SE444887B - TWO LAYER TABLETS CONTAINING PIVALOYLOXIMETHYL-6 - / (HEXAHYDRO-1H-AZEPIN-1-YL) -METHYLENAMINO / PENICILLANATE AND PIVALOYLOXIMETHYL-6- (D-ALFA-AMINOPHYLENE) - Google Patents
TWO LAYER TABLETS CONTAINING PIVALOYLOXIMETHYL-6 - / (HEXAHYDRO-1H-AZEPIN-1-YL) -METHYLENAMINO / PENICILLANATE AND PIVALOYLOXIMETHYL-6- (D-ALFA-AMINOPHYLENE)Info
- Publication number
- SE444887B SE444887B SE8006592A SE8006592A SE444887B SE 444887 B SE444887 B SE 444887B SE 8006592 A SE8006592 A SE 8006592A SE 8006592 A SE8006592 A SE 8006592A SE 444887 B SE444887 B SE 444887B
- Authority
- SE
- Sweden
- Prior art keywords
- tablet
- layer
- component
- pivaloyloximethyl
- penicillanate
- Prior art date
Links
- -1 (HEXAHYDRO-1H-AZEPIN-1-YL) -METHYLENAMINO Chemical class 0.000 title description 2
- 239000007884 disintegrant Substances 0.000 claims description 9
- 101000623895 Bos taurus Mucin-15 Proteins 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 239000007888 film coating Substances 0.000 claims description 5
- 238000009501 film coating Methods 0.000 claims description 5
- 239000012458 free base Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 239000011149 active material Substances 0.000 claims 2
- 239000003826 tablet Substances 0.000 description 35
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 239000008187 granular material Substances 0.000 description 10
- 229960003342 pivampicillin Drugs 0.000 description 8
- ZEMIJUDPLILVNQ-ZXFNITATSA-N pivampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OCOC(=O)C(C)(C)C)=CC=CC=C1 ZEMIJUDPLILVNQ-ZXFNITATSA-N 0.000 description 8
- UHPXMYLONAGUPC-WKLLBTDKSA-N pivmecillinam hydrochloride Chemical compound [H+].[Cl-].N([C@H]1[C@@H]2N(C1=O)[C@H](C(S2)(C)C)C(=O)OCOC(=O)C(C)(C)C)=CN1CCCCCC1 UHPXMYLONAGUPC-WKLLBTDKSA-N 0.000 description 7
- 229940037380 pivmecillinam hydrochloride Drugs 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- NPGNOVNWUSPMDP-UTEPHESZSA-N chembl1650818 Chemical compound N(/[C@H]1[C@@H]2N(C1=O)[C@H](C(S2)(C)C)C(=O)OCOC(=O)C(C)(C)C)=C\N1CCCCCC1 NPGNOVNWUSPMDP-UTEPHESZSA-N 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229960004212 pivmecillinam Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000007098 aminolysis reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
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
- A61K9/2072—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
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
Description
8006592-3 tid p.g.a. att kompositionens båda komponenter har inbördes olika löslighet och påverkar varandra ömsesidigt. 8006592-3 time p.g.a. that the two components of the composition have different solubilities and interact with each other.
Den minskade stabiliteten härrör delvis från inverkan av piv- ampicillinets aminogrupp på pivmecillinammolekylen. Denna undergår då en aminolys, d.v.s. dess molekyl nedbrytes. Denna nedbrytning är särskilt påtaglig då kompositionen lagras utan speciella för- siktighetsåtgärder för utestängande av fuktighet. Den förlängda mïflerfallstiden har sin orsak i den samtidiga närvaron av olösligt pivampicillin och lättlöslig pivmecíllinamhydroklorid i en tablett- grundmassa. Närvaron av ett hjälpmedel i form av ett desintegre- ringsmedel (sprängningsmedel), i typiska fall stärkelse, är verk- ningslös i en tablett som innehåller en sådan blandning. I själva verket behövs emellertid ett desintegreringsmedel för att disper- gora det endast i ringa utsträckning lösliga pivampicillinet i magen, i och för undvikande av höga lokala koncentrationer. Piv- mecillürmhydroklorid är lättlöslig och behöver icke något desinte- groringsmcdel. Tvärtom tenderar pivampicillin + desintegrerings- medel att i närvaro av pivmecillinamhydroklorid bilda ett preparat med långsam läkcmedelsavgivning, troligen på grund av att on grundmassa bildas, ur vilken pivmecillinam friges endast ]_årrfs¿nnt. b Det har nu visat sig, att man kan åstadkomma en två- skiktstablett, med vilken nackdelarna hos de ovan beskrivna blandningarna kan undvikas. Uppfinningen avser sålunda en tab- lett bestående av en terapeutiskt aktiv komponent I, en tera- pevtiskt aktiv komponent II, farmaceutiskt acceptabelt, ogif- tigt bärarämne, desintegreringsmedel och eventuellt ytterligare hjälpmedel, varvid komponent I ingår i ett första tablettskikt och komponent II ingår i ett andra tablettskikt, och varvid tabletten eventuellt är försedd med ett filmöverdrag. Denna tablett kännetecknas av att komponent I är pivaloyloxímetyl-6- -[(hexahydro-1H-azepin-1-yl)-metylenamino]-penicillanat i form av hydroklorid, medan komponent II är pivaloyloximetyl-6-(D-a- -aminofenylacetamido)-penicillanat i form av en fri bas och in- går i nämnda andra skikt tillsammans med desintegreringsmedlet, . varvid viktförhállandet mellan komponent I i form av hydroklo- rid och komponent II i form av fri bas är 1:5 - 5:1.' 8006592-3 3 De enligt uppfinningen avsedda tvåskiktstabletterna kan fram- ställas på en konventionell tabletteringsmaskin, med användning av ett första granulat som innehåller den ena aktiva beståndsdelen tillsammans med bärare och/eller hjälpmedel, och ett andra granu- lat som innehåller den andra aktiva bestândsdelen och de nödvändiga bärarna och/eller hjälpmedlen. Det första granulatet införes i korrekt dos i tablettslagningsformen och undergår en svag förbe- redande sammanpressning; bottenstansen sänkes, det andra granu- latet införes i korrekt dos i det fria hälrummet i formen, och slutligen framställes tabletten genom hoppressning.The reduced stability is due in part to the effect of the amino group of piv-ampicillin on the pivmecillin amm molecule. This then undergoes an aminolysis, i.e. its molecule is broken down. This degradation is particularly noticeable when the composition is stored without special precautions to exclude moisture. The prolonged elimination period is due to the simultaneous presence of insoluble pivampicillin and readily soluble pivmecillinam hydrochloride in a tablet matrix. The presence of an excipient in the form of a disintegrant (disintegrant), typically starch, is ineffective in a tablet containing such a mixture. In reality, however, a disintegrant is needed to disperse the pivampicillin, which is only slightly soluble in the stomach, in order to avoid high local concentrations. Pivemecillurm hydrochloride is readily soluble and does not require a disintegrant. On the contrary, in the presence of pivmecillinam hydrochloride, pivampicillin + disintegrant tends to form a slow drug preparation, probably due to the formation of a matrix from which pivmecillinam is only released annually. It has now been found that a two-layer tablet can be provided with which the disadvantages of the mixtures described above can be avoided. The invention thus relates to a tablet consisting of a therapeutically active component I, a therapeutically active component II, a pharmaceutically acceptable, non-toxic carrier, disintegrant and optionally further auxiliaries, component I being included in a first tablet layer and component II being included in a second tablet layer, and wherein the tablet is optionally provided with a film coating. This tablet is characterized in that component I is pivaloyloxymethyl-6- - [(hexahydro-1H-azepin-1-yl) -methylenamino] -penicillanate in the form of hydrochloride, while component II is pivaloyloxymethyl-6- (Da- -aminophenylacetamido) - penicillanate in the form of a free base and included in said second layer together with the disintegrant,. wherein the weight ratio between component I in the form of hydrochloride and component II in the form of free base is 1: 5 - 5: 1. The bilayer tablets intended according to the invention can be prepared on a conventional tableting machine, using a first granulate containing one active ingredient together with carrier and / or excipients, and a second granulate containing the second active ingredient. and the necessary carriers and / or aids. The first granulate is introduced in the correct dose into the tablet beat form and undergoes a slight preparatory compression; the bottom punch is lowered, the second granulate is introduced in the correct dose into the free cavity of the mold, and finally the tablet is prepared by compression.
Vid beredning av ovan angivna granulat för framställning av de enligt uppfinningen avsedda dubbelskiktstabletterna bör vederbörlig hänsyn tas till de ifrågavarande komponenternas egenskaper.When preparing the above-mentioned granules for the preparation of the double-layer tablets intended according to the invention, due consideration should be given to the properties of the components in question.
Om pivampicillin bringas i kontakt med organiska lös- ningsmedel, kan detta ha till följd att molekylen nedbrytes. Ef- tersom pivampicillin är i endast ringa utsträckning lösligt i vatten, kan man som granuleringsmedel använda en vattenlösning av ett vattenlösligt cellulosaderivat, t ex metylcellulosa.If pivampicillin is brought into contact with organic solvents, this may result in the molecule being degraded. Since pivampicillin is only slightly soluble in water, an aqueous solution of a water-soluble cellulose derivative, eg methylcellulose, can be used as granulating agent.
Pivmecillinamhydroklorid är lättlöslig i vatten. Man mäste därför välja ett organiskt lösningsmedel, vilket har minsta möjliga inverkan på pivmecillinammolekylens stabilitet och i vilket pivmecillinamhydrokloriden är löslig i endast rin- ga utsträckning. Bland de inom farmaceutisk teknik använda or- ganiska lösníngsmedlen är isopropanol och aceton lämpliga; iso- propanol föredras emedan användning av aceton i större mänder kan medföra explosionrisk.Pivmecillinam hydrochloride is readily soluble in water. An organic solvent must therefore be chosen which has the least possible effect on the stability of the pivmecillinam molecule and in which the pivmecillinam hydrochloride is soluble only to a small extent. Among the organic solvents used in pharmaceutical technology, isopropanol and acetone are suitable; isopropanol is preferred because the use of acetone in larger men can pose a risk of explosion.
Som cellulosaderivat föredrar man att använda hydroxipropyl- cellulosa på grund av dess löslighet i isopropanol.As the cellulose derivative, it is preferred to use hydroxypropyl cellulose due to its solubility in isopropanol.
För att förse de färdiga tabletterna med ett filmöverdrag bör man använda ett medel som ger en stark, väl vidhäftande film. Man föredrar sålunda att använda hydroxipropylmetylcellulosa löst i en vattenlösning av en alkanol, t.ex. etanol.To provide the finished tablets with a film coating, you should use a product that provides a strong, well-adhering film. Thus, it is preferred to use hydroxypropyl methylcellulose dissolved in an aqueous solution of an alkanol, e.g. ethanol.
Det har visat sig att en dubbelskiktstablett av ovan angivet slag är stabi , sönderfaller lätt och tillhandahåller de båda akti- va komponenterna i fysiologiskt lättillgänglig form. Denna tablett lämpar sig väl för praktisk klinisk användning.It has been found that a double layer tablet of the type indicated above is stable, decomposes easily and provides the two active components in physiologically readily available form. This tablet is well suited for practical clinical use.
Enligt en annan utföringsform av en tvåskiktstablett kan denna vara en tablett med en kärna av den första aktiva beståndsdelen 8006592-3 4 och ett överdrag innehållande den andra aktiva beståndsdelen; men denna utföringsform är kanske mindre lämplig i de fall, då de båda aktiva beståndsdelarna skall ingå i ungefärligen lika stora mäng- der, enär en korrekt centrering av kärnan ev. kan vålla svårig- heter, med ty âtföljandeolikformighet av överdragets tjocklek samt risk att överdraget spricker under slutproduktens lagring och han- tering.According to another embodiment of a two-layer tablet, this may be a tablet with a core of the first active ingredient and a coating containing the second active ingredient; but this embodiment is perhaps less suitable in cases where the two active ingredients are to be present in approximately equal amounts, since a correct centering of the core is possible. can cause difficulties, with consequent non-uniformity of the thickness of the coating and the risk that the coating will crack during storage and handling of the final product.
Tvåskiktstabletten enligt uppfinningen utgör den lämpligaste beredningsformen för samtidig adminisàering av de båda aktiva kom- ponenterna. Denna farmaceutiska teknik gör det möjligt att variera de båda aktiva komjonenternas mängdförhållanden mellan 1:5 och 5:1.The two-layer tablet according to the invention constitutes the most suitable dosage form for the simultaneous administration of the two active components. This pharmaceutical technique makes it possible to vary the proportions of the two active ingredients between 1: 5 and 5: 1.
Uppfinningen åskådliggöres ytterligare genom nedanstående exempel.The invention is further illustrated by the following examples.
Exempel 1 Framställning av l00.000 tabletter Ingredienser __¿________ Pivampïuíllïn 25,00 kg Pívmecillïnnmhydroklorïd 20,00 kg Hydroxšpropyluwllulouu 0,70 kg Laktou 6,00 kg Ivíaglic-r: i unnzilearzit 0 , 50 kg Metylcellulona 0,30 kg Stärkelse, (Sta-Rx 150063 ) 5,U0 kg Hydroxipropylmetylcellulosa 1,00 kg Framställningsförfarande Pivampicillin och en del av stärkelsen våtgranuleras med en vat- tenlösning av metylcellulosa. Det i svävbäddfiorkade granulatet blandas med resten av stärkelsen och med 1% magnesiumstearat.Example 1 Preparation of l00,000 tablets Ingredients __¿ ________ Pivampïuíllïn 25.00 kg Pívmecillinnm hydrochloride 20.00 kg Hydroxšpropyluwllulouu 0,70 kg Laktou 6,00 kg Ivíaglic-r: i unnzilearzit 0, 50 kg Methylcellulona 0,30 kg Sta-Rx 150063) 5, U0 kg Hydroxypropyl methylcellulose 1.00 kg Preparation process Pivampicillin and part of the starch are wet granulated with an aqueous solution of methylcellulose. The suspended granules are mixed with the rest of the starch and with 1% magnesium stearate.
Detta granulat användes som det första (undre) skiktet i en två- skiktstablett.This granulate was used as the first (lower) layer in a two-layer tablet.
Pivmecillinamhydroklorid och laktos våtgranuleras med en lös- ning av hydroxipropylcellulosa i isopropanol. Det i svävbädd tor- kade granulatet blandas med magnesiumstearat och användes som det andra (övre) skiktet i en tvåskiktstablett. 5 8006592-3 Tabletterna pressas med total fyliviktr 580 ma/tablett första skiktets fyllviktï 310 mg/tablett andra skiktets fyiivikt: 270 mg/tablett cirkulär, l2 mm dia- stans: meter, konvexa ytor Tabletterna förses med filmöverdrag i en svävbäddsanordning, med användning av hydroxipropylmetylcellulosa löst i 25:75 etanolzvat- ten. De med filmöverdrag försedda tabletterna torkas 9 timmar vid 55-Hooc.Pivmecillinam hydrochloride and lactose are wet granulated with a solution of hydroxypropylcellulose in isopropanol. The granulated dried granulate is mixed with magnesium stearate and used as the second (upper) layer in a two-layer tablet. 5 8006592-3 The tablets are pressed with a total fill weight of 580 ma / tablet first layer fill weight 310 mg / tablet second layer fill weight: 270 mg / tablet circular, l2 mm distance: meters, convex surfaces The tablets are provided with a film coating in a fluidized bed device, with use of hydroxypropyl methylcellulose dissolved in 25:75 ethanol water. The film-coated tablets are dried for 9 hours at 55-Hooc.
Exempel 2 Framställning av l00.000 tabletter Ingredienser Pivampicillin 25,00 kg Pivmecillinamhydroklorid 20,00 kg Hydroxipropylcellulosa 0,50 kg flíkrokristallin cellulosa 10,00 kg Mafinosíumutcarat 0,50 kg Metyleellulosa 0,30 kg Stärkelsw (äta-Rx l DÛGÉ ) 3,60 kg Kurhoxïnnflq/lntürknlnn 1,80 kg liyiíp:" }*'_I“¿'3An_::: 1. 1 M_E _rf_1¿ßf_:=_íi'¿}r'f'_.'_1vanílf: i' i vzunpíu I l 1. i n män en tia-l. av ;:1,:'1x'k1:l:;fñvíktygz-:Lxrnif«^r*:'1:í inf-lf? fi? vattwnlönning av metylcßlluløxa. Det torkade granulatet blandas med resten av stärkclsom karboxímetylstärkelsen och 1% magneßiumstcarat.Example 2 Preparation of 100,000 tablets Ingredients Pivampicillin 25.00 kg Pivmecillinam hydrochloride 20.00 kg Hydroxypropylcellulose 0.50 kg flicrocrystalline cellulose 10.00 kg Ma fi nosium mutate 0.50 kg Methyl cellulose 0.30 kg Starchw (eat-Rx 1 DG 1 DÛG 60 kg Kurhoxïnn fl q / lntürknlnn 1,80 kg liyiíp: "} * '_ I“ ¿' 3An _ ::: 1. 1 M_E _rf_1¿ßf _: = _ íi'¿} r'f '_.'_ 1vanílf: i' i vzunpíu I l 1. in men en tia-l. av;: 1,: '1x'k1: l:; fñvíktygz-: Lxrnif «^ r *:' 1: í inf-lf? fi? vattwnlönning av metylcßlluløxa. Det torkade granulatet. mixed with the rest of the starch such as the carboxymethyl starch and 1% magnesium stcarate.
Granulatet användes som det Första (undre):kiktet i en tvåskikts- tablett.The granulate was used as the First (lower): layer in a bilayer tablet.
Pivmecillinamhydroklmüd vâtgranuleras med hydroxipropylcellulosa löst i isopropanol. Det torkade granulatet blandasnæd den mikro- kristallina cellulosan och magnesiumstearatet och användes som det andra (övre) skiktet i en tvåskiktstablett.Pivmecillinam hydrochloride is wet granulated with hydroxypropylcellulose dissolved in isopropanol. The dried granules were mixed with the microcrystalline cellulose and the magnesium stearate and used as the second (upper) layer in a two-layer tablet.
Tabletterna pressas med total fyllvikt: 617 mg/tablett första skiktets fyllvikt: 510 mg/tablett andra skiktets fyllvikt: 507 mg/tablett stans: cirkulär, 12 mm dia- meter,konvexa ytor Tabletterna förses med filmöverdrag i en svävbäddsanordning, med an- vändning av hydroxipropylmetylcellulosa löst i 25:75 etanolzvatten.The tablets are compressed with a total filling weight: 617 mg / tablet first layer filling weight: 510 mg / tablet second layer filling weight: 507 mg / tablet punch: circular, 12 mm diameter, convex surfaces The tablets are provided with film coating in a fluidized bed device, with use of hydroxypropyl methylcellulose dissolved in 25:75 ethanol water.
De sålunda överdragna tabletterna torkas 9 timmar vid 3500.The tablets thus coated are dried for 9 hours at 3500.
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7932902 | 1979-09-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE8006592L SE8006592L (en) | 1981-03-22 |
| SE444887B true SE444887B (en) | 1986-05-20 |
Family
ID=10508005
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8006592A SE444887B (en) | 1979-09-21 | 1980-09-19 | TWO LAYER TABLETS CONTAINING PIVALOYLOXIMETHYL-6 - / (HEXAHYDRO-1H-AZEPIN-1-YL) -METHYLENAMINO / PENICILLANATE AND PIVALOYLOXIMETHYL-6- (D-ALFA-AMINOPHYLENE) |
Country Status (8)
| Country | Link |
|---|---|
| AT (1) | AT371711B (en) |
| AU (1) | AU532764B2 (en) |
| DE (1) | DE3035509A1 (en) |
| FR (1) | FR2465479A1 (en) |
| IT (1) | IT1209809B (en) |
| NL (1) | NL8005252A (en) |
| NZ (1) | NZ194785A (en) |
| SE (1) | SE444887B (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1405866A (en) * | 1919-12-12 | 1922-02-07 | Frank X Ratkovic | Planting machine |
| GB1405886A (en) * | 1971-11-01 | 1975-09-10 | Astra Laekemedel Ab | Synergistic compositions comprising penicillin and cephalosporin antibiotics |
| GB1478598A (en) * | 1974-05-17 | 1977-07-06 | Leo Pharm Prod Ltd | Antibiotic mixture |
-
1980
- 1980-08-27 NZ NZ194785A patent/NZ194785A/en unknown
- 1980-09-15 AT AT0461480A patent/AT371711B/en not_active IP Right Cessation
- 1980-09-19 IT IT8068456A patent/IT1209809B/en active
- 1980-09-19 FR FR8020247A patent/FR2465479A1/en active Granted
- 1980-09-19 AU AU62564/80A patent/AU532764B2/en not_active Ceased
- 1980-09-19 NL NL8005252A patent/NL8005252A/en not_active Application Discontinuation
- 1980-09-19 SE SE8006592A patent/SE444887B/en not_active IP Right Cessation
- 1980-09-19 DE DE19803035509 patent/DE3035509A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| AU532764B2 (en) | 1983-10-13 |
| IT8068456A0 (en) | 1980-09-19 |
| AU6256480A (en) | 1981-04-09 |
| AT371711B (en) | 1983-07-25 |
| ATA461480A (en) | 1982-12-15 |
| FR2465479B1 (en) | 1984-11-02 |
| IT1209809B (en) | 1989-08-30 |
| DE3035509A1 (en) | 1981-04-09 |
| NZ194785A (en) | 1983-05-31 |
| NL8005252A (en) | 1981-03-24 |
| SE8006592L (en) | 1981-03-22 |
| FR2465479A1 (en) | 1981-03-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| NUG | Patent has lapsed |
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