CA2104096C - A method of highlighting intagliations in tablets - Google Patents
A method of highlighting intagliations in tablets Download PDFInfo
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- CA2104096C CA2104096C CA002104096A CA2104096A CA2104096C CA 2104096 C CA2104096 C CA 2104096C CA 002104096 A CA002104096 A CA 002104096A CA 2104096 A CA2104096 A CA 2104096A CA 2104096 C CA2104096 C CA 2104096C
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- tablets
- filling material
- intagliations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
Abstract
A method of highlighting intagliations in white or colored coated tablets by spraying onto said tablets a suspension com-prising a filling material having a different color, a waxy material and a solvent, and removing the solvent and the excess of fill-ing material and waxy material.
Description
A METHOD OF HIGHLIGHTING INTAGLIATIONS IN TABLETS
The present invention relates to a method of highlighting intagliations in tablets by selectively depositing and fixing in said intagliations a filling material having a different color than that of the tablet surface.
As more and more medicines become available, the risk of confusing look-alike or resembling medicines increases. Such poses a potential threat to patients, in particular to the elderly and to those patients taking more than one preparation. A
significant aspect of improving drug safety therefore resides in avoiding and eliminating this risk of confusing different preparations.
Besides distinguishing medicines by means of color or shape, the use of inscriptions has become a method of choice for identifying preparations. Inscriptions are particularly aaractive due to their versatility in conveying information such as, for example, the company name, product name, the dose and the like identifying marks.
The printing of marks on the surface of tablets is a first approach to identify preparations. Drawbacks associated with this technique are the necessity of using specialized machinery and the low quality of the printed marks due to smearing and smudging.
Another method involves the engraving or impressing of a figure, mark, character or any combination thereof, in a tablet by a punching procedure. Such impressed marks are generally termed 'intagliations' and will henceforth be designated as such.
Unfortunately, said intagliations are not easily discerned as their legibility depends on the irregularities on the surface of the tablets and the quality of the outer coating film which may partially or completely fill up said intagliations. This problem is further aggravated by the increasing tendency towards smaller unit dosage forms.
The present invention relates to a method of highlighting intagliations in tablets by selectively depositing and fixing in said intagliations a filling material having a different color than that of the tablet surface.
As more and more medicines become available, the risk of confusing look-alike or resembling medicines increases. Such poses a potential threat to patients, in particular to the elderly and to those patients taking more than one preparation. A
significant aspect of improving drug safety therefore resides in avoiding and eliminating this risk of confusing different preparations.
Besides distinguishing medicines by means of color or shape, the use of inscriptions has become a method of choice for identifying preparations. Inscriptions are particularly aaractive due to their versatility in conveying information such as, for example, the company name, product name, the dose and the like identifying marks.
The printing of marks on the surface of tablets is a first approach to identify preparations. Drawbacks associated with this technique are the necessity of using specialized machinery and the low quality of the printed marks due to smearing and smudging.
Another method involves the engraving or impressing of a figure, mark, character or any combination thereof, in a tablet by a punching procedure. Such impressed marks are generally termed 'intagliations' and will henceforth be designated as such.
Unfortunately, said intagliations are not easily discerned as their legibility depends on the irregularities on the surface of the tablets and the quality of the outer coating film which may partially or completely fill up said intagliations. This problem is further aggravated by the increasing tendency towards smaller unit dosage forms.
EP-B-0,060,023 discloses a method of emphasizing intagliations in colored (i.e. not white) solid articles, in particular tablets, by coating the tablet surface and filling up the intagliations with a coating film comprising an optically anisotropic substance. An optical contrast between the tablet surface and the intagliations is obtained, presumably due to the different orientation of the optically anisotropic substance on the tablet surface and in the intagliations. The technique is limited to colored articles and only allows the use of optically anisotropic filling materials. The optical effect merely being based on a different contrast is not particularly clear.
EP-B-0,088,556 relates to a method of highlighting intagliations in white or colored tablets by contacting said tablets with a dry, powdery material having a different color than the tablet surface and then removing the excess powdery material not deposited in the intagliations. The powdery material is taught to adhere better to the intagliations of coated tablets than to those of uncoated tablets. Adherence can further be increased by using a mixture of a wax and a powdery material as the deposition material and heating the filled tablets to 40-90°C in order to melt the wax. Finally, an outer coating may be applied to the filled tablets.
The method disclosed in EP-B-0,088,556 has several problems. In the first place it has been found that the adhesion of the powdery material to the intagliation is not satisfactory as said material shows a tendency to loosen and fall out. This problem arises particularly when an outer coating film is applied to the filled tablet and the loosened material becomes fixed in said outer coating film, thus yielding speckled tablets.
Addition of a wax to the powdery material in order to improve adhesion on the other hand, adversely affects the distribution of the powdery material in that more of it sticks to the surface of the tablet and is difficult to remove. Several more drawbacks are associated with the use of a wax in the dry powdery material. In particular the necessity to heat the tablets filled with a wax and a powdery material in order to melt said wax, poses a hardly acceptable risk since many medicines are thermolabile and might deteriorate significantly in the process. Further it proves difficult to dye evenly a dry mixture of a wax and a powdery material, which in tum puts a limitation on the effectively possible color combinations.
The method of the present invention differs from the prior method disclosed in E-B-0,088,556 by the fact that an optionally colored filling material and a suitable wax are suspended in a solvent and sprayed onto a coated intagliated tablet.
Following the removal of the solvent and the excess deposition material, tablets are obtained having a firmly fixed amount of said deposition material specifically in the intagliation. Said WO 92/15288 210 4 0 9 6 P~/E)P92/00358 _3_ tablets have superior visual attractivity over those obtained using prior art methods due to the complete and specific filling of the intagliations and absence of deposition material on the surface of the tablets. An outer coating film can easily be applied to the thus obtained highlighted intagliated tablets without danger of loosening the deposition material from the intagliation. The present method further avoids high temperatures and thus is amenable for identifying solid preparations comprising thermolabile medicines.
The present invention relates to a method of highlighting intagliations in white or colored coated tablets by spraying onto said tablets a suspension comprising a filling material having a different color, a waxy material and a suitable solvent, and removing the solvent and the excess of filling material and waxy material; and to tablets obtainable by said method.
The tablets used as a substrate preferably are film-coated. Film-coated tablets allow a more selective bonding of the filling material to the intagliations and less adherence to the tablet surface than uncoated tablets because of the reduced porosity of the tablet surface (decreased roughness). Any material generally used for applying a coating film to tablets may be employed. For example, suitable materials are, e.g. methylcellulose, hydroxy-propyl methylcellulose, hydroxypropylcellulose, carboxymethylethyl cellulose, cellulose acetate phtalate, hydroxypropyl methylcellulose phtalate, acrylates, copolymers of acrylic and methacrylic acid esters and the like.
The coating films may be plasticized with suitable plasticizers such as, e.g.
polyethylene glycol, propylene glycol, glycerol, diethyl phtalate, dibutyl sebacate, citroflex, triacetin and the like. If necessary coloring agents can be added. These can be natural pigments such as talc, kaolin, titanium dioxide, or dyestuffs or lake dyestuff selected from accepted food colors. The coating solvent can be water or any other organic solvent suitable for film-coating such as, for example, an alcohol, e.g. ethanol, 2-propanol, a ketone, e.g. acetone, or a halogenated hydrocarbon, e.g. dichloromethane.
Preferably the coating is applied by spraying a solution on the tablets in a perforated side-vented pan (Pellegrini, Accela-Cota~, Hi-coater~ (HCT-20)) by means of a spraying system worked by air pressure. The process conditions are those generally employed in coating procedures provided that due care is taken to avoid filling of the intagliations.
A wide variety of filling materials can be used for the filling of the intagliations. Suitable filling agents are, for example, starches, e.g. corn starch, rice starch, wheat starch, potato starch, preferably corn starch or rice starch; celluloses, e.g.
methylcellulose, 2104~~6 -4-ethylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropyl methyl-cellulose, hydroxypropyl methylcellulose phthalate, crystalline cellulose, preferably microcrystalline cellulose fibers (Elecma P050~); lactose and other sugars or sugar alcohols, e.g. sucrose or mannitol, preferably micronised lactose 200 mesh, spray-dried and micronised lactose (DCL-11~) or mannitol; organic acids, e.g. stearic acid, fumaric acid, citric acid, preferably fumaric acid; or inorganic 'substances, e.g.
sodium chloride, calcium carbonate, preferably sodium chloride, all giving white intagliations.
Other finely divided filling materials such as titanium oxide, talc, kaolin, magnesium stearate and aluminum lakes in practice are less preferred because of their greater tendency to stick to the surface of tablets. The most prefered filling materials are corn starch and microcrystalline cellulose. Colored intagliations are obtained by previously dyeing the filling material. This is achieved by suspending the filling material in a solution of the dye, filtering off, drying and finally grinding. Starches and celluloses such as cited hereinabove and especially those specifically preferred hereinabove can be dyed in water, with, for example, edible lake pigments, e.g. FD&C blue no. 2, FD&C red no. 3, FD&C yellow no. 6, D&C yellow no. 10 and the like or any combinations thereof.
The weight to weight ratio of said lake pigments to the filling material generally ranges from 0.1:100 to 10:100 and may be choosen in function of the desired intensity.
Water soluble filling materials such as lactose can effectively be dyed by suspending them in a solution of an alcohol-soluble dye such as FD&C red no. 3 or D&C
yellow no.
10 in an alcohol such as ethanol.
The optionally colored filling materials are suspended in a solution of a waxy material in a suitable solvent. The waxy material is added to enhance the adherence of the filling materials. Examples of waxy materials are polyethylene glycols, natural waxes such as, e.g. beewax or carnauba wax, hydrogenated oils, higher fatty acids and fatty acid esters, fatty alcohols and polyoxyethylene ethers of fatty alcohols. Preferred waxy materials are polyethylene glycols (PEG), in particular PEG 400, PEG 600, PEG 1000, PEG 1500 and PEG 4000.
The proportion of waxy material to filling material is a very critical parameter in the filling process. Too little waxy material will lead to insufficient bonding of the filling material; with too much waxy material the filling material will bond too strongly to the tablet surface and consequently will be difficult to remove afterwards. The weight to weight ratio of the waxy material to filling material may range from about 1:3 to about 1:12, in particular from about 1:4 to about 1:9. For waxes having a low molecular weight and low melting point, e.g. PEG 400, PEG 600, PEG 1000 said ratio preferably ranges from 1:4 to 1:6 and in particular is about 1:5. For waxes having a higher WO 92/15288 PGT/EP92/00358.
2104096 _5_ molecular weight and melting point, e.g. PEG 1500, PEG 2000, said ratio preferably ranges from 1:6 to 1:8 and in particular is about 1:7.
Suitable solvents are those solvents wherein the filling material and, if present, the dye, do not dissolve. For example, non-dyed starches and celluloses may be suspended in alcohols, e.g. ethanol, isopropanol and the like, halogenated hydrocarbons, e.g.
dichloromethane, trichloromethane and the like. Dyed starches, dyed celluloses and non-dyed lactose may be suspended in water-free alcohols, in particular absolute ethanol. The amount of solvent in the final suspension for spraying onto the coated intagliated tablets may range from about 70% to about 85% (w/w) in particular from about 75% to about 81 % (w/w), more in particular from about 77% to 81 %.
The filling suspension may be sprayed on the coated tablets in a flow-through type coating pan or in a perforated side-vented pan by means of a spray worked by air pressure. Preferably said suspension is kept at room temperature and is stirred or agitated to prevent sedimentation. The temperature of the tablets within the coating pan is advantageously raised slightly to about 30 to 60°C, in particular 30-40°C by employing warm inlet-air.
After applying the amount of filling material required the spraying process is stopped and the excess of solid material adhering to the tablet surface is removed by blowing off with air, meanwhile keeping the tablets tumbling to rub off the filling material deposited on the tablet surface.
To prevent the loosening of deposited filling material, a thin colorless seal-coating layer can be applied to the tablets. The coating polymer can be one of those mentioned above for the subcoating, especially hydroxypropyl methylcellulose, together with a suitable plasticizer as mentioned hereinabove. In the case of water soluble filling materials or dyes, the solvent used is preferably an organic solvent since water would dissolve the filling material and the dye fixed on the solid filling material. Said seal-coating process may be conducted in any of the usual coating devices such as, for example, flow-through coating pans or side-vented coating pans, employing conventional process conditions.
The tablets obtainable by the aforementioned methods have superior highlighted intagliations and said tablets are meant to constitute an aspect of the present invention.
The different steps involved in the filling and coating processes are described in more detail below by means of examples.
~Mp,vcv;E~a-~MUnC~e.~ C3 .22- 1-93 ; 314 ; +32 14 50552 2 49p923994465;x 3 -_ 2104096 FXPERIME~'T~T.. PART
~mrle 1 aj 50() g of biconvex placebo tablet cores (comprising lactose, corn starch, povidone, :nicrcxrystalline cellulose. silicone dic~xidc and magnesium stearate) were put into a Hi-coate:;"° (HCT-'_'Ul fic~w-through pan and w~:rmed to _~~:L'°C
with air of 6(?°C.
M.
The ;:ores had a dlal?'~eleT Of t7.J mill, a nUn;lnal weight of 1(~ mg and an it) inscription on one side. the other Side being blank. The coating suspension consisted of 1?.0 g of ~yc:rc~:;yprop::l methytceilulose in 0.1 1 of purfie.d water. Z.6~: g of propylene glycol ;aa a plaaticizer, 3.6 g of titaniumdioxide, l.~'. g of FD&C blue no. =
aluminum lake and i) ~.=t g of talc. The uap°nSiUn vv as "c;moa~n:zed fm 10 minutes. The t;:blets wire ccatrd asi:~g ~.he following parameters - pan rotation speed : 35 rgrn - iniec-air ce.nperacure : 65-7t) "C
- l~utlet-air temperature . ?-~? °C
15 - atomizing air pressure : Q. i 8 Mpg ( 1.8 bar) - 1i laid audition rate . .: g.minute~-1 :~~ i r~su!t of the coating process there were obtained blue coated tahlea.
n) Tise blue lliiIl-~~OaieCj. tablets were put in a Hi-coat~r~ (f-:CT-ZOi flow-trrough pa~~
''0 and ~,;~cirmed with air of ~(t°C while rotating at ~ rp:n.
:n a ~elutic7n oF'..:i b of polyethylene glycol :~00 in fit; ml of ethanol there were ~usi sncled'._~)._' S of earn ~~.arcii and the whole was homogenized for 10 minutes.
Thr au5per,sion was sprayed on the tablets at a delivery rate of 9 g.r~.inutes' 1. The tatslets were kept tumbling in the rf~tating pets for another 5 minutes. T'Ze excess of filling .5 n~atrr:al dr'~aosited on the tablet surface was blown off by atomizing air at ().2 W'a i,~ bt~.rj for 10 _ninutes while rotating the pan.
.-~s ;t result thcr~ u.~ere obtained blue tai~lets with Int3r?~anOIIS
highlighted in ~.uhite.
cj Tl-~~ bi~.:e watch tablets with white intagliations were pu: in tl:e Hi-coat~r'~ HCT-?0) s0 and evar:rs~d with air of t;5°C for 5 minutra while rotating at :35 rpm.
The seal-coating SUiutloll C:oWIStL'i~ of 5.0 d of hydrox:.~propyl methylcelluiose in 0.001 of p!irifiec? :~;ater and 1.1 g of propylene glycol a.s a plastici~r.
'rne tablet;, vrere soared using :he following conditions - pan rotation speed , 35 rpm 35 - ir,:~t-W~' teriperature : 6S-7() °C
~:clet-air wmperatur: : ?b-~ 'C
- aeon nzii:g air pres~ur~e : i).? s i~IPa !1.$ h;~'j s~;:~-~~ ~ ~~~T
E~IP,'ICN~EPA-Munch2n G3 ;22- 1-g3 . 814 . +32 14 605522- 496923994465~x 4 - liquid addition rate : 3.5 g.minutes-1 The tablets were kept rotating in the coating pan for another iU minutes while warming ~,v;th air of 70°C.
~mylc~.~
a) 10 ko of biconvex placebo tablets (comprising lactose, corn starch, hydroxypropyi methylc.~eilulose, microcrystalline cellulose, silicon dioxide and magnesium stearate) were put in an Aceela-Coc~~'~ 24 inch flow-through paz and warned to ~0°C
with air of 6U°C.
The tablet cores had a diameter of 9 mm and a nominal weight of 230 mg. They were i0 half Scored with an .~ inscription cn one side and a JANSSEN insctzption on the other.
The coating swpension consisted of l9Ct.tl g of hydroxyproyl methylc~llulose in I.91 of purified water, 60.0 g of propylene glycol (as plastiei2er), 110.0 g of titanium dioxide and -48.0 g cat laic. Ttie suspension wa:: 1-~arr~!~yenized for ?0 minutes.
The tablets were coated using the f~.ilow~ing p:~rarneters 1 ~ - pan rotation 1-4 rpti~
speed :
- in, let-air temperatureS5-60 ''C
:
- outlet-air temperature4ti-42'C
:
- atomizing air pressuret).4? ViPa X4.2 . bona - liquid addition rate27 g.minutes-1 :
?U As a result there were obtsined white film-coated tablets.
b; ic:,e white filin-coated Tablets were put in the Acccla-Cotz~' 24 inch aide-vented pan and warmed with ai-r of 4f)-4j°C while rotating at i4 rpm.
I?~.f) g of naicrocrystalline cellulose were colored with FDcftC blue no. 2 f l~'c ~~w of 2S 1~ICCj by suspending it in an aq, solution of FD&C blue no. ~ dye, tstering the suspension, vacuum drying the solid at 5t)°C and 2rinding it. The colored micro-cry~stalline cellulose was then 5uspensed in a mixture of 26.U g of polyethylene glycol k.7() and 64U g o~ ethanol. The. whole was homogenized for 2U minutas.
The suspension was sprayed on the tablets using the following parameters ,0 - pan rotation speed : I.+ rpm - inlet-air temperature : .:10 °C
- outlet-air tempera~re : aU-35 °C
utomizin; air pressure : t).2 VtPa (?.U ba:~) - Iic~uid addition rate . 3t) g.minutes-I
3S The ;ablets were beet tumbling in the rotation p:zn for another ~ minutes.
The excess of the deposited solids was remolded by blowing atomizing air at 0.4 wLE~a c::+.0 bar) for 5 minutes ~ialet-air temperature: 55~6C~°C ; outlet-air ~mpetamre;
~U°C) while rotating at 14 EntP. ~~0'V~EPA-M;ncnen C3 .22- '-93 ~ 8~'S . ~32 ~4 605522 4989233944E5;~ 5 :pm. As a result, there were obtained white 1~.lm-coated tablets witch intagliations highlighted in blue.
c) The white coated tablets with intagliations highlighted in blue were put in the Accela-S Cota''-° ''4 inch coar:ng-p;ir. and warred with a:.r of 6L~'C for l0 minutes. The seal-coating;
soltttien censistesa of 67.0 g of hydroxypropyl ntethylce?lulose in 1.26 : of purified water and ? 3.4 g of propylene glycol as plas:tetzzr.
The tr,:'tslets were coated using the following conditions - pan rotation speed . 14 rpm t t, - inlet-air temperature . 5t~55 'C
- outlet-air temperature : ~~-45'C
- atomizing air pressure : U.4 ;~IPa (4.0 barj - liquid addition rate : 2~~ g.minttt~s'1 T'.re tablets were kept rot<'tting in the coating pan for another i.5 minutes while ~~~a.-s:~ing 1 ~ with w arm air of fiU° C.
s al ~9 kg of ohlong placebo tablet cores (comprising lactose, corn Starch, fx~rr:done, microcrystaiiine cellulose, silicon diojcide and magr?esium stearate) were pttt in a Glatt ?;) ;type GC-''St)) ficw~~-;hrottgh c;,ating pan and warmed to about ~0°C wah air of about ist;°C. The len~ah of the tartlet cores was I'._.5 rnm, the width a.3 mm and the nominal weigh; was 150 mg. The tablet cores h:a,d ar~ inscription Ke'0 and a s;;or:
line on one side at~~a a ~A?~rSSEN inscription ;.m the other.
25 The coating suspetaion was prepared by dissolving 780 g hydroxypropyl :rethyl-ceilulose in o.$25 1 of purified water, adding 195 g polyethylene glycol 4U0 !:as pla,ticizer) and homogenizing the Solution for 20 nunutes.
The tablets were coated using the following parameters 3f1 - pan rotarion sped S :pm :
- number of spraying nozzles - diatneter of S~pray~ing 1.? mm nozzle, :
inlet-air tempe~an~re . 75-$t? C
- outlet-air ten!perattttY48-S2 C
:
- atcrn:zing air pressure0.3 ~lPa (3 . bar) - li,~uid a~lritiotl rate 9U g.minutea-1 .
As ? result Lhere were te itfrn-coated obtained whi tablets.
..-,..... .- .
~';~P, UC;vEPA-Mu,~chsn 03 ;22- 1-93 ~ 8. ~6 ; X32 '4 305522, s9892a994465;# 6 b) The white film-coated :ablets in the Glatt (type GC-750) side vented coating pan were rotated at 8 rpm while warming with zir of 7,5-80°C.
?.~7,5 g of porn starch were colored with FD&C red no. 40 {0.6°k wlw of corn starch) by suspe~ding the corn. starch in an aqueous solution of FI7~tC red no. 4U, altering the suspension, vacuum dr~irg thv: solid at SU'C and finally grinding it. The colc:'ed corn sfa.rch was then suspended in a r.~ixture of 10.5 g polyethylene glycol 4(100, 4? g poly-echy?eneglycoi :~(lt) ar:d l3ti(? g of dic;iloromethane, :~.tld was homog~;,nized for 15 ~nill~;tes.
The suspension was spry fed on the cM.blets using the following parameters :
- i an rotation speed . 8 rpm - i~um~~er of spraying nozzles - diameter of spraying nuzzles : l.'_ mm - inlet-air t~mpe: ahnE : 7 5-8U ''C
- uutl~t-air ;emperature : 50->5 ''C
- atomiz~.ng air pres~ure : b.''5 '~~.Pa {2.5 bar) S - liquid addit5on rate ' ? 15 g.minutes-=
'w hen all u~ the suspension was applied, the tab:~t~ were kept tut:lhling i,s the r~»tin~
pas for ?G minutes. T a excess of t:le ~'epcsitcd solids was removed ov plowing atcltoizing ;i:r at 0.25 ~'iPii !?.5 bar! at an lnlat-31r t~~tlperiture UI
a.pproxlmat?'v ?5-$(!''C
;J loutlet-ai..r te,r_perature : 60°C). .As a :exalt there we:c obtained white film-cc~ateii ;abl~ts Witl1 il:Liig~dtit)11S dTld the score :ine higl~.ligilted in red.
c) Tl:e white film-coated t;:hlets with red intagliations and score line in the Giatt (type GC-?~ij; cotlang pan were wa:-r:nud wit.l ai: c:f 8()°i for > minutes. The seal-coating soiutiori S ~.~as prepared oy dissolving ?8t) g aye:,roxypropl~lme:h~~lc~llulose in'.45 i c~f pur itied warer, ad~:ing '~0 g polyethyleneglcol as a pla.;ticizer :,nd homogenizing the solutlGll.
The tahiets were coated using the following conditions :
- purl rotation speed : 8 rpm 3U - number of spraying 2 nozzles .
- ctian~.cter of spraying 1.2 mm nozzles - inle-air temperaxare ?S-80 C
:
- outlet-a.ir te;~perature4fi-Stl C
:
- 3tC?1Il?2:I1~ rir pr,;ss0. ~ yips ore : ( bar) ;- l~l~li~j .id~ii.ion 1_~~? g.minutes-1 i;ile .
Whel: ali ,.~t th= ;:oaring solu:ion had >,~en applied, the tabaets wan; kept rotating in the coatz:y pan fnr i0 minutes. I?le,ir..~~'hie supplying wt~.~m air at ~:n inir.t-air tea:perat;:re ~~f 75-fc0°C.
s ~...., i-~ ~T 4~'~".d'
EP-B-0,088,556 relates to a method of highlighting intagliations in white or colored tablets by contacting said tablets with a dry, powdery material having a different color than the tablet surface and then removing the excess powdery material not deposited in the intagliations. The powdery material is taught to adhere better to the intagliations of coated tablets than to those of uncoated tablets. Adherence can further be increased by using a mixture of a wax and a powdery material as the deposition material and heating the filled tablets to 40-90°C in order to melt the wax. Finally, an outer coating may be applied to the filled tablets.
The method disclosed in EP-B-0,088,556 has several problems. In the first place it has been found that the adhesion of the powdery material to the intagliation is not satisfactory as said material shows a tendency to loosen and fall out. This problem arises particularly when an outer coating film is applied to the filled tablet and the loosened material becomes fixed in said outer coating film, thus yielding speckled tablets.
Addition of a wax to the powdery material in order to improve adhesion on the other hand, adversely affects the distribution of the powdery material in that more of it sticks to the surface of the tablet and is difficult to remove. Several more drawbacks are associated with the use of a wax in the dry powdery material. In particular the necessity to heat the tablets filled with a wax and a powdery material in order to melt said wax, poses a hardly acceptable risk since many medicines are thermolabile and might deteriorate significantly in the process. Further it proves difficult to dye evenly a dry mixture of a wax and a powdery material, which in tum puts a limitation on the effectively possible color combinations.
The method of the present invention differs from the prior method disclosed in E-B-0,088,556 by the fact that an optionally colored filling material and a suitable wax are suspended in a solvent and sprayed onto a coated intagliated tablet.
Following the removal of the solvent and the excess deposition material, tablets are obtained having a firmly fixed amount of said deposition material specifically in the intagliation. Said WO 92/15288 210 4 0 9 6 P~/E)P92/00358 _3_ tablets have superior visual attractivity over those obtained using prior art methods due to the complete and specific filling of the intagliations and absence of deposition material on the surface of the tablets. An outer coating film can easily be applied to the thus obtained highlighted intagliated tablets without danger of loosening the deposition material from the intagliation. The present method further avoids high temperatures and thus is amenable for identifying solid preparations comprising thermolabile medicines.
The present invention relates to a method of highlighting intagliations in white or colored coated tablets by spraying onto said tablets a suspension comprising a filling material having a different color, a waxy material and a suitable solvent, and removing the solvent and the excess of filling material and waxy material; and to tablets obtainable by said method.
The tablets used as a substrate preferably are film-coated. Film-coated tablets allow a more selective bonding of the filling material to the intagliations and less adherence to the tablet surface than uncoated tablets because of the reduced porosity of the tablet surface (decreased roughness). Any material generally used for applying a coating film to tablets may be employed. For example, suitable materials are, e.g. methylcellulose, hydroxy-propyl methylcellulose, hydroxypropylcellulose, carboxymethylethyl cellulose, cellulose acetate phtalate, hydroxypropyl methylcellulose phtalate, acrylates, copolymers of acrylic and methacrylic acid esters and the like.
The coating films may be plasticized with suitable plasticizers such as, e.g.
polyethylene glycol, propylene glycol, glycerol, diethyl phtalate, dibutyl sebacate, citroflex, triacetin and the like. If necessary coloring agents can be added. These can be natural pigments such as talc, kaolin, titanium dioxide, or dyestuffs or lake dyestuff selected from accepted food colors. The coating solvent can be water or any other organic solvent suitable for film-coating such as, for example, an alcohol, e.g. ethanol, 2-propanol, a ketone, e.g. acetone, or a halogenated hydrocarbon, e.g. dichloromethane.
Preferably the coating is applied by spraying a solution on the tablets in a perforated side-vented pan (Pellegrini, Accela-Cota~, Hi-coater~ (HCT-20)) by means of a spraying system worked by air pressure. The process conditions are those generally employed in coating procedures provided that due care is taken to avoid filling of the intagliations.
A wide variety of filling materials can be used for the filling of the intagliations. Suitable filling agents are, for example, starches, e.g. corn starch, rice starch, wheat starch, potato starch, preferably corn starch or rice starch; celluloses, e.g.
methylcellulose, 2104~~6 -4-ethylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropyl methyl-cellulose, hydroxypropyl methylcellulose phthalate, crystalline cellulose, preferably microcrystalline cellulose fibers (Elecma P050~); lactose and other sugars or sugar alcohols, e.g. sucrose or mannitol, preferably micronised lactose 200 mesh, spray-dried and micronised lactose (DCL-11~) or mannitol; organic acids, e.g. stearic acid, fumaric acid, citric acid, preferably fumaric acid; or inorganic 'substances, e.g.
sodium chloride, calcium carbonate, preferably sodium chloride, all giving white intagliations.
Other finely divided filling materials such as titanium oxide, talc, kaolin, magnesium stearate and aluminum lakes in practice are less preferred because of their greater tendency to stick to the surface of tablets. The most prefered filling materials are corn starch and microcrystalline cellulose. Colored intagliations are obtained by previously dyeing the filling material. This is achieved by suspending the filling material in a solution of the dye, filtering off, drying and finally grinding. Starches and celluloses such as cited hereinabove and especially those specifically preferred hereinabove can be dyed in water, with, for example, edible lake pigments, e.g. FD&C blue no. 2, FD&C red no. 3, FD&C yellow no. 6, D&C yellow no. 10 and the like or any combinations thereof.
The weight to weight ratio of said lake pigments to the filling material generally ranges from 0.1:100 to 10:100 and may be choosen in function of the desired intensity.
Water soluble filling materials such as lactose can effectively be dyed by suspending them in a solution of an alcohol-soluble dye such as FD&C red no. 3 or D&C
yellow no.
10 in an alcohol such as ethanol.
The optionally colored filling materials are suspended in a solution of a waxy material in a suitable solvent. The waxy material is added to enhance the adherence of the filling materials. Examples of waxy materials are polyethylene glycols, natural waxes such as, e.g. beewax or carnauba wax, hydrogenated oils, higher fatty acids and fatty acid esters, fatty alcohols and polyoxyethylene ethers of fatty alcohols. Preferred waxy materials are polyethylene glycols (PEG), in particular PEG 400, PEG 600, PEG 1000, PEG 1500 and PEG 4000.
The proportion of waxy material to filling material is a very critical parameter in the filling process. Too little waxy material will lead to insufficient bonding of the filling material; with too much waxy material the filling material will bond too strongly to the tablet surface and consequently will be difficult to remove afterwards. The weight to weight ratio of the waxy material to filling material may range from about 1:3 to about 1:12, in particular from about 1:4 to about 1:9. For waxes having a low molecular weight and low melting point, e.g. PEG 400, PEG 600, PEG 1000 said ratio preferably ranges from 1:4 to 1:6 and in particular is about 1:5. For waxes having a higher WO 92/15288 PGT/EP92/00358.
2104096 _5_ molecular weight and melting point, e.g. PEG 1500, PEG 2000, said ratio preferably ranges from 1:6 to 1:8 and in particular is about 1:7.
Suitable solvents are those solvents wherein the filling material and, if present, the dye, do not dissolve. For example, non-dyed starches and celluloses may be suspended in alcohols, e.g. ethanol, isopropanol and the like, halogenated hydrocarbons, e.g.
dichloromethane, trichloromethane and the like. Dyed starches, dyed celluloses and non-dyed lactose may be suspended in water-free alcohols, in particular absolute ethanol. The amount of solvent in the final suspension for spraying onto the coated intagliated tablets may range from about 70% to about 85% (w/w) in particular from about 75% to about 81 % (w/w), more in particular from about 77% to 81 %.
The filling suspension may be sprayed on the coated tablets in a flow-through type coating pan or in a perforated side-vented pan by means of a spray worked by air pressure. Preferably said suspension is kept at room temperature and is stirred or agitated to prevent sedimentation. The temperature of the tablets within the coating pan is advantageously raised slightly to about 30 to 60°C, in particular 30-40°C by employing warm inlet-air.
After applying the amount of filling material required the spraying process is stopped and the excess of solid material adhering to the tablet surface is removed by blowing off with air, meanwhile keeping the tablets tumbling to rub off the filling material deposited on the tablet surface.
To prevent the loosening of deposited filling material, a thin colorless seal-coating layer can be applied to the tablets. The coating polymer can be one of those mentioned above for the subcoating, especially hydroxypropyl methylcellulose, together with a suitable plasticizer as mentioned hereinabove. In the case of water soluble filling materials or dyes, the solvent used is preferably an organic solvent since water would dissolve the filling material and the dye fixed on the solid filling material. Said seal-coating process may be conducted in any of the usual coating devices such as, for example, flow-through coating pans or side-vented coating pans, employing conventional process conditions.
The tablets obtainable by the aforementioned methods have superior highlighted intagliations and said tablets are meant to constitute an aspect of the present invention.
The different steps involved in the filling and coating processes are described in more detail below by means of examples.
~Mp,vcv;E~a-~MUnC~e.~ C3 .22- 1-93 ; 314 ; +32 14 50552 2 49p923994465;x 3 -_ 2104096 FXPERIME~'T~T.. PART
~mrle 1 aj 50() g of biconvex placebo tablet cores (comprising lactose, corn starch, povidone, :nicrcxrystalline cellulose. silicone dic~xidc and magnesium stearate) were put into a Hi-coate:;"° (HCT-'_'Ul fic~w-through pan and w~:rmed to _~~:L'°C
with air of 6(?°C.
M.
The ;:ores had a dlal?'~eleT Of t7.J mill, a nUn;lnal weight of 1(~ mg and an it) inscription on one side. the other Side being blank. The coating suspension consisted of 1?.0 g of ~yc:rc~:;yprop::l methytceilulose in 0.1 1 of purfie.d water. Z.6~: g of propylene glycol ;aa a plaaticizer, 3.6 g of titaniumdioxide, l.~'. g of FD&C blue no. =
aluminum lake and i) ~.=t g of talc. The uap°nSiUn vv as "c;moa~n:zed fm 10 minutes. The t;:blets wire ccatrd asi:~g ~.he following parameters - pan rotation speed : 35 rgrn - iniec-air ce.nperacure : 65-7t) "C
- l~utlet-air temperature . ?-~? °C
15 - atomizing air pressure : Q. i 8 Mpg ( 1.8 bar) - 1i laid audition rate . .: g.minute~-1 :~~ i r~su!t of the coating process there were obtained blue coated tahlea.
n) Tise blue lliiIl-~~OaieCj. tablets were put in a Hi-coat~r~ (f-:CT-ZOi flow-trrough pa~~
''0 and ~,;~cirmed with air of ~(t°C while rotating at ~ rp:n.
:n a ~elutic7n oF'..:i b of polyethylene glycol :~00 in fit; ml of ethanol there were ~usi sncled'._~)._' S of earn ~~.arcii and the whole was homogenized for 10 minutes.
Thr au5per,sion was sprayed on the tablets at a delivery rate of 9 g.r~.inutes' 1. The tatslets were kept tumbling in the rf~tating pets for another 5 minutes. T'Ze excess of filling .5 n~atrr:al dr'~aosited on the tablet surface was blown off by atomizing air at ().2 W'a i,~ bt~.rj for 10 _ninutes while rotating the pan.
.-~s ;t result thcr~ u.~ere obtained blue tai~lets with Int3r?~anOIIS
highlighted in ~.uhite.
cj Tl-~~ bi~.:e watch tablets with white intagliations were pu: in tl:e Hi-coat~r'~ HCT-?0) s0 and evar:rs~d with air of t;5°C for 5 minutra while rotating at :35 rpm.
The seal-coating SUiutloll C:oWIStL'i~ of 5.0 d of hydrox:.~propyl methylcelluiose in 0.001 of p!irifiec? :~;ater and 1.1 g of propylene glycol a.s a plastici~r.
'rne tablet;, vrere soared using :he following conditions - pan rotation speed , 35 rpm 35 - ir,:~t-W~' teriperature : 6S-7() °C
~:clet-air wmperatur: : ?b-~ 'C
- aeon nzii:g air pres~ur~e : i).? s i~IPa !1.$ h;~'j s~;:~-~~ ~ ~~~T
E~IP,'ICN~EPA-Munch2n G3 ;22- 1-g3 . 814 . +32 14 605522- 496923994465~x 4 - liquid addition rate : 3.5 g.minutes-1 The tablets were kept rotating in the coating pan for another iU minutes while warming ~,v;th air of 70°C.
~mylc~.~
a) 10 ko of biconvex placebo tablets (comprising lactose, corn starch, hydroxypropyi methylc.~eilulose, microcrystalline cellulose, silicon dioxide and magnesium stearate) were put in an Aceela-Coc~~'~ 24 inch flow-through paz and warned to ~0°C
with air of 6U°C.
The tablet cores had a diameter of 9 mm and a nominal weight of 230 mg. They were i0 half Scored with an .~ inscription cn one side and a JANSSEN insctzption on the other.
The coating swpension consisted of l9Ct.tl g of hydroxyproyl methylc~llulose in I.91 of purified water, 60.0 g of propylene glycol (as plastiei2er), 110.0 g of titanium dioxide and -48.0 g cat laic. Ttie suspension wa:: 1-~arr~!~yenized for ?0 minutes.
The tablets were coated using the f~.ilow~ing p:~rarneters 1 ~ - pan rotation 1-4 rpti~
speed :
- in, let-air temperatureS5-60 ''C
:
- outlet-air temperature4ti-42'C
:
- atomizing air pressuret).4? ViPa X4.2 . bona - liquid addition rate27 g.minutes-1 :
?U As a result there were obtsined white film-coated tablets.
b; ic:,e white filin-coated Tablets were put in the Acccla-Cotz~' 24 inch aide-vented pan and warmed with ai-r of 4f)-4j°C while rotating at i4 rpm.
I?~.f) g of naicrocrystalline cellulose were colored with FDcftC blue no. 2 f l~'c ~~w of 2S 1~ICCj by suspending it in an aq, solution of FD&C blue no. ~ dye, tstering the suspension, vacuum drying the solid at 5t)°C and 2rinding it. The colored micro-cry~stalline cellulose was then 5uspensed in a mixture of 26.U g of polyethylene glycol k.7() and 64U g o~ ethanol. The. whole was homogenized for 2U minutas.
The suspension was sprayed on the tablets using the following parameters ,0 - pan rotation speed : I.+ rpm - inlet-air temperature : .:10 °C
- outlet-air tempera~re : aU-35 °C
utomizin; air pressure : t).2 VtPa (?.U ba:~) - Iic~uid addition rate . 3t) g.minutes-I
3S The ;ablets were beet tumbling in the rotation p:zn for another ~ minutes.
The excess of the deposited solids was remolded by blowing atomizing air at 0.4 wLE~a c::+.0 bar) for 5 minutes ~ialet-air temperature: 55~6C~°C ; outlet-air ~mpetamre;
~U°C) while rotating at 14 EntP. ~~0'V~EPA-M;ncnen C3 .22- '-93 ~ 8~'S . ~32 ~4 605522 4989233944E5;~ 5 :pm. As a result, there were obtained white 1~.lm-coated tablets witch intagliations highlighted in blue.
c) The white coated tablets with intagliations highlighted in blue were put in the Accela-S Cota''-° ''4 inch coar:ng-p;ir. and warred with a:.r of 6L~'C for l0 minutes. The seal-coating;
soltttien censistesa of 67.0 g of hydroxypropyl ntethylce?lulose in 1.26 : of purified water and ? 3.4 g of propylene glycol as plas:tetzzr.
The tr,:'tslets were coated using the following conditions - pan rotation speed . 14 rpm t t, - inlet-air temperature . 5t~55 'C
- outlet-air temperature : ~~-45'C
- atomizing air pressure : U.4 ;~IPa (4.0 barj - liquid addition rate : 2~~ g.minttt~s'1 T'.re tablets were kept rot<'tting in the coating pan for another i.5 minutes while ~~~a.-s:~ing 1 ~ with w arm air of fiU° C.
s al ~9 kg of ohlong placebo tablet cores (comprising lactose, corn Starch, fx~rr:done, microcrystaiiine cellulose, silicon diojcide and magr?esium stearate) were pttt in a Glatt ?;) ;type GC-''St)) ficw~~-;hrottgh c;,ating pan and warmed to about ~0°C wah air of about ist;°C. The len~ah of the tartlet cores was I'._.5 rnm, the width a.3 mm and the nominal weigh; was 150 mg. The tablet cores h:a,d ar~ inscription Ke'0 and a s;;or:
line on one side at~~a a ~A?~rSSEN inscription ;.m the other.
25 The coating suspetaion was prepared by dissolving 780 g hydroxypropyl :rethyl-ceilulose in o.$25 1 of purified water, adding 195 g polyethylene glycol 4U0 !:as pla,ticizer) and homogenizing the Solution for 20 nunutes.
The tablets were coated using the following parameters 3f1 - pan rotarion sped S :pm :
- number of spraying nozzles - diatneter of S~pray~ing 1.? mm nozzle, :
inlet-air tempe~an~re . 75-$t? C
- outlet-air ten!perattttY48-S2 C
:
- atcrn:zing air pressure0.3 ~lPa (3 . bar) - li,~uid a~lritiotl rate 9U g.minutea-1 .
As ? result Lhere were te itfrn-coated obtained whi tablets.
..-,..... .- .
~';~P, UC;vEPA-Mu,~chsn 03 ;22- 1-93 ~ 8. ~6 ; X32 '4 305522, s9892a994465;# 6 b) The white film-coated :ablets in the Glatt (type GC-750) side vented coating pan were rotated at 8 rpm while warming with zir of 7,5-80°C.
?.~7,5 g of porn starch were colored with FD&C red no. 40 {0.6°k wlw of corn starch) by suspe~ding the corn. starch in an aqueous solution of FI7~tC red no. 4U, altering the suspension, vacuum dr~irg thv: solid at SU'C and finally grinding it. The colc:'ed corn sfa.rch was then suspended in a r.~ixture of 10.5 g polyethylene glycol 4(100, 4? g poly-echy?eneglycoi :~(lt) ar:d l3ti(? g of dic;iloromethane, :~.tld was homog~;,nized for 15 ~nill~;tes.
The suspension was spry fed on the cM.blets using the following parameters :
- i an rotation speed . 8 rpm - i~um~~er of spraying nozzles - diameter of spraying nuzzles : l.'_ mm - inlet-air t~mpe: ahnE : 7 5-8U ''C
- uutl~t-air ;emperature : 50->5 ''C
- atomiz~.ng air pres~ure : b.''5 '~~.Pa {2.5 bar) S - liquid addit5on rate ' ? 15 g.minutes-=
'w hen all u~ the suspension was applied, the tab:~t~ were kept tut:lhling i,s the r~»tin~
pas for ?G minutes. T a excess of t:le ~'epcsitcd solids was removed ov plowing atcltoizing ;i:r at 0.25 ~'iPii !?.5 bar! at an lnlat-31r t~~tlperiture UI
a.pproxlmat?'v ?5-$(!''C
;J loutlet-ai..r te,r_perature : 60°C). .As a :exalt there we:c obtained white film-cc~ateii ;abl~ts Witl1 il:Liig~dtit)11S dTld the score :ine higl~.ligilted in red.
c) Tl:e white film-coated t;:hlets with red intagliations and score line in the Giatt (type GC-?~ij; cotlang pan were wa:-r:nud wit.l ai: c:f 8()°i for > minutes. The seal-coating soiutiori S ~.~as prepared oy dissolving ?8t) g aye:,roxypropl~lme:h~~lc~llulose in'.45 i c~f pur itied warer, ad~:ing '~0 g polyethyleneglcol as a pla.;ticizer :,nd homogenizing the solutlGll.
The tahiets were coated using the following conditions :
- purl rotation speed : 8 rpm 3U - number of spraying 2 nozzles .
- ctian~.cter of spraying 1.2 mm nozzles - inle-air temperaxare ?S-80 C
:
- outlet-a.ir te;~perature4fi-Stl C
:
- 3tC?1Il?2:I1~ rir pr,;ss0. ~ yips ore : ( bar) ;- l~l~li~j .id~ii.ion 1_~~? g.minutes-1 i;ile .
Whel: ali ,.~t th= ;:oaring solu:ion had >,~en applied, the tabaets wan; kept rotating in the coatz:y pan fnr i0 minutes. I?le,ir..~~'hie supplying wt~.~m air at ~:n inir.t-air tea:perat;:re ~~f 75-fc0°C.
s ~...., i-~ ~T 4~'~".d'
Claims (9)
1. A method of highlighting intagliations in white or colored coated tablets, characterized by (a) spraying onto said tablets a suspension comprising a filling material having a different color than the surface of said coated tablets, a waxy material, and a suitable solvent, said suspension having a waxy material to filling material ranges from 1:3 to 1:12, (b) removing the solvent, and (c) removing the excess of filling material and waxy material from the entire surface of said tablets except for the intagliations.
2. A method according to claim 1 wherein the filling material is corn starch or microcrystalline cellulose.
3. A method according to claim 2 wherein the filling material is previously dyed with an edible lake pigment
4. A method according to any one of claims 1, 2 or 3 wherein the waxy material is a polyethylene glycol.
5. A method according to any one of claims 1 to 4 wherein the solvent does not dissolve the filling material nor, if present, the dye.
6. A method according to claim 5 wherein the amount of solvent in the final suspension ranges from 70% to 85%.
7. A method according to claim 6 wherein the solvent and the excess of filling material and waxy material are removed by blowing off with air and keeping the tablets tumbling.
8. A method according to any one of claims 1 to 7 wherein the filled tablets are provided with a further coating film.
9. A tablet obtainable by a method according to any one of claims 1-8.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP91200417 | 1991-02-27 | ||
| EP91200417.3 | 1991-02-27 | ||
| PCT/EP1992/000358 WO1992015288A1 (en) | 1991-02-27 | 1992-02-14 | A method of highlighting intagliations in tablets |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2104096A1 CA2104096A1 (en) | 1992-08-28 |
| CA2104096C true CA2104096C (en) | 2003-06-10 |
Family
ID=8207528
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002104096A Expired - Lifetime CA2104096C (en) | 1991-02-27 | 1992-02-14 | A method of highlighting intagliations in tablets |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US5405642A (en) |
| EP (2) | EP0573462B1 (en) |
| JP (1) | JP3237758B2 (en) |
| AT (1) | ATE143259T1 (en) |
| AU (1) | AU1260392A (en) |
| CA (1) | CA2104096C (en) |
| DE (1) | DE69214130T2 (en) |
| DK (1) | DK0573462T3 (en) |
| ES (1) | ES2094902T3 (en) |
| GR (1) | GR3021929T3 (en) |
| IE (1) | IE75729B1 (en) |
| MX (1) | MX9200831A (en) |
| NZ (1) | NZ241613A (en) |
| TW (1) | TW201697B (en) |
| WO (1) | WO1992015288A1 (en) |
| ZA (1) | ZA921428B (en) |
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| CA2657043A1 (en) * | 2006-07-14 | 2008-01-17 | Boehringer Ingelheim International Gmbh | Use of flibanserin for the treatment of sexual disorders in females |
| WO2008019996A2 (en) * | 2006-08-14 | 2008-02-21 | Boehringer Ingelheim International Gmbh | Formulations of flibanserin and method for manufacturing the same |
| CL2007002214A1 (en) * | 2006-08-14 | 2008-03-07 | Boehringer Ingelheim Int | PHARMACEUTICAL COMPOSITION IN THE FORM OF COMPRESSED, WHERE AT LEAST THE LENGTH OF THE COMPRESSED IN THE PREVIOUS STATE OF THE APPLICATION IS AT LEAST 7/12 OF THE PILOR DIAMETER OF THE PATIENT AND AFTER INGERING IT IN THE FOOD STATE, THE LENGTH OF THE COMP |
| MX2009002031A (en) * | 2006-08-25 | 2009-03-06 | Boehringer Ingelheim Int | Controlled release system and method for manufacturing the same. |
| CL2008002693A1 (en) | 2007-09-12 | 2009-10-16 | Boehringer Ingelheim Int | Use of flibanserin for the treatment of selected vasomotor symptoms of hot flashes, night sweats, mood swings, and irritability |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3125490A (en) * | 1964-03-17 | Tablet with contrasting indicia and method | ||
| US3436453A (en) * | 1963-06-14 | 1969-04-01 | American Cyanamid Co | Surface dyed edible gelatin capsule with pigment marking |
| FR1426194A (en) * | 1964-10-20 | 1966-01-28 | Ile De France | New tablet coating technique |
| US3539380A (en) * | 1968-01-08 | 1970-11-10 | Upjohn Co | Methylcellulose and polyalkylene glycol coating of solid medicinal dosage forms |
| IE53157B1 (en) * | 1981-03-09 | 1988-08-03 | Ici Plc | Coated coloured intagliated articles |
| JPS58152813A (en) * | 1982-03-08 | 1983-09-10 | Sumitomo Chem Co Ltd | Tablet having clear carved seal and its preparation |
| JPS58192819A (en) * | 1982-05-04 | 1983-11-10 | Sumitomo Chem Co Ltd | Production of tablets with clear stamps |
| KR840000624A (en) * | 1982-06-02 | 1984-02-25 | 원본미기재 | Corrosion inhibitor paint compositions |
| ATE29664T1 (en) * | 1982-06-10 | 1987-10-15 | Ici Plc | MAKING CLEARLY RECESSED EMBOSSED ITEMS. |
| US4576646A (en) * | 1983-07-06 | 1986-03-18 | Seppic | Film-forming compositions for enveloping solid forms, particularly pharmaceutical or food products or seeds, and products obtained, coated with said compositions |
| FR2548675B1 (en) * | 1983-07-06 | 1987-01-09 | Seppic Sa | FILM-FORMING COMPOSITIONS FOR COATING SOLID FORMS OF PHARMACEUTICAL OR FOOD PRODUCTS AND PRODUCTS OBTAINED COATED WITH SUCH COMPOSITIONS |
| US5006362A (en) * | 1988-05-09 | 1991-04-09 | Berwind Pharmaceutical Services, Inc. | Branding pharmaceutical dosage forms, food and confectionery products with aqueous ingestible inks |
| US5098715A (en) * | 1990-12-20 | 1992-03-24 | Burroughs Wellcome Co. | Flavored film-coated tablet |
-
1992
- 1992-02-13 NZ NZ241613A patent/NZ241613A/en not_active IP Right Cessation
- 1992-02-14 JP JP50490492A patent/JP3237758B2/en not_active Expired - Lifetime
- 1992-02-14 DE DE69214130T patent/DE69214130T2/en not_active Expired - Lifetime
- 1992-02-14 US US08/094,137 patent/US5405642A/en not_active Expired - Lifetime
- 1992-02-14 EP EP92904760A patent/EP0573462B1/en not_active Expired - Lifetime
- 1992-02-14 CA CA002104096A patent/CA2104096C/en not_active Expired - Lifetime
- 1992-02-14 ES ES92904760T patent/ES2094902T3/en not_active Expired - Lifetime
- 1992-02-14 EP EP92200418A patent/EP0501553A1/en active Pending
- 1992-02-14 DK DK92904760.3T patent/DK0573462T3/en active
- 1992-02-14 AT AT92904760T patent/ATE143259T1/en active
- 1992-02-14 WO PCT/EP1992/000358 patent/WO1992015288A1/en active IP Right Grant
- 1992-02-14 AU AU12603/92A patent/AU1260392A/en not_active Abandoned
- 1992-02-25 TW TW081101368A patent/TW201697B/zh active
- 1992-02-26 ZA ZA921428A patent/ZA921428B/en unknown
- 1992-02-26 MX MX9200831A patent/MX9200831A/en unknown
- 1992-02-26 IE IE920611A patent/IE75729B1/en not_active IP Right Cessation
-
1996
- 1996-12-06 GR GR960403339T patent/GR3021929T3/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE69214130T2 (en) | 1997-02-06 |
| ES2094902T3 (en) | 1997-02-01 |
| MX9200831A (en) | 1992-08-01 |
| AU1260392A (en) | 1992-10-06 |
| DK0573462T3 (en) | 1996-11-11 |
| US5405642A (en) | 1995-04-11 |
| EP0501553A1 (en) | 1992-09-02 |
| ATE143259T1 (en) | 1996-10-15 |
| GR3021929T3 (en) | 1997-03-31 |
| JPH06504935A (en) | 1994-06-09 |
| DE69214130D1 (en) | 1996-10-31 |
| IE920611A1 (en) | 1992-09-09 |
| CA2104096A1 (en) | 1992-08-28 |
| EP0573462B1 (en) | 1996-09-25 |
| ZA921428B (en) | 1993-08-26 |
| TW201697B (en) | 1993-03-11 |
| JP3237758B2 (en) | 2001-12-10 |
| NZ241613A (en) | 1993-06-25 |
| WO1992015288A1 (en) | 1992-09-17 |
| EP0573462A1 (en) | 1993-12-15 |
| IE75729B1 (en) | 1997-09-24 |
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