WO2011078832A1 - Formulations effervescentes comprenant cefixime - Google Patents

Formulations effervescentes comprenant cefixime Download PDF

Info

Publication number
WO2011078832A1
WO2011078832A1 PCT/TR2010/000262 TR2010000262W WO2011078832A1 WO 2011078832 A1 WO2011078832 A1 WO 2011078832A1 TR 2010000262 W TR2010000262 W TR 2010000262W WO 2011078832 A1 WO2011078832 A1 WO 2011078832A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
composition according
sodium
acid
effervescent
Prior art date
Application number
PCT/TR2010/000262
Other languages
English (en)
Inventor
Mahmut Bilgic
Original Assignee
Mahmut Bilgic
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 Mahmut Bilgic filed Critical Mahmut Bilgic
Publication of WO2011078832A1 publication Critical patent/WO2011078832A1/fr
Priority to US13/532,120 priority Critical patent/US8614315B2/en
Priority to US14/089,355 priority patent/US20140079647A1/en

Links

Classifications

    • 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
    • A61K31/546—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 containing further heterocyclic rings, e.g. cephalothin
    • 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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent

Definitions

  • Cefixime was first described in European patent no EP0030630 (Bl) and it is known with the chemical name of 6R,1R)-1- ⁇ [2-(2-amino-l,3-thiazol-4-yl)-2-
  • Cefixime physically appears as white or light yellow crystal powder. It is freely soluble in methanol and propylene glycol, partially soluble in ethanol and acetone however it does not dissolve in ether, ethyl acetate, hexane and water. Its solubility in aqueous solutions changes with respect to the pH of the solution. Accordingly its solubility in a solution with a pH value of 3.2 is 0.5 mg/mL at room temperature; however when the pH of the solution is increased to 4.2 solubility increases to 18 mg/mL.
  • the product named as SUPRAX that is sold by Fujisawa/Astellas comprises cefixime as active agent and is present in oral tablet or oral suspension forms and in dosages comprising high amounts like 200 mg and 400 mg cefixime.
  • Suprax is indicated for use in the treatment of upper and lower respiratory tract infections, urinary tract infections and infections arising from microorganisms, especially beta-lactamase.
  • Formulations comprising cefixime are generally present in oral tablet or oral suspension forms. In these dosage forms where large amounts of cefixime. that is used as active agent, become bigger in size when formulated with the excipients and this affects the usage negatively. Alternatively, the use of reliable and user-friendly effervescent forms is suggested. In addition to the active agent, some excipients are incorporated into the efervesan formulations comprising cefixime in order to obtain a final product having the desired physical properties. For instance, it. is aimed to bring .hardness of the final product to a desired point and make the product disperse in water effectively by adding at least one binder into the granulation solution during granulation.
  • binder used in the effervescent formulations comprising an antibiotic of cephalosporin group like cefixime affects the physical properties of effervescent forms negatively.
  • binder causes increase the dispersion time of the obtained tablet in water, also some problems are confronted during handling or the hardness of tablets are not become sufficient for effective dispersion. These problems causes ineffective dispersion of the drug in the effervescent form during the use of the final product and thus the absorption and depending on that bioavailability of the product decrease.
  • effervescent formulations which are desirably hard, suitable for carrying and handling and which can disperse in water rapidly. Therefore, it is also seen that these effervescent formulations provide high absorption and bioavailability without confronting the problems observed in the prior art.
  • the present invention is related to the effervescent formulations comprising cefixime used as active agent and the methods for the preparation of these formulations.
  • the ratio of cefixime: binder used in the formulation is in the range of 20: 1 and 8: 1, preferably 17: 1 and 10:1 and more preferably 15: 1 and 11 :1, it was surprisingly seen that effervescent tablets which have the desirable hardness, suitable for carrying and handling and can also disperse in water rapidly were obtained.
  • the first aspect of the present invention is effervescent formulations comprising cefixime and binder in an amount such that cefixime :povidone ratio is in the range of 20: 1 and 8:1, preferably 17: 1 and 10: 1 and more preferably 15:1 and 11 : 1.
  • "Effervescent formulations" term mentioned in the text includes effervescent tablets, effervescent granules and effervescent powders.
  • Binder used in the effervescent formulation in accordance with the present invention can be selected from a group comprising; alginic acid, chitosan, carbomer, carboxymethyl cellulose sodium, dextrin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose ethyl cellulose, gelatine, hypromellose, magnesium aluminium silicate, maltodextrin, polyethylene oxide and povidone or a combination thereof.
  • povidone is used.
  • the present invention is the effervescent formulations comprising cefixime and povidone in an amount such that cefixime :povidone ratio is in the range of 20:1 and 8:1, preferably 17:1 and 10:1 and more preferably 15:1 and 11 : 1.
  • Second aspect of the present invention is use of cefixime in an amount 1-55%, preferably in an amount 5-45% and more preferably in an amount 10-35% in said effervescent formulation.
  • cefixime or its pharmaceutically acceptable salts, hydrates, solvates and/or a combination thereof can be used.
  • cefixime used in the present invention can be present in monohydrate, dihydrate, trihydrate and/or anhydrous form.
  • Another aspect of the invention is pharmaceutical composition comprising cefixime, at least one binder and in addition to that pharmaceutically acceptable excipients.
  • composition formulated in effervescent form in accordance with the present invention comprises cefixime as active agent and at least one binder, preferably povidone and can also include one or more of pharmaceutically acceptable excipients such as effervescent acid and base comprising effervescent couple, sweetener and/or taste regulator, water soluable lubricant, flavoring agent, glidant, diluents, disintegrant, coloring agent, surfactant, anti-foaming agent, humectants, acidic agent, basic agent and stabilizing agent.
  • Effervescent acid used in the present invention can be selected from organic acids such as citric acid, tartaric acid, malic acid, fumaric acid, ascorbic acid, adipic acid and succinic acid. Preferably citric acid is used.
  • Effervescent base used in the present invention can be selected from basic agents such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, potassium bicarbonate, potassium hydrogen carbonate, sodium glycine carbonate, lysine carbonate, arginine carbonate and calcium carbonate.
  • basic agents such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, potassium bicarbonate, potassium hydrogen carbonate, sodium glycine carbonate, lysine carbonate, arginine carbonate and calcium carbonate.
  • sodium hydrogen carbonate is used.
  • Sweetener and/or taste regulator that can be used in effervescent formulations of the present invention can be selected from, but not limited with, a group of acesulfame, aspartame, dextrose, fructose, maltitol, xylitol, saccharine, sodium cyclamate, sucralose, sucrose, saccharin, saccharin sodium, lactitol, maltitol, maltose, sorbitol, sodium cyclamate, sucrose and xylitol or a combination thereof.
  • Lubricant that can be used in effervescent formulations of the present invention can be selected from a group comprising PEG6000 and sodium benzoate.
  • Flavoring agent that can be used in effervescent formulations of the present invention can be selected from, but not limited with, natural aroma oils (peppermint oil, oil of wintergreen, oil of cloves, parsley oil, eucalyptus oil, lemon oil, orange oil), menthol, menthane, anethole, methyl salicylate, eucalyptole, cinnamon, 1 -methyl acetate, sage, eugenol, oxanon, alpha-irison, marjoram, lemon, orange, blackberry, propenyl guaethol acethyl, cinnamon, vanilla, thymol, linalol, cinnamalaldehyde glycerol acethal, N-quadric p-menthan-3-carboxamide, 3,1-methoxy propane 1,
  • Glidant that can be used in effervescent formulations of the present invention can be selected from, but not limited with, sodium lauryl sulfate, sodium benzoate, sodium chloride, sodium acetate, sodium acetate, sodium fumarate, carbowax 4000, L-leucine(17), PEG or a combination thereof.
  • Disintegrant that can be used in effervescent formulations of the present invention can be selected from, but not limited with, a group comprising carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, silicone dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminium silicate and starch or a combination thereof.
  • Diluent that can be used in effervescent formulations of the present invention can be selected from, but not limited with, a group comprising calcium carbonate, calcium sulfate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch and xylitol or combinations thereof.
  • Coloring agent that can be used in effervescent formulations of the present invention can be selected from, but not limited with, caratenoids and chlorophyl and a combination thereof.
  • Surfactant that can be used in effervescent formulations of the present invention can be selected from, but not limited with, sodium lauryl sulfate and magnesium lauryl sulfate and a combination thereof.
  • Anti-foaming agent that can be used in effervescent formulations of the present invention can be selected from, but not limited with, simethicone and dimethyl siloxane, silicone oil or a combination thereof.
  • Humectant that can be used in effervescent formulations of the present invention can be selected from, but not limited with, anhydrous sodium sulphate, silica gel and potassium carbonate or combinations thereof.
  • Acidic agent that can be used in effervescent formulations of the present invention can be selected from, but not limited with, a group of acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid or combinations thereof.
  • Basic agent that can be used in effervescent formulations of the present invention can be selected from, but not limited with, a group of potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium bicarbonate, or combinations thereof.
  • Stabilizing agent that can be used in effervescent formulations of the present invention can be selected from agents such as antioxidants, chelating agents, alkalinizing agents and photo- protectors.
  • Antioxidants can be selected from some substances such as butylated hydroxyanisole (BHA), sodium ascorbate, butylated hydroxytoluene (BHT), sodium sulfite, gallates (like propil gallates), tocoferole, citric acid, malic acid, ascorbic acid, acetylcysteine, fumaric acid, lecithin, ascorbil palmitate, ethylenediamine tetraacetate.
  • Chelating agents can be selected from disodium EDTA, edetic acid, citric acid, sodium citrate, potassium citrate or their combinations.
  • Alkalinizing agents can be selected from the organic compounds such as sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, sodium silicate, disodium hydrogen orthophosphate, alkali metal salts like sodium aluminate; calcium carbonate, calcium hydroxide, dibasic calcium phosphate, calcium sulfate, calcium acetate, calcium gluconate, calcium glycerophosphate, magnesium carbonate, magnesium hydroxide, magnesium sulfate, magnesium acetate, magnesium silicate, the alkaline earth metal salts like magnesium aluminate, primary, secondary and tertiary amines, cyclic amines, ⁇ , ⁇ '-dibenzylethylenediamin, dietanolamine, ethylenediamin, meglumine, monosodium glutamate, polacrilin sodium, sodium alginate.
  • Photo-protecting agents can be selected from metal oxides such as titanium oxide, iron oxide or zinc oxide.
  • “Final product” means the final state of drug, which is ready for use and is obtained by the process wherein the formulations comprise at least one antibiotic in effervescent dosage form.
  • cefixime in an amount of 1-55%
  • effervescent couple in an amount of 10-85%
  • sweetener in an amount of 0.2-6%
  • binder in an amount of 0.2-15%
  • water soluble lubricant in an amount of 0.2- 5%
  • flavoring agent in an amount of 0.2-6%
  • Another aspect of the present invention is the use of the pharmaceutical composition prepared in accordance with said invention in the treatment of the diseases of upper respiratory tract infections such as pharyngitis, tonsillitis and otitis media, lower respiratory tract infections such as acute pneumonia, acute and chronic bronchitis and urinary tract infections such as acute cystitis, cystourethritis.
  • upper respiratory tract infections such as pharyngitis, tonsillitis and otitis media
  • lower respiratory tract infections such as acute pneumonia, acute and chronic bronchitis
  • urinary tract infections such as acute cystitis, cystourethritis.
  • Another aspect of the invention is related to processes for use in the preparation of effervescent tablet and granules comprising cefixime. Said process comprises use of wet and/or dry granulation techniques present in the state of the art.
  • a process for the preparation of the effervescent formulation in accordance with the present invention comprises granulation of cefixime, effervescent couple, sweetener and binder with water or an aqueous solution, drying of the formed granules, mixing dried granules with flavoring agent and water soluble lubricant and optionally compressing the formed mixture in tablet pressing machine.
  • efervescent formulations in accordance with the present invention can be prepared according to the following examples.
  • a granulation solution comprising water and/or optionally another solvent is prepared.
  • the mixture comprising cefixime, effervescent base, effervescent acid, sweetener and binder is added to the fluid bed dryer and granulated with the granulation solution. Dried granules are mixed with flavoring agent and water soluble lubricant. Finally, obtained mixture is optionally compressed in the tablet pressing machine.

Landscapes

  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cephalosporin Compounds (AREA)

Abstract

La présente invention concerne des formulations effervescentes et leur préparation.
PCT/TR2010/000262 2009-12-25 2010-12-24 Formulations effervescentes comprenant cefixime WO2011078832A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US13/532,120 US8614315B2 (en) 2009-12-25 2012-06-25 Cefdinir and cefixime formulations and uses thereof
US14/089,355 US20140079647A1 (en) 2009-12-25 2013-11-25 Cefdinir and cefixime formulations and uses thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2009/09786 2009-12-25
TR2009/09786A TR200909786A1 (tr) 2009-12-25 2009-12-25 Sefiksim içeren efervesan tablet ve granül formülasyonu.

Related Child Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2010/000261 Continuation-In-Part WO2011078831A1 (fr) 2009-12-25 2010-12-24 Compositions pharmaceutiques améliorées comprenant cefdinir

Publications (1)

Publication Number Publication Date
WO2011078832A1 true WO2011078832A1 (fr) 2011-06-30

Family

ID=43532584

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/TR2010/000241 WO2011078821A1 (fr) 2009-12-25 2010-12-03 Comprimé effervescent et formulation granulaire comprenant cefixime
PCT/TR2010/000262 WO2011078832A1 (fr) 2009-12-25 2010-12-24 Formulations effervescentes comprenant cefixime

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/TR2010/000241 WO2011078821A1 (fr) 2009-12-25 2010-12-03 Comprimé effervescent et formulation granulaire comprenant cefixime

Country Status (3)

Country Link
EP (1) EP2515849A1 (fr)
TR (2) TR200909786A1 (fr)
WO (2) WO2011078821A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103976894A (zh) * 2013-02-12 2014-08-13 强生消费者公司 使用黑莓提取物增强发质的方法和组合物
CN104366648A (zh) * 2014-10-21 2015-02-25 宣城柏维力生物工程有限公司 甜橙vc泡腾片
CN113440530A (zh) * 2021-07-08 2021-09-28 广州白云山医药集团股份有限公司白云山制药总厂 一种头孢克肟药物及其制备方法

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103494821B (zh) * 2013-10-01 2018-09-25 迪沙药业集团有限公司 一种头孢克肟组合物
CN111544412B (zh) * 2020-04-17 2022-06-24 广州白云山医药集团股份有限公司白云山制药总厂 头孢克肟组合物及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0030630B1 (fr) 1979-11-19 1987-04-01 Fujisawa Pharmaceutical Co., Ltd. Dérivés de l'acide 7-acylamino-3-vinyl céphalosporanique, procédé pour leur préparation, compositions pharmaceutiques les contenant; leurs produits de départ et leur préparation
US20020051816A1 (en) * 1996-02-29 2002-05-02 Hisami Yamaguchi Beta-lactam antibiotic-containing tablet and production thereof
CN1850087A (zh) * 2006-03-07 2006-10-25 中国药科大学 一种含有头孢克肟的泡腾片及制法
CN101606913A (zh) * 2009-07-16 2009-12-23 广州白云山制药股份有限公司广州白云山制药总厂 头孢克肟分散片及其制备方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3887179T2 (de) 1987-03-02 1994-06-16 Brocades Pharma Bv Pharmazeutische Zusammensetzung, pharmazeutisches Granulat und Verfahren zu ihrer Herstellung.

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0030630B1 (fr) 1979-11-19 1987-04-01 Fujisawa Pharmaceutical Co., Ltd. Dérivés de l'acide 7-acylamino-3-vinyl céphalosporanique, procédé pour leur préparation, compositions pharmaceutiques les contenant; leurs produits de départ et leur préparation
US20020051816A1 (en) * 1996-02-29 2002-05-02 Hisami Yamaguchi Beta-lactam antibiotic-containing tablet and production thereof
CN1850087A (zh) * 2006-03-07 2006-10-25 中国药科大学 一种含有头孢克肟的泡腾片及制法
CN101606913A (zh) * 2009-07-16 2009-12-23 广州白云山制药股份有限公司广州白云山制药总厂 头孢克肟分散片及其制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 200729, Derwent World Patents Index; AN 2007-293208, XP002621234 *
DATABASE WPI Week 201007, Derwent World Patents Index; AN 2010-A27982, XP002630963 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103976894A (zh) * 2013-02-12 2014-08-13 强生消费者公司 使用黑莓提取物增强发质的方法和组合物
US8962041B2 (en) * 2013-02-12 2015-02-24 Johnson & Johnson Consumer Companies, Inc. Methods and compositions for enhancing hair quality using blackberry extract
US9084810B2 (en) 2013-02-12 2015-07-21 Johnson & Johnson Consumer Companies, Inc. Methods and compositions for enhancing hair quality using blackberry extract
US9789150B2 (en) 2013-02-12 2017-10-17 Johnson & Johnson Consumer Inc. Methods and compositions for enhancing hair quality using blackberry extract
CN104366648A (zh) * 2014-10-21 2015-02-25 宣城柏维力生物工程有限公司 甜橙vc泡腾片
CN113440530A (zh) * 2021-07-08 2021-09-28 广州白云山医药集团股份有限公司白云山制药总厂 一种头孢克肟药物及其制备方法
CN113440530B (zh) * 2021-07-08 2023-08-08 广州白云山医药集团股份有限公司白云山制药总厂 一种头孢克肟药物及其制备方法

Also Published As

Publication number Publication date
TR200909786A1 (tr) 2011-07-21
EP2515849A1 (fr) 2012-10-31
WO2011078821A1 (fr) 2011-06-30
TR201003856A1 (tr) 2011-08-22

Similar Documents

Publication Publication Date Title
EP2528594B1 (fr) Formulations effervescentes contenant de la céphalosporine de deuxième génération
JP2008528501A (ja) 固体投与形中のテトラサイクリン金属錯体
WO2011078832A1 (fr) Formulations effervescentes comprenant cefixime
WO2011142731A2 (fr) Formulations comprenant une céphalosporine et un acide clavulanique de troisième génération
EP2515860B1 (fr) Compositions pharmaceutiques améliorées comprenant cefdinir
US20130129791A1 (en) Preparations of effervescent formulations comprising second and third generation cephalosporin and uses thereof
WO2011139249A2 (fr) Composition pharmaceutique renfermant du cefdinir
EP2568957A1 (fr) Composition pharmaceutique comprenant la céfixime et un composé dérivé de l'acide clavulanique
WO2011093831A2 (fr) Formulations effervescentes contenant du cefprosil comme principe actif
WO2011129792A1 (fr) Formulations dispersibles dans l'eau comprenant le cefpodoxime proxétil
EP2515858A1 (fr) Composition pharmaceutique très pure
WO2011139251A1 (fr) Compositions pharmaceutiques comprenant du cefditorène pivoxil
WO2011078830A1 (fr) Formulation effervescente à dispersion rapide
WO2011093821A1 (fr) Formulations effervescentes comprenant du cefdinir et de l'acide clavulanique
EP2566450A2 (fr) Compositions pharmaceutiques comprenant du céfétamet
WO2012060787A1 (fr) Comprimés contenant du cefdinir
WO2012060791A2 (fr) Procédé de production de compositions pharmaceutiques comprenant du cefdinir
WO2012060792A1 (fr) Compositions pharmaceutiques comprenant au minimum 6% en poids de délitants
WO2012060789A2 (fr) Procédé de production de formulations de cefdinir
WO2012078121A2 (fr) Forme posologique orale solide comprenant cefdinir

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10809258

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10809258

Country of ref document: EP

Kind code of ref document: A1