SK116393A3 - Oral medicamentous form - Google Patents

Abstract

The invention relates to an oral drug form containing at least one active substance and at least one coating material which envelops the active substance and which contains at least one film former which is insoluble in water and the digestive fluids, characterised in that the coating material additionally contains at least one cyclodextrin and/or at least one of its derivatives.

Description

4'- - ·? U mi-To

Oral dosage form

SUMMARY OF THE INVENTION The present invention provides a novel oral dosage form comprising at least one active ingredient, at least comprising a water-insoluble and digestive insoluble film-forming agent, which additionally comprises at least a cyclodextrin and / or at least one derivative thereof.

It is a further object of the present invention to provide an oral dosage form comprising at least one water-insoluble and digestive insoluble film-forming agent which additionally comprises at least a cyclodextrin and / or at least one derivative thereof.

Previous status

It is an object of the present invention to provide oral medicaments in which the release of active ingredients in the colon is achieved.

As a rule, a gastric and small intestinal resistant coating is obtained which breaks down in the large intestine to release the active ingredient. No. 4,335,840 A2 discloses a coating composition comprising a polysaccharide degradable in the colon and in admixture therewith with a film-forming polymeric substance. However, such a lubricant composition still has significant disadvantages in that it is brittle and the active ingredients are not always specifically released in the colon. DE 41 31 292 A1 describes a galactomannan derivative for coating or coating an active substance,

1 4 λΧ ·! νβ t-i-olvnnnnnnnnnnnnnnnn PT PT i ľ ľ gt & gt & & & gt gt gt gt gt gt gt gt gt; Infi o HOVU - - - - - - 0 -------------------- · --- ·· ... ~ -2-substance, evidence of which toxic in other cases, for example, microcapsules with smip ermeably coatings, 2 '

SUMMARY OF THE INVENTION

These disadvantages of known dosage forms are eliminated or at least reduced from the above-described oral dosage form.

Particularly suitable dosage forms are tablets, peanuts, sachets, capsules, pellets, granules, granules, crystals or powders. The dosage form may also be in an encapsulated form which comprises at least an active agent which is co-cocultured with at least the cyclodextrin in the digestive insoluble film-forming substance.

Suitable film-forming agents according to the invention are preferably polyacrylates, polymethacrylates, as well as their copolymers, as well as ethylcellulose, especially highly substituted ethylcellulose. Especially preferred are commercially available dispersions which contain a copolymer formed from acrylic esters and methacrylic esters and have a low content of quaternary ammonium groups, wherein the molar ratio of these ammonium groups to the remaining neutral esters of acrylic acid and the neutral methacrylic acid ester is from about 1: 10 to 1:50, preferably 1:20 to 1:40 and a mean molecular weight of about 150,000,

rt.-l-T Λ / ifiv + v *! W r > r * l? ^ ΜΓ, οηώ yv riSV j. account. w b - w - - - - - - - - - - - -. · —— jr ------ ~ --- v - a-glycosidic Bound oligcsaccharides, unlike β _ v1 " * " V · * rVv v? and " pr.h nl " t r-nnochari in which S:?. OOU:

w in -ju U k. CA r > λ o o bV ·, w -1 ^ - o ^ .... Z. ~ - r-, ~ J ---.-- f- ·· -t £ U.i " O kt iv; i ujjcí b u: a b u ·. ".ο

As cyclodextrin, 6-cyclodextrin (" CD ", seven glucose units) is preferred. [0105] A- cyclodextrin (six glucose units) and T- cyclodextrin (eight glucose units) are also suitable. -CD and poly-CD

The coating substance may contain additional excipients and / or additives. A preferred additive is a softening agent. As such, particularly preferred are the esters of dicarboxylic or trixooxylic acids, such as diethyl terephthalate (" DE ' P ") or triethyl citrate (" TEC ") * As can be detected by the polarizing microscope, the CD in TEC-containing materials is substantially unchanged form, with DE-containing substances? on the other hand, they have a crystalline structure. Other suitable softening agents are, for example, (other) citric acid esters or tartaric esters (acetyl triethyl, acetyltributyl or tributyl citrate), glycerin and glycerol esters (glycerol diacetate, triacetate, acetylated mono-saccharides or castor oil), esters of violet (dioutyl) -, diamyl-, dimethyl-, dipropyl-, di- (2-methoxy- or -ethoxyethyl) phthalate, ethylphthalyl- and butylphthalyl ethyl and -butylgylcolate), alcohols (propylene glycol or polyethylene glycol of varying chain length), adipates ( diethyl-, di- (2-methoxy- or ethoxyethyl) adipate), benzophenone, diethyl- and dibutyl-sebacate, -succinate or -tartrate, diethylene glycol dipropionate, ethylene glycol diacetate, -aibutylate or dipropionate, tributyl phosphate, tributyrin, polyethylene glycosol sorbitan monooleate, sorbitan monooleate or polyethylene oxide block polymer and polypropyl oxide.

In addition, the addition of a small amount of water-soluble substances, such as polyethylene glycol, polyvinylpyrrolidone, is possible. n-phenylethylpyrrolidinone and oolvvine acetate, hydroxypropylcellulose or hydroxypropylmethylcellulose. Also, solid substances such as talc and / or magnesium stearate as well as colorants or pigments may be added to the coating substance. In addition, the addition of lipophilic substances such as 20 to 30% stearic acid improves the water permeability of the aqueous steam and thus improves the ability to store moisture-sensitive substances #

Alternatively, an insulating layer may be placed between the core and the coating material, which may be composed of, for example, hydroxypropylcellulose, hydroxypropylmethylcellulose, or polyvinylpyrrolidone. hydroxypropylmethylcellulose, carboxymethylcellulose, cellulose trimellitate acetate or copolymers made from maleic acid and violet acid derivatives,

The coating material is suitably composed of from about 30 to 90%, preferably from 40 to 75%, of a formulating agent, from 0 to 30%, preferably from 8 to 15%, of a plasticizer and from 10 to 70%, preferably from 12 to 50%, of cyclodextrin.

The coating of the active ingredient or pharmaceutical composition, i.e. the formulation in which the active ingredient is treated together with the usual or suitable pharmaceutical auxiliaries, is carried out by methods known in the pharmaceutical art, optionally in a conventional manner for coating pharmaceutical forms.

The encapsulation of therapeutically active substances is also accomplished by methods known in the pharmaceutical art. In doing so, they are used instead. and: hitherto customary plastic or molten casting materials such as wax, castor oil, elastic materials such as cellulose ethers or cellulose esters, or poly (acrylic or methacrylic acid) esters of the present invention.

In addition, other conventional pharmaceutical auxiliaries or additives may be used together, for example, wetting agents, flavoring agents, sweetening agents, auxiliaries such as talc, calcium carbonate, mannitol, powdered cellulose, soluble dyes and pigments.

Excipients, if any, form a coating composition, for example in an amount of from 10 to 100% by weight, preferably from 20 to 40% by weight, based on the weight of the cyclodextrin used.

Flavoring, sweetening and coloring agents may be added to the compositions in small amounts, for example, from 0.001 to 2%. . v v. more data on excipients and additives are available in the literature, for example in a monograph published by J.H. Saunders and K.C. Frisch " High Polymers " Interscience Publishers, $ 62 or 1964.

The coating is conveniently effected by spraying solutions in organic solvents, or by suspending or dispersing said substances in organic solvents or in water, with the addition of other auxiliaries such as surfactants or pigments.

Spraying is carried out, for example, in draining drums or perforated boilers, or in a slurry-based manner in air or in a floating layer (e.g., in a WSG5 device, allowing the formation of a complete fluidized bed).

The coating can also be carried out in a coacervation manner in which so-called microcapsules or microparticles are formed.

The coating can also be carried out by coagulating the aqueous dispersions or suspensions at a temperature above the lower temperature to form the film and the said materials, when the active ingredient is mixed with the dispersion and the water is removed by evaporation.

The coated particles of the active substance and the coated granulate can be compressed into tablets, the coated pellets filled into hard gelatin capsules.

When coating the active substance or granulate particles containing the active substance, a more coated substance is usually used than in the case of pellets or tablets, because the surface, 4 ' ^ rpfip-i # ηρ? 2 x m x í iol iol iol iol iol iol iol iol iol iol iol iol v v v v v v v v v v v v v v v v v v or tablets.

As the tablets are generally larger than the pellets, the surface area of the tablets to be coated is correspondingly smaller. For example, ITa 1 part by weight of active ingredient or medicament can be used from C02 to 1 part by weight of the coating. A weight ratio of 1 part active substance to 0.04 to 0.7, in particular 0.05 to 0.7 part by weight of the coating material is suitable, particularly 0.1 to 0.7 part by weight of the coating. Coating is carried out in solution, suspension, or coating. / os r? -? the temperature and the UO A mm W mm mm of the elevated temperature, preferably in the air flow (temperature of the introduced air from 60 to 120 ° C, the temperature of the exhaust air up to 100 ° C).

For example, G, O5 to 5.0 parts by weight, for example 0.08 to 3.0 parts by weight, especially -7 to 0.1 to 2.0 parts by weight, are used for 1 part by weight of active ingredient. . The preparation of this preparation is conveniently carried out at a temperature of from 10 to 100 ° C. and;

By dissolving or dispersing the active substances or their salts in a coating substance according to the invention or in a mixture of such substances, also by melting said substances and finally by re-cooling, grinding and optionally adding other substances such as water-soluble or water-soluble substances. tablets · Cooling of the melt and milling can also be included in a single step if the melt is dispersed in cold water or left to dissipate.

Suitable swelling agents are, for example, hydrophilic, hydroxypropylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose (mixed cellulose ether containing propoxy, ethoxy and methoxy), alginic acid and its salts (sodium). or calcium salt, also mixtures of sodium alginate and calcium salts, for example calcium hydrogen phosphate), starches, carboxymethyl starches, carboxymethylcellulose and its salts (e.g. sodium salt), acacia, karaya gum, gum Ghatti, agar, karragen, xanthan gum , polypropylene glycol alginate, pectin and tragacanth. b) Mixing the active ingredients with the coating materials and optionally swelling agents or mixtures with the use of the formulation and, for example, compressing the mixture, optionally after addition of other excipients to the pellets or pellets, pellets as well as granules. c) admixing the active ingredient with the coating solutions of the present invention in organic solvents such as ethanol, ethyl acetate, acetone or isopropanol, optionally by admixing with excipients such as cellulose derivatives, as well as subsequent evaporation of the solvent and admixing the active ingredient obtained therein with other excipients and processing to form such as tablets, granules or pellets. d) wetting the active compound / coating composition of the present invention, as well as the aforementioned swelling agents with organic solvents such as ethanol, ethyl acetate, acetone or isopropanol, optionally with the addition of binders such as nolyvinylnyrrolidone or copolymers of polyvinylpyrrolidone and polyvinyl acetate, by granulating the resulting mixture, followed by drying, adding optionally further excipients and, for example, compressing the mixture into tablets. In general, the preparation of these drug preparations is carried out in a manner known per se, in addition to the coating substance according to the invention, known and pharmaceutical pharmaceutical auxiliaries as well as other excipients and diluents can be used.

Suitable carrier and diluents are, for example, those which are recommended or listed in the literature cited below as auxiliaries for pharmaceuticals, cosmetics and neighboring regions of Ullmanns Encyclopedia of Ceramic Chemistry, Vol. 4/1953 / * str.1 as 39, Journal of O H · O J / *

Pharmaceuíical Sciences ,. 2 (1563) H. V. C of Lindenwald, Kilfsstoffe Pharmazie und "angrenzende Gebiete, Pharm. Ind., Vol. 2/1961 /, p. 82 et seq. H. P. Fiedler, Lexicon der Hilfsotoffe fur Pharmasie, Kosme tik und angrenzende Gebiete, 2nd edition, edition Cantor, Aulendorf in Wurttemberg / 1981 /.

Examples of customary excipients, carriers and diluents are gelatin, natural sugars, such as cane sugar or lactose, lecithin, pectin, starches (e.g., corn starch), as well as derivatives thereof, galactannanate, polyvirylpyrrolidone, gelatin, acacia, acid alginic, tyloic, talc, silicic acid (e.g. colloidal) or highly disperse silica, lavulose, tragacanth, sodium chloride, stearate, calcium carbonate and calcium salts of C12-C22 fatty acids, especially saturated (e.g. stearate), polyethylene glycol having an average molecular weight of from 200 to 20,000, preferably from 200 to 5800, particularly preferably from 200 to 1000 or mixtures thereof and / or a polymer made of vinylpyrrolidone and / or co-polymer made of vinylpyrrolidone and vinyl acetate, aliphatic saturated esters or unsaturated fatty acids (2 to 22 carbon atoms, especially 10 to 18 carbon atoms) with monovalent aliphatic alcohols (1 to 20 carbon atoms) or polyvalent alcohols such as glycols, glycerin, diethylene glycol, pentaerythritol, sorbitol, mannitol; and the like, which may optionally also be in the form of ethers, benzyl benzoate, dioxolane, glycerinformal, tetrahydrofurfuryl alcohol, polygylcolethers with 1 to 12 carbon atoms, dimethylacetamide, lactamide, lactate, ethylcarbate, silicone (especially medium viscosity dimethylsiloxane) , calcium carbonate, sodium carbonate, sodium phosphate, magnesium carbonate, acacia, alginic acid, stearate, fats and the like.

In addition, the forms to be administered may contain interfacial agents. Examples of such substances include alkaline soaps, such as alkali salts of higher fatty acids (e.g., sodium palmitate and sodium stearate) or derivatives thereof (e.g., sulfuric acid sodium salt of ricinoleic acid), sulfurated compounds or sulfonated compounds which are formed by the reaction of higher aliphatic alcohols with sulfuric acid or chlorosulphonic acid and are presented, for example, as sodium salts (e.g. sodium lauryl sulphonate, sodium cetyl sulphate, sodium stearyl sulphate or sodium gallic acid sodium salts, quaternary ammonium compounds, partial fatty acid esters of sorbitan, partial fatty acid esters of esters of polyoxyethylene sorbitan with fatty acids, ether polyoxyethylene of sorbitol, ester of polyoxyethylene with fatty acids, ether of polyoxyethylene with aliphatic alcohols, esters of sucrose with fatty acids, esters of polyglycerol with fatty acids, protein and lecithin.

The forms to be administered may also contain fillers, especially compresses. Possible as such are purified cellulose or microcrystalline cellulose, calcium hydrogen phosphate, lactose, starches (e.g. potato starch or corn starch), glucose, mannitol and sucrose, as well as fillers with a binder function such as microcrystalline cellulose, hydrolysed or partially degraded starches and microcrystallizate formed from cellulose powder and lactose · T? Λ VW '»V ^ PTM ^ V * v» OTT1 4 * Γ fsV Vi r * J ^ if «k. J.L.A. Fluid-regulating agents such as highly disperse Silicic Acid · By means of the addition of mold release formulations, talc or silixo should be mentioned as such - new talc , calcium stearate, magnesium stearate, stearic acid, paraffin, hydrogenated fats and oils, and other silicone oil emulsions. However, as a rule, the addition of the composition. it is not necessary to release the mold, since the cyclodextrin itself already has the character of a formulation that helps release from the mold.

Other auxiliaries include disintegrating agents such as quaternized polyvinylpyrrolidone, sodium carboxymethylated starches, sodium carboxymethyl cellulose, formaldehyde gelatin, formaldehyde casein, poly (acrylic acid) and ultra-amylpectin.

In addition, the addition of stabilizers, binders, antioxidants, and complexing compounds (e.g., ethylenediaminetetraacetic acid), as well as acids such as citric acid, tartaric acid, maleic acid, or fumaric acid is possible *

As antioxidants, for example, sodium metabisulphite, cysteine, ascorbic acid, and esters thereof (e.g., palmitate), flavanoids, gallic alkyl esters, butylhydroxyanisole, nordihydroguaic acid, cotopherol, as well as tocopherol and synergist (substances that bind heavy metals forming complexes such as lecithin, ascorbic acid, citric acid and phosphoric acid).

Suitable preservatives are, for example, sorbic acid, benzoic acid β-hydroxy ester (e.g. lower alkyl ester), benzoic acid, sodium benzoate, trichloroisobutyl alcohol, phenol, cresol, benzethonium chloride and formalin derivatives. Solvents from the group consisting of aqueous solvents, alcohols, ketones, esters, ethers, aliphatic hydrocarbons, halogenated hydrocarbons, cycloaliphatic or heterocyclic solvents, and mixtures thereof with conventional solvents can be used to introduce the coating compositions of the present invention. 1 include, but are not limited to, acetone, diacetone alcohol, methanol, ethanol, isopropyl alcohol, butyl alcohol, methyl acetate, ethyl acetate, isopropyl acetate, n-butyl acetate, methyl isobutyl ketone, methylpropyl ketone, n-heptane, n-heptane, ethylene glycol monoethyl ether, monoethyl acetate ethylene glycol, dichloromethane, 1,2-dichloroethane, 1,2- or 1,3-dichloropropane, carbon tetrachloride, nitroethane, nitropropane, tetrachloroethane, cyclohexane, cyclo-butane, benzene, toluene, naphtha, 1,4-diozane, tetrahydro-furan, dimethyl ether diethyl -len glycol, water and mixtures thereof such as a mixture of acetone and water, acetone and methanol, acetone and ethanol, dichloromethane and methanol as well as 1 , 2-dichloroethane and methanol. During the coating process, these solvents are removed again.

applicability

The active ingredients which can be formulated with the coating according to the invention are all those which can be administered orally and whose released dose may be desirable in the colon. These include, for example, preparations for the treatment of the intestine, such as meta-salazine (5-aminosalicylic acid) or laxants such as bisacodyl, peptides, therapeutic agents for the treatment of the heart and blood circulation, antirheumatic and analgesic agents, preparations for the treatment of diseases small intestine (Crohn's disease, ulcerative colitis), anti-asthmatics, antifibrinolytics, antihemorrhagics, antitumor agents, enzyme preparations, antibiotics, antimycotics, and central nervous system (C1'S) agents. An important group of active substances to be released only in the intestine are those which they have

a peptide or protein structure, such as insulin T1, T1, T1, T1, V1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1, T1; aj n.. uj.. UIVÁ1J.J · u u. u < xx u. in c * u «j- .............-

In the case of lytic enzymes of the body itself, they may not be effective. In the colon, the content of proteolytic enzymes - X · X-X ^ 1. , -Γ-Τ-ί f'X A— r ~ J _ X X Xà > Λ -i »p ^ p- ~ .Ä. iaov naproa 1.0mu 00. «. luuxy, ac «, -x - sobory or rezorbeiu ·

Examples of peptides as active ingredients are, in particular, adrunocorticotropic hormone (ACTH), corticostatin, calcium-tonin, insulin, cytotoxic, eomatostatin, and analogs, analogues of HLP.H, bombesin analogs, cholecystckinin and its derivatives, endothelin and its analogs, tnromoin inhibitors peptide growth factors (e.g., IGF, EGF, NGF), magainin (PGS peptides), gastrin analogs, parathyroid hormone analogs, neurokinin and analogs thereof, vasoactive intestinal poly peptides (71?) and analogs thereof, atrial natriurethiapeptide (Α1ΊΡ) ) and analogs thereof, neokyotropin and its analogs, angiotensin analogs, enkephaline, dynorphin, dermorphin, deltophin, renin-inhibiting peptides, cancer growth factor peptides, MS H analogs (mithocytes stimulating hormone), mitotoxin, tyrphostin, chromogranin A, thymopentin, hormones releasing thyrotropin (TRH) and its analogs, substance P, tuftzine, fibronectin, and peptic immuno-modulators such as cyclic spores A, FX 506 and neuropeptide Y,

The coating material of the present invention is almost impermeable to artificial digestive juice. On the other hand, after incubation in CMT (" microflora test in the colon ", unequal dissertation by C. Wohlschlegel, Preiburg, 1990), enzymatic degradation of CDs is found for which the films are porous and thus permeable, so that the coated active substances can be released and can act in the colon. -Η-

A particular advantage of the new coating substance is that it is 4 4 ľ t * 4 r Ί r > γμ i i7 n ci-nc o < r Ά λ! V aV ”1 C 1 I.'Am ro Ci r? R d rl O U d - d - · í · U I I I I I I I I I I I I. j WW w v--. ^ ^ ^ O. ** w _ w «

Exemplary embodiments of the invention are described below

* * 1 CL ^ " * GťU4’OAV

- -r 4- 1 r · τ r °. w -. -% by weight. Temperatures are given in degrees Celsius.

EXAMPLE 1: Coating (film) 1.1 Production Method To 66.6 g of a 30% aqueous dispersion (commercially available preparation) of a copolymer composed of 30 parts of ethyl acetate, 65 parts of methyl methacrylate and 5 parts of trimethylammonium methacrylate and frequency. the dispersion f 0 for 10 minutes is sieved at a speed of 180 rpm) a composition composed of To disperse the film, the dispersion thus obtained is drawn onto a film in a film-drawing apparatus Erichsen model 509/1 at 40 ° C 12 mm / s on a polyester film. In this case, a scraper blade with a slot height of 200 m is used. The film treatment takes about 30 minutes, finally the film is stretched at 20 to 25 ° C on the film and redissolved for its own characterization from the carrier film.

In an analogous manner, dispersions of this composition are obtained (given in%): 1 c '- / Number of Filming Softeners CD Y from a η χα Ktiια .t.: Ľ n ΤΜΓ * 7 ?. UUi 1 19.23 3.85 0 3.85 73.07 2 19.23 3.85 0 5.77 71.15 3 19.23 3.8.5 0 7.69 69.23 A " t >. r > 3 / j. £ > 0 o or o 9 < - > J n p r- P, - P 7 9 ΠΟ • > ~ ~ 9 7! - · > - J n or Jr-r * " 7 'r > - * 71.15 6 - / - »- > ‘I - u 0 · u, -. · O 7, áS 69,23 n 1 c p o n u 3,85 c .po £ < 7 ~ 0 O; , v - 1 7 P / 1 • »* - r 0 3.45 10.34 6 8.9 7 Q " 6 oc 0 3.39 1.1.86 67.80 10 * rfrio, Q ooo PP ^ is 13 , 33 0 0, bc 11 16,39 0 p OO -s 9- ^ 14,75 65,58 12 16,13 0 • m -) '-iu, 2u 16, 13 9 J · Ί " 3 1 - / ú - p-} n 3 1 ^ oj - ✓ 18.75 POAC ~ 1'r * '1.2 Characterization, Film 1.2.1 Determination of Film Thickness (Minitest 3000, Prichsen) · Six dew points are measured and the results are averaged.The film thickness is between 35 and 70 m 1.2.2 Permeability in artificial small intestine juice

The screening of the film with respect to its permeability is done by means of Pranzschen cells (cf. CLGummer and kel., Int, J. Pharm, 40, 101-104 (1987)). and an acceptor. The acceptor vessel is filled with artificial thin-blood vessel (phosphate buffer pH b, b P, DAJ)

* N y- i u; ; Ο - with magnetic plaster. Dor.ore is concentrated

- > · * -.F? ·! ·· -v- / ~ \ t «-Λ h r r, / vil f £ 7 11 r ~ / 'Vt i T r > f λ η τ O Ί " Atel r nn · ί?, Ν »* c * Vi r? > Π 4 "/ -vTI u. v_ 'JUV «* - il' - 'OCAj -' - Ali - UlACi · JM * £ > / / V - / i ^ / Ui.u VU» > PH 6.3. The drug serves as an indicator substance for determining the permeability of the film. After 2, 4 and 6 hours, the assay was performed with X1 X1. C 1 -C 11 -; U y -Í ^ V J? N n 0 i J-CIIj. i Cv 'u. i i i i i w in g < J ^ b *.

The test sample is measured photometric (Uvikon 820, wave /! - f SVOS on -.- ~ Λ v -j τ, - · p- o ií / wl ^ --.- 1 --... ..... .J- “> < - 'i ----- i-- ·· ^ .....- - < - · - * - · o · - " / When the mesalasin concentration in the acceptor is detected, the film permeability is determined 7 ", and the films listed in Section 1.1 (c) of (2) " VC " T 'O' T '/ T'cB.lC't) l C ΐ V V Γ, 6: T) ľ * Ί. SO U K " ¾: é £. From jLj D íl 0 ô. CMT (CMT) is used to determine degradation in the small intestine (cf. Pharm. Pharmacol. Lett. 2, 65-65 / 1952). &Quot; 0 “lT: 9 £ l0u i. ^ Zr ~ Z Blind 2T6V & The secretion secretion of patients suffering from ileostomy and phosphate buffer of 6.4 H, DAB 10, in the ratio 5: 5: 1 · rt r q is incubated under anaerobic conditions t; λ * 7, τ · p n; reiukavam piyncracite in the ratio 5: 1, at 37 C. J X ^ ί 1 ^ - w1 Ό. La. O U * 1. Ú — 7 Or nhl ·:

Round pieces of film with a radius of about 0.7 cm are incubated with the above-described mixture of ileostomic secretion and caecal content of the pig in a time period (between 2 and 6 hours), then rinsed with water and dried at room temperature. To perform the test, the film pieces are then glued to the support object and from .ps.?oi.a with gold. Film surfaces are screened electron microscopy. It shows a distinctly porous structure as opposed to the test film which has not been treated with CMT.

- H-gô. · 3 O '--... 1--. X-17- of ethylcellulose is stirred for 2 minutes (1: 1). DBF and dispersions of 4? 7 g CD? 3b, 3 g of water and all else for 15 minutes at room temperature »

In a similar manner, the dispersions of this composition are obtained (in X 'T' υ i ε 1 ľ ľ mot mot ná ná ná ná ail ail oda oda oda oda oda oda oda oda oda oda oda oda oda oda oda); ! f 2 ^ · J 0 0 0 3.44 1 Q, i VU 2 1C, 70 1.30 Q 0 5V5 p. 9 cc 9 V- »5? - > 11.53 0 1.45 0 3.44 33.18 A 1 n < 7r- rv .u, / u 1.30 0 5.15 62.55 5 11.93 0 0 1.45 3.44 83,18 δ 10,70 0 0 1,30 5,15 82,85 +) DBS = dibutyl sebacate Example 3: Coated tablets 3.1 Method of preparation 330 g of the commercially available preparation of Example 1.1 is mixed with a suspension of 20 g of TB and 30 g of CD in 370 ml of water by stirring with a wing mixer and then further stirring for 10 minutes.

With this dispersion, 1.5 kg of cores 4 · λ VI ^ -1_ · · ^ 1 are sprayed.

mesalazine microcrystalline cellulose lactose polyvinylpyrrolidone? 1? v? Ί X V-s tr C? Highly disperse silicic acid 0 0 sodium carboxymethylcellulose neat stearate total 100 mg 35 mg 35 mg 7 mg 20 mg

3.6 mg 1.8 mg i, O 204, P ΤΠ £ Γ (Diameter 3 mm, published 76 mm, surface area c-, c, .2 s i, y o c m i

During the spraying process, the dispersion is mixed with a wing stirrer (continual spraying method, air blowing at a pressure of 300 kPa, a flow rate of 10 g.min -1.4 * νν · r · - 0.6 mm, temperature Wk oo) r- 44 ° C, ina). Obtained tablets of the substance. The mixture is dried overnight at 40 ° C. 3.2 Characterization of the tablets 3.2.1 Stability in the artificial small intestine The tablets are examined in a test device for determination of disintegration for 6 hours in order to test the tablets for stability and finally the tablets are examined optically. In addition, the mesalazine content of the test medium is determined. All tablets are still under these conditions for at least 6 hours.

-J r + +. J urate in o T - .. τ ^ η t · m i- i -

U. 1

A

The 500 s of commercially available nodl-19-71-, -, 1, 717c: r-r < t * u O ^ Pi '- ie

PH acts in the bath and in the Padale, that the stupa permea. tablet abilities with n r J * s * ľ ľ ľ ľ ľ ľ ľ ľ ľ ľ ľ ľ ľ ľ ľ ľ li li li li Do Do Do Do Do Do .liíxu UaC 2. e e, * t Θ f; p “hl p-f-V'.r • --- ♦ · ··· - *; water, while stirring for a further 10 minutes. Next, proceed as described in '', " y > r, * with p JX JtuC J) o t

Claims (2)

-20- -20- 0 V E REQUIREMENTS * 1 · > λ. í T y * r * · " 1 > λ1 »« ** η ηC * / * * y * * »» * r * s λ " V > ηη 1λ «< Ί ί λ '¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ i i ¾ i ± ± ± ± ± ±. . the active ingredient and at least one coating substance surrounding the active ingredient, which comprises a water-insoluble insoluble substance and a digestive juice, characterized in that the coating substance comprises in the first place an active ingredient and a non-water-soluble substance. rt in *, o? / - »7 r 1Ό / · > -3 c tt ν »v. o / n 1 o r * ά'Ο in ':,' 'fiu m .O; íl *%; -cu 'vcf X.iti.t? J ‘-'J /•-OV.-w-à. V -x. In addition, in the following, the following is additionally provided 2. An oral dosage form coating composition comprising a water insoluble fabric insoluble substance comprising at least a cyclodextrin and / or at least one of its derivatives.