DE2246013A1 - PROCESS FOR THE MANUFACTURING OF POROUS TABLETS - Google Patents
PROCESS FOR THE MANUFACTURING OF POROUS TABLETSInfo
- Publication number
- DE2246013A1 DE2246013A1 DE2246013A DE2246013A DE2246013A1 DE 2246013 A1 DE2246013 A1 DE 2246013A1 DE 2246013 A DE2246013 A DE 2246013A DE 2246013 A DE2246013 A DE 2246013A DE 2246013 A1 DE2246013 A1 DE 2246013A1
- Authority
- DE
- Germany
- Prior art keywords
- tablets
- tablet
- excipient
- urethane
- mixed
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S516/00—Colloid systems and wetting agents; subcombinations thereof; processes of
- Y10S516/01—Wetting, emulsifying, dispersing, or stabilizing agents
Description
BOEHRINGER MANNHEIM GMBH 1838BOEHRINGER MANNHEIM GMBH 1838
Verfahren zur Herstellung von porösen TablettenProcess for the production of porous tablets
Gegenstand der vorliegenden Erfindung ist ein neues Verfahren zur Herstellung von porösen Tabletten.The present invention relates to a new process for the production of porous tablets.
Wegen ihrer leichten Handhabung und der Einfachheit der Dosierung werden nicht nur Arzneimittel-Tabletten sondern auch Reagenztabletten für diagnostische und analytische.Zwecke in immer stärkerem Maße verwendet. Die meisten Wirkstoffe oder Reagenzien sind allein nicht tablettierbar, da sie harte, schlecht zerfallende Tabletten bilden und zudem in vielen Fällen zum Kleben am Preßwerkzeug neigen.Because of their ease of use and the simplicity of dosage, not only are drug tablets but also Reagent tablets for diagnostic and analytical purposes used to an increasing extent. Most active ingredients or reagents cannot be tabletted on their own because they are hard, Form poorly disintegrating tablets and also tend in many cases to stick to the pressing tool.
Erst durch Zusatz von Sprengmitteln, wie Carboxymethylcellulose, Stärke etc., Füllstoffen wie Milchzucker, Phosphate etc. und Gleitmitteln wie Talkum, Stearinsäure, Paraffin etc., werden Tabletten erhalten, die rasch zerfallen. Während es leicht ist, für Arzneimittel geeignete physiologisch verträgliche Hilfsstoffe zu finden, lassen sich Reagenztabletten,- die im allgemeinen optisch klare Lösungen ergeben sollen, auf diese Weise nicht oder nur unter Schwierigkeiten herstellen. Insbesondere sind die üblicherweise verwendeten Gleitmittel, die das Anhaften der Tablettenmasse am Preßwerkzeug verhindern sollen, meist unlöslich in Wasser. Es ist deshalb vorgeschlagen worden, klebrige Reagenzien mit sehr großen Mengen von gut tablettierbaren Füllstoffen zusammen zu verpressen oder beim Pressen hohe Drucke anzuwenden. Beide Verfahren sind nicht befriedigend, da entweder unnötig große oder zu harte, schlecht zerfallende Tabletten entstehen.Only by adding disintegrants such as carboxymethyl cellulose, starch etc., fillers such as lactose, phosphates etc. and lubricants such as talc, stearic acid, paraffin, etc., tablets are obtained which disintegrate quickly. While it is easy is physiologically compatible for medicinal products To find auxiliary materials, reagent tablets can be found - the im should generally give optically clear solutions, in this way not or only with difficulty. In particular are the commonly used lubricants that prevent the tablet compound from sticking to the pressing tool should, mostly insoluble in water. It is therefore suggested to compress sticky reagents together with very large amounts of fillers which can be easily made into tablets or use high pressures when pressing. Both procedures are unsatisfactory because they are either unnecessarily large or too hard, Poorly disintegrating tablets arise.
409813/112 6409813/112 6
Ein anderes Verfahren führt zu den sogenannten "Moulded Tablets". Dabei werden die Tablettenxnhaltsstoffe mit Wasser oder einem organischen Lösungsmittel, in dem sich mindestens eine der Komponenten teilweise löst, zu einem steifen Brei angeteigt, der auf speziellen Maschinen zu Tabletten ausgeformt und vorsichtig getrocknet wird. Beim Verdampfen des Lösungsmittels verklebt die darin gelöste Substanz die ungelösten Teilchen miteinander, wodurch die Tablette ihre Festigkeit erhält; gleichzeitig bleiben feine Hohlräume zurück, in die Lösungsmittel beim Wiederauflösen eindringen kann. Obwohl diese Tabletten von der Auflösungsgeschwindigkeit her gesehen befriedigend sind, sind sie durch die zahlreichen sehr feinen Kanäle häufig zu weich und brüchig, so daß Verpackungs- und Transportschwierigkeiten auftreten. Weiterhin ist die Verwendbarkeit des Verfahrens dadurch eingeschränkt, daß viele Reagenzien, insbesondere Enzyme und Indikatoren, durch Lösungsmittel geschädigt werden und organische Lösungsmitteldämpfe spezielle Sicherheitsanforderungen bei der Herstellung der Tabletten notwendig machen.Another method leads to the so-called "molded tablets". The tablet ingredients are mixed with water or an organic solvent, in which at least one of the components is partially soluble, made into a paste to form a stiff paste, which is shaped into tablets on special machines and carefully dried. When the solvent evaporates the substance dissolved therein adheres the undissolved particles to one another, which gives the tablet its strength; simultaneously fine cavities remain, into which solvent can penetrate when redissolving. Although these tablets are satisfactory from the point of view of the speed of dissolution, they are often too high due to the numerous, very fine channels soft and brittle, so that packaging and transport difficulties arise. Furthermore, the usability of the process limited by the fact that many reagents, in particular Enzymes and indicators to be damaged by solvents and organic solvent vapors have special safety requirements make necessary in the manufacture of the tablets.
Aufgabe der vorliegenden Erfindung war es deshalb» ein Verfahren zu schaffen, das es erlaubt, leicht lösliche, poröse Tabletten auf normalen Tablettenpressen zu fertigen, ohne £a& Gleitmittel, Sprengmittel oder Lösungsmittel zugesetzt werden.The object of the present invention was therefore “a method to create, which makes it possible to manufacture easily soluble, porous tablets on normal tablet presses, without £ a & lubricants, Disintegrants or solvents are added.
Erfindungsgemäß wird deshalb ein Verfahren zur Herstellung von porösen Tabletten vorgeschlagen, daß dadurch gekennzeichnet ist, daß man die Tabletteninhaltsstoffe mit einem inerten» leicht zu verflüchtigenden, festen Hilfsstoff zusammen gu hart verpreßt und den Hilfsstoff verflüchtigt.According to the invention is therefore a method for producing Porous tablets proposed that is characterized in that the tablet ingredients with an inert »easily to be volatilized, solid excipient together gu pressed hard and the excipient volatilized.
409813/1126409813/1126
Durch das harte Verpressen auf normalen Tablettiermaschinen entstehen Tabletten großer mechanischer Stabilität und gleichzeitig wird der Zusatz der schlechtlöslichen Gleitmittel unnötig. Da die gepreßte Tablette im Gegensatz zur "Moulded Tablet " formstabil ist, schrumpft sie beim Entfernen des Hilfsstoffes nicht mehr zusammen. Der heraussublimierte Hilfsstoff hinterläßt deshalb größere Hohlräume und Kanäle, durch die Lösungsmittel eindringen kann.By pressing hard on normal tablet machines tablets of great mechanical stability result and at the same time the addition of poorly soluble lubricants becomes unnecessary. Since the compressed tablet is dimensionally stable in contrast to the "molded tablet", it shrinks when the Auxiliary material no longer together. The sublimated auxiliary material therefore leaves larger cavities and channels through which solvent can penetrate.
Als Hilfsstoffe kommen grundsätzlich alle leicht sublimierbaren oder leicht in gasförmige Zersetzungsprodukte überführbaren Stoffe infrage, die gut tablettierbar sind und mit den übrigen Tabletteninhaltsstoffen nicht reagieren. Beispielhaft seien folgende Substanzen genannt: Urethan, Harnstoff, Ammoniumbicarbonat, Hexamethylentetramin, Benzoesäure, Phthalsäureanhydrid, Naphthalin oder Kampfer. Besonders bevorzugt ist Urethan.In principle, all easily sublimable substances are used as auxiliaries or substances easily convertible into gaseous decomposition products, which can be easily made into tablets and with the other tablet ingredients not react. The following substances may be mentioned as examples: urethane, urea, ammonium bicarbonate, Hexamethylenetetramine, benzoic acid, phthalic anhydride, Naphthalene or camphor. Urethane is particularly preferred.
Die Tablettenmassen für wasserlösliche Reagenztabletten und Arzneimittel-Tabletten können neben einem und mehreren Wirkstoffen übliche lösliche Trägerstoffe wie Natriumchlorid, Kaliumchlorid, Borax, Phosphate, Oligosaccharide, Polyäthylenglykole, Tenside und andere geeigneten anorganische und organische Stoffe enthalten. Der flüchtige feste Hilfsstoff soll etwa 5-50 %, vorzugsweise 10-30 % der gesamten Tablettenmasse ausmachen, wobei es selbstverständlich ist, daß bei einem hohen Hilfstoffanteil größere Hohlräume und damit rascher zerfallende, aber auch brüchigere Tabletten entstehen, als bei einem geringen Hilfsstoffanteil. Obwohl die Hilfsstoffe vollständig entfernt werden können, verkürzt es die Herstellungszeit der erfindungsgemäßen Tabletten, wenn die Hilfsstoffe spurenweise, z.B. unter 1 %, in der Tablette zurückbleiben dürfen.The tablet compositions for water-soluble reagent tablets and pharmaceutical tablets can contain, in addition to one or more active ingredients, the usual soluble carriers such as sodium chloride, potassium chloride, borax, phosphates, oligosaccharides, polyethylene glycols, surfactants and other suitable inorganic and organic substances. The volatile solid excipient should make up about 5-50 %, preferably 10-30 % of the total tablet mass, whereby it goes without saying that with a high proportion of excipients larger cavities and thus more rapidly disintegrating, but also more fragile tablets arise than with a low proportion of excipients. Although the excipients can be completely removed, the production time of the tablets according to the invention is shortened if the excipients are allowed to remain in the tablet in traces, for example less than 1%.
A098 1 3/ 1125 ·/· A098 1 3/1125 · / ·
Bei genügender thermischer Stabilität kann der Hilfsstoff durch einfaches Erhitzen der Tabletten über den Sublimations- bzw. Zersetzungspunkt entfernt werden. Bei empfindlichen Tabletteninhaltsstoffen, beispielsweise Enzymen, ist es vorteilhaft unter Vakuum zu arbeiten, wobei handelsübliche Gefriertrocknungsanlagen mit Kondensatabscheider besonders vorteilhaft verwendet werden können.If there is sufficient thermal stability, the excipient can pass through simply heating the tablets above the sublimation or decomposition point can be removed. For sensitive tablet ingredients, for example enzymes, it is advantageous to work under vacuum, using commercially available freeze-drying systems particularly advantageous with a condensate separator can be used.
Durch die folgenden Beispiele ist das erfindungsgemäße Verfahren näher erläutert.The process according to the invention is explained in more detail by the following examples.
0 9-87I 3/11250 9-8 7 I 3/1125
BexspiellFor example
Tablette A: 1,850 kg Kaliumchlorid werden gesiebt und zu 185 mg Kaliumchlorid-Tabletten von 8 mm Durchmesser verpreßt.Tablet A: 1.850 kg of potassium chloride are sieved and closed 185 mg potassium chloride tablets of 8 mm diameter compressed.
Tablette B 1: 1,850 kg Kaliumchlorid werden mit 350 gTablet B 1: 1.850 kg of potassium chloride are added with 350 g
Urethan (Äthylenurethan) gemischt«, gesiebt und zu 185 mg Kaliumchlorid - 35 mg Urethan-Tabletten von 8 mm Durchmesser verpreßt.Urethane (ethylene urethane) mixed «, sieved and to 185 mg potassium chloride - 35 mg urethane tablets with a diameter of 8 mm.
Aus diesen Tabletten wird anschließend fünf Stunden in einer Gefriertrocknungsanla*These tablets are then placed in a freeze-drying machine for five hours.
Urethan absublimiert.Sublimated urethane.
ο —1 —3 Gefriertrocknungsanlage bei 20 C und 10 - 10 Torr dasο -1-3 freeze-drying system at 20 C and 10-10 Torr das
Tablette B 2: 1,850 kg Kaliumchlorid werden mit 350.g Ammoniumhydrogencarbonat gemischt, gesiebt und zu 185 mg Kaliumchlorid - 35 mg Ammoniumhydrogencarbonat-Tabletten von 8 mm Durchmesser verpreßt.Tablet B 2: 1.850 kg of potassium chloride are mixed with 350 g of ammonium hydrogen carbonate mixed, sieved and added to 185 mg potassium chloride - 35 mg ammonium hydrogen carbonate tablets with a diameter of 8 mm.
Aus diesen Tabletten wird acht Stunden im Trockenschrank bei 90 C das Ammoniumhydrogencarbonat ausgetrieben.These tablets are used for eight hours in the drying cabinet 90 C expelled the ammonium hydrogen carbonate.
Tablette B 3: 1,850 kg Kaliumchlorid werden mit 350 g Harnstoff gemischt, gesiebt und zu 185 mg Kaliumchlorid -35 mg Harnstoff-Tabletten von 8 mm Durchmesser verpreßt.Tablet B 3: 1.850 kg of potassium chloride are mixed with 350 g of urea mixed, sieved and made 185 mg potassium chloride -35 mg urea tablets of 8 mm Crimped diameter.
Aus diesen Tabletten wird 16 Stunden im Vakuumschrank bei 110 C und 15 Torr der Harnstoff absublimiert.The urea is sublimed off from these tablets for 16 hours in a vacuum oven at 110 ° C. and 15 torr.
0 9 a;.3 /112 50 9 a; .3 / 112 5
Tablette B 4: 1,850 kg Kaliumchlorid werden mit 350 g Urotropin gemischt, gesiebt und zu 185 mg Kalium chlorid - 35 mg Urotropin-Tabletten von 8 mm Durchmesser verpreßt.Tablet B 4: 1.850 kg of potassium chloride are mixed with 350 g of urotropin, sieved and made into 185 mg of potassium chloride - 35 mg urotropin tablets of 8 mm diameter compressed.
Aus diesen Tabletten wird 16 Stunden im Vakuumschrank bei C und 15 Torr das Urotropin entfernt.The urotropin is removed from these tablets for 16 hours in a vacuum cabinet at C and 15 Torr.
Höhe Härte Auflösezeit Zerdrückbarkeit (mm) (Kp) (Sek.) (Sek.)Height hardness disintegration time crushability (mm) (Kp) (sec.) (Sec.)
Bestimmung der Tablettenhärte: Mit ERWEKA-HärtetesterDetermination of the tablet hardness: With the ERWEKA hardness tester
Bestimmung der Auflösezeit: 200 ml Wasser von RaumtemperaturDetermination of the dissolution time: 200 ml of water at room temperature
werden in einem 250 ml-Becherglas mit einem gebogenen Glasstab als Rührer von 150 U/min gerührt. Die vollständige Auflösezeit wird bestimmt. are in a 250 ml beaker with a curved glass rod as Stirrer stirred at 150 rpm. The complete dissolution time is determined.
Bestimmung der Zerdrückbarkeit: Eine in eine Petrischale hochkantDetermination of crushability: Place one on edge in a Petri dish
gestellte Tablette wird von einem Stab mit Auflagegewicht von zusammen 500 g gedrückt. Die Petrischale wird mit Wasser von Raumtemperatur gefüllt und die Zeit bis zum Zerdrücken der Tablette bestimmt.The tablet is made up of a stick with a weight of 500 g pressed. The Petri dish is filled with room temperature water and the time determined until the tablet is crushed.
£098 13/1125
-A£ 098 13/1125
-A
Beispiel 2Example 2
Tablette A: 1,5 kg Dextrose werden mit 40 %igem Alkohol granuliert, getrocknet und gesiebt. Das Granulat wird mit 50 g Polyathylenglykol 5-6000 trocken vermischt und zu 150 mg Dextrose-Tabletten von 8 mm Durchmesser verpreßt.Tablet A: 1.5 kg of dextrose are granulated with 40% alcohol, dried and sifted. The granulate is mixed dry with 50 g of polyethylene glycol 5-6000 and compressed into 150 mg dextrose tablets of 8 mm diameter.
Tablette B 1: 1,550 kg Dextrose-Polyäthylenglykol-Granulat werden mit 300 g Urethan trocken vermischt. Die Tablettenmasse wird zu 150 mg Dextrose 30 mg Urethan-Tabletten von 8 mm Durchmesser verpreßt.Tablet B 1: 1.550 kg of dextrose polyethylene glycol granules are mixed dry with 300 g of urethane. The tablet mass becomes 150 mg dextrose 30 mg urethane tablets 8 mm in diameter pressed.
Aus diesen Tabletten wird 8 Stunden im Trockenschrank bei C das Urethan absublimiert.The urethane is sublimated from these tablets in a drying cabinet at C for 8 hours.
Tablette B 2: 1,550 kg Dextrose-Polyäthylenglykol-GranulatTablet B 2: 1.550 kg dextrose polyethylene glycol granules
werden mit 300 g Ammoniumcarbonat trocken vermischt. Die Tablettenmasse wird zu 150 mg Dextrose - 30 mg Ammoniumcarbonat-Tabletten von 8 mm Durchmesser verpreßt.are mixed dry with 300 g of ammonium carbonate. The tablet mass becomes 150 mg Dextrose - 30 mg ammonium carbonate tablets of 8 mm diameter compressed.
Aus diesen Tabletten wird 8 Stunden im Trockenschrank bei 75° C das Ammoniumcarbonat entfernt.The ammonium carbonate is removed from these tablets in a drying cabinet at 75 ° C. for 8 hours.
Tablette B 3: 1,550 kg Dextrose-Polyäthylenglykol-GranulatTablet B 3: 1.550 kg of dextrose polyethylene glycol granules
werden mit 300 g Benzoesäure trocken vermischt. Die Tablettenmasse wird zu 150 mg Dextrose 30 mg Benzoesäure-Tabletten von. 8 mm Durchmesser verpreßt.are dry mixed with 300 g of benzoic acid. The tablet mass becomes 150 mg dextrose 30 mg benzoic acid tablets of. Pressed 8 mm diameter.
Aus diesen Tabletten wird 16 Stunden im Vakuumschrank bei 90° C und 15 Torr die Benzoesäure absublimiert.These tablets are used for 16 hours in a vacuum oven at 90 ° C and 15 Torr sublimates the benzoic acid.
A 0 9 8 1 3 / 1 1 2 5A 0 9 8 1 3/1 1 2 5
Tablette B 4: 1,550 kg Dextrose-Polyäthylenglykol-GranulatTablet B 4: 1.550 kg of dextrose polyethylene glycol granules
werden mit 300 g Campher trocken vermischt. Die Tablettenmasse wird zu 150 mg Dextrose - 30 mg Campher-Tabletten von 8 mm Durchmesser verpreßt.are dry mixed with 300 g of camphor. The tablet mass becomes 150 mg of dextrose - 30 mg Compressed camphor tablets with a diameter of 8 mm.
Aus diesen Tabletten wird 8 Stunden in einer Gefriertrocknungsanlage bei 40° C und 10~ - 10" Torr der Campher entfernt.These tablets become 8 hours in a freeze dryer at 40 ° C and 10 ~ - 10 "Torr the camphor is removed.
Höhe Härte Auflösezeit ZerdrückbarkeitHigh hardness, dissolving time, crushability
(mm) (Kp) (Sek.) (Sek.)(mm) (Kp) (sec.) (sec.)
Tablette A T/j - 4,5 360 ' 210Tablet A T / j - 4.5 360 '210
Tablettetablet
Bl-4 3,3 1,0 270 <10BI-4 3.3 1.0 270 <10
Die Bestimmung der Werte erfolgte wie im Beispiel 1.The values were determined as in Example 1.
Tablette A: 15 g Polyäthylenglykol 5-6000 werden in 40 %igem Alkohol gelöst. Mit dieser Lösung werden 388 g Glucose granuliert, 12,5 g NAD (Nicotinamid-adenindinucleotid), 3,75 g MTT (2,5-Diphenyl-3-(4,5-dimethylthiazolyl-2)-tetrazolium-bromid) und 0,75 g PMS (Phenazinmethosulfat) zugemischt. Die Mischung wird zu Reagenztabletten von 12 mm Durchmesser verpreßt, die pro Tablette 12,5 mg NAD, 3,75 mg MTT und 0,75 mg PMS enthalten.Tablet A: 15 g of polyethylene glycol 5-6000 in 40% Alcohol dissolved. 388 g of glucose are granulated with this solution, 12.5 g of NAD (nicotinamide adenine dinucleotide), 3.75 g MTT (2,5-diphenyl-3- (4,5-dimethylthiazolyl-2) tetrazolium bromide) and 0.75 g of PMS (phenazine methosulfate) mixed in. The mixture is compressed into reagent tablets with a diameter of 12 mm, which contain 12.5 mg NAD, 3.75 mg MTT and 0.75 mg PMS per tablet.
^09813/1125^ 09813/1125
Tablette B: 15 g Polyäthylenglykol 5-6000 werden in 40 %igem Alkohol gelöst. Mit dieser Lösung werden 388 g Glucose granuliert, dann getrocknet und gesiebt. Dem Granulat werden trocken 12,5 g NAD, 3,75 g MTT, 0,75 g PMS und 80 g Urethan zugemischt. Die Mischung wird zu Reagenztabletten von 12mm Durchmesser verpreßt, die pro Tablette 12,5 mg NAD, 3,75 mg MTT und 0,75 mg PMS enthalten. Aus diesen Tabletten wird das Urethan 8 Stunden in einer Gefriertrocknungsanlage bei 0 C und 10 - 10 Torr absublimiert.Tablet B: 15 g of polyethylene glycol 5-6000 in 40% Alcohol dissolved. 388 g of glucose are granulated with this solution, then dried and sieved. 12.5 g of NAD, 3.75 g of MTT, 0.75 g of PMS and 80 g of urethane are mixed dry with the granules. the Mixture turns into reagent tablets 12mm in diameter compressed containing 12.5 mg NAD, 3.75 mg MTT and 0.75 mg PMS per tablet. From these The urethane becomes tablets for 8 hours in a freeze-dryer at 0 C and 10-10 Torr sublimated.
Höhe Härte Äuflösezeit Zerdrückbarkeit (mm) (mm) (Sek.) (Sek.) Height hardness dissolving time crushability (mm) (mm) (sec.) (Sec.)
Tablette A 3,5 12 660 540Tablet A 3.5 12 660 540
Tablette B 4,2 3 480 <15Tablet B 4.2 3 480 <15
Die Bestimmung der Werte erfolgte wie im Beispiel 1.The values were determined as in Example 1.
Tablette A: 500 g Natriumchlorid werden gemahlen, mit 116 g p-Nitro-phenylphosphat-Natrium gemischt, vorkomprimiert und gesiebt. Es werden Tabletten von 5 ram Durchmesser und einem Gehalt von 11,6 mg p-Nitrophenylphosphat-Natrium verpreßt.Tablet A: 500 g of sodium chloride are ground, mixed with 116 g of p-nitro-phenylphosphate sodium, pre-compressed and sifted. The tablets are 5 ram in diameter and contain 11.6 mg of sodium p-nitrophenyl phosphate pressed.
A 0 9 8/1 3 / 1 1 2 5A 0 9 8/1 3/1 1 2 5
Tablette B: 500 g Natriumchlorid werden gemahlen, mit 116 g p-Nitrophenylphosphat und 134 g Urethan gemischt, vorkomprimiert und gesiebt. Es werden Tabletten von 5 mm Durchmesser mit einem Gehalt von 11,6 mg p-Nitrophenylphosphat verpreßt. Diese Tabletten werden 10 Stunden im Trockenschrank auf 30 C ei wärmt, um das Urethan abzusublimieren.Tablet B: 500 g of sodium chloride are ground, mixed with 116 g of p-nitrophenyl phosphate and 134 g of urethane, pre-compressed and sieved. There are tablets with a diameter of 5 mm and a content of 11.6 mg p-nitrophenyl phosphate is pressed. These tablets are 10 hours in the drying cabinet at 30 C ei warms to sublimate the urethane.
Höhe Härte Auflösezeit ZerdrückbarkeitHigh hardness, dissolving time, crushability
(mm) (mm) (Sek.) (Sek.)(mm) (mm) (sec.) (sec.)
Tablette A i,g 3 300 60Tablet A i, g 3 300 60
Tablette B '2,4 1 120 <1OTablet B '2.4 1 120 <10
Die Bestimmung der Werte erfolgte wie im Beispiel 1.The values were determined as in Example 1.
13/112513/1125
Claims (6)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2246013A DE2246013A1 (en) | 1972-09-20 | 1972-09-20 | PROCESS FOR THE MANUFACTURING OF POROUS TABLETS |
| US395796A US3885026A (en) | 1972-09-20 | 1973-09-10 | Preparation of porous tablets |
| GB4318773A GB1381588A (en) | 1972-09-20 | 1973-09-14 | Process for the preparation of porous tablets |
| CH1329273A CH579394A5 (en) | 1972-09-20 | 1973-09-17 | |
| IT7328973A IT998618B (en) | 1972-09-20 | 1973-09-17 | PROCEDURE FOR THE PRODUCTION OF POROUS PADS |
| FR7333392A FR2199973B1 (en) | 1972-09-20 | 1973-09-18 | |
| SE7312753A SE395366B (en) | 1972-09-20 | 1973-09-19 | PROCEDURE FOR PREPARING POROSA TABLETS |
| AT806973A AT324568B (en) | 1972-09-20 | 1973-09-19 | PROCESS FOR THE MANUFACTURING OF POROUS TABLETS |
| JP48106458A JPS4969819A (en) | 1972-09-20 | 1973-09-20 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2246013A DE2246013A1 (en) | 1972-09-20 | 1972-09-20 | PROCESS FOR THE MANUFACTURING OF POROUS TABLETS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2246013A1 true DE2246013A1 (en) | 1974-03-28 |
Family
ID=5856791
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2246013A Pending DE2246013A1 (en) | 1972-09-20 | 1972-09-20 | PROCESS FOR THE MANUFACTURING OF POROUS TABLETS |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US3885026A (en) |
| JP (1) | JPS4969819A (en) |
| AT (1) | AT324568B (en) |
| CH (1) | CH579394A5 (en) |
| DE (1) | DE2246013A1 (en) |
| FR (1) | FR2199973B1 (en) |
| GB (1) | GB1381588A (en) |
| IT (1) | IT998618B (en) |
| SE (1) | SE395366B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2556561A1 (en) * | 1975-12-16 | 1977-06-30 | Boehringer Mannheim Gmbh | PROCESS FOR THE MANUFACTURING OF POROUS TABLETS |
| DE2744493A1 (en) * | 1976-10-06 | 1978-04-13 | Wyeth John & Brother Ltd | SHAPED CARRIER FOR CHEMICALS AND / OR PHARMACA |
| DE3734796A1 (en) * | 1986-10-14 | 1988-04-21 | Beaufour Lab | METHOD FOR PRODUCING SOLUBLE AND / OR DIVISIBLE TABLETS AND TABLETS OBTAINED BY THIS METHOD |
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4078046A (en) * | 1975-03-10 | 1978-03-07 | University Of Southern California | Process for the catalytic oxidation of carbon monoxide with sulfur dioxide and water |
| GB1548022A (en) * | 1976-10-06 | 1979-07-04 | Wyeth John & Brother Ltd | Pharmaceutial dosage forms |
| US4568547A (en) * | 1979-08-30 | 1986-02-04 | Herschler R J | Solid pharmaceutical compositions comprising MSM and their production |
| US4883182A (en) * | 1985-05-31 | 1989-11-28 | Hughes Raymond J | Tamper evident capsule and insert device |
| JP2614409B2 (en) * | 1991-12-20 | 1997-05-28 | ファイザー・インコーポレーテッド | Porous shaped release formulation and method of making same |
| ATE147261T1 (en) * | 1992-01-13 | 1997-01-15 | Pfizer | METHOD FOR PRODUCING HIGH STRENGTH TABLETS |
| HUT75616A (en) * | 1992-03-17 | 1997-05-28 | Pfizer | Method for prooucing porous delivery devices |
| US6586006B2 (en) | 1994-08-04 | 2003-07-01 | Elan Drug Delivery Limited | Solid delivery systems for controlled release of molecules incorporated therein and methods of making same |
| US6290991B1 (en) | 1994-12-02 | 2001-09-18 | Quandrant Holdings Cambridge Limited | Solid dose delivery vehicle and methods of making same |
| WO1996008979A1 (en) | 1994-09-22 | 1996-03-28 | Quadrant Holdings Cambridge Limited | Compositions for use in rehydration and nutrition during athletic exercise and methods of making same |
| US6964771B1 (en) | 1995-06-07 | 2005-11-15 | Elan Drug Delivery Limited | Method for stably incorporating substances within dry, foamed glass matrices |
| US5958455A (en) * | 1996-02-09 | 1999-09-28 | Quadrant Holdings Cambridge Ltd | Oral solid dosage forms, methods of making same and compositions thereof |
| US5762961A (en) * | 1996-02-09 | 1998-06-09 | Quadrant Holdings Cambridge Ltd. | Rapidly soluble oral solid dosage forms, methods of making same, and compositions thereof |
| US6632648B1 (en) | 1996-05-14 | 2003-10-14 | Elan Drug Delivery Limited | Methods of terminal sterilization of fibrinogen |
| US8071128B2 (en) | 1996-06-14 | 2011-12-06 | Kyowa Hakko Kirin Co., Ltd. | Intrabuccally rapidly disintegrating tablet and a production method of the tablets |
| KR100481583B1 (en) * | 1996-06-14 | 2005-07-12 | 교와 핫꼬 고교 가부시끼가이샤 | Tablets disintegrate quickly in the oral cavity |
| CA2258159C (en) * | 1996-06-14 | 2006-03-21 | Kyowa Hakko Kogyo Co., Ltd. | Intraorally rapidly disintegrable tablet |
| US6294151B1 (en) | 1996-08-13 | 2001-09-25 | Kyowa Hakko Kogyo, Co., Ltd. | Isotopic urea tablets |
| US6468782B1 (en) | 1996-12-05 | 2002-10-22 | Quadrant Healthcare (Uk) Limited | Methods of preserving prokaryotic cells and compositions obtained thereby |
| US20040023948A1 (en) * | 1997-03-24 | 2004-02-05 | Green Richard David | Fast-dispersing dosage form containing 5-HT1 agonists |
| US20060165606A1 (en) | 1997-09-29 | 2006-07-27 | Nektar Therapeutics | Pulmonary delivery particles comprising water insoluble or crystalline active agents |
| US6565885B1 (en) | 1997-09-29 | 2003-05-20 | Inhale Therapeutic Systems, Inc. | Methods of spray drying pharmaceutical compositions |
| GT199900061A (en) * | 1998-05-15 | 2000-10-14 | Pfizer | PHARMACEUTICAL FORMULATIONS. |
| CA2350304A1 (en) | 1998-11-10 | 2000-05-18 | Teva Pharmaceutical Industries, Ltd. | Dispersible compositions containing l-dopa ethyl ester |
| GB9908014D0 (en) * | 1999-04-08 | 1999-06-02 | Scherer Corp R P | Pharmaceutical compositions |
| US6284270B1 (en) | 1999-08-04 | 2001-09-04 | Drugtech Corporation | Means for creating a mass having structural integrity |
| MXPA02001323A (en) | 2000-05-10 | 2004-07-16 | Alliance Pharma | Phospholipid-based powders for drug delivery. |
| US8404217B2 (en) | 2000-05-10 | 2013-03-26 | Novartis Ag | Formulation for pulmonary administration of antifungal agents, and associated methods of manufacture and use |
| US7871598B1 (en) | 2000-05-10 | 2011-01-18 | Novartis Ag | Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use |
| US20020001617A1 (en) * | 2000-05-26 | 2002-01-03 | Chang-Hyun Lee | Rapidly disintegrating tablet and process for the manufacture thereof |
| US20030185886A1 (en) * | 2000-05-26 | 2003-10-02 | Hanmi Pharm. Co., Ltd. | Process for the preparation of rapidly disintegrating tablet |
| GB0028709D0 (en) * | 2000-11-24 | 2001-01-10 | S P A | Process |
| US6544552B2 (en) * | 2001-01-11 | 2003-04-08 | Particle And Coating Technologies, Inc. | Method of producing porous tablets with improved dissolution properties |
| KR20030074810A (en) * | 2001-02-08 | 2003-09-19 | 파마시아 코포레이션 | Rapid-onset medicament for treatment of sexual dysfunction |
| WO2002069934A1 (en) * | 2001-03-06 | 2002-09-12 | Kyowa Hakko Kogyo Co., Ltd. | Preparations quickly disintegrating in oral cavity |
| US6509040B1 (en) | 2001-06-22 | 2003-01-21 | R.P. Scherer Corporation | Fast dispersing dosage forms essentially free of mammalian gelatin |
| US9358214B2 (en) | 2001-10-04 | 2016-06-07 | Adare Pharmaceuticals, Inc. | Timed, sustained release systems for propranolol |
| CA2468958C (en) | 2001-12-19 | 2012-07-03 | Nektar Therapeutics | Pulmonary delivery of aminoglycosides |
| EP2085072A1 (en) * | 2002-03-26 | 2009-08-05 | Teva Pharmaceutical Industries Ltd. | Drug microparticles |
| BR0314525A (en) * | 2002-10-04 | 2005-07-26 | Pharmacia Corp | Compositions and methods for treating sexual dysfunction |
| EP1558211A2 (en) * | 2002-10-30 | 2005-08-03 | Pharmacia Corporation | Oral extended release tablets and methods of making and using the same |
| US8367111B2 (en) * | 2002-12-31 | 2013-02-05 | Aptalis Pharmatech, Inc. | Extended release dosage forms of propranolol hydrochloride |
| AU2004238321B2 (en) * | 2003-05-07 | 2009-08-27 | Samyang Biopharmaceuticals Corporation | Highly plastic granules for making fast melting tablets |
| US7390503B1 (en) | 2003-08-22 | 2008-06-24 | Barr Laboratories, Inc. | Ondansetron orally disintegrating tablets |
| US8747895B2 (en) * | 2004-09-13 | 2014-06-10 | Aptalis Pharmatech, Inc. | Orally disintegrating tablets of atomoxetine |
| US9884014B2 (en) * | 2004-10-12 | 2018-02-06 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions |
| NZ589750A (en) * | 2004-10-21 | 2012-07-27 | Aptalis Pharmatech Inc | Taste-masked pharmaceutical compositions with gastrosoluble pore-formers |
| ATE398444T1 (en) * | 2004-10-28 | 2008-07-15 | Pantec Ag | PRODUCTION OF A RAPIDLY DISSOLVING SOLID DOSAGE FORM FROM A POWDER AND A FREEZE DRYING STEP |
| US20060105038A1 (en) * | 2004-11-12 | 2006-05-18 | Eurand Pharmaceuticals Limited | Taste-masked pharmaceutical compositions prepared by coacervation |
| US9161918B2 (en) | 2005-05-02 | 2015-10-20 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| GB0516604D0 (en) * | 2005-08-12 | 2005-09-21 | Sandoz Ag | Rapidly dispersing/disintegrating compositions |
| US20090068262A1 (en) * | 2007-04-04 | 2009-03-12 | Ilan Zalit | Rapid dissolution of combination products |
| JP5269894B2 (en) * | 2007-06-27 | 2013-08-21 | ハンミ ファーム． シーオー．， エルティーディー． | Method for producing fast-dissolving preparation for oral administration, its production, and packaging device |
| US20090060983A1 (en) * | 2007-08-30 | 2009-03-05 | Bunick Frank J | Method And Composition For Making An Orally Disintegrating Dosage Form |
| KR101560176B1 (en) * | 2007-10-31 | 2015-10-14 | 맥네일-피피씨, 인코포레이티드 | Orally disintegrated dosage form |
| WO2011004799A1 (en) * | 2009-07-06 | 2011-01-13 | 杏林製薬株式会社 | Tablet having hollow structure |
| US20110318411A1 (en) | 2010-06-24 | 2011-12-29 | Luber Joseph R | Multi-layered orally disintegrating tablet and the manufacture thereof |
| US8807979B2 (en) | 2009-09-24 | 2014-08-19 | Mcneil-Ppc, Inc. | Machine for the manufacture of dosage forms utilizing radiofrequency energy |
| US20110070286A1 (en) * | 2009-09-24 | 2011-03-24 | Andreas Hugerth | Process for the manufacture of nicotine-comprising chewing gum and nicotine-comprising chewing gum manufactured according to said process |
| US8313768B2 (en) | 2009-09-24 | 2012-11-20 | Mcneil-Ppc, Inc. | Manufacture of tablet having immediate release region and sustained release region |
| AU2010325746B2 (en) | 2009-12-02 | 2016-02-25 | Adare Pharmaceuticals S.R.L. | Fexofenadine microcapsules and compositions containing them |
| UY33173A (en) * | 2010-01-08 | 2011-07-29 | Eurand Inc | |
| US9233491B2 (en) | 2012-05-01 | 2016-01-12 | Johnson & Johnson Consumer Inc. | Machine for production of solid dosage forms |
| US9511028B2 (en) | 2012-05-01 | 2016-12-06 | Johnson & Johnson Consumer Inc. | Orally disintegrating tablet |
| US9445971B2 (en) | 2012-05-01 | 2016-09-20 | Johnson & Johnson Consumer Inc. | Method of manufacturing solid dosage form |
| MX368159B (en) | 2014-01-10 | 2019-09-20 | Johnson & Johnson Consumer Inc | Process for making tablet using radiofrequency and lossy coated particles. |
| KR102488486B1 (en) | 2016-04-21 | 2023-01-12 | 아스트라제네카 아베 | Orally disintegrating tablets |
| US10493026B2 (en) | 2017-03-20 | 2019-12-03 | Johnson & Johnson Consumer Inc. | Process for making tablet using radiofrequency and lossy coated particles |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1742515A (en) * | 1924-10-08 | 1930-01-07 | Ambrose J Mandell | Method of making porous objects |
| US2887437A (en) * | 1956-08-22 | 1959-05-19 | Pfizer & Co C | Palatable vitamin tablet containing an amino acid |
| US3175521A (en) * | 1961-02-23 | 1965-03-30 | Schering Corp | Apparatus for punching miniature tablets |
| US3371984A (en) * | 1963-09-06 | 1968-03-05 | Colgate Palmolive Co | Air freshener |
| DE1228029C2 (en) * | 1964-05-09 | 1973-05-17 | Merck Ag E | Process for the production of tablets by pressing powder mixtures without prior granulation |
| US3450494A (en) * | 1967-07-18 | 1969-06-17 | Conrad J Gaiser | Amorphous sodium silicate having inherent binding properties and method of producing same |
| US3639286A (en) * | 1968-05-28 | 1972-02-01 | Mario Ballestra | Synthetic detergent in bar or cake form and the method to manufacture same |
| GB1303102A (en) * | 1969-01-16 | 1973-01-17 | ||
| US3719599A (en) * | 1969-11-25 | 1973-03-06 | Lepetit Spa | Solid lubricant composition and method of preparation |
| LU60170A1 (en) * | 1970-01-09 | 1971-11-18 | ||
| US3653914A (en) * | 1970-03-20 | 1972-04-04 | Alberto Culver Co | Production of tablets |
| US3632778A (en) * | 1970-06-10 | 1972-01-04 | Hoffmann La Roche | Tablets containing l-dopa |
| US3739048A (en) * | 1971-05-26 | 1973-06-12 | Sumitomo Electric Industries | Method of granulating powder |
| US3789119A (en) * | 1971-06-01 | 1974-01-29 | Parke Davis & Co | Stabilized molded sublingual nitroglycerin tablets |
-
1972
- 1972-09-20 DE DE2246013A patent/DE2246013A1/en active Pending
-
1973
- 1973-09-10 US US395796A patent/US3885026A/en not_active Expired - Lifetime
- 1973-09-14 GB GB4318773A patent/GB1381588A/en not_active Expired
- 1973-09-17 IT IT7328973A patent/IT998618B/en active
- 1973-09-17 CH CH1329273A patent/CH579394A5/xx not_active IP Right Cessation
- 1973-09-18 FR FR7333392A patent/FR2199973B1/fr not_active Expired
- 1973-09-19 SE SE7312753A patent/SE395366B/en unknown
- 1973-09-19 AT AT806973A patent/AT324568B/en not_active IP Right Cessation
- 1973-09-20 JP JP48106458A patent/JPS4969819A/ja active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2556561A1 (en) * | 1975-12-16 | 1977-06-30 | Boehringer Mannheim Gmbh | PROCESS FOR THE MANUFACTURING OF POROUS TABLETS |
| DE2744493A1 (en) * | 1976-10-06 | 1978-04-13 | Wyeth John & Brother Ltd | SHAPED CARRIER FOR CHEMICALS AND / OR PHARMACA |
| DE3734796A1 (en) * | 1986-10-14 | 1988-04-21 | Beaufour Lab | METHOD FOR PRODUCING SOLUBLE AND / OR DIVISIBLE TABLETS AND TABLETS OBTAINED BY THIS METHOD |
Also Published As
| Publication number | Publication date |
|---|---|
| GB1381588A (en) | 1975-01-22 |
| FR2199973A1 (en) | 1974-04-19 |
| US3885026A (en) | 1975-05-20 |
| AT324568B (en) | 1975-09-10 |
| IT998618B (en) | 1976-02-20 |
| SE395366B (en) | 1977-08-15 |
| FR2199973B1 (en) | 1979-01-05 |
| CH579394A5 (en) | 1976-09-15 |
| JPS4969819A (en) | 1974-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2246013A1 (en) | PROCESS FOR THE MANUFACTURING OF POROUS TABLETS | |
| DE2556561C2 (en) | Process for the production of porous tablets | |
| EP0078430B1 (en) | Process for preparing solid fast-releasing drug formulations of dihydropyridines | |
| DE3420283A1 (en) | NIFEDIPINE DRY PREPARATIONS AND METHOD FOR THE PRODUCTION THEREOF | |
| DE60036205T2 (en) | Granules consisting of starch and lactose | |
| DD292837A5 (en) | PROCESS FOR PREPARING CHOLESTYRAMINE TABLETS | |
| EP0122574B1 (en) | Divisible tablet with sustained release of the active ingredient, and process for its production | |
| DE69728857T3 (en) | SOLID MEDICAMENTS CONTAINING TREHALOSE | |
| DE3505433A1 (en) | DIRECT TABLETING AIDS | |
| CH672736A5 (en) | ||
| DE1517787A1 (en) | Enzyme preparation and process for its production | |
| CH499325A (en) | Source combination for the production of swallowable tablets or capsules | |
| DE4122217A1 (en) | METHOD FOR PRODUCING MECHANICALLY STABLE, GOOD-DISPOSING COMPRESSES FROM SMALL ACTIVE FORM BODIES | |
| EP0819429A1 (en) | Direct tabletting aid | |
| DE69913958T2 (en) | Non-crystalline solid dispersing composition with cefuroxime axetil | |
| US4203997A (en) | Directly-pressable ascorbic acid-containing granulates | |
| DE2241960C2 (en) | Free-flowing granules for tablet production | |
| US20020142044A1 (en) | Pharmaceutical dosage forms with enhanced cohesive and compressiblity properties | |
| CH643737A5 (en) | Preparation of a solid material composed of ergot peptide alkaloids and polyvinylpyrrolidone | |
| US4645664A (en) | Microporous powder form polylactides | |
| DE2741755A1 (en) | POLYMER-BASED COATING COMPOUNDS FOR BIOLOGICALLY ACTIVE PREPARATIONS AND PROCESSES FOR MANUFACTURING THE FIRST AND BIOLOGICALLY ACTIVE PREPARATIONS AND PROCESSES FOR MANUFACTURING THE LATER | |
| EP1965760B1 (en) | Finely dispersed cross-linked polyvinylpyrrolidone for use as tablet disintegrant | |
| DE04078149T1 (en) | Stable solid composition of enalapril salt and its preparation | |
| DE3142853C2 (en) | ||
| US3493659A (en) | Compositions and process for the production thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OHA | Expiration of time for request for examination |