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Publication numberUS2853421 A
Publication typeGrant
Publication dateSep 23, 1958
Filing dateOct 4, 1956
Priority dateOct 4, 1956
Publication numberUS 2853421 A, US 2853421A, US-A-2853421, US2853421 A, US2853421A
InventorsAdams Howard R, Max Cherkas
Original AssigneeMerck & Co Inc
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Gelatin pan coating
US 2853421 A
Abstract  available in
Previous page
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Claims  available in
Description  (OCR text may contain errors)

. pill cores by the pan coating technique.

United States Paten GELATIN'PAN COATING Claims. "(C131 67=82) This invention relates to a 'process for "pan coating medicinal tablet or pill cores "which are to 'be used primarily 'for therapeutic purposes and more particularly to a composition suitable for coating -tablets as well as the tablets andpillswhich'have beenwoated thereby.

In particular, our invention relatestomedicinal tablets and pills which have 'been'pan eoated with'gelatin and which therefore have highstructural'strength and elasticity but which nevertheless will dissolve-readilyinthe "secretions of the stomach and intestines when brought into contact therewith. The-coating of this-invention additionally protects the =ta'blet core containing the medicament from moisture, oxygen "or other substances which may cause variation in the medicinal 'valuefof the active ingredient or ingredients :con'tained i'therein,

The problem of coating-pill ancl tablet cores containing medicinal substances: constantly :confronts drug: manufac- "turers particularly because most medicinal-agents aretrepugnant to the taste and rrnany of :them :react withithe coating material in a deleterious :manner with theresult that aftera certain time the coating and/'orathercore tmaterial break downand=the tablet-or .pilhbecomesworthi'less either because "of the "inactivation :of; the therapeutic his book entitled, Table Coating describes pan coating coreswitha gelatin-acacia 1nixture,'- but while two or threelayers .oiithis. solution can'Ibe applied to cores,.it is not feasible toapply-the multiple layers needed to make a durable, hardand;pharmaceutically"elegant and com- .mercially .acceptable coating. A coating comprising a mixture of gelatin iandlacacia. remains. permanently tacky and as the viscosity decreases as the .temperature increases the coated tablets and, pills stick together'forniing unusable agglomerates. '.The. gelatin coating of this invention however .setsto a hard, elastic film which shows notendency to become .tacky at temperatures of 100- 120 F. .or higher and arela'tivefhumidity'lkH) as high as ,60+l0'0% such as would be-encountered in tropical or subtropical countries whereipills and tablets may be stocked. V

In carrying out this invention, a compositionfor coating medicinal .pill and tablet cores is prepared comprising .a solutionin water of gelatin and sugar in 'theproportion of 1 /2 to 4% ,parts'by weight ofgelatin'to lpartl'by weightof .sugar. vIf va vcolored coating is desired, the ldyeis "dissolvedin this gelatin syrup. An advantageous ,ge latinsyrupfifor use in coating the medicinal cores containsfrom .about '25 to about 40% total solids and prefverably"3'3 .totalsolids on a 'weight-to-weight ,basis in .theaqueoussolution. "The tablet or pill cores are coated .by applying a multiplicity of thin superimposed layers of this .syrup to the core itself or to cores pretreated with a subcoating and/orisizing or other material inert to the medicament contained in the core and to the, gelatin coating to be applied thereto. "Ifa sizing is applied to the core itis preferred to superimpose thereon a'binding material suhas a"film of age'latin-acacia solution, ;or

' other mucilaginous substance as agar, tragacanth, methylingredients in the core or spoilage of the coatingimaterial which gives rise to a product which meets consumer resistance.

Many coatingsihave'beensuggested by priorworkers one or more drawbacks. Some'coatings require :special equipment for their application to .-the .core material, .others require the use of unusual-or expensive ingredients which may or may'notproducetsometoxic manifestations in some people, in others the coating does-,notrsuflioiently readily dissolve in the intestinal vtract, or-theicoatingdoes not possess the necessary hardness and elasticty which ensures that the coating 'will not chip-ortbreak readily if the pill 'or tabletshould'bebitten-ibyitheiindividual taking it or by bumping againsteachother-in:the routinepackaging and handling of merchandise of thistype.

It is the object of this .-invention ato=provide :agelatin coating composition which can be applied to'the tablet or The coating of this invention provides all of the desirable characteristics of hardness combined'with sufiicient elasticity to produce a coating highly resistant to chipping and breaking .bnt which nevertheless rapidly vdisintegrates in the ;.gastric juices. It has the added .advantage't-hat thelingredients employed in the coating material areknown to .besuitable for ingestion 'by humans and, in addition, ithaslbeen discovered that by employing the technique which is a feature of this invention the coating can be applied in an apparatus of the type "conventionally used in pan coating medicinal pill.andtab1et cores.

While gelatin has been used.'forcoatingtablet and pill .cores, the only practical methodheretofore employed for its application has been to encase the cores Lin sheet gelatin which requiresspecial apparatus. "Clarks'on, in

cellulose, carboxymethylcellulose, zein or other known substances useful for this purpose. ".The application of the bin'ding material. ensures afirmbond with the gelatin syrup charges to be applied thus avoiding 'any possibility of pulling as'the gelatin coatingis built up.

,"The, gelatin syrup is prepared'by conventional methods such asby dissolving vthe gelatin and sugar in hot or cold Water, and either by dissolving eachseparatelyand then subsequently mixing the two solutions, or-by first dissolving the gelatin or .sugar and subsequently the other ingredientin the same aqueous "medium or by intimately mixing thegel-atin and sugar and then slowly adding the mixture with constant stirring to water heated in a steam-jacketed kettle and continuing the stirring and heatingsuntil all of the gelatin and sugar has dissolved, or by soaking the gelatin in cold water overnightand then dissolving the sugar in the gelatin solution by heating andflstirring. "The "important consideration in prepairingv gelatin syrup is to-maintain the ratio of gelatin to sugar Withinftheratio .of'l /z to 4 /2 parts by'weight of gelatin to 1 part by weightof sugar to ensure that the gelatin syrup. can *be applied'in multiple layers by thepan coating process and upon drying will have the desirable characteristics described above for it.

'Either ofthe two fundamental types of gelatin, type A or type B, can be employed in preparing the gelatin syrup, and jelly strengths ranging from .to 300 Bloom have been used successfully in preparing the syrup, although it is, pre'ferred to-use jelly strengths ranging between .20() to 250 Bloom .and preferably 225 Bloom gelatincanbe employed. YITypeAgelatin is made'from acid-conditioned collagen .and typeB from limeecon- .ditionedcollagen. For the most part, gelatin'from acidoonditione'distoek .(type A) .is-made from frozenpo'rkskins and limed gelatin (type BLfifrom .calfskins, vbeef- Published byDrugJdnCosmetic Industry, Copyright .1951, Drug Markets, Inc, New York 1, N. Y,

hides and also from dimineralized cattle bones (ossein). Although there are some differences in characteristics of type B gelatins, depending on whether they are manufactured from calfskins, beefhides or ossein, these differences are slight and for use as a protective colloid it is usually possible to substitute one for another and generally manufacturers do not differentiate one from another when the gelatin is prepared and sold. The jelly strength of gelatin is determined by making up a gelatin gel under standard conditions (6%% concentration chilled for 17 hours at C.) and testing by means of the Bloom gelometer which is a type of penetrometer. The Bloom value is the number of grams required to force a /2-inch plummet 4 millimeters into the jelly. The Bloom value is roughly proportional to the molecular weight and also the viscosity. An especially satisfactory gelatin syrup for use in pan coating tablet and pill cores according to this invention can be made from 100% porkskins (type A gelatin) having a jelly strength of approximately 225 Bloom.

The medicinal cores are coated by placing the untreated or pretreated cores in a pan coating apparatus and applying warm gelatin syrup maintained at about 70 C., while rotating the cores in the pan at a temperature of about 76 F. and a relative humidity (RH) of about 37%. As stated above, the cores can be used in their untreated form or, if necessary or desired, the cores can be pretreated in any of the usual ways such as applying a subcoating of a heavy syrup, i. e., sugar solution and the like, or by applying a sizing coating such as a gelatin-acacia solution, shellac or other known sizing coatings or a combination of subcoating and sizing coating if this is considered desirable or necessary for any particular type core which is to be coated sub sequently with gelatin. It is important that only enough gelatin syrup is poured over the rotating cores to coat all of the cores with a thin film. If too much solution is used, it is more difficult to dry the film and overcome the tackincss of the coating thus greatly increasing the possibility of spoiling the coating. Ordinarily, about 5 fluid ounces per charge of about 70,000 cores weighing about 60 pounds is a suitable amount of gelatin syrup when applied at about 70 C. This quantity of gelatin syrup can be slightly increased or decreased depending upon prevailing temperature and humidity conditions.

After applying the gelatin solution, rotation of the pan is continued and the condition of the tablets is closely observed. Initially all of the coated cores roll freely, but as the water evaporates the coating becomes more viscous and the cores begin to coalesce. At the moment the tablets become tacky, which is indicated by their tendency to adhere one to another, i. e., coalesce, a small amount of talc, just enough to overcome the tackiness of the coating, is dusted through gauze onto the coated cores. The gauze is advantageously of medium grade porosity or of fine porosity as this ensures precision in dusting which is important in pan coating tablet cores with a gelatin syrup. Too little talc will not overcome the tendency of the coated cores to adhere one to another and if they are permitted to coalesce, the coating is spoiled. On the other hand, too much talc will roughen the surface of the coating and also cause spotting. The amount of talc dusted on the coated cores must be adjusted by observation, and, as stated above, must be just suificient to overcome the tackiness of the coating and prevent the cores from sticking one to another. The U. S. P. grade talc generally is used to dust the coating but any other talc of substantially the same purity and fineness could be substituted in this step. If the gelalin syrup used in pan coating the tablet and pill cores is colored, the same dye also is added to the tale as this too, will overcome spotting as this coating is built up.

As soon after dusting with talc as the coated cores roll free, cold air is blown over the rotating coated cores until they become thoroughly dry. For a load of ap- 4 proximately 70,000 cores weighing about 60 pounds, the drying time is approximately 25 minutes. The drying time will, of course, vary with the number of cores in each load and also with the amount of gelatin syrup applied and with the relative humidity. It is important that cold air be used in the drying to effect hardening of the gelatin syrup on the cores as Warm air will soften the gelatin and prevent proper hardening of the film. Air, cooled to from about 60 to 65 F., has been used satisfactorily in the drying step.

it is also important that the relative humidity of the room where the pan coating is being done be maintained below about 40% and preferably between 3038% RH and that the temperature preferably be maintained between about 80 F. Above this relative humidity, the moisture in the air tends to make the gelatin too soft and retards the rate of drying. The more moisture, of course, the softer the gelatin becomes and the greater is the chance that some of the moisture will seep into the core material which can cause deleterious efifects such as inactivation of the active ingredient and the like. In general, the lower the humidity the quicker the coating will dry to a hard, durable film.

The above described coating, dusting and drying steps are known in the art as a charge. This charge is repeated any number of times to produce a coated tablet of any desired size. As few as 10 charges provides a coating which will pass the hardness and stability tests for most tablets. If, of course, it is desired to prepare a coating which will not break or readily dissolve if held in the mouth or chewed, then 25 or more charges can be applied to the cores. Hexylresorcinol containing cores which received 10 charges of the gelatin syrup of this invention were found to satisfactorily pass the hardness test defined for them by the United States Pharmacopoeia and were found to disintegrate in less than 4 hours as is required for tablets or pills containing hexylresorcinol.

If the coating on the core is to be colored, then the dye must be added to the gelatin solution as well as to the tale and in each instance the dye can be added by known methods.

As a rule, it is not necessary to polish the gelatin coatings of this invention as a smooth, lustrous surface generally results from the pan coating of this composition. However, the coated pills and tablets can be run in a polishing machine if it is desired to enhance the lustre but no talc or wax should be used if this is done.

The following example illustrates the method by which tablet and pill cores are pan coated with a gelatin syrup as well as a suitable gelatin syrup for use in this procedure. It is to be understood, of course, that modifications can be made in the technique and in the materials employed to adjust each of them to the particular condition of temperature, humidity, and quantity of cores to be coated, all of which modifications are within the skill of those working in this art.

EXAMPLE I.GELATIN PAN COATING OF CORES EACH CONTAINING 0.15 GRAM HEXYLRES The sugar, gelatin and dye were placed in a stainless steel container and intimately mixed 'by stirring. The water was added slowly with continued stirring and then the mixture was heated in a water bath maintained at a temperature between about -95 C. with stirring until a clear solution was obtained. This solution was strained 5 through a double thickness of gauze havinga' 28--24me sh to remove any un'dissolve'd"particles.

(b) Dusting powder Talc'U.i'S. P 100.lbs.

' & C. .No. 3; 1 11:.

Water, distilled q. s (Approx.=2 gal.,

2;pints) The dye was dissolved -in .2 gallons of the distilled water by stirring and the solution then put through smooth surfaced qualitative type filter paper such as that sold by Arthur H. Thomas Company as filter paper No. 5268. The talc was placed in a ponymixer and while the mixer was running, the dye solution was'added slowly thereto. While still running, the additional2 pintsof distilled water were added and mixing 'con'tinue'dfor about 20 to 30 minutes. 'The dyed talc then was -granulat'ed by passing through a comminuting machine equippedwith a'No. 4 screen andimpacters and run at medium speed after which it was returned to the pony mixer "and'remixed for about 'five minutes. The granulesthemwere spread out about /2 inch thick on dry'i'ngtrays and dried for about 12 hours at 130 to 150 F. Whenthe granu- Sixty pounds (71,186'ta'blets, weighing59-grs.) of the hexylresorcinol-containiug*cores having 2 charges of a gelatin-acacia solution, were placed in a coating-pan and the pan started in motion. "The room "conditions were regulated to about76F.'and the to'about37 and about 5 'fluid ounces-of-the gelatin solution, previously heated to 70 C., was poured overthesized cores. The pan was maintained in rotation and as'soon as the cores showed a tendency'to adhere one toflanother about Z ounces of the red talcwas'dustedon'thecores through a double thickness of medium gauge gauze having a 28 x 24 mesh. The coated cores were observed'to roll freely and cold air, maintained at about -'1"7"C., 'then was blown over the rotating cores for'fromZO to"2-5 minutes or until the coating material was thoroughly dry. The charge was repeated-49 times thus applying 50; charges to the sized hexylresorcinol'cores. The coated tablets'then were transferred to a polishing pan which was 'set in motion and allowed to run "for approximately 30 minutes to produce a high luster. "Itis to "be'observe'd that "no dusting or wax is needed to produce a high luster on gelatin coating such as applied'tothese'cores.

Samples of the coatedtablets"were' taken'when 10 charges had been applied and also when 25, 43 and 50 charges had been applied'to the cores. "These samples were tested and found to have 'the."following character- 1 Figures represent 10 readings on Strong Cobb Hardness Tester Apparatus and represents withstanding at least pounds total pressure exerted upon tablet.

2 Disintegration time determined by method outlined in U. S. Phar maeopoeia, vol. XV, pp. 936-38, employing simulated gastric fluid.

Moisture content represents average percent loss in weight of crushed tablets after drying 4 hours in a vacuum oven maintained at EXAMPLEII;GELATIN PAN CO-ATINGOFEOKES TEACH "CONTAINING r MG."FLUDROCOR-FISONE ACETATE .(a) Gelatin. syrup Sugar .EISP medium granular.- 1 51b.

Erythrosine certified, No. 773 'FRe d.R..F."Z&

C. No. 3 :1 1oz. Water, distilled 1. gal.

"The water'was placedin a steam jacketed "ke'ttle'an'd the gelatin, sugar and dye which hadprevi'ouslyheen intimately mixed was aa'dded'. theretot's'low'ly with constant stirring. The steam then was turned on and the contents of the kettle-Was heated with @continu'e'd stirring until all .of the gelatin and *sugar had dissolved and'a clear solution was obtained. Thissolution then was 'stra'inedfthroug'h a double thickness of gauge having a28 x24. mesh.

(Ir) Dusting P'owder Prepared :asdescribedin Examplel; (.b)

(0) Pan. coating Sixty pounds of untreated fludrocortisone =acetate containingcores were-placed in'a coating pan and coated with the type B gelatin syrup,;prepared as described'instep (a) "aboveyinthesamemannerdescribed'in Example 'I (-c). Twenty-five charges-were applied and samples "of the "finished product were found "to' "Withstand atleast 'TS p'oundspressure 'whentested on the Strong Cobb 'Har'd- 'ness "Tester Apparatus, they disintegratedin IeSsthan -'4 hours and had a moisture content of lessthan 1%.


The jgelatin was added to tthe distilled water -.and allowed to stand overnight at room temperature. The next day, the sugar was ad'dedfslowly with stirring and the dye dissolved in a small quantity of water then was added with stirring. lhe 'mixturewasheatedwithconstant stirring until aiclear solution was obtained. The solution-then was strainedlhrough a .double thickness of gauzehaving a 28 x24 mesh.

(b) Dusting powder "The *d-usting "powder was prepared in "substantiallythe same "manner as describedin -Example I ('17) =withthe exception an equal 'quantity of *ta'rtrazine F. D. & C.

'Yellow' No. 5 was employed inSteadof Red-FJD. &"C. No. 3.

(0) -Pan-. coating Sixty pounds .of. untreated cores each containing 50,0'0'0'units'vitamin A p'almitate were placedina coating pan and coated with the'type A, 'Bloom gelatin syrup, prepared as described abovein step "(121), inthe same manner described in Example I (0). 'Fiftycharges were applied to the cores and samples of the finished coated tablets satisfactorily passed the hardness, disintegration and moisture tests in that they resisted a pressure of at least 15 pounds when tested on the Strong Cobb Hardness Tester Apparatus, disintegrated in less than 4 hours and had a moisture content of less than 1%,

EXAMPLE IV.-GELATIN PAN COATING OF CORES EACH CONTAINING 0.3,GM. OF A 1:3 M I X T U R E OF HEXYLRESORCINOL AND PIPERAZINE (a) Gelatin syrup Sugar USP medium granular 1 lb. Gelatin USP (type A, 250 Bloom) 1 1b., 8 oz. Guinea Green B, F. D. & C. Green No. 1 1 02. Water, distilled 1 gal.

The gelatin syrup was prepared by substantially the same method described in Example I (a), but using the above ingredients.

(I?) Dusting powder Sixty pounds of the hexylresorcinol-piperazine-containing cores, previously sized with shellac and having a binding coating comprising two charges of a gelatinacacia solution, were placed in a coating pan and coated with the Type A, 250 Bloom gelatin syrup prepared as described above. Fifteen charges were applied to the cores by substantially the same procedure described in Example I (c) and samples of the finished coated tablets satisfactorily passed the hardness, disintegration and moisture tests in that they withstood at least 15 pounds pressure on the Strong Cobb Tester Apparatus, they disintegrated in less than 4 hours and had a moisture content of less than 1%.

EXAMPLE V.GELATIN PAN COATING OF CORES EACH CONTAINING 0.1 GM. HEXYL- The gelatin syrup was prepared in the same manner described in Example I (a) but using the above ingredients.

(b) Dusting powder Prepared as described in Example I (b).

(c) Pan coating Sixty pounds of the hex'ylresorcinol-containing cores having two charges of a gelatin-acacia solution were placed in a coating pan and coated with the type A, 225 Bloom gelatin syrup prepared as described above in substantially the same manner as described in Example I (c). Fifteen charges were applied to the cores and samples of the coated tablets satisfactorily passed the hardness, disintegration and moisture tests in that they withstood a pressure of at least 15 pounds on the Strong Cobb Hardness Tester Apparatus, they disintegrated in less than 4 hours and had a moisture content of less than 1%.

While the invention has been described with reference to certain particular cores it is to be understood that .any untreated or treated cores can be employed in the invention can be applied thereto to form a hard, tenacious, pharmaceutically elegant coating thereon.

Similarly any suitable dusting powder can be applied and the tale USP employed in preparing the dusting powders in the examples contained herein can be replaced by any other suitable talc having substantially the same fineness and purity as talc USP and the coloring material can be replaced by any coloring material ap proved for use in food, drugs and cosmetics (F. D. & C.) or in drugs and cosmetics (D. & C.).

Slight modifications can be made in the temperature and relative humidity conditions under which the cores are pan coated with the gelatin syrup of this invention provided the temperature and relative humidity conditions do not prevent proper hardening of the charges as they are applied to the cores.

What we claim is:

1. A medicinal tablet or. pill including a core comprising the medicament and a coating exterior thereto comprising a multiplicity of thin, superimposed layers of a composition containing as the essential coating material ingredients intermixed gelatin and sugar in the proportion of 1 /2 to 4 /2 parts by weight of gelatin to 1 part by weight of sugar.

2. A composition for coating medicinal pill and tablet cores containing a medicament containing as the essential coating material ingredients a solution in water of gelatin and sugar in the proportion of 1 /2 to 4 /2 parts by weight of gelatin to 1 part by weight of sugar.

3. A composition for coating medicinal pill and tablet cores containing the medicament containing as the essential coating material ingredients an aqueous solution containing from 25% to 40% total solids and representing gelatin and sugar employed in the proportion of 1 /2 to 4% parts by weight of gelatin to 1 part by weight of sugar.

4. A composition for coating medicinal pill and tablet cores containing the medicament containing as the essential coating material ingredients an aqueous solution containing.33% total solids and representing gelatin and sugar employed in the proportion of 1 /2 to 4 /2 parts by weight of gelatin to 1 part by weight of sugar.

5. In a process for pan coating medicinal pill and tablet cores containing the medicament the steps comprising applying to a member of the group consisting of untreated cores and cores pretreated with a subcoating and sizing material while rotating in a coating pan a composition containing as the essential coating material ingredients solution in water of gelatin and sugar in the proportion of 1 /2 to 4 /2 parts by weight of gelatin to 1 part by weight of sugar at a temperature of about C. and at the moment the coated cores begin to adhere one to another applying suflicient tale to allow the coated cores to roll free and then drying the coating with cold air and repeating these steps in sequence until a coating of desired thickness is obtained.

References Cited in the file of this patent UNITED STATES PATENTS 1,161,690 Kawai et a1. Nov. 23, 1915 2,145,317 Salzberg Jan. 31, 1939 2,487,975 Koree Nov. 15, 1949 OTHER REFERENCES Remingtons Practice of Pharmacy, 9th ed., 1948, Mack Pub. Co., Easton, Pa., pp. 1301 and 1302.

Little et al.: Tablet Making, Northern Pub. Co., Liverpool, Eng., 1949, p. 86.

Patent Citations
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US1161690 *Mar 31, 1913Nov 23, 1915Kametaro KawaiComposition for coating pharmaceutical preparations.
US2145317 *Jun 15, 1937Jan 31, 1939Borden CoFoundry core binder
US2487975 *Feb 14, 1947Nov 15, 1949Jacques Loewe Res Foundation ITherapeutic preparations for intramuscular or subcutaneous injection and methods of making the same
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3116205 *Feb 27, 1959Dec 31, 1963Olin MathiesonVeneer coated tablets
US3247066 *Sep 12, 1962Apr 19, 1966Parke Davis & CoControlled release dosage form containing water-swellable beadlet
US3542916 *Aug 15, 1967Nov 24, 1970Richardson Merrell IncWater dispersible nitrofuran compositions and method of preparing the same
US4965089 *Apr 10, 1989Oct 23, 1990Sauter Manufacturing Corp.Method and apparatus for the gelatin coating of caplets
US5093130 *Sep 26, 1989Mar 3, 1992Plant GeneticsPowder coated hydrogel capsules
US6258380Mar 5, 1999Jul 10, 2001Banner Pharmacaps, Inc.Chewable soft capsule
US8097279Apr 24, 2003Jan 17, 2012Banner Pharmacaps Inc.Chewable soft capsule
US8241665Oct 10, 2011Aug 14, 2012Banner Pharmacaps, Inc.Chewable soft capsule
US8414916Jun 8, 2012Apr 9, 2013Banner Pharma Caps, Inc.Chewable soft capsule
US8765174Dec 15, 2011Jul 1, 2014Banner Pharmacaps Inc.Chewable soft capsule
US9072677Jun 27, 2014Jul 7, 2015Banner Life Sciences LlcChewable soft capsules
US20050169983 *Apr 24, 2003Aug 4, 2005Hassan Emadeldin M.Chewable soft capsule
DE1215302B *Feb 13, 1960Apr 28, 1966Dr Gerhard WesterburgVerfahren zum Dragieren von Tabletten
WO1987006128A1 *Feb 24, 1987Oct 22, 1987Clemetson Ab CharlesCatechin coated ascorbic acid and method
U.S. Classification424/478, 106/146.1, 427/2.18, 424/479
International ClassificationA61K9/40, A61K9/30, A61K9/28
Cooperative ClassificationA61K9/2873, A61K9/2826
European ClassificationA61K9/28H4B, A61K9/28H6H