[52] us. a.
`
`[51]
`
`Int. 01.4
`
`AfllW 1/02; AGIK 9/00,
`A61K 15/00», A61K 21/00
`421/1; 424/473;
`424/479; 427/3
`[58} Field of Search ................ 427/2, 3; 424/473, 479
`
`United States Patent
`
`[19]
`
`Schmidt
`
`[11] Patent Number:
`
`4,849,246
`
`[45] Date of Patent:
`
`Jul. 18, 1989
`
`[54] PROCESS FOR PRODUCING AN
`summon on DOSAGE FORM
`FOR DRUGS, REAGENTS OR OTHER
`ACTIVE INGREDIENTS
`
`[56]
`
`References Cited
`ULS. PATENT DOCUMENTS
`
`3,444,853 5/i969 Russell ................................ 123/260
`
`[76]
`
`Inventor: Wolfgang Schmidt, Reembroden 44,
`13-2003 Hamburg 63, Fed. Rep. of
`Germany
`
`[21] Appl. No.:
`
`60,689
`
`[22] PCT Filed:
`
`Oct. 7, 1986
`
`[36] PCT No.:
`
`POEM/00571
`
`§ 371 Date:
`
`Jun. 9, 1987
`
`§ 102(e) Date:
`
`Jun. 9, 1987
`
`[37] PCT Pub. No»: won/02241
`
`PCT Pub. Date: Apr. 23, 1907
`
`Foreiun Application Priorin Date
`[30]
`Oct. 9, 1985 [DE]
`Fed. Rep. of Germany
`
`353mm
`
`FOREIGN PATENT DOCUMENTS
`
`2746414 4/1919 Fed. Rep. of Germany .
`51-54917 6/1976 Japan .
`139077
`2/1920 United Kingdom .
`1061557
`3/1967 United Kingdom .
`
`OTHER PUBLICATIONS
`
`Chemical Abstracts, vol. 85, 1916, p. 364.
`
`Promo Examiner—Michael Lusignan
`Attorney, Agent. or firm—Cushman, Darby J: Cushman
`
`[5?]
`
`mm
`
`A process for producing an administration or dosage
`form of drugs, reagents or other active ingredients. A
`watersoluble foil composed of starch. gelatin. glycerin
`and/or sot-bit and if necessary other additives is coated
`by a roll coating process with a layer containing the
`active ingredients and composed of the samebasic ingre-
`dients. After a. corresponding prefragmentation,
`the
`administration form thus produced is particularly useful
`as an oral administration drug.
`
`Emmerich-urinal
`
`Dr. Reddy's - EX1020
`
`Page 1
`
`Dr. Reddy's - EX1020
`Page 1
`
`

`

`1
`
`4,849,246
`
`PROCESS FOR PRODUCING AN
`ADMINISTRATION OR DOSAGE FORM FOR
`DRUGS, REAGENTS OR OTHER ACTIVE
`INGREDIENTS
`
`Drugs or pharmaceuticals can be orally administered
`in the form ofpowders, dropping solutions or juices. As
`precise dosing is difficult with such administration
`forms, preference is generally given to manufacturer-
`dosedadministrafionformssuchastablets,drageesor
`capsules. Reagents and other active ingredients, e.g.
`sweeteners or devouring agents are frequently also
`tableted for a precisely dosed administration. The pro-
`duction procedure for tablets, dragons. capsules, etc. has
`largely been completely developed, but it is not possible
`to overlook a number of system-related disadvantages.
`For low-dosed active ingredients, a large proportion
`of adjuvants must be added in order to obtain a handle-
`ble size of the
`dose. It is also substantially
`impomible to precisely mark
`tablets or
`dragees. Therefore blister packs have been adopted.
`whichcontsinalargenumberoftablemdrageesand
`also capsules and which are printed with the necessary
`informationandinparticulartheproduct name.The
`manufacture of such packs naturally involves an addi-
`tional operation and pack transfers in the form of fold—
`ing boxes are required, which have a considerable
`pty volume and therefore take up additional storage
`space. Another serious disadvantage of dragees and
`capsules is that splitting up is not possible, so that the
`minimum dose is predetermined. An accurate breaking
`up is also difficult in the case oftablets and only larger
`tablets provided with a notch as a predetermined break-
`ing point can be split, but frequently fragments of un-
`equal size are obtained.
`Attempts have already been made to find a new ad-
`ministration form for the oral
`ofdrugs in
`the form of active ingredient-containing films or foils.
`Belgian Pat. No. 631,363 discloses a paper-like support
`material (if insoluble cellulose fibres impregnated with
`an active ingredient solution or coated by application or
`sprinkling, dosing being achieved by perforating the
`supportfilminthemanner cfa sheetofpostagestamps.
`The dosing of the active ingredient is necessarily ex-
`tremely imprecise. DE-OS No. 24 32 925 and DE—OS
`No. 24 49 865 More the incorporation of drug active
`ingredients into film forming agents, which are prefera-
`bly in the form of water-soluble campounds, such as
`methyl and ethyl cellulose, but in particular hydroxy-
`propyl cellulose, hydroxyethyl cellulose or methylhy-
`droxypropyl cellulose. The films can also contain fillers
`and parting agents. The thus obtained active ingredient-
`containing films can also be subdivided into individual
`portions by perforation for dosing purposes.
`However, these proposals have not led to practical
`adoption and in the latest text book "Arzneiformerl-
`lehre" by P.H. List, fourth edition. Stuttgart 1985, no
`mention is made thereof. This is clearly based on the
`fact that the hitherto known proposals do not make it
`possible to obtain the requisite constant weight and
`uniform active ingredient distribution, such as are
`nowadays required. The Pharmakopoea Europae e.g.
`sets criteria for the uniformity of the weight of individu-
`ally dosed drugs. which are graded according to the
`maximum permitted variations in per cent correspond-
`ing to the particular average weight. This requirement
`is generally-:5 to max. 10%. Carresponding values
`
`10
`
`15
`
`25
`
`30
`
`35
`
`«II-5
`
`50
`
`SS
`
`65
`
`2
`exist for solid drugs with respect to other parameters,
`such as the disintegration time and dissolving rate.
`The aforementioned prior art proposals lead to prod-
`ucts with an inadequate acceptance by the patient (eg.
`it is difficult to ingest paper portions) and do not permit
`an accurate dosing per surface unit, as is an absolute
`requirement. When incorporating the active ingredient
`into a film, difficulties are caused not only by the precise
`dosing,butalso itisnecassarytOproduceaseparatetilm
`for
`active ingredient, so that the production pro-
`cess Is not economic.
`The problem of the present invention is to provide a
`"two-dimensio
`” administration and dosage form,
`which does not suffer from the aforementioned disad-
`vantages. which can be easily produced and can be very
`flexibly adapted to the requirements of the market and
`different active ingredients.
`The invention therefore relates to a process for the
`production of an
`and dosage form for
`drug active ingredients, reagents or other active ingre-
`dientsintheformofafilmwithanacfiveingredient-
`containing coating, which is characterized in that.
`(a) a water—soluble support film is produced from an
`aqueous composition based on starches, gelatins, glyc-
`erol and/or sorbitol, as well as optionally natural and-
`[or synthetic resins and/or gums,
`(b) an aqueous coating material is prepared from the
`active ingredient, as well as starches, gelatins, glycerol
`and/or sorbitol, as well as optionally natural and/or
`synthetic resins and/or gums, and
`(c) the coating material is continuously applied by
`means of a roll coating process and in a precisely prede-
`termined quantity (coating thickness) to at least one side
`of the support film.
`The inventiver produced
`large number of important advantages:
`One support film can be used for the most varied
`active ingredients and can therefore be economically
`produced in larger numbers.
`The active ingredient-containing coating can be very
`thin in the case of very efficaceous drugs, because the
`support material ensures an adequate mechanical
`strength.
`With the aid of modern roll application processes the
`active ingredient-containing coating can be applied
`with a constant thickness, so that the necessary toler-
`ances can be respected.
`If sterilization is necessary, this can be achieved with-
`out difficulty by radiation treatment due to the limited
`coating thickness.
`The support can be printed with different information
`on the front and in particular rear surface using physio—
`logically acceptable printing inks.
`As a result of the relatively large surface area of e.g.
`4 to 10 cm3, detailed information for the user can be
`printed on the uncoated support material, or even subse-
`quently.
`The dosage units canbe rendered flexible by a. corre-
`sponding pare-separation, eg. by perforation, so that iris
`only neCesSary to produce one product for different
`dosages (eg. for adults and children); whereby the pre-
`separatiOn can optionally be carried out in the pharma-
`cists or hospital in accordance with details provided by
`the doctor.
`The inventive administration form shares the com-
`mon advantage of the known film-form administration
`forms of extremely small space requirements. Thus, in
`place of folding boxes, it is eg. possible to use pouches
`
`form has a
`
`Page 2
`
`Page 2
`
`

`

`3
`or bags made fmm plastic film or phsdcmated paper,
`into which the product is sealed, in much the same way
`as moist refreshing cloths.
`Thesupportfilmismanufacturedinperseknown
`manner using a continuously operating roll-based film
`machine. The coating process for producing the sup-
`port film is based on the roller principle, i.e. the aquacus
`composition for the support film is applied by means of
`rollsanddoctorbladesandspreadouttoform thin
`webs, prodded on the rolls andtheninthemaindrying
`process subsequently dried to the desired final moisture
`content. The end product obtained is so strong and
`elastic that it canbe-woundonto reelsand stored. ifthe
`residual moisture content is not too high (risk of mould
`formation).
`The widthofthefilmcanbe ofaraudomnatureand
`is advantageously adapted to- the coating machine
`width. It is obvious to adapt the two widths to one
`anotherat thetimeofmanutacture. Itistechnically also
`possible to carry out film production and coating in
`time succession on the same plant, which significantly
`improves the economics of the process.
`The composition used is kept at the desired tempera-
`ture, viscOsity and homogeneity, accompanied by
`pumping round. The film is subsequently dried in a
`heating tunnel. The thus obtained support film consti-
`tutes the inert support for the subsequent coating with
`the different coating materials.
`A physiologically unobjectiouable composition is
`used forproducing the water-soluble support film. The
`"water solubility” is to be defined in such a way that the
`film is produced from an aqueous composition and the
`finished film subsequently dissolves or swells during use
`in water or in gastric juice.
`Thefilmfcrmers areinparticular gelatins, aswell as
`starches (potato starch. wheat starch, corn starch), as
`well as polyvinyl-pyrrolidone (PVP), methyl and ethyl
`cellulose, as well as polyvinyl alcohol (PVA). It is also
`possible to use water-soluble acrylic resin
`Suitable plasticizers are in particular pclyfunctional
`alcohols, such as glycerol and sorbitcl (Karicn).
`The components are appropriately cold mixed with
`water and accompanied by slight heating and constant
`stirring are processed to a coatable slime. The stirring in
`of air must be avoided to the greatest possible extent, in
`order to obtain a clear, but slight Opalescent material.
`The thickness of the support film is preferably be-
`tween approximately 50 and 250 pm. it can be con-
`trolled to a considerable extent. The characteristics of
`the support film can undergo significant quality influ- 50
`euces by corresponding combination of film formers
`and plasticizers. The support film must have a uniform
`thickness (preferably e.g. 100 pm), must be slightly
`elastic and bendable, but without breaking. The starch
`proportion should be adequately high, so that moisture
`is absorbed on applying the coating material, without
`there being any sticking ofthe surface or sofiening of
`the complete film.
`The following basic formulation has proved satisfac-
`tory for the support film:
`Gelatin 8 to 10 3
`Starch 4 to 8 g
`Glycerol 1 to 2 g
`Polyvinylpyrrolidone l to 2 g
`Water 30 to 50 g
`Water-soluble natural and/or synthetic resins, e.g.
`acrylic resins and gums are also suitable. It is also possi-
`ble to add to the material other conventional substances,
`
`60
`
`lO
`
`15
`
`25
`
`30
`
`35
`
`45
`
`55
`
`65
`
`-
`
`4, 849,246
`
`4.
`e.g. preservatives, such as p-hydrorybenzoates, inert
`soluble or insoluble fillers, sugar or other sweeteners,
`other polyols. waxes or dyes.
`The possibility of printing the front and back of the
`support film is a particular advantage of the invtivc
`administration form. For example, it is possible to print
`on the marking, details on the constituents, together
`with dosage details. It is optionally even possible to
`print on the back the entire content of a pack-in label,
`thereby rendering superfluous the need for such a sepa-
`rate label, which is frequently lost. In the case of drugs
`or pharmaceuticals which are regularly taken, e.g. in
`the case of hormonal contraceptives, the complete ad-
`ministration program can be given in such a way that it
`is possible to simply check the taking thereof. For print-
`ing purposes it is necessary to use physiologically ac-
`ceptable inks (food colours), because the support film
`forms part 'of the orally administered administration
`form.
`The active ingredient-containing coating material is
`an aqueous composition which is physiologically inert
`and whose individual constituents are suitable for phar-
`maceuticals or foods. Importance is attached to the
`reciprocal physical-chemical afiinity and compatibility
`between the coating material and the support film and
`this is always particularly good if the components usad
`are identical or have similar characteristics Whilst tak-
`ing account of the active ingredient added, the coating
`compound formulation coasequently corresponds to
`that given hereinbefcre for the support film, the precise
`setting of the solids content and viscosity taking place
`by means of inert swelling and filling agents.
`Thus, the material contains polymeric film forming
`agents, preferably gelatins and swelling or soluble
`starches, as well as optionally ceflnloses or hemicellu-
`loses. lu addition, plasticizers are added, particularly
`polyhydric alcohols, such as glycerol or .sorbitol. In
`order to set the desired viscosity of the coating com-
`pound, which has the consistency of a slime, use is made
`of polymeric swelling agents. preferably alginates, pec-
`tins, chitins, lecithins or polyethylene glycols. These
`latter substances can simultaneously serve as adhesives.
`It is also possible to add water—soluble synthetic or
`natural resins or gums or gum Arabic. in order to im-
`prove the adhesicn of the coating to the support mate-
`rial. It is finally possible to add preservatives, such as
`eg. p-hydroxybenzoates, dyes (food dyes), pigments,
`such as titanium dioxide, or flavour-lug agents and
`sweeteners.
`Coating materials with a water content of approxi--
`mately 50% and a viscosity of approximately 30 to
`10,000 cPs have proved particularly satisfactory. The
`formulation and production is similar to that of a phar-
`maceutical juice, in which the-active ingredient or ac-
`tive ingredient combination is dissolved or uniformly
`dispersed. The coating material must have an adequate
`homogeneity and galenic stability, so that a uniform
`active ingredient content of the finished coating is- en-
`sured.
`The following basic formulation has proved Satisfac-
`lory:
`Gelatin 8 to 10 g
`Starch 3 to 8 g
`Glycerol l to 2 g
`Water 30 to 50 g
`The active ingredient is dissolved or dispersed in this
`basic material. When a dispersion is used, for uniform
`distribution purposes,
`the active ingredient must be
`
`Page 3
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`

`

`5
`extremely finely divided and preferably the average
`particle size is in the range approximately 1 to 20 pm.
`The desired active ingredient dose and the sought
`surface of the dosage units determine the coating thick-
`ness, whilst account must be taken of the moisture con-
`tentofthe coating materialandthefinishedcoating.
`The inventive
`form is particularly
`suitable for drugsI which are administered with a low -
`dose rate, is. in which the
`dose for oral ad-
`ministration is between 0 mg (placebo) and approxi-
`mately 20 mg. Suitable drug active ingredients occur in
`all fields of Oral therapy, particular reference being
`made inter alia to analeptic. antibiotic, antidiabetic,
`antiemetic, antiepileptic, antihypertonic. corticoid, geri-
`attic, hypnotic, cardiac, hypostatic and bio-active ingre-
`clients.
`
`Approximately 4 to 20 g of active ingredient per in2
`(=10,000 cm?) of support film can be applied in one
`coating process, so that 10 cm2 (=2 standard postage
`stamps) can absorb up to 20 mg of active ingredit.
`The coating material is normally applied to One side
`ofthesupportfilm,butitisalsopossible tocoatboth
`sides, particularly in the case of two different active
`ingredits.
`Each coating can contain one or more drug active
`ingredients. If, when using several active ingredients,
`they are not readily compatible with one another and
`cannot be contained in one coating material, it is possi—
`ble in the case ofthe administration form according to
`the invention to apply the coating in the form of several
`individual coatings with dill'erent compositions and to
`separate the active ingredients from one another in this
`way; ifnecessary an active-ingredient-free intermediate
`coating being provided. It is also possible to provide
`above the active
`casting, a fur-
`ther protective coating, which protects the active ingre-
`dient or ingredients against contact with the atmo-
`sphere and/or light. In such cases, the protective coat-
`ing must cansequently be impermeable to air and mois-
`ture and/or must be made impermeable to light by the
`addition of corresponding dyes or pigments.
`Through a corrapcnding build-up of the coating, it is
`possible to control the supply of active ingredient fol-
`lowing the administration of the drug. For example. it is
`possible to place an active ingredient coating between at
`least two further coatings, which control the active
`ingredient resorption in the gastrointestinal tract in per
`se known manner. The active ingredient coating can
`eg. be located between two acid-insoluble coatings, so
`that on administration it passes through the stomach and
`resorption only takes place in the gastric tract. In a
`similar way, different active ingredients can be superim-
`posed indiii‘erentcoatingsonthesupport film, sothat
`Eesorption takes place successively and/or in delayed
`orm.
`Similar pharmacokinetic effects can be obtained
`through the incorporation (cg. suspension) of differ—
`ently pie-prepared microencapsulated active ingredi-
`ents.
`
`Coating of the support material with the active in-
`gredient-containing coating material
`takes place by
`means of a roll application or coating process. This
`process, which is particularly suitable for quantitative
`coating, operates according to a process similar to inta-
`glio printing and which is called “Akkugravuf‘. Suit-
`able machines are commercially available (Pagendarm.
`Hamburg) and permit application or coating weights of
`up to 80 g/m2 in the case of web speeds of several 100
`
`10
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`15
`
`25
`
`30
`
`35
`
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`65
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`4,849,246
`
`6
`is only
`m/min. The reproducible constant weight
`:l:2.5% for 20 3/3111 and approximately 110% for l
`g/m2 over entire surface. The coating material is ap-
`plied continuously by means of rollers with a special
`line engraving. the engraved grooves forming an angle
`of 30 to 60, particularly 45° to the direction of move-
`ment of the support film. 27 to 30 grooves/cm can be
`etched into the rollers. Corresponding to its shape and
`depth, the engraving can absorb a given quantity of
`coating material and subsequently supply it to the sup-
`port film. By varying the advance rate, running direc-
`tion and engraving, as well as indirect application by
`means of a. further speed-variable roller, it is possible to
`very accurately adjust the coating quantities.
`A two-sided coating frequently gives advantages,
`because problems due to the warping of the support
`material and differing hygroscopicity are compensated.
`Multiple and even strip coatings and in fact even print-
`ing style coatings are possible and offer a considerable
`variability when processing incompatible active ingre-
`dients.
`
`Another suitable application process cOrrespOnds to
`the coating of paper or films. Raw papers are improved
`in that they are coated with coating materials on one or
`bath sides. The aqueous coating materials initially pass
`onto a rolling mill, which receives same by means of a
`rotary roller, strips same to a clearly defined coating
`thickness with a doctor blade at a given spacing and
`then the roller supplies the coating material to the sup—
`port. The support film, which has a width of 0.30 to 1.50
`to, subsequently passes through a drying tunnel and is
`wound onto reels. This process can be repeated on one
`orbothsidesinoneormorestagesandanalready
`coated. surface can be coated again. The weight of the
`support material increases by that of the dry weight.
`The accuracy ofthe application process using this doc-
`tor blade method is reproducibly 15% and is depen-
`dent on the coating thickness, which can vary between
`4 and 40 g/m2. Within the individual production runs, it
`is possible to achieve a weight tolerance per surface unit
`down to 11%.
`When applying several coatings, as described herein-
`before, they are successively applied and Optionally
`each coating previously passes through a drying station.
`This can e.g. comprise a temperature-controlled pair of
`rollers and a drying tunnel which is controllable in
`sections. Following the final coating process, the coat—
`ing material is wound onto reels.
`The active ingredient-coated support film is subse-
`quently pre—divided into dosage units, which can be
`separated in much the same way as postage stamps. This
`pre-dividing is normally can-led out by the drug manu-
`facturer, but it is also conceivable to supply the coated
`material. e.g. to hospitals or pharmacists, where the
`pro-dividing can then be carried out in dose-dependent
`manner, or individually in accordance with information
`supplied by the doctor.
`Pie-dividing takes place in a very simple manner by
`perforation or punching, it being possible to combine
`this step with the printing of the support material. In
`many cases it is more advantageous to carry out the
`printing of the support material prior to coating.
`Before or preferably after pure—division of the active
`ingredient-coating into dosage units, the coated support
`material is cut into ready-for—use portions containing a
`given number of dosage units. It is also possible to cut
`the material on reels into narrow strips. It is then possi-
`
`Page 4
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`

`

`7
`'
`ble to separate the individual dosage units from the reel
`in much the same way as individual postage stamps.
`As mainly natural substances, such as starches and
`gelatin are used as basic substances for producing the
`inventive
`form, products are obtained,
`which are similar to known wafers and whose oral
`ingestion presents no problems. it is important that the
`finished product is largely free from water, i.e. has a
`watercontentoflessthan 10andpreferablylessthan
`2%. because otherwise mould can form.
`The invention has been largely described hereinbe-
`fore in connection with drugs, but is in no way limited -
`thereto. For example, it is also possible to adopt the
`same procedure for dosage forms for chemical reagents,
`11an substances and the like.
`The following examples serve to further illustrate the
`invention.
`
`5
`
`10
`
`15
`
`EXAMPLE
`
`Preparation of a drug administration form in the form 20
`of a coated film.
`The following composition was used for producing a
`water-soluble support film:
`
`
`[no parts by weight = 25%
`Gelatin
`8.0 parts by weight = 20%
`Potato starch
`1.5 parts by weight = 3.15%
`Glycerol
`
`Purified water ms parts-by weight: 51.25%
`
`25
`
`The viscosity of the slime-like compositiOn was ap- 30
`proximately 3000 cPs at 50° C. With the aid of a coating
`pmcmthematedalwasprocessedtoafilmwhich,
`alter drying, had a 9.3% residual water content.
`Using the same basic substances as for the support
`filmmecoadngmateflalwaspreparedinaccordance 35
`with the following formulation:
`
`
`10.0 partsby weight = 10.2%
`Gelatin
`5.0 may weight = 9.1%
`Potato starch
`LO parts by weight = 1.39s
`cumin
`input-Isby weight = 9.1%
`Actlveingrediem
`
`Purified water 34.0 parts by weight = arses
`
`40
`
`The viscosity of the slime-like composition was be-
`tween 4000 and 10000 cPs, as a function of the tempera- 45
`ture and active ingredient. To produce the coating ma-
`terial, the gelatin was firstly dissolved in. an adequate
`quantity of water, whereby firstly water at 90° to 95° C.
`was provided and into which the gelatin was intro-
`duced. accompanied by stirring. The active ingredient 50
`was dissolved together with the glycerol in water in a
`separate mixture. Finally, the potato starch was mixed
`in an adequate quantity of water at 50° to 60' C. and
`accompanied by stirring. The gelatin solution and po-
`tato starch suspension were added together and the 55
`active ingredient suspension was slowly stirred into the
`mixture, whilst avoiding air inclusions.
`The temperature was kept at 55‘ to 60" C. Finally, the
`desired water content was adjusted by adding further
`water.
`By means of Akkugravur, the coating material was
`. applied to the support film with a wet coating weight of
`55 g/m2. After drying, the coating weight was 23 g/m2,
`corresponding to an active ingredient content of 5
`g/mz. The active ingredient-coated film was then perfo- 65
`rated in box-like manner. so that the individual portions
`have a-surface of 5 cm3, in the case of dimensions of
`2x15 cm, such a portion containing 2.5 mg of active
`
`60
`
`4,849,246
`
`8
`ingredient. The residual moisture content of the prod-
`1.10: was 8.6% after drying.
`An administration form was obtained, which on oral
`administration rapidly swells and dissolves in the mouth
`and can therefore be easily swallowed.
`I claim:
`1. In a process for the production ofan administration
`and dosage form for drugs, reagents or other active
`ingredients in the form ofa film with an active ingredi-
`ent-containing coating, in which process
`(a) a water-soluble support film is produced from an
`aqueous composition based on an effective amount
`of a compound selected from starches, gelatins, and
`their mixtures and an effective amount of a com-
`pound selected from glycerol, sorbitol and their
`mixtures,
`(b) an aqueous coating material is prepared from an
`effective amount of the active ingredient, as well as
`an effective amount of a compound selected from
`starches, gclatins, and their mixtures and an effec—
`tive amount of a compound selected from glycerol,
`sorbitol and their mixtures, and
`(c) the coating material is continuously applied by
`means ofa roll coating procesa and in a precisely
`predetermined quantity to at least one side of the
`“PM film.
`'
`the improvent that the basic composition of the sup-
`port film corresponds to that of the coating material.
`2. Process according to claim 1, characterized in that -
`thesupportfilmandthecoatingmaterial also comprises
`a substance selected from the group comprising natural
`and synthetic resins and gums and their mixtures.
`3. Process according to claim 1, characterized in that
`the compoaition of the support film contains further
`additives selected from the group consisting of inert
`soluble and insoluble fillers, sugar and other sweeteners,
`plasticizers such as polyols, waxes and dyes, flavouring
`substances and preservatives.
`4. Process according to claim 1. characterized in that
`the coating material contains further additives selected
`from the group consisting of soluble and insoluble fill-
`ers. sugar and other sweeteners, plasticizers such as
`polyols, waxes and dyes. flavourng substances and
`preservatives.
`-
`5. Process according to claim 1, characterized in that
`the coating compound is applied to the support film in
`a continuous manner by means of grooved rollers,
`which absorb a clearly defined quantity of coating ma-
`terial and then transfer it to the support film.
`.
`6. Process according to claim 1, characterized in that
`the coating material is continuously applied to the sup-
`port film by means of smooth roller pairs, which in
`speed-displaced synchronism absorb the material and
`transfer it to the support film in a clearly defined quan-
`tity.
`7. Process according to claim 1, characterized in that
`the composition of the support film and of the coating
`material comprises 3 to 10 parts by weight of gelatin, 4
`to 8 parts by weight ofstarch, l to 2 parts by weight of
`glycerol and 20 to 50 parts by weight of water.
`8. Process according to claim 7, characterized in that
`the coating material comprises up to 10 parts by weight
`of the active ingredient.
`9. Process according to claim 1, characterized in that
`different active ingredients are applied to the top and
`bottom surfaces of the support film for producing a
`combination product.
`
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`

`4,849,246
`
`.9
`10. Process according to claim 1, characterized in
`that a coating material is used which comprises more
`than one active ingredient.
`'11.Processaccordingtoclaiml,charactefizedin
`that mutually incompatible active ingredients are ap-
`pliedintheformofseparatecoafingstothesupportfilm
`and an ingredient-free intermediate coating is provided
`betwoen the two ingredient-containing coatings.
`12.Proceasaccordingtoclaim1,charactefizedin
`that an active ingredient coating is placed between at
`least two further coating, which control the active
`ingredient resorption in the gastrointestinal tract and
`one of the coatings can be the support film.
`
`10
`13. Process according to claim 1. characterized in
`that a further coating is placed over the active ingredi-
`ent coating and protecrs the active ingredient against
`contact with the atmosphere, against light or against
`both.
`14. Process according to claim 1, characterized in
`that the active ingredient-coated water-soluble film is
`subdivided into portions by perforation or punching
`and said portions contain defined dosage units of the
`active ingredient
`15. Process according to claim 1. characterized in
`that the back ofthe support material is printed with the
`active ingredient composition or information relating to
`its medical application.
`-
`¢
`t
`i
`l
`t
`
`10
`
`15
`
`25
`
`3O
`
`35
`
`4s
`
`50
`
`55
`
`65
`
`Page 6
`
`Page 6
`
`