, which, however, in no way limit the scope of the claims.

Example 1

Preparation of a Medical Plaster Containing DicloNa 140 mg

[0076] The ingredients for the preparation of each medical plaster having dimensions of 140×100 mm containing 140 mg of diclofenac sodium are:

TABLE-US-00001 mg/ Ingredients plaster % Diclofenac sodium 140 7.25 Eudragit ® NE40D 894.5 46.3 (dry weight corresponding to 2236,38 mg of wet weight) Tributyl citrate (TBC) 894.5 46.3 (Proviplast 2604 - Proviron) Butylated hydroxyanisole (BHA) 2.9 0.15

Method

[0077] TBC and BHA were mixed under stirring and under vacuum for about 15 minutes, until they were completely dissolved. Diclofenac sodium was then added to the mixture, stirring under vacuum until complete dissolution, at a temperature not exceeding 25° C. Eudragit® NE40D was then added, stirring rapidly for about 1 minute, then passing to medium stirring for 10 minutes and finally reducing the stirring rate to a minimum and maintaining it for 2 hours, at a temperature not higher than 25° C., continuing to operate under vacuum.

[0078] The mass was finally left to rest for 8 hours, continuously under vacuum.

[0079] The mass thus obtained was spread on a temporary liner made of siliconized polyester, and placed in a forced ventilation dryer for 5 minutes to dry, within a temperature gradient ranging from 65 to 115° C. The product thus obtained was then coupled by compression with the backing of 100% non-woven polyester and the temporary liner was subsequently replaced with the definitive liner, consisting of monosilicone paper, the plasters were then cut into the desired size (140×100 mm) with the final primary packaging of the plasters thus obtained.

Example 2

Diclofenac Release (Dissolution Test)

[0080] The release of diclofenac from the medical plasters of the present invention was evaluated with the Dissolution Test, using as a comparison a commercial product that releases the active ingredient within 24 hours. The reference product is Flector® (lot 1506031), which contains 180 mg of diclofenac hydroxyethylpyrrolidine salt corresponding to 140 mg of diclofenac sodium.

[0081] The active ingredient that exerts the pharmacological activity and whose release must be evaluated is diclofenac and not its salt, whatever it may be.

[0082] The Dissolution Test is performed as described in the European Pharmacopoeia (Ph. Eur. 5.0, 2.9.4), with the rotating cylinder method, using as Dissolution Medium a phosphate buffer in saline solution with a pH=7.4 (PBS-Ph. Eur. 4.1.3), under the following operating conditions:

TABLE-US-00002 Volume of Dissolution Medium 900 ml Temperature 32° C. ± 0.5° C. Rotation Rate 100 rpm (revolutions/minute) Sampling times 1, 3, 6, 24 hours Sampled quantity 2 ml

[0083] The analysis of the medium sampled was effected with HPLC equipment (Agilent 1100), according to what is known to skilled persons in the field.

[0084] Sample A is the plaster prepared according to Example 1, whereas Sample B is Flector®.

[0085] A portion of 20 cm.sup.2 (2×10 cm) was cut from each sample and, without removing the protective liner, was applied to the external surface of the cylinder with double-sided tape, so as to expose the surface containing the PSA matrix and the diclofenac dispersed therein to the Dissolution Medium, and in such a way that the greater axis of the portion of plaster corresponds perfectly to the circumference of the cylinder. When the temperature of the Dissolution Medium reached the expected value, the protective liner was removed, the sample was coated with a Cuprophan membrane, exceeding the sample size by at least 1 cm, and fixed with adhesive tape; the cylinder was finally immersed in the medium and immediately set in rotation at the prescribed speed. At the established intervals, a sample of 2 ml was taken from an intermediate area between the surface of the Dissolution Medium and the upper edge of the cylinder. The volume withdrawn was immediately replaced with an equal volume of fresh Dissolution Medium.

[0086] The dissolution values and the relative profile are shown respectively in the following Table 1 and in the Graph shown in FIG. 1.

TABLE-US-00003 TABLE 1 Sample A Sample B Time (hours) % Diclofenac release % Diclofenac release 1 29.66 27.35 3 57.38 57.34 6 78.67 80.75 24 100.24 104.66

[0087] It is evident that the diclofenac present in Sample A has a release profile that is absolutely comparable to the diclofenac contained in the Flector® product (Sample B), a reference product among long-lasting medical plasters.

[0088] Sample A, specifically the medical plaster object of the invention, therefore releases the diclofenac from its sodium salt in a constant, continuous and gradual manner over 24 hours, which can effectively exert its pharmacological effect.

[0089] These data are quite surprising as they show that [0090] starting from a PSA matrix which is known to adequately release diclofenac diethylamine salt, but not diclofenac sodium salt and [0091] using diclofenac sodium salt which is known to be unsuitable for use in medical plasters [0092] by adding BHA to the PSA matrix formulation, i.e. a substance known for its antioxidant properties not necessary here, a medical plaster is obtained which [0093] releases the active principle in a constant, continuous, prolonged manner, at locally therapeutically active doses for a duration of 24 hours, and can therefore be replaced only once a day by the person using it; [0094] does not contain linear aliphatic amines or cyclic amines, and therefore does not cause exposure to the risk of toxic or irritative phenomena, and therefore can also be applied on sensitive or easily irritated skin; [0095] is industrially convenient, as the process for the preparation of the sodium salt is rapid, economical and does not involve the controlled disposal of processing waste.