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WO2016088041A1 - Composition de cefpodoxime proxétil à libération prolongée - Google Patents

Composition de cefpodoxime proxétil à libération prolongée Download PDF

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Publication number
WO2016088041A1
WO2016088041A1 PCT/IB2015/059254 IB2015059254W WO2016088041A1 WO 2016088041 A1 WO2016088041 A1 WO 2016088041A1 IB 2015059254 W IB2015059254 W IB 2015059254W WO 2016088041 A1 WO2016088041 A1 WO 2016088041A1
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WO
WIPO (PCT)
Prior art keywords
release
composition
acid
cefpodoxime
extended
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.)
Ceased
Application number
PCT/IB2015/059254
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English (en)
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WO2016088041A8 (fr
Inventor
Harinder Singh
Rachna ANAND
Vivek Sharma
Varinder Kumar
Lalit Kumar KHURANA
Romi Barat Singh
Shavej AHMAD
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.)
Sun Pharmaceutical Industries Ltd
Original Assignee
Sun Pharmaceutical Industries Ltd
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 Sun Pharmaceutical Industries Ltd filed Critical Sun Pharmaceutical Industries Ltd
Priority to BR112017011591A priority Critical patent/BR112017011591A2/pt
Priority to ROA201700339A priority patent/RO132297A2/ro
Priority to RU2017121505A priority patent/RU2017121505A/ru
Priority to MX2017007287A priority patent/MX2017007287A/es
Publication of WO2016088041A1 publication Critical patent/WO2016088041A1/fr
Publication of WO2016088041A8 publication Critical patent/WO2016088041A8/fr
Anticipated expiration legal-status Critical
Ceased 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
    • 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
    • A61K9/20—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
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention relates to a stable extended-release composition of cefpodoxime proxetil and a process for its preparation.
  • the composition comprises cefpodoxime proxetil, a stabilizer, and a release -controlling agent, wherein the composition is characterized by having a pH of less than about 4.
  • the composition is suitable for once-daily dosing for treating bacterial infections.
  • Cefpodoxime proxetil a third generation cephalosporin antibiotic, is known to have poor bioavailability because of its hydrophobic nature and poor aqueous solubility. Further, it has been reported that cefpodoxime exhibits gel formation and forms a gelatinous mass when it is in contact with aqueous media. These factors result in slow and erratic dissolution of the pharmaceutical compositions, which lead to poor bioavailability. Besides, cefpodoxime proxetil is susceptible to degradation in the presence of moisture, heat, and alkaline pH.
  • Cefpodoxime proxetil has been widely used for treatment of infections caused by gram-positive and gram-negative bacteria. It is available in the form of a tablet or granules for oral suspension with a twice-daily dosage regimen.
  • the primary goal of an antibiotic dosage regimen is to maximize the time during which the microorganism is exposed to the drug, since the bactericidal activity correlates more to duration above minimum inhibitory concentration (MIC) than to magnitude of dose. Consequently, it is expected that the concentration of cefpodoxime above the MIC for 40% to 60% duration of dosage interval should achieve optimal clinical results.
  • MIC minimum inhibitory concentration
  • Extended-release compositions of cefpodoxime proxetil remain highly desirable as they maintain therapeutic plasma concentrations of the antibiotic over a prolonged period of time, thereby contributing to better therapeutic action. Further, reducing the frequency of dosage administration leads to enhanced patient compliance.
  • the prior art discloses extended-release compositions of cefpodoxime proxetil with improved dissolution and bioavailability.
  • composition of a beta lactam antibiotic such as cefpodoxime proxetil
  • a mixture of polymers comprising a water soluble N-vinyl-2- pyrrolidone/vinyl acetate copolymer and polysaccharide(s); a release enhancer(s); and other pharmaceutically acceptable excipients.
  • nanoparticulate composition of a cephalosporin such as cefpodoxime proxetil, comprising particles of a cephalosporin with an effective average particle size of less than 2000 nm and at least one surface stabilizer.
  • the present invention provides extended-release compositions of cefpodoxime proxetil which maintain the plasma level over a prolonged period of time.
  • the extended- release compositions are provided with a once-daily dosage regimen which is simple and convenient to use. Further, the extended-release compositions are provided with improved dissolution and reduced gel formation of cefpodoxime proxetil, leading to enhanced bioavailability and stability.
  • the present invention relates to a stable extended-release composition of cefpodoxime comprising cefpodoxime proxetil, a stabilizer, and a release-controlling agent, wherein the composition is characterized by having a pH of less than about 4. It also relates to a process for its preparation. Further, the extended-release composition is suitable for once-daily dosing, which overcomes the problem of multiple administrations, thereby providing enhanced patient compliance.
  • a first aspect of the present invention provides a stable extended-release composition of cefpodoxime comprising cefpodoxime proxetil, a stabilizer, and a release- controlling agent, wherein the composition is characterized by having a pH of less than about 4.
  • the pH of the composition is in a range of about 2 to about 4. In a preferred embodiment of this aspect, the pH of the composition is in a range of about 3 to about 4.
  • a second aspect of the present invention provides a stable extended-release composition of cefpodoxime comprising cefpodoxime proxetil, a stabilizer, and a release- controlling agent, wherein the composition is characterized by having an in-vitro dissolution release profile as determined by USP type II apparatus at 100 r.p.m., in 900 mL of glycine buffer (pH 3) with 0.5% sodium lauryl sulfate at 37°C as follows:
  • a third aspect of the present invention provides a stable extended-release composition of cefpodoxime comprising cefpodoxime proxetil, a stabilizer, and a release- controlling agent, wherein the cefpodoxime proxetil is present in an amount of not more than about 55% w/w based on the total weight of the composition.
  • the stabilizer is a combination of an organic acid and a silicon dioxide.
  • the organic acid and the silicon dioxide are present in a weight ratio of about 1 : 1 to 1 :5.
  • the silicon dioxide and cefpodoxime proxetil are present in a weight ratio of about 1 : 1 to about 1 : 10.
  • the organic acid and cefpodoxime proxetil are present in a weight ratio of about 1 :5 to about 1 :20.
  • the stable extended-release composition of cefpodoxime further comprises one or more pharmaceutically acceptable excipients.
  • the stable extended-release composition of cefpodoxime is administered once daily for treating bacterial infections.
  • a fourth aspect of the present invention provides a process for the preparation of an extended-release composition of cefpodoxime comprising:
  • step (ii) optionally granulating the blend of step (i); (iii) mixing one or more release-controlling agents with the blend of step (i) or the granules of step (ii);
  • step (iv) compressing the mixture of step (iii) to form a tablet
  • step (v) optionally applying a coating comprising one or more film-forming polymers and coating additives onto the tablet of step (iv).
  • extended-release refers to cefpodoxime release over a longer period of time than is ordinarily experienced after administration of a
  • immediate-release cefpodoxime proxetil formulation corresponding immediate-release cefpodoxime proxetil formulation.
  • extended-release refers to the release of cefpodoxime over a period of 6, 8, 12, 16, or 24 hours.
  • cefpodoxime proxetil refers to (RS)- l(isopropoxycarbonyloxy) ethyl (+)-(6R,7R)-7-[2-(2-amino-4-thiazolyl)-2- ⁇ (Z)methoxyimino ⁇ acetamido] -3 -methoxymethyl-8-oxo-5 -thia- 1 -azabicyclo [4.2.0] oct-2- ene-2-carboxylate.
  • the cefpodoxime proxetil used in the extended-release composition of the present invention is present an amount of not more than about 55% w/w based on the total weight of the composition. Particularly, it is present in a range of about 25% to about 55% w/w based on the total weight of the composition.
  • stabilizer means a compound that prevents the degradation of cefpodoxime proxetil.
  • the stabilizer as used herein is a combination of an organic acid and a silicon dioxide. The organic acid and silicon dioxide are present in a weight ratio of about 1 : 1 to 1:5.
  • organic acid refers to a pharmaceutically acceptable organic compound which has acidic properties.
  • the organic acid creates an acidic microenvironment around cefpodoxime proxetil particles. This acidic environment helps to prevent degradation and improve dissolution.
  • Suitable examples of organic acids are selected from the group comprising fumaric acid, citric acid, tartaric acid, oxalic acid, malic acid, succinic acid, ascorbic acid, pyruvic acid, malonic acid, glutaric acid, adipic acid, gluconic acid, lactic acid, and mixtures thereof.
  • the percentage of organic acid used in the extended-release composition of the present invention ranges from about 0.5% to about 15% w/w, based on the total weight of the composition. Further, the organic acid and cefpodoxime proxetil are present in a weight ratio of about 1 :5 to about 1 :20.
  • silicon dioxide refers to a chemical compound which is an oxide of silicon. Silicon dioxide prevents the gel formation of cefpodoxime proxetil as particles of silicon dioxide get evenly distributed between the particles of cefpodoxime proxetil, thereby reducing the electric charge and minimizing the attractive forces responsible for gelation. Additionally, silicon dioxide creates an acidic microenvironment around cefpodoxime proxetil particles, thereby preventing the degradation.
  • the silicon oxide includes both hydrous and anhydrous forms of silicon dioxide.
  • the silicon dioxide can be selected from various available forms such as colloidal silicon dioxide, fumed silica, precipitated silica, light anhydrous silicic acid, silicic anhydride, aluminum magnesium silicate, and mixtures thereof.
  • the percentage of silicon dioxide used in the extended-release composition of the present invention ranges from about l% to about 15% w/w, based on the total weight of the composition. Further, silicon dioxide and cefpodoxime proxetil are present in a weight ratio of about 1 : 1 to about 1 : 10.
  • stable means not more than 10% w/w of total related substances are formed on storage at a temperature of 40°C and a relative humidity of 75% or at a temperature of 25 °C and a relative humidity of 60% for a period of at least three months to the extent necessary for the sale and use of the extended-release cefpodoxime composition.
  • cefpodoxime proxetil with a silicon dioxide and an organic acid is done by conventional methods known in the art.
  • release-controlling agent refers to an agent that helps to control the release of cefpodoxime proxetil. Suitable examples of release-controlling agents are selected from the group comprising cellulosic polymers such as
  • hydroxypropylmethyl cellulose e.g., Hypromellose K4M and Hypromellose K100 LVCR, methyl cellulose, hydroxypropyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, carboxy methylcellulose, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate, cellulose acetate butyrate, cellulose acetate, and cellulose acetate trimellitate; acrylic copolymers such as methacrylic acid copolymers, e.g., Eudragit ® RS, Eudragit ® RL, and Eudragit ® NE 30 D; polyvinyl alcohol; polyvinyl acetate; polyalkylene glycol such as polyethylene glycol; triglycerides; waxes, e.g., Compritol , Lubritab , and Gelucire ® ; lipids
  • the release-controlling agent may control the release of cefpodoxime proxetil based on a matrix or a reservoir system.
  • the percentage of release -controlling agent used in the extended-release composition of the present invention ranges from about 5% to about 30% w/w, based on the total weight of the composition.
  • composition includes tablets, granules, powders, capsules, pellets, and spheroids, in particular tablets.
  • pharmaceutically acceptable excipients refers to excipients that are routinely used in pharmaceutical compositions.
  • the pharmaceutically acceptable excipients may comprise fillers, binders, glidants, disintegrants, lubricants, wetting agents, and combinations thereof.
  • Suitable fillers are selected from the group comprising microcrystalline cellulose, mannitol, sorbitol, lactose, dibasic calcium phosphate, sodium phosphate, kaolin, calcium carbonate, sodium carbonate, calcium sulfate, starch, magnesium oxide, cellulose acetate, dextrates, dextrin, erythritol, maltodextrin, maltose, sodium chloride, and mixtures thereof.
  • Suitable binders are selected from the group comprising polyvinyl pyrrolidone; celluloses, e.g., methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, ethyl cellulose, and sodium carboxy methyl cellulose; polymethacrylates; carboxyvinyl polymers; gums, e.g., acacia, alginic acid, sodium alginate, tragacanth, and guar gum; sugars, e.g., lactose, liquid glucose, sucrose, and dextrin; polydextroses; starch or its derivatives; kaolin; povidone; copovidone;
  • polyethylene oxide polyvinyl alcohol; poly-N-vinyl amide; polyethylene glycol; gelatin; polypropylene glycol; glyceryl behenate; oils, e.g., hydrogenated vegetable oil, castor oil, and sunflower oil; zein; paraffin; higher aliphatic alcohols; higher aliphatic acids; fatty acid esters; fatty acid glycerides; agar; chitosan; maltodextrin; magnesium aluminum silicate; inulin; waxes; and mixtures thereof.
  • oils e.g., hydrogenated vegetable oil, castor oil, and sunflower oil
  • zein paraffin
  • higher aliphatic alcohols higher aliphatic acids
  • fatty acid esters fatty acid glycerides
  • agar chitosan
  • maltodextrin magnesium aluminum silicate
  • inulin waxes; and mixtures thereof.
  • Suitable glidants/lubricants are selected from the group comprising sodium stearyl fumarate, calcium stearyl fumarate, magnesium stearate, aluminum stearate, calcium stearate, zinc stearate, silica, calcium silicate, magnesium silicate, aluminum silicate, colloidal silicon dioxide, polyethylene glycol, poloxamer, cornstarch, talc, polyvinyl alcohol, glyceryl behenate, glyceryl monostearate, glyceryl palmitostearate, potassium benzoate, sodium benzoate, mineral oil, palmitic acid, myristic acid, stearic acid, hydrogenated vegetable oil, sodium lauryl sulfate, and mixtures thereof.
  • Suitable disintegrants are selected from the group comprising cross-linked polyvinyl pyrrolidone (crospovidone); starches, e.g., starch, pregelatinized starch, hydroxypropyl starch, sodium carboxymethyl starch, and sodium starch glycolate;
  • crospovidone cross-linked polyvinyl pyrrolidone
  • starches e.g., starch, pregelatinized starch, hydroxypropyl starch, sodium carboxymethyl starch, and sodium starch glycolate
  • cellulose or its derivatives e.g., low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, carboxymethyl calcium cellulose, and microcrystalline cellulose; gums, e.g., guar gum, sodium alginate, calcium alginate, and alginic acid; ion- exchange resins, e.g., polacrillin potassium; clays, e.g., bentonite and veegum; povidone; cross-linked polyvinyl pyrrolidone; formalin-casein; chitosan; magnesium aluminum silicate; colloidal silicon dioxide; and mixtures thereof.
  • gums e.g., guar gum, sodium alginate, calcium alginate, and alginic acid
  • ion- exchange resins e.g., polacrillin potassium
  • clays e.g., bentonite and veegum
  • povidone cross-linked polyvinyl
  • Suitable wetting agents are selected from the group comprising surfactants such as nonionic, cationic, anionic, and zwitterionic surfactants.
  • Suitable anionic surfactants include those containing carboxylate, sulfonate, and sulfate ions such as sodium lauryl sulfate, sodium laurate, dialkyl sodium sulfosuccinates, particularly bis-(2-ethylhexyl) sodium sulfosuccinate, sodium stearate, potassium stearate, and sodium oleate.
  • Suitable cationic surfactants include those containing long chain cations, such as benzalkonium chloride and bis-2-hydroxyethyl oleyl amine.
  • Suitable non-ionic surfactants include polyoxyethylene sorbitan fatty acid esters; fatty alcohols such as lauryl, cetyl, and stearyl alcohols; glyceryl esters such as the naturally occurring mono-, di-, and tri-glycerides; fatty acid esters of fatty alcohols and other alcohols such as propylene glycol,
  • the extended-release compositions of the present invention can be prepared by any method known in the art, such as blending, dry granulation, wet granulation, direct compression, melt granulation, or extrusion-spheronization.
  • the extended-release compositions of the present invention may further comprise an immediate-release portion of cefpodoxime proxetil.
  • the tablets of the present invention may be coated with one or more non-functional coating layers.
  • the non-functional coating layer comprises one or more film-forming polymers and coating additives.
  • Suitable film-forming polymers are selected from the group comprising cellulose or its derivatives, e.g., hydroxypropylmethyl cellulose, hydroxypropyl cellulose, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, cellulose acetate, hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate, and cellulose acetate trimellitate; waxes, e.g., polyethylene glycol; methacrylic acid polymers, e.g., Eudragit ® ; and polyvinyl pyrrolidone.
  • coating compositions comprising film-forming polymers marketed under various trade names, such as Opadry ® , may also be used.
  • compositions may be selected from the group consisting of film-forming polymers, binders, diluents, plasticizers, opacifiers, coloring agents, lubricants, and pore-formers.
  • Suitable plasticizers are selected from the group comprising triethyl citrate, dibutyl sebacate, acetylated triacetin, tributyl citrate, glycerol tributyrate, acetyl tributyl citrate, diacetylated monoglyceride, rapeseed oil, olive oil, sesame oil, glycerin, sorbitol, diethyl oxalate, diethyl phthalate, diethyl malate, diethyl fumarate, dibutyl succinate, diethyl malonate, dioctyl phthalate, and combinations thereof.
  • Suitable opacifiers are selected from the group comprising titanium dioxide, manganese dioxide, iron oxide, silicon dioxide, and combinations thereof.
  • Suitable pore-formers are selected from the group comprising polyethylene glycols, e.g., polyethylene glycol 6000 and polyethylene glycol 400; celluloses, e.g., hydroxypropylmethyl cellulose, hydroxypropyl cellulose, and methyl cellulose;
  • polysaccharides e.g., alginates, xanthan gum, chitosan, carrageenan, and dextran;
  • polyalkylene oxides e.g., polyethylene oxide; vinyl acetate copolymers; methacrylic acid copolymers; maleic anhydride/methyl vinyl ether copolymers; carboxyvinyl polymers; and combinations thereof.
  • Coating may be performed by applying the coating composition as a
  • solution/suspension/blend using any conventional coating technique known in the art, such as spray coating in a conventional coating pan or fluidized bed processor, dip coating, or compression coating.
  • solvents used for preparing the solution/dispersion of coating substances and for granulation include methylene chloride, isopropyl alcohol, acetone, methanol, ethanol, purified water, and the like.
  • the extended-release composition of the present invention maintains the drug concentration in the blood above MIC for more than 40% of dosing interval so as to achieve the desired clinical effect.
  • Cefpodoxime proxetil, microcrystalline cellulose, fumaric acid, colloidal silicon dioxide, sodium lauryl sulfate, and sodium stearyl fumarate were sifted and blended.
  • step 1 The blend of step 1 was compacted and milled to form granules. 3.
  • Crospovidone, hydroxypropylmethyl cellulose (Hypromellose K4M CR and Hypromellose K100 LVCR), polyvinyl pyrrolidone, and mannitol were sifted and mixed.
  • step 3 The mixture of step 3 was blended with the granules of step 2.
  • step 5 The mixture of step 5 was compressed into a tablet.
  • Opadry ® was dispersed in purified water and stirred to form a dispersion.
  • step 6 was coated with the dispersion of step 7.
  • Example 1 was determined by crushing the extended-release tablet using a mortar and pestle. The crushed powder was transferred to a flask containing 100 mL of purified water. The flask was shaken for 5 minutes and the pH of the medium was measured. The pH of the composition prepared as per Example 1 was found to be 3.21.
  • Cefpodoxime proxetil, microcrystalline cellulose, fumaric acid, colloidal silicon dioxide, sodium lauryl sulfate, and sodium stearyl fumarate were sifted and blended.
  • step 2 The blend of step 1 was compacted and milled to form granules.
  • Crospovidone, hydroxypropylmethyl cellulose, polyvinyl pyrrolidone, and mannitol were sifted and mixed.
  • step 3 The mixture of step 3 was blended with granules of step 2.
  • step 5 The mixture of step 5 was compressed into a tablet.
  • Opadry ® was dispersed in purified water and stirred to form a dispersion.
  • step 6 was coated with the dispersion of step 7. Examples 3-6
  • Cefpodoxime proxetil, microcrystalline cellulose, fumaric acid, colloidal silicon dioxide, sodium lauryl sulfate, and sodium stearyl fumarate were sifted and blended.
  • step 2 The blend of step 1 was compacted and milled to form granules.
  • Crospovidone, hydroxypropylmethyl cellulose (Hypromellose K4M CR and Hypromellose K100 LVCR), polyvinyl pyrrolidone, and mannitol were sifted and mixed.
  • step 3 The mixture of step 3 was mixed with the granules of step 2.
  • step 5 The mixture of step 5 was compressed into a tablet.
  • Cefpodoxime proxetil, microcrystalline cellulose, tartaric acid, colloidal silicon dioxide/aluminum magnesium silicate, sodium lauryl sulfate, and sodium stearyl fumarate were sifted and blended.
  • step 2 The blend of step 1 was compacted and milled to form granules.
  • Crospovidone, hydroxypropylmethyl cellulose (Hypromellose K4M CR and Hypromellose KIOOLVCR), polyvinyl pyrrolidone, and mannitol were sifted and mixed.
  • step 3 The mixture of step 3 was blended with the granules of step 2.
  • Cefpodoxime proxetil, microcrystalline cellulose, fumaric acid, colloidal silicon dioxide, sodium lauryl sulfate, and sodium stearyl fumarate were sifted and blended.
  • step 2 The blend of step 1 was compacted and milled to form granules.
  • Crospovidone, hydroxypropylmethyl cellulose (Hypromellose K4M CR and Hypromellose KIOOLVCR), polyvinyl pyrrolidone, and mannitol were sifted and mixed.
  • step 3 The mixture of step 3 was blended with the granules of step 2.
  • step 5 The mixture of step 5 was compressed into a tablet. 7. Opadry was dispersed in purified water and stirred to form a dispersion.
  • step 6 was coated with the dispersion of step 7.
  • Table 3 Percentage (%) of the In-Vitro Cefpodoxime Release in USP Type II Apparatus (Media: Glycine buffer (pH 3) + 0.5% sodium lauryl sulfate, 900 mL, and 100 r.p.m.)

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Abstract

La présente invention concerne une composition de cefpodoxime proxétil stable à libération prolongée et un procédé pour sa préparation. Cette composition comprend du cefpodoxime proxétil, un stabilisant et un agent de contrôle de libération, la composition étant caractérisée en ce qu'elle possède un pH inférieur à 4 approximativement. Ladite composition est adaptée à un dosage quotidien unique pour le traitement d'infections bactériennes.
PCT/IB2015/059254 2014-12-01 2015-12-01 Composition de cefpodoxime proxétil à libération prolongée Ceased WO2016088041A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
BR112017011591A BR112017011591A2 (pt) 2014-12-01 2015-12-01 composição de liberação prolongada estável, processo para a preparação da composição de liberação prolongada
ROA201700339A RO132297A2 (ro) 2014-12-01 2015-12-01 Compoziţie cu cefpodoxim proxetil cu eliberare extinsă
RU2017121505A RU2017121505A (ru) 2014-12-01 2015-12-01 Композиция цефподоксима проксетила с пролонгированным высвобождением
MX2017007287A MX2017007287A (es) 2014-12-01 2015-12-01 Composicion de cefpodoxima proxetil de liberacion prolongada.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN3489/DEL/2014 2014-12-01
IN3489DE2014 2014-12-01

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WO2016088041A1 true WO2016088041A1 (fr) 2016-06-09
WO2016088041A8 WO2016088041A8 (fr) 2017-01-26

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RO (1) RO132297A2 (fr)
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WO (1) WO2016088041A1 (fr)

Cited By (2)

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CN115813868A (zh) * 2022-12-06 2023-03-21 江西省保灵动物保健品有限公司 一种高溶出头孢泊肟酯片剂及其制备方法
CN117659047A (zh) * 2023-12-05 2024-03-08 上海欣峰制药有限公司 头孢米诺钠化合物的药物制剂及其制备方法

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US20090269400A1 (en) * 2005-05-16 2009-10-29 Elan Pharma International Limited Nanoparticulate and Controlled Release Compositions Comprising a Cephalosporin
US7976871B2 (en) * 2002-08-05 2011-07-12 Torrent Pharmaceuticals Limited Modified release composition of highly soluble drugs
WO2012060786A2 (fr) * 2010-11-05 2012-05-10 Mahmut Bilgic Formulations de proxétil cefpodoxime comprenant un agent de viscosité
WO2012068076A2 (fr) * 2010-11-15 2012-05-24 Dr. Reddy's Laboratories Ltd. Formulations pharmaceutiques contenant des médicaments solubles

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CN115813868A (zh) * 2022-12-06 2023-03-21 江西省保灵动物保健品有限公司 一种高溶出头孢泊肟酯片剂及其制备方法
CN117659047A (zh) * 2023-12-05 2024-03-08 上海欣峰制药有限公司 头孢米诺钠化合物的药物制剂及其制备方法

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RU2017121505A3 (fr) 2019-01-09
WO2016088041A8 (fr) 2017-01-26

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