WO2013038323A1 - Compositions pharmaceutiques de céfuroxime axétil à goût masqué - Google Patents

Compositions pharmaceutiques de céfuroxime axétil à goût masqué Download PDF

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Publication number
WO2013038323A1
WO2013038323A1 PCT/IB2012/054686 IB2012054686W WO2013038323A1 WO 2013038323 A1 WO2013038323 A1 WO 2013038323A1 IB 2012054686 W IB2012054686 W IB 2012054686W WO 2013038323 A1 WO2013038323 A1 WO 2013038323A1
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WO
WIPO (PCT)
Prior art keywords
cefuroxime
pharmaceutically acceptable
acceptable salts
pharmaceutical composition
taste masked
Prior art date
Application number
PCT/IB2012/054686
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English (en)
Inventor
Vishwanath Sudhir Nande
Valsaraj EDATHUMPADIKKAL
Original Assignee
Unimark Remedies 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 Unimark Remedies Ltd. filed Critical Unimark Remedies Ltd.
Publication of WO2013038323A1 publication Critical patent/WO2013038323A1/fr

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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—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
    • A61K31/54—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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules

Definitions

  • the present invention relates to a process for preparation of taste masked and non gelling pharmaceutical compositions of Cefuroxime or its pharmaceutically acceptable salts such as Cefuroxime axetil.
  • the present invention further relates to a taste masked non gelling pharmaceutical composition of Cefuroxime or its pharmaceutically acceptable salt.
  • Cefuroxime axetil is a semi synthetic broad spectrum cephalosporin antibiotic for oral administration. Chemically, it is (RS)-l-hydroxyethyl (6R, 7R)-7- [2- (2- furyl) glyoxylamido]-3- (hydroxymethyl)-8-oxo-5-thia-l-azabicyclo [4.2. 0] oct-2-ene-2- carboxylate, 72-(Z)-(0-meth l-oxime), 1-acetate 3-carbamate.
  • Cefuroxime axetil is available as tablet and oral suspension marketed as Ceftin by GSK.
  • the oral suspension is available in dry powder form which, when constituted with water provides 125mg or 250mg of Cefuroxime per 5mL of suspension.
  • Cefuroxime as disclosed in GB 1453049, is a valuable broad spectrum antibiotic. Preparation of Cefuroxime is described in US 3974153. 1-acetoxyethyl ester of Cefuroxime which is known as Cefuroxime axetil improves the effectiveness on oral administration as disclosed in GB 1571683. Preparation of Cefuroxime axetil is described in DE 2706413.
  • Cefuroxime axetil is extremely bitter in taste which is long lasting and makes unpleasant especially for pediatric patients.
  • US 4865851 discloses bitter taste of Cefuroxime axetil may be overcome by the application of integral lipid coatings to Cefuroxime axetil particles which are substantially insoluble in water but which are readily dispersed or dissolved in gastro-intestinal fluid using conventional technique.
  • the coated particles are prepared by atomizing a dispersion of particulate Cefuroxime in the molten lipid and cooling the coated particles. The process is time consuming and requires complicated machinery to perform coating operations with strict control on process parameters such as temperature and pressure.
  • WO 2005002540 discloses dry powder pharmaceutical composition of Cefuroxime axetil with at least one lubricant and at least one glidant.
  • the process of coating involves slugging/compaction. As the dose of the drug is high, the process of slugging/compaction does not provide desired taste masking. Additionally probability of gelling is high, when the reconstituted suspension is stored on shelf due to improper coating by such process. The problem associated with the process of slugging/compaction is that it does not result in proper coating and results in bitter taste. It is also anticipated that on commercial scale, the process may generate heat during compaction and make it difficult to process.
  • US 20090022809 disclose stable taste masked composition of cephalosporin eg. Cefuroxime axetil.
  • the process involves granulation using one or more cephalosporins together with excipient using conventional technique like granulation, extrusion and spheronisation.
  • the problem associated with this technique is multiple processing steps adding complexity and making validation and control difficult.
  • US 20090022809 disclose preparation of core pellets by various known techniques and taste masking with known taste-masking polymers by spray coating.
  • the process involves multiple processing steps and taste masking by polymer spray coating is generally slow and requires rigorous monitoring of temperature and spray rate.
  • excipients yielded a more efficiently taste- masked and non- gelling dry product for constitution with water or other suitable vehicle before use for administration as a suspension, or for direct administration with water or other suitable liquid or formulated with suitable excipients to have a ready-to-use suspension dosage form
  • the principal object of the invention provides a process for preparation of taste masked pharmaceutical composition of Cefuroxime or its pharmaceutically acceptable salts such as Cefuroxime axetil.
  • Another object of the invention is to provide taste masked pharmaceutical composition of Cefuroxime or its pharmaceutically acceptable salts such as Cefuroxime axetil.
  • Yet another object of the invention is to provide a process for preparation of taste masked pharmaceutical composition of Cefuroxime or its pharmaceutically acceptable salts such as Cefuroxime axetil in the form of coated discrete units.
  • Yet another object of the invention provides a process for preparation of taste masked pharmaceutical composition of Cefuroxime or its pharmaceutically acceptable salts such as Cefuroxime axetil in the form of coated discrete units using hot melt extrusion technique comprising a core consisting of Cefuroxime and one or more layer/s comprising lipid in the ratio of 1: 1 to 1: 10.
  • Yet another object of the invention provides a process for preparation of taste masked pharmaceutical composition of Cefuroxime or its pharmaceutically acceptable salts such as Cefuroxime axetil in the form of coated discrete units using hot melt extrusion technique comprising a core consisting of Cefuroxime and one or more layer/s comprising lipid in the ratio of 1 :1 to 1:10, which is non-gelling, readily dispersible suspension upon reconstitution with water.
  • Figure 1 depicts the dissolution profile of the taste masked formulation according to the present invention in 0.1 N HC1.
  • Figure 2 depicts the dissolution profile of the taste masked formulation according to the present invention in pH 4.5 Acetate buffer
  • Figure 3 depicts the dissolution profile of the taste masked formulation according to the present invention in pH 7.0 phosphate buffer.
  • Figure 4 depicts the dissolution profile of the taste masked formulation according to the present invention in pH 7.0 phosphate buffer SUMMARY OF THE INVENTION
  • a taste masked non gelling pharmaceutical composition of Cefuroxime or its pharmaceutically acceptable salts prepared by hot melt extrusion technique comprising the steps of:
  • the present invention relates to a process for preparation of taste masked pharmaceutical composition of Cefuroxime or its pharmaceutically acceptable salts such as Cefuroxime axetil in the form of discrete units using hot melt extrusion.
  • the present invention further relates to taste masked and non gelling pharmaceutical composition of Cefuroxime axetil prepared in accordance with the present invention.
  • Another object of the invention is to provide a process for preparation of taste masked non gelling pharmaceutical composition of Cefuroxime or its pharmaceutically acceptable salts in the form of coated discrete units using hot melt extrusion technique comprising the steps:
  • Another object of the present invention is to provide taste masked non- gelling pharmaceutical composition of Cefuroxime or its pharmaceutically acceptable salts prepared by hot melt extrusion technique comprising the steps:
  • coated discrete units optionally milling and sifting the resultant matrix to form coated discrete units. e. mixing the coated discrete units with one or more pharmaceutically acceptable excipient.
  • the term “Cefuroxime” includes but is not limited to esters, prodrugs, and isomer or its derivative.
  • pharmaceutically acceptable salt includes, but is not limited to, salts of acidic or basic groups that can be present in the compounds provided herein such as axetil.
  • pharmaceutical composition means a mixture containing a therapeutic compound to be administered to a mammal, e.g., a human in order to prevent, treat or control a particular disease or condition affecting the mammal.
  • discrete units comprise pellets, granules, beads, microspheres.
  • pellets comprises spherical as well as non-spherical particles.
  • pharmaceutically acceptable in context with excipient(s) means approved by a regulatory agency of the federal or a state government or listed in recognized pharmacopoeia for use in humans.
  • Hot melt extrusion refers to a process of embedding the bitter drug in hot melt extrudable material, using elevated temperature, dispersing the drug in the matrix at a molecular level providing an efficient coating on bitter drug to mask its taste.
  • hot-melt extrudable refers to a material or mixture of different materials that may be hot-melted and extruded.
  • the material used in the present invention must have a melting point less than the melting point of cefuroxime or its pharmaceutical acceptable salts, preferably lipids.
  • the hot-melt extrusion may be conducted employing a slurry, solid, suspension, liquid, powdered. Dry feed is advantageously employed in the process of the present invention.
  • the term "powder for oral suspension (PFOS)” refers to dry product reconstituted with water or other suitable vehicle before use for administration as a suspension.
  • PFOS powder for oral suspension
  • the hot melt extrusion involves thermal processes with elevated temperatures and the application of shear forces. Upon solidification, the material may be ground into powders for post-processing or cut into tablets, mini-rods or cylinders for post spheronization.
  • Hot-melt extrusion commonly uses single or twin screw extruders of varying sizes and with one or several temperature zones.
  • the energy input by the extrusion system should be sufficient to render the material molten or softened.
  • the applied energy by the extrusion system should not be so great as to cause degradation of the hot melt extrudable material or of the other formulation components.
  • the diameter and shape of the extruded strand is primarily governed by the diameter and geometry of the die orifice, but may also be influenced by the viscoelastic properties of the melt. Circular dies with diameters between 100 and 4000 micrometer are suitable.
  • the extruded strands may be cut into cylindrical pellets or as powders in the hot state or after cooling to room temperature and may further be spheronized.
  • Several technologies have been developed for the subsequent pelletization and spheronization in a continuous or semi-continuous manner and which are well-known in the art.
  • the process of the present invention involves an effective amount of Cefuroxime being mixed with a lipid in a certain ratio depending on the masking ability of a particular lipid.
  • the mixture is then placed in the extruder hopper and passed through the heated area of the extruder at a temperature which will melt or soften the lipid to form a matrix throughout, in which Cefuroxime is dispersed.
  • the hot melt extrusion process employs a feed rate of 1 to 15, preferably 3 to 12, more preferably 6 to 9 hertz; Pressure 10 to 30, preferably 14 to 26, more preferably 16 to 22 torque; Screw RPM 100 to 400, preferably 150 to 350, more preferably 200 to 300.
  • the molten or softened mixture then exits via a die, or other such element, at which time, the mixture (now called the extrudate) begins to harden. Since the extrudate is still warm or hot upon exiting the die, it may be easily shaped, molded, chopped, ground, molded, spheronized into beads, cut into strands or otherwise processed to the desired physical form.
  • the hot melt extrudates may be directly obtained in powder form or other forms of extrudes that can be milled using suitable milling operation to obtain powder form in suitable size range.
  • Extrudate formed using the hot-melt processes of the present invention can be directly obtained in the form of powder or as rod shaped extrudes or granules which can be sized/sifted to suitable size range.
  • Processing aids like adsorbents, lubricants and antioxidants may be employed in the extrusion process.
  • Doses employed for human treatment will typically be in the range 100-3000mg Cefuroxime per day, e.g. 250 to 2000mg Cefuroxime per day for adults and 125 to lOOOmg Cefuroxime per day for children, although the precise dose will depend on inter alia the frequency of administration.
  • the invention relates to a hot melt extrusion process for preparation of taste masked pharmaceutical composition of Cefuroxime or its pharmaceutical acceptable salts thereof in the form of discrete dosage units comprising of a core consisting of Cefuroxime or its pharmaceutically acceptable salts thereof and one or more layers comprising lipid in the ratio of 1 : 1 to 1 : 10.
  • the invention relates to taste masked pharmaceutical composition of Cefuroxime or pharmaceutically acceptable salts thereof prepared by using hot-melt extrusion process in the form of discrete dosage units comprising of a core consisting of Cefuroxime or its pharmaceutically acceptable salts thereof and one or more layers comprising lipid in the ratio of 1 : 1 to 1 : 10.
  • a core consisting of Cefuroxime or its pharmaceutically acceptable salts thereof
  • lipid in the ratio of 1 : 1 to 1 : 10.
  • the process of the present invention provides non-gelling readily dispersible suspensions on shelf which is a typical problem associated with Cefuroxime axetil suspensions.
  • the melting point of the lipid used should be sufficiently high to prevent melting of the coated particles in the mouth, thereby avoiding release of the bitter tasting active ingredient, but not so high that the Cefuroxime axetil active ingredient itself melts and/or degrades chemically during the taste masking process.
  • the lipid or mixture of lipids employed in the present invention will conveniently have a melting point of from 30° to 80°C and preferably from 40° to 70°C where the composition according to the invention contains amorphous Cefuroxime axetil, the melting point of the lipid or mixture of lipids is still more preferably from 45° to 60°C.
  • the lipid coated particles according to the invention will preferably contain lipid in the ratio of 1: 1 to 1: 10 (Cefuroxime axetil: Lipid), more preferably 1 :1 to 1:8, still more preferably to 1:3 or 1:4.
  • Suitable lipids include fatty acids or monohydric alcohols thereof, fixed oils, fats, waxes, sterols, phospholipids and glycolipids.
  • the lipid may, for example, be a high molecular weight (Cio-3o) straight chain saturated or unsaturated aliphatic acid, such as stearic acid or palmitic acid; a triglyceride for example a glyceryl ester of a high molecular weight (C 10-30 ) aliphatic acid, such as glyceryl trilaurate or glyceryl trimyristate; a partially hydro genated vegetable oil such as cottonseed oil or soyabean oil; a wax for example beeswax or carnauba wax; a high molecular weight (C 10-30 ) straight chain aliphatic alcohol such as stearyl alcohol or cetyl alcohol; or a mixture thereof.
  • Mixtures of high molecular weight fatty acids such as mixtures of stearic and palmitic acids, mixtures of high molecular weight straight chain aliphatic alcohols, such as cetostearyl alcohol, mixtures of partially hydrogenated cottonseed and soyabean oils and mixtures of high molecular weight aliphatic acids and glyceryl esters such as a mixture of stearic acid and glyceryl trilaurate may, for example, be used.
  • the present invention may employ a single or mixture of lipids for taste-masking as cited above.
  • the particulate products according to the invention may be used in pharmaceutical compositions for oral administration and may be presented as a suspension for administration, as a dry product for constitution with water or other suitable vehicle before use for administration as a suspension, or for direct administration with water or any other suitable liquid or formulated with suitable excipients to have a ready-to-use suspension dosage form.
  • the taste-masked particles of Cefuroxime axetil of the present invention may be blended with pharmaceutically acceptable excipients.
  • the taste-masked particles of Cefuroxime axetil of the present invention employs lipid for taste masking and optionally a processing aid such as adsorbent or lubricant or an antioxidant in a hot melt extrusion process.
  • the pharmaceutically acceptable excipients used in the present invention can be selected from the group consisting of but not limited to wetting agents, sweeteners, thickening agents, dispersing agents, pH-stabilizing agents, adsorbents, flavouring agents, taste— enhancing agents, preservatives, coloring agents, lubricants and flow aids, antifoaming agents and the like.
  • One excipient can perform more than one function.
  • Wetting agents can include, but are not limited to, surfactants, either singly or in admixture.
  • surfactants include, but are not limited to, the polysorbates, sodium lauryl sulphate, poloxamers and the like.
  • Suitable sweeteners include, but are not limited to, natural sweeteners such as sugars e.g. fructose, glucose, sucrose, sugar alcohols such as mannitol and sorbitol or mixtures thereof and artificial sweeteners such as sucralose, sodium saccharine, sodium cyclamate and aspartame.
  • Suitable thickening agents function as suspending agents and include, but are not limited to, hydrocolloid gums known for such purpose, examples of which include xanthan gum, guar gum, locust bean gum, gum tragacanth, and the like and mixtures thereof.
  • synthetic suspending agents may be used such as sodium carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropylcellulose and the like or mixtures thereof.
  • Dispersing agents include, but are not limited to, colloidal silicon dioxide and surfactants such as sodium lauryl sulphate, polysorbates and the like, wherein the surfactant is used alone or as an admixture with one or more surfactant. Combinations of colloidal silicon dioxide with one or more surfactants can also be used.
  • the composition may also contain a pH-stabilizing agent to maintain a desired pH upon reconstitution, as discussed above.
  • a pH-stabilizing agent encompasses buffers and pH-altering agents. Suitable pH-stabilizing agents include tribasic sodium phosphate, anhydrous sodium carbonate, glycine, citric acid and the like or mixtures thereof.
  • Adsorbents include, but are not limited to, magnesium aluminum silicate (eg. Neusilin ® ), calcium silicate, cellulose, microcrystalhne cellulose, collidal silicon dioxide, magnesium carbonate, wherein the adsorbent is used alone or as an admixture with one or more adsorbent.
  • magnesium aluminum silicate eg. Neusilin ®
  • calcium silicate e.g. Neusilin ®
  • cellulose cellulose
  • microcrystalhne cellulose microcrystalhne cellulose
  • collidal silicon dioxide e.g., magnesium carbonate
  • Flavoring agents are well known to persons skilled in the art and include, but are not limited to, one or more fruity flavors such as tutti frutti.
  • Taste enhancing agents include, but are not limited to, sodium chloride, glycine, citric acid and the like and mixtures thereof.
  • Suitable preservatives include, but are not limited to, benzoic acid and sorbic acid and their salts, methyl paraben, butylparaben, propylparaben and the like.
  • Suitable coloring agents include, but are not limited to, titanium dioxide pigments, lake colors and iron oxide pigments.
  • Lubricants and flow aids such as, but not limited to, talc, stearic acid and its salts as well as its derivatives, calcium silicate and colloidal silicon dioxide can also be used.
  • Antifoaming agents include, but are not limited to simethicone, dimethyl polysiloxane.
  • the excipients can be used at levels well known to the person skilled in the art.
  • the invention has been described with respect to 'stearic acid' as lipid, the invention is applicable to suitable lipid components described herein above.
  • the following Examples illustrate the invention but not limited to the same:
  • Cefuroxime axetil and stearic acid 600-1000 gm was weighed and blended. The mixture was fed in hopper of the hot-melt extruder.
  • the barrel of the hot-melt extruder consisted of seven temperature controlled blocks plus the die which was maintained with set parameters as shown in Example 1 and Example 2 to disperse Cefuroxime axetil in stearic acid and solidified product was collected at the end of the process. Obtained extrudes were milled to appropriate particles and evaluated for taste masking checked for bitter taste and non gelling tendency on reconstitution with water.
  • Example 1 Process Parameters (Temperature in °C)
  • step 2 Blended the material of step 2 and 3 together in a blender for 5 min.
  • composition of the present invention was found to be comparable CEFTIN ®
  • compositions prepared according to the processes described in the present invention were reconstituted with water.
  • the reconstituted suspension thus obtained was acceptable in taste and comparable to CEFTIN® (GSK). It also had a good mouth feel with negligible gritty-feeling in the mouth.
  • Cefuroxime axetil, Colloidal silicon dioxide and Stearic acid mixture two cycles of slug and deslug) and further milling of the slugs showed improper coating of Stearic acid and insufficient taste masking.
  • the ratio (Cefuroxime: stearic acid) used were 1 : 1 and 1 :3. These samples also showed gelling within 24hrs, when placed in water.
  • composition of the present invention was prepared by slugging.

Abstract

L'invention concerne un procédé de préparation de compositions pharmaceutiques de céfuroxime non gélifiantes à goût masqué ou de leurs sels pharmaceutiquement acceptables, tels que le céfuroxime axétil, avec des lipides ou un mélange de lipides pour masquer l'amertume du céfuroxime axétil au moyen d'une technique d'extrusion à chaud. Le procédé consiste : à disperser le céfuroxime axétil dans un lipide fondu ou dans le mélange de lipides, à solidifier le lipide fondu ou le mélange de lipides sur le céfuroxime particulaire ou ses sels pharmaceutiquement acceptables, et à récupérer le lipide ou le mélange de lipides enrobé de particules de céfuroxime. L'invention concerne également une composition pharmaceutique de céfuroxime non gélifiante à goût masqué ou de ses sels pharmaceutiquement acceptables préparée au moyen d'une technique d'extrusion à chaud.
PCT/IB2012/054686 2011-09-13 2012-09-10 Compositions pharmaceutiques de céfuroxime axétil à goût masqué WO2013038323A1 (fr)

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IN2596MU2011 2011-09-13
IN2596/MUM/2011 2011-09-13

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CN103330683A (zh) * 2013-06-26 2013-10-02 神威药业集团有限公司 一种富马酸替诺福韦酯细粒剂
CN103610680A (zh) * 2013-11-07 2014-03-05 深圳致君制药有限公司 一种头孢呋辛酯组合物及其制备方法
CN110302170A (zh) * 2019-06-28 2019-10-08 北京新领先医药科技发展有限公司 一种头孢类抗生素制剂及其制备方法

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GB2204792A (en) * 1987-05-14 1988-11-23 Glaxo Group Ltd Cefuroxime axetil compositions
WO2005002540A2 (fr) 2003-07-01 2005-01-13 Ranbaxy Laboratories Limited Compositions de cefuroxime axetil sous forme de suspensions pharmaceutiques pulverulentes seches
US20060141053A1 (en) * 2004-12-23 2006-06-29 Council Of Scientific And Industrial Research Pharmaceutical composition for improving palatability of drugs and process for preparation thereof
WO2007063552A1 (fr) * 2005-12-02 2007-06-07 Lupin Limited Formulations stables de céphalosporines au goût masqué
US20080187594A1 (en) * 2005-04-25 2008-08-07 Gruenenthal Gmbh Dosage Form With Improved Release Of Cefuroximaxetil
WO2010116385A2 (fr) * 2009-04-08 2010-10-14 Rubicon Research Private Limited Compositions pharmaceutiques pour atténuer un goût désagréable

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US3974153A (en) 1971-05-14 1976-08-10 Glaxo Laboratories Limited 7-Hydrocarbonoxy imino-acetamido-3-carbamoyloxy methylceph-3-em-4 carboxylic acids
GB1453049A (en) 1973-08-21 1976-10-20 Glaxo Lab Ltd Cephalosporing antibiotics
DE2706413A1 (de) 1976-02-16 1977-08-18 Glaxo Lab Ltd Cephalosporinantibiotika, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen
GB1571683A (en) 1976-02-16 1980-07-16 Glaxo Operations Ltd Ester derivatives of cefuroxime
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US4865851A (en) 1987-05-14 1989-09-12 Glaxo Group Limited Pharmaceutical composition comprising cefuroxime axetil
WO2005002540A2 (fr) 2003-07-01 2005-01-13 Ranbaxy Laboratories Limited Compositions de cefuroxime axetil sous forme de suspensions pharmaceutiques pulverulentes seches
US20060141053A1 (en) * 2004-12-23 2006-06-29 Council Of Scientific And Industrial Research Pharmaceutical composition for improving palatability of drugs and process for preparation thereof
US20080187594A1 (en) * 2005-04-25 2008-08-07 Gruenenthal Gmbh Dosage Form With Improved Release Of Cefuroximaxetil
WO2007063552A1 (fr) * 2005-12-02 2007-06-07 Lupin Limited Formulations stables de céphalosporines au goût masqué
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CN103610680B (zh) * 2013-11-07 2015-12-30 国药集团致君（深圳）制药有限公司 一种头孢呋辛酯组合物及其制备方法
CN110302170A (zh) * 2019-06-28 2019-10-08 北京新领先医药科技发展有限公司 一种头孢类抗生素制剂及其制备方法

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