GB2087235A - A granular delayed-release form of pharmaceutical active substances - Google Patents

A granular delayed-release form of pharmaceutical active substances Download PDF

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Publication number
GB2087235A
GB2087235A GB8133812A GB8133812A GB2087235A GB 2087235 A GB2087235 A GB 2087235A GB 8133812 A GB8133812 A GB 8133812A GB 8133812 A GB8133812 A GB 8133812A GB 2087235 A GB2087235 A GB 2087235A
Authority
GB
United Kingdom
Prior art keywords
pharmaceutical active
active substances
release form
granular delayed
substances according
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
Application number
GB8133812A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis AG
Original Assignee
Ciba Geigy AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Ciba Geigy AG filed Critical Ciba Geigy AG
Publication of GB2087235A publication Critical patent/GB2087235A/en
Pending legal-status Critical Current

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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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Description

SPECIFICATION A granular delayed-release form of pharmaceutical active substances The invention relates to a novel granular delayed-release form of pharmaceutical active substances. It is known that pharmaceutical active substances can be mixed together and coated with coating substances retarding the release of the active substances, the mixture then being processed into the form of granules, which can either be administered directly in this form, or be administered after being filled into capsules or after further processing into tablet form. Granular delayed-release forms of pharmaceutical active substances known hitherto have various disadvantages. There are difficulties in connection with their production: the mode of production is complicated, or the use of organic solvents is necessary, or the auxiliaries used are not ideal with regard to the effect aimed at, namely, the correctly delayed release of active substances.Problems arise also with respect to the external properties of these granules, for example unsatisfactory free flowability or sensitivity to moisture, disadvantages which become unpleasantly evident either with the direct administration, that is to say, with dosing and possibly with the simultaneous taking of food or stimulants, or with the filling of the capsules. The granular delayed-release form of pharmaceutical active substances according to the invention, which form contains granulated or crystalline pharmaceutical active substances, which are coated with coating materials retarding the release of the active ingredients, is characterised in that these coating materials consist essentially of a homogeneous mixture of a polyacrylate which is insoluble but dispersible in water and a cellulose etherwhich is insoluble but dispersible in water. The two coating materials used according to the invention are known individually as coating materials. Each applied on its own is not however suitable for the present invention. The first-mentioned is very thermoplastic and coated granules produced therewith tend to stick together, and the second-mentioned, when used in customary amounts and processing processes, gives in the case of the present mode of application a coating which is insufficiently retarding. It was not therefore possible to anticipate that the combination of the coating materials, individually not suitable for the present purpose, would give a very good result in every respect. The pharmaceutical active-substance granules produced according to the invention are hence free-flowing, insensitive to moisture and neutral in taste, and they produce the desired delayed release of active substance with great uniformity.A microscopic examination has moreover shown that the individual active-substance granule is very evenly ccoated, so that it substantially retains its original shape. It is thus possible with a homogeneous starting material to easily obtain a homogeneous end product. A further advantage of the present invention is that in the production of the products according to the invention the coating materials are used as an aqueous dispersion, a factor ensuring greater safety and less environmental contamination than in the case of the customary coating materials which have to be dispersed in organic solvents. Suitable active ingredients for the granular delayed-release form of pharmaceutical active substances according to the invention are in particular granular or crystalline substances. Especially suitable are solid granules or monocrystals within the range of size of 0.3 - 2 mm (diameter), which have a certain mechanical strength, a property which is of special importance when the coated granules are subsequently to be processed into pressed shapes. Suitable as coating materials are on the one hand in particular polyacrylates of the formula
Substances of this type are obtained by emulsion polymerisation, and they contain the copolymer having a molecular weight of some 100,000 in the formof latex particles with a diameter of around or below 1 Microm. A corresponding product which is particularly suitable is sold by Rohm Pharma GmbH, Darmstadt (Fed. Rep. of Germany) under the name of Eudragit E30D; this is in the form of an aqueous dispersion, and is an ethyl acrylate/methyl methacrylate 70:30 copolymer having a molecular weight of 800,000. And on the other hand the coating material used is preferably ethyl cellulose. A particularly suitable product is that sold by FMC Corporation, Philadelphia, (Pennsylvania, USA) under the name of Aquacoat ECD-30, this being in the form of a 30% aqueous polymeric dispersion having a low particle size (latex form) and a narrow particle-size distribution. The above two coating materials [poly(H + meth)-acrylic acid-(methyl + ethyl) ester and ethyl cellulose] are preferably used in the weight ratio of 2.5 : 1 to 5 : 1, but particularly in the ratio of 3 : 1. It is advantageous to mix in with the granules coated according to the invention small amounts, for example 0.5 to 1%, of colloidal silicon dioxide, for example Aerosil which is marketed by Degussa, Frankfurt (Fed. Rep. of Germany). The free flowability of the granules is improved by this addition. There can naturally be added to the coating-material mixture also other auxiliaries in small amounts, for example dyestuffs or flavouring agents. The pharmaceutical active-substance granules produced according to the invention can be marketed as such, being then used for individual dosing and optionally for incorporation into foodstuffs or stimulants. The commercial preparation would then be contained in customary containers for solids, with or without a dosing device. Capsules are also suitable for the pre-measured administration of the pharmaceutical active-substance granules. The pharmaceutical active-substance granules according to the invention can be produced in a manner known per se, that is, in fluidised-bed spraying apparatus known for this purpose, or in coating pans. The coating-material mixture is fed in as an aqueous dispersion at room temperature, and spraying is best performed with air at a temperature of 25 to 30[deg]C. It is possible to operate according to either the co-current or countercurrent principle; the former is however preferred. The individual granules are readily obtained in this manner, that is to say, no undesirable agglomeration of granules occurs. Surprisingly, the pharmaceutical active-substance granules produced according to the invention can easily be pressed together with a disintegrating agent having good disintegrating and binding properties, and with customary auxiliaries otherwise used for tabletting, within a wide dosage range into moulded shapes, for example tablets, or capsular or rod-shaped compressed products. The formed shapes thus obtained have the property of rapidly disintegrating into separate granules in the stomach of the person being treated and hence becoming well dispersed. A localised overconcentration of the active substance in the digestive tract is in this way prevented, and a uniform, slowly occurring release of active substance dispersed over a large resorption area ensured.It has been established by microscopic examination that the individual granules have scarcely been damaged as a result of compression so that on release of the active substance from the granules, the active substance is able to bring into effect its original advantageous properties virtually completely. When a formed or moulded shape has to be produced with two or more active substances, the individual dyed pharmaceutical active-substance granules can be prepared separately, a factor which improves identification, and which renders the patient aware of the fact that the preparation being taken contains two or more active substances. Suitable as disintegrating agents having binding properties for the formed shapes obtainable according to the invention are in particular crosslinked polyvinyl-polypyrrolidone (PVPP), for example Polyplasdone XL marketed by the GAF Corporation, New York, N.Y. (USA), or Kollidon CL (BASF, Ludwigshafen/Rhein, Fed. Rep. Germany), or sodium carboxymethyl starches, for example Primojel marketed by W.A. Scholten's Chemische Fabriken N.V. Foxhol (NL), or Explotab marketed by E. Mendell Co. Inc., New York (USA). In the case of the auxiliaries customarily used fortabletting, these are in particular binders, lubricants and antisticking agents. The usual tablet-compressing machines can be used for producing the formed shapes obtainable according to the invention. Since the mechanical strength of the formed shapes is surprisingly good, it is possible to produce all the desired customary forms, for example tablets and capsules or rod-shaped moulded products, with or without breaking grooves. These pressed products can be provided if desired with a protective coat of lacquer known for this purpose. All pharmaceutical active substances which can be used for peroral administration and for which a delayed release in the gastro-intestinal tract is desired are essentially suitable, in the form of granules or crystals of an appropriate size, for being processed according to the invention. The present invention is however particularly advantageous with respecctto the use of active substances which, when used at a fairly high concentration, can cause local irritation of the mucous lining of the gastro-intestinal tract, and which are administered in large single doses. This applies for example in the case of potassium chloride administered in the treatment of hypopotassaemia, or in the case of lithium salts in psychotherapy. The following Examples further illustrate the present invention.
Example 1 Composition: perdose perbatch
Production: 1. starting material is potassium chloride: 2. Eudragit E30D and Aquacoat ECD30 are mixed together with slight stirring; 3. 1. sprayed with 2. in a fluidised-bed granulator (fluidised-bed granulator Aeromatik ST 7): - sprayed according to co-current principle, - the mixture of the two dispersions is stirred during the spraying operation, - inlet-air temperature 28[deg]C, - throughput about 8 g/minute; 4. drying at 28[deg]C inlet-air temperature (fluidised-bed dryer ST 7) for about 10 minutes; 5. dry coated granules are mixed with Aerosil 200 for 10 minutes; 6. mixture 5. is sieved, sieve size 1.5 - 2.0 mm. Properties: free-flowing, tasteless, release properties for potassium chloride (Vanderkamp disintegration tester, in water at 37[deg]C): after 1 hour about 24%, after 2 hours about 45% after 4 hours about 81 % after 6 hours about 96%. Filling into gelatin capsules: The granules produced according to Example 1 are filled, by means of a Hofliger and Karg capsule-filling machine GKF 330 having a granule-dosing device (dosing-chamber size 15 mm, 85 r.p.m.) into gelatin capsules (Snap Fit@ [Capsugel AG] or Lok Caps [Elanco], size 0.
Example 2: Composition:
Production: as Example 1 Properties: free flowing, tasteless, release properties for potassium chloride (Vanderkamp disintegration tester, in water at 37[deg]C): after 1 hour about 38% after 2 hours about 74% after 3 hours about 96%.
Example 3 Filling into gelatin capsules: as Example 1 Composition:
Production: 1. starting material: pirprofen; 2. Eudragit E30D and Aquacoat ECD 30 are mixed together with slight stirring; 3. 1. sprayed with 2. in a fluidised-bed granulator Aeromatik Strea 1: - sprayed according to co-current principle, - inlet-air temperature 35[deg]C, - throughput about 8 g/minute; 4. drying at 35[deg]C inlet-air temperature (fluidised-bed dryer Strea 1) for about 10 minutes; 5. dry coated granules are mixed with Aerosil 200 for 10 minutes; 6. mixture 5. is sieved through sieve size 1.5 - 2.0 mm.
Example 4 Round or irregularly shaped particles of a solid melt consisting of diclofenac-sodium (35%), cetyl alcohol (62%) and lecithin (3%) are coated by covering with a lacquer film comprising Eudragit E30D and Aquacoat ECD 30 (ratio of solids 3 parts : 1 part) according to Example 2. These coated particles are subsequently mixed with Aerosil 200, by which means an agglomerating of the coated particles is prevented.

Claims (9)

CLAIMS 1. A granular delayed-release form of pharmaceutical active substances, which form contains a granulated or crystalline pharmaceutical active substance coated with coating materials retarding the release of the active substances and consisting essentially of a homogeneous mixture of a polyacrylate insoluble but dispersible in water and a cellulose ether insoluble but dispersible in water.
1. A granular delayed-release form of pharmaceutical active substances according to Claim 1, wherein the coating-material mixture consists essentially of poly(H + meth)-acrylic acid-(methyl + ethyl) esters and ethyl cellulose in the weight ratio of
2.5 : 1 to 5 : 1.
3. A granular delayed-release form of pharmaceutical active substances according to Claim 2, wherein the mixture ratio of coating materials is 3 : 1.
4. A granular delayed-release form of pharmaceutical active substances according to Claim 1 wherein the coating-material mixture also contains colloidal silicon dioxide.
5. A granular delayed-release form of pharmaceutical active substances according to Claim 1 wherein the pharmaceutical active substance is potassium chloride in the range of size of 0.3-1.2 mm diameter.
6. A granular delayed-release form of pharmaceutical active substances according to Claim 1, wherein the pharmaceutical active sustance is potassium chloride in the range of size of 0.5-1.2 mm diameter.
7. A granular delayed-release form of pharmaceutical active substances according to Claim 1 wherein the pharmaceutical active substance is pirprofen.
8. A granular delayed-release form of pharmaceutical active substances according to Claim 1, wherein the pharmaceutical active substance is diclofenac sodium.
9. A granular delayed-release form of pharmaceutical active substances according to claim 1 substantially as described with reference to any of the Examples.
GB8133812A 1980-11-12 1981-11-10 A granular delayed-release form of pharmaceutical active substances Pending GB2087235A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH839280 1980-11-12

Publications (1)

Publication Number Publication Date
GB2087235A true GB2087235A (en) 1982-05-26

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ID=4339623

Family Applications (1)

Application Number Title Priority Date Filing Date
GB8133812A Pending GB2087235A (en) 1980-11-12 1981-11-10 A granular delayed-release form of pharmaceutical active substances

Country Status (13)

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EP (1) EP0052075A1 (en)
JP (1) JPS57109716A (en)
AR (1) AR229777A1 (en)
AU (1) AU7738181A (en)
DK (1) DK499081A (en)
ES (1) ES8303088A1 (en)
FI (1) FI813531L (en)
GB (1) GB2087235A (en)
GR (1) GR76336B (en)
IL (1) IL64254A0 (en)
NO (1) NO813827L (en)
PT (1) PT73965B (en)
ZA (1) ZA817794B (en)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2157170A (en) * 1984-03-23 1985-10-23 Ciba Geigy Ag Quick-disintegrating pressed shapes
US4600645A (en) * 1985-01-31 1986-07-15 Warner-Lambert Company Process for treating dosage forms
US4600577A (en) * 1983-02-11 1986-07-15 Leo Pharmaceutical Products Ltd. A/S (Lovens Kemiske Fabrik Produktionsaktieselkab) Pharmaceutical preparations of pinacidal
US4728513A (en) * 1985-07-31 1988-03-01 Zyma Sa Granular delayed-release form of pharmaceutically active substances
US4784858A (en) * 1985-08-29 1988-11-15 Zyma Sa Controlled release tablet
US4917900A (en) * 1987-03-27 1990-04-17 Burroughs Wellcome Co. Controlled release formulations containing zidovudine
US4954350A (en) * 1987-03-27 1990-09-04 Burroughs Wellcome Co. Pharmaceutical formulations containing acrivastine
US5478573A (en) * 1992-12-23 1995-12-26 Kinaform Technology, Inc. Delayed, sustained-release propranolol pharmaceutical preparation
WO1999042087A2 (en) * 1998-02-20 1999-08-26 EGIS Gyógyszergyár Rt. Controlled release potassium chloride pellet based pharmaceutical compositions having a high active ingredient content
US6106861A (en) * 1997-07-21 2000-08-22 Laboratoires Prographarm Multiparticulate tablet disintegrating in less than 40 seconds in the mouth
US8062672B2 (en) 2003-08-12 2011-11-22 Shionogi Inc. Antibiotic product, use and formulation thereof
US8246996B2 (en) 2003-08-29 2012-08-21 Shionogi Inc. Antibiotic product, use and formulation thereof
US8299052B2 (en) 2006-05-05 2012-10-30 Shionogi Inc. Pharmaceutical compositions and methods for improved bacterial eradication
US8303988B2 (en) 2000-10-13 2012-11-06 Shionogi Inc. Antifungal once-a-day product, use and formulation thereof
US8313776B2 (en) 2003-07-21 2012-11-20 Shionogi Inc. Antibiotic product, use and formulation thereof
US8313775B2 (en) 2003-07-21 2012-11-20 Shionogi Inc. Antibiotic product, use and formulation thereof
US8357394B2 (en) 2005-12-08 2013-01-22 Shionogi Inc. Compositions and methods for improved efficacy of penicillin-type antibiotics
US8425936B2 (en) 2003-07-21 2013-04-23 Shionogi Inc. Antibiotic product, use and formulation thereof
US8460710B2 (en) 2003-09-15 2013-06-11 Shionogi, Inc. Antibiotic product, use and formulation thereof
US8715727B2 (en) 2004-07-02 2014-05-06 Shionogi Inc. Tablet for pulsed delivery
US8758820B2 (en) 2003-08-11 2014-06-24 Shionogi Inc. Robust pellet
US8778924B2 (en) 2006-12-04 2014-07-15 Shionogi Inc. Modified release amoxicillin products
US8889187B2 (en) 2000-02-24 2014-11-18 Shionogi Inc. Once a day amoxicillin product comprising immediate and delayed release dosage forms

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0153105B1 (en) * 1984-02-10 1992-09-09 Benzon Pharma A/S Diffusion coated multiple-units dosage form
DK62184D0 (en) * 1984-02-10 1984-02-10 Benzon As Alfred DIFFUSION COATED POLYDEPOT PREPARATION
DE3405378A1 (en) * 1984-02-15 1985-08-22 Röhm GmbH, 6100 Darmstadt MEDICINE COVER
JPS6144811A (en) * 1984-08-10 1986-03-04 Ss Pharmaceut Co Ltd Sustained release diclofenac sodium pharmaceutical
ZA86252B (en) * 1985-01-30 1986-09-24 Warner Lambert Co Coated dosage forms
CH666405A5 (en) * 1985-06-24 1988-07-29 Ciba Geigy Ag SOLID, DURABLE PHARMACEUTICAL FORMS WITH ELASTIC FILM COVER.
CH669523A5 (en) * 1986-06-25 1989-03-31 Mepha Ag
US4800087A (en) * 1986-11-24 1989-01-24 Mehta Atul M Taste-masked pharmaceutical compositions
CH675537A5 (en) * 1988-03-25 1990-10-15 Ciba Geigy Ag
DE3838094A1 (en) * 1988-11-10 1990-05-17 Nordmark Arzneimittel Gmbh SOLID PHARMACEUTICAL RETARD FORM
IT1227899B (en) * 1988-12-23 1991-05-14 Poli Ind Chimica Spa TOTAL OR PARTIAL COATING OF PHARMACEUTICAL ACTIVE SUBSTANCES AND RELATED COMPOSITIONS
US20090060995A1 (en) 2005-01-13 2009-03-05 Kamalinder Kaur Singh Dispersible sustained release pharmaceutical compositions
ITMI20010220A1 (en) * 2001-02-05 2002-08-05 Valpharma Sa MULTI-PARTICULAR FORMULATIONS FOR ORAL ADMINISTRATION OF LITHIUM SALTS SUITABLE FOR ADMINISTRATION PER DAY
US11957792B2 (en) 2012-04-19 2024-04-16 Glatt Ag Taste-masked pharmaceutical compositions containing diclofenac
CN112566668A (en) 2018-06-22 2021-03-26 快力胶囊股份有限公司 Enteric hard capsule

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2336218C3 (en) * 1973-07-17 1985-11-14 Byk Gulden Lomberg Chemische Fabrik Gmbh, 7750 Konstanz Oral dosage form
US4140756A (en) * 1976-06-10 1979-02-20 Mead Johnson & Company Film-coated matrix core tablet
LU77353A1 (en) * 1977-05-16 1979-01-19
JPS5535031A (en) * 1978-09-04 1980-03-11 Shin Etsu Chem Co Ltd Enteric coating composition

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4600577A (en) * 1983-02-11 1986-07-15 Leo Pharmaceutical Products Ltd. A/S (Lovens Kemiske Fabrik Produktionsaktieselkab) Pharmaceutical preparations of pinacidal
US4666703A (en) * 1984-03-23 1987-05-19 Ciba-Geigy Corporation Storage-stable, quick-disintegrating pressed shapes containing pharmaceutical active substances
GB2157170A (en) * 1984-03-23 1985-10-23 Ciba Geigy Ag Quick-disintegrating pressed shapes
US4600645A (en) * 1985-01-31 1986-07-15 Warner-Lambert Company Process for treating dosage forms
US4728513A (en) * 1985-07-31 1988-03-01 Zyma Sa Granular delayed-release form of pharmaceutically active substances
US4784858A (en) * 1985-08-29 1988-11-15 Zyma Sa Controlled release tablet
AU592363B2 (en) * 1985-08-29 1990-01-11 Zyma S.A. Controlled release tablet
US4917900A (en) * 1987-03-27 1990-04-17 Burroughs Wellcome Co. Controlled release formulations containing zidovudine
US4954350A (en) * 1987-03-27 1990-09-04 Burroughs Wellcome Co. Pharmaceutical formulations containing acrivastine
US5370880A (en) * 1987-03-27 1994-12-06 Burroughs Wellcome Co. Pharmaceutical formulations containing acrivastine
US5478573A (en) * 1992-12-23 1995-12-26 Kinaform Technology, Inc. Delayed, sustained-release propranolol pharmaceutical preparation
US6106861A (en) * 1997-07-21 2000-08-22 Laboratoires Prographarm Multiparticulate tablet disintegrating in less than 40 seconds in the mouth
CZ299182B6 (en) * 1998-02-20 2008-05-14 EGIS GYOGYSZERGYáR RT. Multiple dosage controlled release pharmaceutical composition in peroral solid form, preferably in tablet or hard gelatin pellet form containing potassium chloride
WO1999042087A2 (en) * 1998-02-20 1999-08-26 EGIS Gyógyszergyár Rt. Controlled release potassium chloride pellet based pharmaceutical compositions having a high active ingredient content
WO1999042087A3 (en) * 1998-02-20 1999-11-25 Egyt Gyogyszervegyeszeti Gyar Controlled release potassium chloride pellet based pharmaceutical compositions having a high active ingredient content
US8889187B2 (en) 2000-02-24 2014-11-18 Shionogi Inc. Once a day amoxicillin product comprising immediate and delayed release dosage forms
US8303988B2 (en) 2000-10-13 2012-11-06 Shionogi Inc. Antifungal once-a-day product, use and formulation thereof
US8425936B2 (en) 2003-07-21 2013-04-23 Shionogi Inc. Antibiotic product, use and formulation thereof
US8313776B2 (en) 2003-07-21 2012-11-20 Shionogi Inc. Antibiotic product, use and formulation thereof
US8313775B2 (en) 2003-07-21 2012-11-20 Shionogi Inc. Antibiotic product, use and formulation thereof
US8758820B2 (en) 2003-08-11 2014-06-24 Shionogi Inc. Robust pellet
US9144548B2 (en) 2003-08-12 2015-09-29 Shionogi Inc. Antibiotic product, use and formulation thereof
US8062672B2 (en) 2003-08-12 2011-11-22 Shionogi Inc. Antibiotic product, use and formulation thereof
US8246996B2 (en) 2003-08-29 2012-08-21 Shionogi Inc. Antibiotic product, use and formulation thereof
US8460710B2 (en) 2003-09-15 2013-06-11 Shionogi, Inc. Antibiotic product, use and formulation thereof
US8715727B2 (en) 2004-07-02 2014-05-06 Shionogi Inc. Tablet for pulsed delivery
US8357394B2 (en) 2005-12-08 2013-01-22 Shionogi Inc. Compositions and methods for improved efficacy of penicillin-type antibiotics
US8299052B2 (en) 2006-05-05 2012-10-30 Shionogi Inc. Pharmaceutical compositions and methods for improved bacterial eradication
US8778924B2 (en) 2006-12-04 2014-07-15 Shionogi Inc. Modified release amoxicillin products

Also Published As

Publication number Publication date
JPS57109716A (en) 1982-07-08
ES506980A0 (en) 1983-02-01
EP0052075A1 (en) 1982-05-19
DK499081A (en) 1982-05-13
NO813827L (en) 1982-05-13
AU7738181A (en) 1982-05-20
PT73965A (en) 1981-12-01
GR76336B (en) 1984-08-04
AR229777A1 (en) 1983-11-30
IL64254A0 (en) 1982-02-28
ES8303088A1 (en) 1983-02-01
PT73965B (en) 1983-11-23
ZA817794B (en) 1982-10-27
FI813531L (en) 1982-05-13

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