DE2013039A1 - Medicinal tablet for oral administration - Google Patents
Medicinal tablet for oral administrationInfo
- Publication number
- DE2013039A1 DE2013039A1 DE19702013039 DE2013039A DE2013039A1 DE 2013039 A1 DE2013039 A1 DE 2013039A1 DE 19702013039 DE19702013039 DE 19702013039 DE 2013039 A DE2013039 A DE 2013039A DE 2013039 A1 DE2013039 A1 DE 2013039A1
- Authority
- DE
- Germany
- Prior art keywords
- tablet according
- compound
- water
- citrate
- tablet
- 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
- 150000001875 compounds Chemical class 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 15
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 13
- 150000007513 acids Chemical class 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 230000003139 buffering effect Effects 0.000 claims description 8
- -1 5-indanyloxy Chemical group 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 239000002526 disodium citrate Substances 0.000 claims description 6
- 235000019262 disodium citrate Nutrition 0.000 claims description 6
- 229940079896 disodium hydrogen citrate Drugs 0.000 claims description 6
- CEYULKASIQJZGP-UHFFFAOYSA-L disodium;2-(carboxymethyl)-2-hydroxybutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O CEYULKASIQJZGP-UHFFFAOYSA-L 0.000 claims description 6
- 235000019371 penicillin G benzathine Nutrition 0.000 claims description 6
- 229940056360 penicillin g Drugs 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000000084 colloidal system Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 230000001681 protective effect Effects 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 239000002244 precipitate Substances 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 239000001509 sodium citrate Substances 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 3
- 229940038773 trisodium citrate Drugs 0.000 claims description 3
- 241000845082 Panama Species 0.000 claims description 2
- 150000008051 alkyl sulfates Chemical class 0.000 claims description 2
- 125000000129 anionic group Chemical group 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
- 241001398967 Colonia Species 0.000 claims 1
- 229940001468 citrate Drugs 0.000 claims 1
- 239000006185 dispersion Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 229930182555 Penicillin Natural products 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 150000002960 penicillins Chemical class 0.000 description 5
- 239000002775 capsule Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 229930186147 Cephalosporin Natural products 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 229940124587 cephalosporin Drugs 0.000 description 3
- 150000001780 cephalosporins Chemical class 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000004141 Sodium laurylsulphate Substances 0.000 description 2
- 150000008043 acidic salts Chemical class 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 210000002837 heart atrium Anatomy 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 241000237858 Gastropoda Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960003669 carbenicillin Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000016615 flocculation Effects 0.000 description 1
- 238000005189 flocculation Methods 0.000 description 1
- 210000003736 gastrointestinal content Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Description
RECHTSANWÄLTELAWYERS
DR. JUR. DiPL-CHEM. WALTER BEIL DR. JUR. DiPL-CHEM. WALTER BEIL
ALFRED HO-PPENER 1« MärZ 1970ALFRED HO-PPENER 1 «March 1970
DR. JUR. DiPL-CICvA. H.-J. WOLFF ' l0 *DR. JUR. DiPL-CICvA. H.-J. WOLFF ' l0 *
DR. JUR. HANS CrS. "EIL' . J ' DR. JUR. HANS CrS. "EXPRESS ' . J '
FRANKFURTAM MAIN-HÖCHSI FRANKFURTAM MAIN-HÖCHSI
- unsere ITr. 16 210 -- our ITr. 16 210 -
Pfizer Corporation Colon / PanamaPfizer Corporation Colon / Panama
Arzneimitteltablette zur oralen VerabreichungMedicinal tablet for oral administration
Die vorliegende Erfindung betrifft Arzneimittel; sie betrifft insbesondere pharmazeutische Gemische aus pharmakologisch wirksamen Verbindungen zur oralen Verabreichung.The present invention relates to pharmaceuticals; it relates in particular to pharmaceutical mixtures from pharmacologically active compounds for oral administration.
Ein Problem bei der Formulierung einer zur Verabreichung auf oralem Wege bestimmten sauren Verbindung besteht -darin, daß im Magen oder Darm eine ausreichend gute Dispersion der Verbindung sichergestellt werden muß, damit sie gut daraus absorbiert wird und eine pharmakologisch wirksame Konzentration der Verbindung im Blut, des Patienten erreicht wird. Da der Mageninhalt in der Regel starkThere is a problem with the formulation of an acidic compound for administration by the oral route -in that in the stomach or intestines a sufficiently good dispersion of the compound must be ensured so that it is well absorbed from it and a pharmacologically effective concentration of the compound in the blood of the patient is achieved. Because the stomach contents are usually strong
00983 9/213700983 9/2137
BAD ORIGINALBATH ORIGINAL
sauer ist, d.h. einen pH-Wert von nur 1,2 hat, ist eine derartige Verbindung in der^ i.Iagenflüssi^keif nä'-u'i;· unlöslich, und es wird dann besonders wichtig, durch eine geeignete Formulierung der Dosierungsform der Verbindung eine gute Dispersion im Magen sicherzustellen.is acidic, i.e. has a pH of only 1.2, is a Such a compound in the skin fluid, is insoluble, and then it becomes particularly important through a appropriate formulation of the dosage form of the compound ensure good dispersion in the stomach.
Durch Verabreichung der Verbindung in Form einer v/yssrigen Lösung oder eines ilier Salze wird gewöhnlich eine gute Dispersion und eine wirksame Konzentration im Blut erreicht; sie ist jedoch weniger geeignet als eine Verabreichung in Form einer Tablette oder Kapsel. Kapseln, die die feinverteilte Verbindung oder eines ihrer wasserlöslichen Salze allein oder in Verbindung r.it einem Arzneimittel träger enthalten, bewirken gewöhnlich ecenfalls eine gute Dispersion und eins wirksame Konzentration im Blut; es wurde jedoch -refunden, dn.ß einige saure Verbindungen bei Verabreichung in Form von Kapseln eine schlechte Dispersion und geringe Konzentrationen im Blut bewirken. Dies ist vor allem cei^-Carbcxyestersubstituierten Arylmethylpenicillinen der Fell; es wurde gefunden, daß sie bei Verabreichung in Form ein-jr Lösung eines löslichen Salzes .wirksam im iilut absorbiert wurden, während sie bei Verabreichung als Salz in Form einer Kapsel unwirksam waren.By administering the compound in the form of a aqueous solution Solution or one of these salts usually becomes one achieving good dispersion and effective concentration in the blood; however, it is less suitable than administration in the form of a tablet or capsule. Capsules containing the finely divided compound or one of its water-soluble Salts alone or in combination with one Containing excipients usually cause ecenfalls a good dispersion and an effective concentration in blood; It was, however, found, some acidic compounds when administered in capsule form have poor dispersion and low concentrations in the Cause blood. This is especially the case with carbxyester-substituted ones Arylmethylpenicillins of fur; it has been found that when administered in the form of a solution of a soluble salt. were effectively absorbed in the iilut, while when administered as a salt in the form of a Capsule were ineffective.
Tabletten, die durch Verpressen von Gemischen einer Verbindung mit den üblichen Arsrieimittelträgera, beispielsweise Stärke oder lactose hergestellt v/urden, sind gewöhnlich ebenfalls wirksam; es wurde jedoch wiederum gefunden, daß, im Falle der genannten Penicilline, Tabletten der löslichen Salze der genannten Penicilline, die mit solchen Trägern formuliert werden, in den lüagenflüssigkeiten nicht gut dispergieren oder keine wirksameTablets made by compressing mixtures of a compound with the usual Arsrieimmittelträgera, for example Starch or lactose are common also effective; however, it has again been found that, in the case of the penicillins mentioned, tablets the soluble salts of the penicillins mentioned, which are formulated with such carriers, in the layer fluids does not disperse well or not effective
Π 0 9 8 3 ' J / 2 1 3 7Π 0 9 8 3 'J / 2 1 3 7
BADBATH
Konzentration im Blut der Patienten bewirken. . " ■ Cause concentration in the blood of the patient. . "■
Es wurde nunmehr gefunden, daß bei sauren Verbindungen, wie diesen Penicillinen, wirksame Konzentrationen im Blut erreicht werden können, wenn sie in Form von Tabletten, die ein wasserlösliches Salz dieser Verbindung und einen wasserlöslichen Arzneimittelträger enthalten, der bei einem pH-Wert, der größer, ist als der, bei dem die Verbindung aus der wässrigen Lösung ausfällt, eine Pufferwirkung aufweist, oral verabreicht werden. Es wird angenommen, daß dadurch die Bildung einer Schutzschicht der ausgefallenen Verbindung -auf der Oberfläche der Tablette vermieden wird und die Verbindung vor dem Ausfällen gut dispergiert wird.It has now been found that with acidic compounds, like these penicillins, effective concentrations im Blood can be obtained when in the form of tablets, which contain a water-soluble salt of this compound and a water-soluble excipient, that at a pH that is greater than that at which the compound precipitates from the aqueous solution, a Has buffering effect, be administered orally. It will believed that this results in the formation of a protective layer of the precipitated compound -on the surface of the tablet is avoided and the compound is well dispersed before precipitation.
Andere saure Verbindungen, auf die die Erfindung anwendbar ist, sind analoge Cephalosporine, d.h. die*C-Carboxyester-substituierten Arylmethylcephalosporine.Other acidic compounds to which the invention is applicable are analogous cephalosporins, i.e. the * C-carboxyester substituted ones Arylmethylcephalosporins.
Es wurde gefunden, daß es vorteilhaft ist, ein Schutzkolloid sur. Zwecke ler Ausflockung der fein verteilten Verbindung nach der Dispersion in der Kagenflüssigkeit und nach dem Ausfvällen sowie" ein anionisches oder nicht ionisches, oberflächenaktives Kittel zur Förderung der Dispersion in die Formulierung einzuschließen.· Ebenso kann ein bei der Jablettenherstellung gewöhnlich verwendetes Gleitmittel,, beispielsweise I.'agnesiumstearat eingearbeitet werden.It has been found that it is advantageous to use a protective colloid. Purposes of flocculation of the finely divided Compound after dispersion in the neck fluid and after precipitation as well as "an anionic or not include ionic surfactant in the formulation to promote dispersion. · Likewise, may one commonly used in tablet manufacture Lubricant, for example, magnesium stearate incorporated will.
Wie vorstehend erwähnt, soll der Arzneimittelträger bei einem pM-'.Vert, der über dem liegt, bei dem die saure Verbindung ausfällt, eine Pufferwirkung besitzen. Bei demc</-Carboxyeöter-substituierten Ärylmethyl^penicillin oder den «CT-Carboxyester-substituierten Arylmethylcephalosporinen wird das Penicillin oder Cephalosporin bei pH-Werten vonAs mentioned above, the drug carrier is intended to contribute a pM - '. Vert, which is above that at which the acidic compound precipitates, have a buffering effect. In the case of the carboxy-substituted one Arylmethyl penicillin or the CT carboxy ester-substituted aryl methyl cephalosporins the penicillin or cephalosporin at pH values of
009 839/213 7009 839/213 7
etwa 4,8 an aufwärts ausgefällt; geeignete puffernde Arzneimittelträger sind daher wasserlösliche, anorganische saure Salze, wie Natriumcarbonat oder Natriumbicarbonat, die im pH-Bereich von 9 bis 10 bzw, 6 bis 7 eine Pufferwirkung aufweisen, und wasserlösliche organische saure Salze, wie Dinatriumhydrogencitrat, das im pH-Bereich von 5,0 bis 5,5 eine Pufferwirkung besitzt, oder Gemishe aus Dinatriumhydrogencitrat und Trinatriumcitrat, z.B. ein Gemisch in einem Gewichtsverhältnis von 1 zu 5, dessen Pufferwirkung im pH-Bereich von 6,0 bis 6,5 auftritt. Es kann auch jeder andere wasserlöslic -■>, pharmazeutisch verträgliche Arzneimittelträger verwendet werden, der bei einem pH-Wert, der über dem liegt, bei dem die saure Verbindung ausfällt, eine Pufferwirkung aufweist, z.B. Dinntriumhydrogenphosphat, Natriumsuccinat, IT atriummal eat oder KatriuniEialonat. Kaliumsalze sind ebenfalls geeignet.precipitated about 4.8 upwards; suitable buffering Pharmaceutical carriers are therefore water-soluble, inorganic acidic salts such as sodium carbonate or sodium bicarbonate, which have a buffer effect in the pH range from 9 to 10 or 6 to 7 and water-soluble organic acidic salts, such as disodium hydrogen citrate, which are in the pH range from 5.0 to 5.5 has a buffering effect, or Gemishe from disodium hydrogen citrate and trisodium citrate, e.g. a mixture in a weight ratio of 1 to 5, the buffering effect of which occurs in the pH range from 6.0 to 6.5. Any other water-soluble, pharmaceutical Compatible excipients are used which are at a pH above that at which the acidic compound is used fails, has a buffering effect, e.g. Trium hydrogen phosphate, sodium succinate, IT atrium mal eat or Katriuni egg month. Potassium salts are also suitable.
Geeignete Schutzkolloide, die die dispergierte Verbindung ausflocken, sind lolyvinylpyrrolidone, Polyäthylenglycole, Kethylcellulose und andere wasserlösliche Cellulosederivate. Als oberflächenaktive Mittel zur Förderung der Dispersion eignen sich langkettige Alkylsulfate, wie liatriumlaurylsulfat.Suitable protective colloids that flocculate the dispersed compound are polyvinylpyrrolidones, polyethylene glycols, Kethyl cellulose and other water-soluble cellulose derivatives. As a surface active agent for promotion Long-chain alkyl sulfates, such as liatrium lauryl sulfate, are suitable for the dispersion.
Viele der^-Garboxyester-substituierten Arylmethy'lpenicilline, auf die die Erfindung Anwendung findet, wurden in der Britischen Patentschrift 1 133 886 beschrieben und beansprucht. Analogec^-Carboxyester-substituierte Arylmethylcephalosporine wurden irjder Belgischen Patentschrift 729 514 offenbart und beansprucht.Many of the ^ -Garboxyester-substituted Arylmethy'lpenicillins, to which the invention applies have been described and claimed in British Patent 1,133,886. Analog C ^ carboxy ester substituted arylmethylcephalosporins are disclosed and claimed in each Belgian patent specification 729,514.
Die nachstehenden Beispiele dienen der Erläuterung der Erfindung.The following examples serve to illustrate the invention.
009839/2137009839/2137
BADBATH
Das Kaliumsalz deso£-/"~Carbo-(2-iso-propylphenoxy)7 benzylpenicillin wurde zu Tabletten der folgenden Zusammensetzung formuliert:The potassium salt deso £ - / "~ carbo- (2-iso-propylphenoxy) 7 Benzylpenicillin was formulated into tablets of the following composition:
Aktive Verbindung 550 mgActive compound 550 mg
Natriumbicarbonat 200 "Sodium bicarbonate 200 "
Polyvinylpyrrolidon^ ' " 100 "Polyvinylpyrrolidone ^ '"100"
Natriumlaurylsulfat ' ■ " 20 "Sodium Lauryl Sulphate '■ "20"
Magnesiumstearat 14 "Magnesium stearate 14 "
884 " (1) nominaler Molekulargewicht-Bereich 20 000 - 80 000.884 "(1) nominal molecular weight range 20,000-80,000.
Die Bestandteile wurden gut miteinander vermischt, zu Rohlingen (slugs) gepreßt, in Körnchen zerkleine:* und anschließend erneut zu Tabletten gepreßt.The ingredients were mixed well together, too Blanks (slugs) pressed, cut into granules: * and then pressed again into tablets.
Das Natriumsalz des gleichen Penicillinderivats wie in Beispiel 1 wurde gemäß dem gleichen Verfahren, wie in Beispiel 1 beschrieben, zu Tabletten mit der folgenden Zusammensetzung formuliert:The sodium salt of the same penicillin derivative as in Example 1 was prepared according to the same procedure as in Example 1 described, formulated into tablets with the following composition:
Aktive.Verbindung 275 mgActive.compound 275 mg
Natriumbicarbonat 100 "■Sodium Bicarbonate 100 "■
Polyvinylpyrrolidon 50Polyvinyl pyrrolidone 50
Natriumlaurylsulfat ■ 10
Magnesiumstearat 10 "Sodium Lauryl Sulphate ■ 10
Magnesium stearate 10 "
445 "445 "
00 9 83 97-2 1 3 700 9 83 97-2 1 3 7
BM)BM)
Das IT atriums al ζ destC-/~Carbo-(5-indanyloxy)7 benzylpenicillins wurde nacli dem gleichen Verfahren zu Tabletten formuliert. Die Tabletten hatten lie gleiche Zusammensetzung wie die im Beispiel 1 aufgeführten Tabletten.The IT atrium al ζ destC- / ~ carbo- (5-indanyloxy) 7 benzylpenicillin was formulated into tablets according to the same procedure. The tablets had the same composition as the tablets listed in Example 1.
Das ITatriumsalz des gleichen Pen ic illinder ivats wie in den Beispielen 1 und 2 wurde nach dem gleichen Verfahren, wie in Beispiel 1 beschrieben, zu Tabletten mit der folgenden Zusammensetzung formuliert:The sodium salt of the same penic illinder ivate as in Examples 1 and 2 was formulated into tablets with the following composition by the same procedure as described in Example 1:
Aktive Verbindung 275 mg Active compound 275 mg
Dinatriumhydrogencitrat 20 "Disodium Hydrogen Citrate 20 "
Trinatriumcitrat^2' 100 » Trisodium citrate ^ 2 ' 100 »
Polyvinylpyrrolidon^ ' 50 lf Polyvinylpyrrolidone ^ '50 lf
Natriumlaurylsulfat 15" Sodium lauryl sulfate 15 "
Magnesiumstearat 10 "Magnesium stearate 10 "
470 "470 "
(2) wasserfrei(2) anhydrous
Das ITatriumsalz des gleichen Penicillinderivats wie inThe I sodium salt of the same penicillin derivative as in
Beispiel 3 wurde nach den gleichen Verfahren zu I1-? biet tenExample 3 became I 1 -? By the same procedures. offer
formuliert, die die gleiche Zusammensetzung -.vie -lie im Beispiel 4 aufgeführten Tabletten besaßen.formulated the same composition -.vie -lie im Example 4 listed tablets.
0098 'J 0/21370098 'J 0/2137
badbath
Das Natriumsalz des^~/~"Carbo-(4-carbomethoxymethylphenoxy)/benzylpenicillins wurde nach dem gleichen Verfahren zu Tabletten formuliert. Die Tabletten hatten die gleiche Zusammensetzung wie die im Beispiel 4 aufgeführten Tabletten.The sodium salt of carbo- (4-carbomethoxymethylphenoxy) / benzylpenicillin was formulated into tablets by the same procedure. The tablets had them the same composition as those listed in Example 4 Tablets.
Die gemäß den vorstehend genannten Beispielen formulierten Tabletten wurden auf oralem V/ege an Personen verabreicht und bewirkten eine wirksame Konzentration an oC-CarbOxyester-substituiertem: Benzylpenicillin oder an freiem0^—Carboxybenzylpenicillin im Blut, wobei diese Konzentrationen mit denjenigen vergleichbar sind, die durch orale Verabreichung von Lösungen der.natrium- oder Kaliunsalse der gleichen Ester an die gleichen Versuchspersonen erreicht wurden» The Examples above formulated as tablets / ege orally administered to subjects and V caused an effective concentration of oC-carboxy-substituted: benzylpenicillin or Wi 0 ^ -Carboxybenzylpenicillin in the blood, and these concentrations are comparable to those obtained by oral administration of solutions of the sodium or potassium salts of the same esters to the same test subjects were achieved »
009 8 39/2 137009 8 39/2 137
BAD ORܻģBAD ORÜ »Ä £
Claims (9)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB04670/69A GB1291281A (en) | 1969-03-20 | 1969-03-20 | Improvements in pharmaceutical compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2013039A1 true DE2013039A1 (en) | 1970-09-24 |
Family
ID=10045462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19702013039 Pending DE2013039A1 (en) | 1969-03-20 | 1970-03-19 | Medicinal tablet for oral administration |
Country Status (10)
| Country | Link |
|---|---|
| BE (1) | BE747656A (en) |
| DE (1) | DE2013039A1 (en) |
| DK (1) | DK128674B (en) |
| ES (1) | ES377725A1 (en) |
| FI (1) | FI51653C (en) |
| FR (1) | FR2035118B1 (en) |
| GB (1) | GB1291281A (en) |
| IL (1) | IL34089A (en) |
| NL (1) | NL143419B (en) |
| SE (1) | SE379284B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2115116C3 (en) * | 1970-03-27 | 1982-04-15 | Sankyo Co., Ltd., Tokyo | Lubricants and process for their manufacture |
| US3940483A (en) | 1971-02-05 | 1976-02-24 | E. R. Squibb & Sons, Inc. | Antibiotic compositions and method |
| US3969524A (en) * | 1974-08-13 | 1976-07-13 | Hoffmann-La Roche Inc. | Stable amoxicillin dosage form |
| JPS5329936A (en) * | 1976-08-31 | 1978-03-20 | Takeda Chem Ind Ltd | Antibiotic composition |
| EP0012495B1 (en) * | 1978-12-08 | 1983-06-22 | Beecham Group Plc | Pharmaceutical composition comprising a water soluble salt of amoxycillin and polyvinylpyrrolidone, and a vial containing a unit dose of said composition |
| CA2061520C (en) * | 1991-03-27 | 2003-04-22 | Lawrence J. Daher | Delivery system for enhanced onset and increased potency |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2438106A (en) * | 1944-06-09 | 1948-03-23 | Wyeth Corp | Peroral penicillin compositions |
| US2864744A (en) * | 1955-09-02 | 1958-12-16 | American Home Prod | Penicillin in solid dosage unit form |
| US3131123A (en) * | 1959-03-13 | 1964-04-28 | Lab Francais De Therapeutique | Enteric tablets and manufacture thereof |
| GB1276839A (en) * | 1968-08-02 | 1972-06-07 | Sandoz Products Ltd | Antibiotic compositions |
-
1969
- 1969-03-20 GB GB04670/69A patent/GB1291281A/en not_active Expired
-
1970
- 1970-03-16 IL IL34089A patent/IL34089A/en unknown
- 1970-03-19 BE BE747656D patent/BE747656A/en not_active IP Right Cessation
- 1970-03-19 FI FI700775A patent/FI51653C/en active
- 1970-03-19 DK DK138070AA patent/DK128674B/en not_active IP Right Cessation
- 1970-03-19 DE DE19702013039 patent/DE2013039A1/en active Pending
- 1970-03-20 NL NL707004004A patent/NL143419B/en not_active IP Right Cessation
- 1970-03-20 SE SE7003870A patent/SE379284B/xx unknown
- 1970-03-20 FR FR7010069A patent/FR2035118B1/fr not_active Expired
- 1970-03-20 ES ES377725A patent/ES377725A1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| BE747656A (en) | 1970-09-21 |
| FR2035118A1 (en) | 1970-12-18 |
| NL7004004A (en) | 1970-09-22 |
| FI51653C (en) | 1977-03-10 |
| GB1291281A (en) | 1972-10-04 |
| NL143419B (en) | 1974-10-15 |
| IL34089A0 (en) | 1970-05-21 |
| ES377725A1 (en) | 1972-10-16 |
| IL34089A (en) | 1974-05-16 |
| FI51653B (en) | 1976-11-30 |
| FR2035118B1 (en) | 1974-08-30 |
| SE379284B (en) | 1975-10-06 |
| DK128674B (en) | 1974-06-17 |
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