FR2670112A1 - TOTAL OR PARTIAL COATING OF PHARMACEUTICAL ACTIVE INGREDIENTS AND CORRESPONDING COMPOSITIONS. - Google Patents

Abstract

The invention relates to pharmaceutical compositions. The invention relates to pharmaceutical compositions comprising a solid substrate consisting of one or more active ingredients optionally mixed with traditional excipients, characterized in that said solid substrate is fully or partially coated with a mixture of at least one derivative of cellulose and at least one vinyl, acrylic and / or methacrylic and / or cyanoacrylic polymer or copolymer. Application in the pharmaceutical industry.

Description

The present invention relates to pharmaceutical compositions

  in which the active ingredient is subjected to a coating operation There are numerous reasons justifying the use of the technique of total or partial recovery of the active principle or combination of drug-excipients: for example: improved stability vis-à- screw elements of

  the environment, masking of organoleptic

  adverse effects, reduced powderiness of the product with beneficial effects on environmental pollution, greater ease of absorption of the drug by the patient; increased stability of the product by decreasing the possibilities of interaction with other elements involved in the formula, changing the profile of the issuance of the

  drug from the pharmaceutical form, modifies

  cation of the place of absorption of the active ingredient according to the changes in the provision of

  active substance during gastrointestinal transit

intestinal.

  The above results can be obtained: by film-forming coatings of the pharmaceutical form, for example, coated tablets or coated tablets, by formation of a matrix structure which is not applied directly to the surface of the particles of the active ingredient but which is obtained by compression of a mixture of the drug with suitable excipients, by microencapsulation of the active ingredient with barrier substances, using known techniques (Remington's Pharm Sci AR Gennaro Ed, Mack Publ.

  Co U S A 17th Edition, 1985, Chapter 91, pages 1633-

  1643, such as coacervation, emulsion polymerization, interfacial polymerization, etc. i

  Chemical substances that are able to function

  physical barrier in the above sense may be of natural origin or synthetic in nature

or semi-synthetic.

  Gelatin, certain sugars, beeswax or solid oily substances at temperatures below 400 C, natural gums,

  lacquers and others are examples of the former.

  On the other hand, belong to the second group,

  cellulosic derivatives such as hydroxypropyl-

  cellulose, hydroxyl-propyl-methyl-cellulose, ethyl

  cellulose, cellulose acetate / phthalate, cellulose acetate and the like, derivatives of acrylic acid and

  methacrylic, such as methyl acrylate, methacrylate

  methylate, hydroxy-methyl methacrylate, methacrylate

  hydroxy-ethyl crylate, cyanoacrylates and the like, both polymers and copolymers, vinyl derivatives, such as polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl acetate, polyvinyl acetate / phthalate and the like, again, both homopolymers and copolymers, and

  other substances, essentially of a polymeric nature

  such as polylactic acid, polygly acid

  colic, epsilon caprolactone, polyhydroxy-butyric acid

and others.

  The use of each of these substances has advantages and disadvantages associated with application technologies and the achievement of specific objectives. The object of the invention relates to the use of a mixture composed of a cellulose derivative and a polymer of acrylic and / or methacrylic and / or vinylic nature in appropriate proportions to form into grains a powder consisting of only an active ingredient or a mixture of several active ingredients with one or more excipients in order to achieve one or more of the characteristic objectives of the coating operation, namely: to mask the color, the odor and the flavor of the treated substances, improve the stability of the substances

  against the atmospheric agents of the envi-

ronment,

  improve the technological characteristics

  (density, fluidity, degree of consistency, state of agglomeration, cohesion characteristics of the treated substances),

  modification of the solubility characteristic

  and dissolution of the treated substances, modification of the bioavailability of drugs obtained from the treated substances

according to the claims.

  Another object of the present invention is the use of said mixture of cellulosic derivatives and

  acrylic and / or methacrylic and / or vinyl derivatives

  for lamination or coating of medicinal

  caments in the form of tablets, capsules, lozenges, pills, granules, applied by known techniques,

  such as coating in the tank or granulator-

fluid bed desiccator.

  Still another object of the present invention is the use of said mixture of cellulosic derivatives with acrylic and / or vinyl derivatives and / or

  methacrylics and / or cyanoacrylics for the micro-

  encapsulation and coating of crystals of active principle or mixtures of active ingredients or mixtures of active ingredient with excipients by techniques

  known, such as coacervation, inter-

  Facial, spray drying, powder freezing

authorization.

  Indeed, the use of said mixture of poly-

  the practical characteristics of the polymers in question and gives the product characteristics that the functional properties of the different poly-

  mothers do not contain when we consider them isolated-

  is lying. Indeed, by the use of a mixture

  copolymers of esters of acrylic or methacrylic acid

  crylic (known under the trademark Eudragit NE D) and an aqueous dispersion of ethylcellulose (known under the tradename Aquacoat ECD-30), as a solution for granulating a mixture of powders the following advantages can be obtained: compared with the use of Eudragit alone, the waiting time is eliminated to obtain a perfect lamination of the applied film, but without resorting to

  the use of plasticisers, and the temperature of

  The characteristic softening of the copolymer is enhanced, which allows the coated granule to be subjected immediately to operations which can release heat by friction, such as the regularization of the particle size by means of apparatus known to those skilled in the art, for example oscillating granulators or granulators rotating at high speed, without loss of product as a result of the melt of the copolynere and with a net gain in productivity due to the reduction of the treatment times of the product; compared with the use of Aquacoat alone, on the contrary, the total release of the powder or mixture of powders which have been granulated after only a few minutes of immersion in a fluid is obtained.

  aqueous acid, such as the fluid simulating the envi-

  physiological environment of the stomach and known as

that artificial gastric juice.

  The importance of the quantitative and timely availability of the active ingredient from the pharmaceutical form for the purpose of complete bioavailability of the drug is fundamental for the establishment of a correct dosage regimen: the association of a dissolving polymer such as Eudragit type E, with basic functional groups on the side chains, under environmental conditions which promote protonation, with a polymer insoluble in

  all environments, such as ethylcellulose,

  sets up the development of a film which does not present a solution of continuity under conditions of p H higher than 5, whereas in the clearly acidic environments, it is in the form of a grid rich in orifices, and of which the drug

  can be easily extracted by dissolution.

  The mechanism by which the drug is released is a reflection of the proportional contribution

  two polymers; in fact, in a film with

  a clearly cellulosic

  advantage of the release, while in the case of an acrylic or methacrylic or vinylic component greater than 15%, it is the erosion of the film, due to the partial solubilization of the aforementioned component, which governs the speed at which the

drug is available.

  A judicious choice of the two polymers

  film makes it possible to act on the modalities and

  the time the product is released from

  such as hydroxy-propyl methylcellulose with high viscosity (Methocel E 15) and Eudragit RL, or ethyl cellulose (Ethocel or Aquacoat) with Eudragit RL / RS will be very useful for obtaining delayed release medicaments or deferred or controlled, whether obtained by means of a granulation process, or that they are at the level of the coating directly on the pharmaceutical form by known methods Combinations of copolymer of methyl acrylate and methacrylate methyl (MAMMA) with cellulose acetate / phthalate (CAP) or with hydroxypropyl methylcellulose phthalate, or the combination of ethylcellulose or cellulose acetate with Eudragit L or Eudragit S or with polyvinyl acetate phthalate, can guarantee, if the

  proportions are adequate, good gastrointestinal

  resistant and the total release of the active ingredient for conditions of p H similar to those of the

  middle or terminal part of the digestive tract.

  The direct use of these polymers in

  mixture also makes it unnecessary to add a

  to promote the application of the film and the regularity of recovery of the substrate under the

  decrease in their particular transition temperature

and characteristic.

  However, the addition of plasticizers may

  prove useful in reinforcing some of the characteristics

  The properties of the coating can be selected in a well-adapted manner depending on the final characteristics of the product. If it is simply a question of covering the organoleptic characteristics, it is possible to choose plasticizers that are soluble in an aqueous medium, such as

  polyethylene glycols of different polymer levels

  propylene glycol, glycerine; if it is a question of reinforcing resistance to the penetration of water, it is possible to use acetylated monoglycerides or diethyl phthalate or dibutyl phthalate or dibutyl sebacate. Triethyl citrate and triacetin are

  other substances often used as plasticizers

cants.

  At any stage of the formulation of the coating films, conventional excipients, for example, surfactants, opacifying or coloring pigments, flavor modifiers, bacteriostats, solid dyes,

blisters or anti-foam agents.

  The percentage of these auxiliary substances, expressed with respect to the total content, in the solid material of the coating material is generally less than 25%. More particularly, it is between 0.1 and 15% for lakes and dyes, opacifiers and bacteriostats and

  sweeteners or modifiers of sapi-

  ity; often, but not exclusively, this percentage varies from 0.01 to 5% p p for soluble dyes and surfactants; for antifoam agents it is

generally less than 1%.

  Among the solvents for applying the coating

  Water is certainly the most used for reasons of cost and environmental pollution The properties of the coating however remain unaltered even if particularly in the case of certain polymers which are not commercially available in the form of latex organic solvents such as acetone, ethyl alcohol, isopropyl alcohol, chloroform, dichloromethane, ethyl acetate, are used.

  alone or mixed in indifferent proportions.

  The typical method of application of the invention is to choose the pair of polymers or copolymers which are most suitable for achieving the objective.

  among those listed below,

  top and to formulate a solution or a suspension which makes easy the capillary and uniform distribution

  on the solid substrate to be treated, possibly using

  to traditional excipients.

  Therefore, a solution or a suspension

  type of coating will be composed of the basic elements

  One or more polymers or copolymers derived from cellulose, selected from the group of substances listed above, in weight ratios in percent P / V with respect to the total volume of the solution or suspension between 0. , 3 and 33%,

preferably between 1 and 20%.

  One or more polymers or copolymers derived from an acrylic and / or methacrylic and / or vinylic structure, chosen from the group of substances

  above, in weight ratios in terms of

  percent W / V based on the total volume of solution or suspension between 0.3 and 33%, preferably between 1 and 20% A solvent or a mixture of solvents miscible with them, which can dissolve or homogeneously disperse the polymers and the following accessory elements: One or more surfactants, in weight ratios in percent P / V with respect to the total volume of solution or suspension included, preferably but

not exclusively, between 0 and 10%.

  Substance modifying the sapwood

  such as sweeteners, mineral salts or aromatics

  in weight ratios in percent P / V by

  in relation to the total volume of the solution or suspension

  generally, but not exclusively, less than

10%.

  Plasticizing substances, in weight ratios in% w / v with respect to the total volume of the solution or of the suspension included, generally but not exclusively between 2 and 50%, and preferably,

between 8 and 33%.

  Coloring substances, whether under

  lacquer or soluble and / or opaque pigment

  in weight ratios in percent w / v of the total volume of the solution or suspension, generally but not exclusively,

  10% and preferably between 0.01% and 5%.

  Anti-foaming substances, in weight ratios in percent W / V with respect to the total volume of the solution or suspension generally, but not exclusively, less than 3%, and preferably

between 0.1% and 1%.

  The polymeric solution or suspension

  cited can find application in the total or partial coating of solid substrates of different morphology, consistency and dimension: it can indeed be used for the recovery of isolated crystals of active principle, by the techniques normally used for this type of microencapsulation, or again for the recovery of a mixture of one or more principles

  with other inert pharmaceuticals

  only by means of a mixing and granulating operation, or also to coat with a thin polymeric film pharmaceutical forms such as tablets, capsules or pellets by proceeding according to the known techniques of film coating in tank or

fluid bed desiccator.

  In particular, the coating operation

  powder can be done in

  known as kneaders or kneaders-

  granulators, arm, ring-type, rotary-blade, whether or not equipped with an appropriate agglomerated grinding device, or in dynamic flow apparatus known as fluid bed dehydrators When working with these machines, the operation of the coating is improved by pouring, or better still, by spraying, by means of a nozzle of

  nebulization, a fine mist of the solution / -

  granulation suspension / coating on the mass of

  powders kept in motion by the rotation of

  In the case of a fluid bed apparatus, it is obviously important, particularly with the latter type of apparatus, that the solution / suspension spreads uniformly. on the surface of the powder crystals so as to leave in deposit, after evaporation of the solvent, a thin film, homogeneous and sufficiently elastic to withstand the mechanical stresses and friction that accompany the following operations of sieving, sizing and possible mixing with Subsequent excipients The granules thus coated can indeed be used also for the preparation of pharmaceutical forms of more complex composition: by mixing with other excipients, they can enter into the composition of oral granules for suspensions prepared or stagnant by simple mixing and / or or subsequent granulation with binders for distribution in capsules or in granular form take directly or after dispersion in water or in an appropriate solvent; by mixing with lubricants or disintegrating agents, they can then be compressed to form

  monodose oral pharmaceutical products with strong cohesion.

  The present invention also finds

  applications in the coating of pharmaceutical forms

  In this case, too, it is the objective which has been fixed for the application of the coating film which determines the choice of the pair of polymers, while that their proportions

  reciprocal in the composition of the solution / -

  The suspension used for the coating is chosen according to the level of performance that we want to achieve. If we take as an example the association Ethylcellulose / Eudragit E, it is obvious indeed that if the first of these polymers dominates in the mixture, the tendency will be to obtain a delayed release product, immediately after a phase of therapeutic inertia proportional to the duration of the passage in the stomach, whereas, if the second polymer dominates clearly quantitatively, we will obtain only a good gastro-resistance Similarly, if we consider for example the couple of polymers or

  methyl methacrylate / hydroxypropyl copolymers

  methylcellulose of medium viscosity, if the former clearly dominates, a retardation product with pronounced bio-adhesivity characteristics will be obtained, while a clearly

  favorable to the second will have an effect that does not go well

  beyond the mere masking of

Leptics of the substrate.

  The operation of the coating of pharmaceutical forms

  Solid technologies can be perfected by means of known techniques which make use of equipment which has become traditional, such as the different types of vats or fluid bed desiccators. With both types of installation, it is possible to use aqueous or organic solvents: Since many of the abovementioned polymers are insoluble in aqueous solvents, the use of latexes, namely microscopic or sub-microscopic dispersions obtained using very advanced homogenization These latex

  make it possible to apply pseudo-solutions macrosco-

  homogeneous amounts of insoluble substances, without increasing the manufacturing costs by subsequent recovery and solvent treatment costs

  According to the invention, it is possible to treat

  All types of known active ingredients are examples of active ingredient classes that can be advantageously used:

  anti-inflammatory, bronco-dilator, anti-spasmodic

  that, vasoconstrictor, positive inotropic, inotropic

  negative, anti-pyretic, immunomodulatory, anti-

  neoplastic, analgesic, mucolytic, antacid, vaso-

dilator, anti-thrombosis.

  Particular preference is given to the use of one of the following active ingredients: ergot alkaloids and their derivatives, thiaprophenic acid, theophylline, paracetamol,

  lysine acetyl salicylate, thiazolidine

  arginine carboxylate, theophylline-acetate

  broxol, carbocysteine, sobrerol, diclofenac,

  aminophylline, N (1-pyroglutamoyl) thiazo-

  lidine-4-carbosilicic acid, L-pyroaminoadipyl-leucyl-

prolinamide (RGH 2202).

  The examples shown below serve to better

  illustrate the invention without limiting it on the other hand.

EXAMPLE 1

  The following quantities of powders are loaded into a blade mixer-granulator: Thiaprophenic acid 9 kg Sodium chloride 1.2 kg Saccharin sodium 0.9 Mannitol 4.5 kg

  and mixed until homogeneity is achieved.

  On the mixture which is kept in agitation

  Then, a polymeric dispersion obtained by dissolving 180 g of sodium dioctylsylfosuccinate in 720 ml of water and adding successively 800 g of acrylic and methacrylic ester copolymer known under the trade mark Eudragit NE 30 D (R ) and 1.6 kg of aqueous ethylcellulose latex, known as

  trademark AQUACOAT ECD-30 (R).

  Once the vaporization phase of the coating suspension has been completed, the mixture is homogenized.

  by a vigorous agitation and regulates the granulation

  lometri by sieving with a sieve of 2 mm mesh.

  The granulate is dried in a hot air stream at 40 ° C until a residual moisture content of not more than 3% is reached and the dried granule is forced through a sieve of appropriate size. The granulate has a good masking of the bitter and pungent flavor characteristic of thioprophenic acid.

EXAMPLE N 2

  550 g of coated granule obtained obtained by proceeding as described in Example 1 are mixed with the following excipients: aroma mint 50 g ammonium glycyrrhizate 20 g colloidal silica 8 g sucrose 2,372 kg A granulate mixed with the powder that is easy to divide into unit doses of 3 g

  means of an industrial-type packaging machine

  triel. The taste of the granules, mixed with a little water

  cold, is clearly sweet and aromatic.

  The dissolution rate in a gastric juice

  artificial scale is practically equal to a granule of the same composition obtained by granulating the powder with a syrup of sugar rather than with the pair of polymers

Eudragit NE 30 D / Aquacoat ECD-30.

EXAMPLE N 3

  6.7 kg of granulate obtained by proceeding as described in Example 1 are placed in a mixer-granulator with rotating blades, as well as 600 g of mint flavor, 240 g of ammonium glycyrrhizate and 28 kg of sugar. refined and then wetted with 1 kg of 60% syrup When the wetting is completed, the grinding device is actuated to break up the agglomerates that may be formed, and then the granule is dehydrated until

  with a residual moisture content of less than 2%.

  After screening on a sieve of appropriate size, the granule is divided into unit doses of 3 g by means of high speed packaging machines. The flavor of the granules, dispersed in a little water is perfectly sweet and aromatic, so that the objective of an effective coating masking the bitter and pungent taste of the active ingredient is perfectly achieved. EXAMPLE NO. 4 3 kg of tablets containing thiaprophenic acid are placed in a tank and film-coated, according to the known technique, with a solution composed of: (%) Eudragit L 30 D 32% Aquacoat ECD 30 8%

PEG 6000 1.2%

  Dibutyl phthalate 0.1% Defoaming emulsion 0.1% Purified water, 100% qs At the end of the film coating, the tablets overcame the gastro-resistance test by supporting without alteration a two-hour stay in a room. solution of p H 1,2 (artificial gastric juice), thermostatically controlled at a temperature of 37 * C + 1 C Tablets can disintegrate in 60 minutes in a

  buffer of p H 6.8 (artificial enteric juice).

EXAMPLE N 5

  13 kg of inert excipient are mixed with 2 kg of methane.

  dihydroergocristine sulfonate and is wetted by a

  coating solution composed as follows (in

  percent): ethylcellulose latex (commercially known as Aquacoat ECD-30 (R)) 48% acrylic and methacrylic ester copolymer latex (commercially available under the trade name Eudragit NE 30 D (R) 24% ionic surfactant 3% purified water 25% until the appropriate pasty consistency is obtained The mixture is granulated on sieves with 1.2 mm openings, and dehydrated until a

  residual moisture content less than 3%.

  The dehydrated granulate is finally regulated

  rised through a sieve of dimensions

  appropriate, before mixing with the appropriate excipients

  then divided into unit doses, equivalent to 20 mg of active ingredient, in

  equipped with a drill of appropriate size.

  The reservoir plugs are mounted on a vial containing 7 ml of an aqueous solution, flavored and sweetened, buffered to a pH greater than 5. By means of plug perforations made by shears, the granule is dispersed in the solvent solution. by forming a suspension of pleasant flavor, the very bitter taste of the alkaloid which constitutes the active ingredient being completely masked by the

  film deposited during granulation.

  The amount of active ingredient dissolved in the solvent solution after two minutes after reconstitution was measured as less than 1% of the dose, whereas after five minutes this amount was 1%. Despite the insolubility in water of the active ingredient, due to the presence of the coating film, the bioavailability of the product should not be impaired if it is considered that the product has the following dissolution profile in a juice. artificial gastric: Time (minute) 5 10 20 30% dissolved 61 + 16 81 + 12 93 + 7 100 + 3

EXAMPLE N 6

  Proceeding as described in Example 5, the same amount of nicergoline was used as the active ingredient, instead of the dihydroegocristin.

  The results obtained reflect, from the point of view of

  bility and dissolution, those given about dihydroergocristine: Time (minutes) in gastric juice art 100% 100% 100% 100% in enteric juice art 3.2%

EXAMPLE N 7

  650 g of the granulate obtained were mixed by proceeding as described in Example 5 but doubling the amount of the polymers with ten grams of magnesium stearate, and they were pressed in a rotary press machine with multiple diameter punches.

10 mm.

  Tablets with a unit weight of 330 mg containing 20 mg of active ingredient, hardness are obtained.

  4 Kp, disintegrating in the water in about 15 minutes.

  In comparison with complete disintegration in this period of time, the dissolution profile obtained with USP XXI apparatus 2 is as follows: Time (minutes) 15 30 60% dissolved 40.0 68.7 96.1 D after the data described above, it can be deduced that a partial recovery of the active ingredient is obtained which also determines the slowing down of the release rate.

  dissolution obtained under the same experimental conditions

  for a single tablet without coating film on the granule reaches 90% dissolution

within ten minutes.

EXAMPLE 8

  200 g of theophylline-ambroxol acetate are mixed with 250 grams of inert carrier and 10 grams of sodium saccharin. The mixture is put in an aqueous suspension composed of: Methyl acrylate-methyl methacrylate latex (MAMMA) 25% w / v Hydroxypropyl methylcellulose 2.5% w / v Carboxyvinyl polymer 0.5% w / v Aluminum lacquer 0.5% W / V

PEG 6000 1.25% w / v

  After granulation, dehydration and sieving, the granule is added to the inert excipients and is divided into unit doses equal to

active ingredient of 100 mg.

  The dissolution test in artificial gastric juice determined that the active ingredient

  is released at 100% within fifteen minutes.

EXAMPLE N 9

  To 484 g of granulate, produced by proceeding as described in Example No. 8, dehydrated and sieved,

  add 6 g of magnesium stearate.

  After mixing, the granulate is compressed to the unit weight of 490 mg using curved punches of

11 mm in diameter.

  Tablets with a hardness greater than 6 Kp are obtained and, despite a disintegration time of about 30 minutes, the tablets have shown the following profile for dissolution in a juice.

  artificial gastric with the device 2 USP XXI.

  Time (minutes) 15 30 60 120% dissolved 12.2 35 44 58 EXAMPLE 10 One hundred grams of L-pyroaminoadipyl-leucine-prolinamide (RGH 2202) are mixed with 1.35 kg of inert carrier and are wetted until to obtain a consistency

  pasty, by means of a suspension of coating pre-

  the following percent composition: Ethylcellulose latex (suspension

at 30% w / w) 40%

  Latex of copolymers of acrylic and methacrylic esters (susp 30% w / w) 45% Sodium saccharin 3% purified water 12% The mixture is granulated on a steel sieve with 1.2 mm openings until 'a content

  residual moisture not exceeding 3%.

  Finally, the dehydrated pellet is passed through a sieve of appropriate size steel and mixed with the appropriate excipients before being divided into unit doses. We obtain a mixture that is easy to divide and,

  after dispersion in water, free from bad taste.

  400 g of paracetamol are mixed with 30 g of microgranular cellulose and 20 g of corn starch before being granulated with a binder solution having the following percentage composition: Polyvinylpyrrolidone 1.14% Ethyl cellulose 74.6% Acrylic copolymer latex (Eudragit RS 30 D) 1.14% Hydrogenated castor oil 13.6% Diethyl phthalate 6.9% Stearic acid 0.35% Magnesium stearate 22.27% Apres drying and sieving, the granule is compressed to the unit weight of 550 mg; slow-release tablets are obtained which, in an artificial enteric juice of pH 6.8, give the following dissolution profile: Time (hours) 0, 5 1 2 4 6 8 12% dissolved 7.6 12, 6 20.1 32.8 44.9 52.9 63.7

Claims (6)

  Pharmaceutical compositions comprising a solid substrate consisting of one or more principles   active ingredients possibly mixed with traditional excipients   characterized in that said solid substrate is wholly or partially coated with a mixture of at least one derivative of cellulose and at least one vinyl or acrylic polymer or copolymer   and / or methacrylic and / or cyanoacrylic.   Compositions according to Claim 1, in which the cellulose derivatives are chosen   among the following: hydroxypropylcellulose, hydroxyl   ethylcellulose, hydroxypropyl methylcellulose, carboxy   methylcellulose, ethylcellulose, cellulose acetate,   cellulose acetate phthalate, acetate phthalate   droxypropyl methylcellulose, carboxyethylcellulose, acetic acid   hydroxypropyl cellulose acetate, acetate phthalate   droxy-propylcellylose. Compositions according to claim 1, in which the acrylic or methacrylic polymers or copolymers are chosen from polyacrylates of   methyl, polymethyl methacrylates, poly-   methyl acrylate-methyl methacrylate, alcohol   polyvinyl acetate, polyvinyl acetate, acetate-phthalate   polyvinylate, polyvinylpyrrolidone.   4 Compositions according to any one of   claims 1 to 3, characterized in that the   The cellulose derivative used is a latex of ethyl   cellulose. 5 Compositions according to any one of   preceding claims characterized by the fact   that the polyacrylic derivative used is a latex of   copolymers of esters of acrylic or methacrylic acid   crylique. 6 Compositions according to any one of   preceding claims characterized by the fact   that the cellulose derivative and the polymer or copo-   vinyl, acrylic and / or methacrylic polymers are present in weight ratios between 1/10 and 10/1.   7 Compositions according to any one of   preceding claims characterized by the fact   that the cellulose derivative and the vinyl, acrylic and / or methacrylic polymer or copolymer are   present in weight ratios   between 1/3 and 3/1, preferably 1/3. 8 Compositions according to any one of   preceding claims, in the form of tablets,   capsules, granules, extemporaneous suspensions.   9 Compositions according to any one of   preceding claims characterized by the fact   that the ratios between the cellulose derivative and / or the vinyl and / or acrylic and / or methacrylic polymer or copolymer are chosen so as to obtain a   deferred release of the active ingredient.   Compositions according to any one of   preceding claims characterized by the fact   that the active ingredient is represented by a substance   anti-inflammatory activity, broncodilator, anti-inflammatory   moderate, vasoconstrictor, inotropic, positive, inotropic   negative, antipyretic, antibiotic, immunomodulatory   trice, antineoplastic, analgesic, mucolytic, anti- acid, vasodilator.   11 Compositions according to claim 10, characterized in that the active ingredient is selected from the group consisting of ergot alkaloids and their derivatives, thiaprophenic acid, theophylline, paracetamol, B ^ h acetylsalicylate 2670112 lysine, arginine thiazolidinecarboxylate, ambroxol theophyllineacetate, carbocysteine,   sobrerol, diclofenac, aminophylline, N   pyroglutamoyl) -thiazolidin-4-carboxylic acid, L-pyroamide   noadipil-leucine-prolinamide (RGH 2202). 12 Process for preparing the compositions   claims 1-11, characterized by the steps   following: (a) mixing of an active ingredient or a mixture of active ingredients or of several active ingredients with excipients, (b) mixing and granulation of the mixture of (a) above with a solution or suspension of latex compound a mixture of a cellulose derivative and a vinyl, acrylic and / or methacrylic and / or cryanoacrylic polymer or copolymer, c) optionally mixing the granulate with excipients, diluents, sweeteners, slip agents,   hydrostatic or flavoring agents.