AU2002328168B2 - Novel pharmaceutical composition of ceftiofur - Google Patents

Novel pharmaceutical composition of ceftiofur Download PDF

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Publication number
AU2002328168B2
AU2002328168B2 AU2002328168A AU2002328168A AU2002328168B2 AU 2002328168 B2 AU2002328168 B2 AU 2002328168B2 AU 2002328168 A AU2002328168 A AU 2002328168A AU 2002328168 A AU2002328168 A AU 2002328168A AU 2002328168 B2 AU2002328168 B2 AU 2002328168B2
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oil
oily suspension
ceftiofur
resuspendibility
suspension
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AU2002328168A1 (en
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Kour Chand Jindal
Majid Razzak
Nilendu Sen
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Merial Ltd
Orchid Health Care
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Merial Ltd
Orchid Health Care
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Priority claimed from PCT/IB2002/003165 external-priority patent/WO2004014390A1/en
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Assigned to ORCHID HEALTH CARE, MERIAL LTD. reassignment ORCHID HEALTH CARE Request for Assignment Assignors: ANCARE NEW ZEALAND LTD., ORCHID HEALTH CARE
Priority to AU2008229988A priority Critical patent/AU2008229988A1/en
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    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

WO 2004/014390 PCT/IB2002/003165 1 NOVEL PHARMACEUTICAL COMPOSITION OF CEFTIOFUR TECHINICAL FIELD This invention relates to a novel pharmaceutical composition comprising cephalosporin antibiotic or its pharmaceutically acceptable salts. Particularly the invention relates to oily suspension of Ceftiofur or its pharmaceutically acceptable salts. More particularly the present invention provides oily suspension of Ceftiofur hydrochloride, which has improved properties, such as resuspendibility and chemical stability.
BACKGROUND ART Ceftiofur is a third generation Cephalosporin antibiotic, which is administered to cattl4 and svine for control of bacterial infections of the respiratory tract. It is used in veterinary medicine as both, the sodium salt and the hydrochloride salt. It is administered intra nuscular y to cattle and swine. It is also intended to be used as crystalline free acid f6r intramusc lar and subcutaneous administration in cattle and swine. Ceftiofur is poorly absorbed a er oral administration while rapidly absorbed after intramuscular administratio The Ceftiofur hydrochloride intramuscular injection is an oily suspension.
A sus ension is a particular class or type of dispersion system in which the internal or suspended phase is dispensed uniformly with mechanical agitation through out the external phase, called the suspending medium or vehicle. The internal phase, consisting of a homogenous or heterogeneous distribution of solid particles having a specific range of sizes, these particles are maintained uniformly in time throughout the suspending vehicle with the aid of a single, or a particular combination of suspending agents.
The three general classes of phanmaceutical suspensions are orally administered suspensions, externally applied suspensions (topical) and injectable (parenterals) susp nsions (Ref: A Martin P Bustamante, Coarse Dispersion in physical pharmacy 45 th edn. Lea andiFebiger, Philadelphia, 1993, PP 117 124). The Parenteral suspensions are designed fo! intramuscular, intradermal, intralesional, intraarticular or subcutaneous admnistration. Common vehicles for parenteral suspensions include preserved sodium chloide solution or a parenterally acceptable vegetable oil.(Ref: J P Partnoff, E M Cohen M M Henlay, Development of Parenteral and Sterile ophthalmic suspensions, Bull.
Parenter. Drug Assoc 31 136-143 (1977)).
The stability of suspensions is complicated by the fact that the physical stability of pharnaceutical suspensions and the factors affecting such stability are equally important to WO 2004/014390 PCT/IB2002/003165 2 chemical stability. This i's based on the fact that since a suspension exists in more than one state (liquid and solid), there are different ways in which the system can undergo either chemical or physical change (Ref: T Higuchi, some physical chemical aspects of suspension formulation, J. Am. Pharm. Assoc. Sci Ed; 47: 657-660 (1958)).
Haines Martin, Hiestand and Econow Coworkers (Ref: J. Pharm. Sci., 61; 268 272, (1972) and J. Pharm. Sci., 52; 757 762, 1031-1038, (1963)) and are generally credi ed with establishing the structured particle concept or flocculated pharmaceutical suspension.
The fllowing definitions will prove useful in differentiating the three closely relatd terms; flocculation, agglomeration and coagulation.
Flocc lation refers to the formation of a loose aggregation of discrete particles held tdget er in network-like structure either by physical absorption of macromolecules, brid ing durin g chemical interaction, or when the longer range Vander Waals forces of attraction exceeds the shbrter range force of repulsion.
In agglomeration, a large number of particles are closely bound together as aggregates either in a dry or liquid state.
Coagulation or flocculation refers to the massing of particles in a liquid state alone and sometimes in the form of a fluid gel structure.
The main advantages of the stable flocculated systems are as follows: 1. The aggregates tend to break up easily under the application of a small amount of shea stress such as gentle agitation of a bottle or vials or by the flow through a small orifice (hypodermic needle and for syringe) 2J In co trast to deflocculated systems, the stable flocculation will settle rapidly and may be easily resuspended even after standing for prolonged time period of storage.
3. The table flocculation can be; produced if required by employing aseptic techliques u ing vehicle components that are safe for intramuscular injection.
There, are several methods of producing flocculated pharmaceutical suspensions.
The ihoice of method depends on the properties of the drug and the class of suspension desired.
The relevant prior art methods, which teach adaptation of diverse methods of preparation, are as follows.
US Patent No. 5,736,151 claims a pharmaceutical composition comprising Ceftiofur HC1 water. This patent claims a pharmaceutical composition comprising a Ceft ofur H 1, a biocompatible oil (selected from canola oil, corn oil, cottonseed oil, olive 00 3 oil, peanut oil, sesame oil, soybean oil, safflower oil, coconut oil, sunflower oil and palm oil) and water present in an amount between 0.25% and 20.20% of the composition as a flocculating agent in order to have better resuspendibility than the formulation having no water.
U.S. Pat. No. 4,902,683, discloses crystalline hydrochloride and hydrobromide 00 salts of the cephalosporin antibiotic, Ceftiofur, processes for their manufacture, and pharmaceutical compositions thereof This patent discloses preparations for systemic 00 ,I administration, which include carriers, vehicles, diluents, surfactants, excipients, preservatives, isotonic agents and the like.
In order to achieve an improved pharmaceutical composition, applicants have conducted lot of experiments with different composition, studied their resuspendability, chemical stability, and finally come out with a new composition with desired results.
The present invention is based on Applicants observation that when a resuspendibility enhancer is added to the oily suspension the resuspendibility of the suspended particles is improved dramatically, thus giving a better physical stability to the oily suspension.
Applicants have also observed the chemical stability of the oily suspension is improved with the decrease in the moisture content. In addition, applicants have initiated formulation trials to stabilize the suspension physically and chemically using agents such as polyoxyl hydrogenated castor oil, polyoxyl castor oil, glycerol, propylene glycol, polyethylene glycol, alcohols and the like. Different formulations were kept in stoppered cylinders and the rate of sedimentation was calculated. The comparative sedimentation ratio (Ratio of sedimentation volume to total volume of the suspension) of different batches of Ceftiofur hydrochloride is shown in Figure 1.
OBJECTIVE OF THE INVENTION It is desirable that the present invention provides a suspension of Ceftiofur or its pharmaceutically acceptable salts which has high physico-chemical stability and easy to administer.
It is also desirable that the present invention provides a physically stable suspension using resuspendibility enhancers and a chemically stable suspension by reducing the moisture content.
It is also desirable the present invention provides a suspension with adequate dispersion of the particles in the vehicle.
It is also desirable that the present invention provides a suspension which does not form caking of the dispersed particles in the sediment which is difficult to redisperse.
216551_l.doc 00 4 SSUMMARY OF THE INVENTION Accordingly, the present invention relates to an oily suspension comprising ceftiofur or its pharmaceutically acceptable salts, at least a biocompatible oil, a wetting agent, a dispersing agent, a resuspendibility enhancer, 0 o wherein the resuspendibility enhancer is not water.
SPreferably the said composition comprises of 0.025% to 1.0% by weight of oO Ci wetting agent, 0.05% to 2.5% by weight of dispersing agent and 0.05% to 10% by C weight of a resuspendibility enhancer.
More preferably, the said composition comprises of 0.025% to 0.1% by weight c of a wetting agent, 0.05% to 0.5% by weight of dispersing agent and 0.05% to 10% by weight of a resuspendibility enhancer.
In a further related aspect, the invention provides a process for the preparation of novel oily suspension of ceftiofur or its pharmaceutically acceptable salt, said process comprising steps of: i) heating a biocompatible oil to a temperature in the range of 40°C to 160°C, based on the dosage form, ii) adding a wetting agent, to step liquid and allowing to cool with stirring, iii) adding a dispersing agent and a resuspendibility enhancer to step (ii) mixture with stirring, if required, iv) stirring the mixture at about 160°C up to 2 hrs, v) adding Ceftiofur or its pharmaceutically acceptable salt to step (iv) mixture and mixing well with stirring, vi) homogenizing step mixture using a suitable homogenizer and vii) filling in the primary packaging components, and wherein the resuspendibility enhancer is not water.
BRIEF DESCRIPTION OF ACCOMPANYING DRAWING Figure 1 represents a graphical representation of sedimentation rate of various formulae using different flocculating agents.
DETAILED DESCRIPTION OF THE INVENTION In accordance, applicants have initiated formulation trials to stabilize the suspension physically and chemically using agents such as polyoxyl hydrogenated castor oil, polyoxyl castor oil, glycerol, propylene glycol, polyethylene glycol, alcohols 216551_1.doc WO 2004/014390 PCT/IB2002/003165 was balculated. The comparative sedimentation ratio (Ratio of sedimentation volume to total volume of the suspension) of different batches of Ceftiofur hydrochloride is shown in Figure 1.
In an embodiment of the present invention provides an oily suspension comprising ceftidfur or its pharmaceutically acceptable salts, at least a biocompatible oil, a wetting agent, a dispersing agent, a resuspendibility enhancer and optionally acceptable excipients.
In another embodiment of the present invention, there is provided an injectable suspension, which has improved physical stability using resuspendibility enhancers.
In stilt another embodiment of the present invention there is provided an injectable susp nsion, Wjich has greater chemical stability by reducing the moisture content.
In an ambodiment of the present invention, the pharmaceutically acceptable salts of Ceftiofur are selected frbm sodium, hydrochloride or hydrobromide, preferably Ceftiofur hydr chlorid In an' embodiment of the present invention Ceftiofur or its pharmaceutically acceptable salt may be present in amount of 1% to 20% by weight of the suspension, preferably in amount of 1% to 10%. Further, the Ceftiofur hydrochloride may be present in an amount of 10 mg to about 200mg/ml, preferably in an amount of 10 mg to about 100mg/ml.
In an embodiment of the present invention, the biocompatible oil used may be selected from the group consisting of monoglyceride, diglyceride, triglyceride medium chair succinic acid triglyceride, corn oil, cottonseed oil, olive oil, sesame oil, soybean oil, safflower oil coconut oil, sunflower oil or palm oil, preferably cottonseed oil, peanut oil, corn il is us1d.
In ye f another embodiment of the present invention, the wetting and dispersing agents used ia the suspension are selected from lecithin, fatty acid ester of sorbitan or glycerol.
In yet another embodiment of the present invention, the resuspendibility enhancer is selected from polyoxyl hydrogenated vegetable oil, polyoxyl vegetable oil, glycerol, propylene glycol, polyethylene glycols.
In yet another embodiment of the present invention, the oily suspension of Ceftibfur hydrochloride is used for oral, topical or parenteral administration.
In yet another embodiment of the present invention, the oily suspension can be steril zed by s!erilization techniques known in the art.
WO 2004/014390 PCT/IB2002/003165 6 The oily suspension of the present invention has improved resuspendibility. The addition of the resuspendibility enhancers improves the particle interaction, which result in a "loose" parAicle aggregation so when the suspension is shaken the particles can separate to so me extet and a uniform dose can be obtained.
The resent invention is detailed by the examples below, which are provided by way f illust% tion only and should not be considered to limit the scope of the invention.
Exainple 1 Composition: Ceftiofur (as Ceftiofur HC1): Lecithin: 0.5 g Sorbitan monooleate: Propylene glycol: 5 g Cottonseed oil q.s. to 1000ml 8001 1 of Cottonseed oil is heated to above 100 °C and lecithin is added and stirred well until dissolved. The oil containing the wetting agent is then cooled with continuous stirr ng. Sorbitan monooleate is added next with agitation. Next the required amount of Prof ylene glycol is added and mixed well with stirring. Sterile Ceftiofur Hydrochloride is add d and ixed for 15 to 45 minutes. Volume is made up to 1000 ml by adding sufficient amount of cottonseed oil. The suspension is then homogenized using a suitable hormogenize It is then filled in vials, closed with a stopper, sealed and sterilized.
Exainple 2 Composition Ceftiofur (as Ceftiofur HC1): Lecithin: 0.5 g Sorbitan monooleate: Polyethylene Glycol- 400: 5 g Cottonseed oil q.s. to 1000ml 800 n of C ttonseed oil is heated to above 100 °C and lecithin is added and stirred well ulnti dissolved. The oil containing the wetting agent is then cooled with continuous stirring. Soriitan monooleate is added next with agitation. Next the required amount of Polyethylen glycol 400 is added and mixed well with stirring. Sterile Ceftiofur Hy rochloride is added and mixed for 15 to 45 minutes. Volume is made up to 1000 ml by WO 2004/014390 PCT/IB2002/003165 7 addig sufficient amount of cottonseed oil. The suspension is then homogenized using a suitaple homo genizer. It js then filled in vials, closed with a stopper, sealed and sterilized.
Example 3 Composition: Ceftiofur (as Ceftiofur HC1): Lecithin: 0.5 g Sorbitan monooleate: Polyoxyl 40 hydrogenated castor oil: 1g Cottonseed oil q.s. to 1000ml 800 ml of Cottonseed oil is heated to above 100 'C and lecithin is added and stirred well until dissolved. The oil containing the wetting agent is then cooled with continuous stirring. Sorbtan monooleate is added next with agitation. Next the required amount of Polyoxyl 40 hydrogenated castor oil is added and mixed well with stirring. Sterile Cefti fur Hydrochloride is added and mixed for 15 to 45 minutes. The suspension is then homogenized using suitable homogenizer. Volume is made up to 1000 ml by adding sufficient amount of cottonseed oil. It is then filled in vials, closed with a stopper, sealed and sterilized.
Example 4 Composition: Ceftiofur (as Ceftiofur HC1): Lecithin: 0.5 g Sorbitan monooleate: Polyoyl 40 hydrogenated castor oil: 1 g Cottoniseed oil q.s. to 1000ml 800 il of Cottonseed oil is heated to above 100"C and lecithin is added and stirred well until dissolved. Sorbitan monooleate is added next with agitation. Next the required amount of Pc yoxyl 40 hydrogenated castor oil is added and mixed well with stirring. The oily mixture] is heated to 160°C, for 2 hours and is then cooled. Sterile Ceftiofur Hydrochloride is added and mixed for 15 to 45 minutes. The suspension is then homogenized using suitable homogenizer. Volume is made up to 1000 ml by adding sufficient amount of cottonseed oil. It is then filled in vials, closed with a stopper and sealed.
WO 2004/014390 PCT/IB2002/003165 Chemical Stability and Shelf-life The stability of suspensions, and ultimately their shelf life, is based on both chemical and physical stability. The chemical stability is assessed to insure that the product does not become subpotent during shelf life. The chemical stability of the current formulation has been studied extensively at different temperatures and different time periods. The results for example 3 are shown below: Agsa Initial Assay 2wks 1 Month 2 Months 3 Month of Label claim) 25°C/60%RH 1 99.16 98.68 -98.61 Assay f Label claim 0 C/75%RHl 99.16 97.11 97.32 96.75 Assay of Label claim) 99.16 99.22 Restispendibility or Physical Stability Resuspendibility is a very important parameter that determines the dosage accuracy in the dispensed volume of the suspension during the entire shelf life of the product. If the resuspension is not adequate the initial doses shall be subpotent as some small amount of drug remains at the bottom of the container.
The i vention describes of such formulation where the resuspendibility is achieved effortlessly td get uniform dispersion.
Free e-Thav Study Samles were subjected to four cycles of 0°C 40 0 C each of 48 hours and then obsetved for any physical changes in the suspension characteristics and also analyzed for chemical stability. The results are shown below: Test Example No. 1 Example No. 3 Physical Appearance No significant change No significant change Appearance after Freeze-thaw No significant change No significant change cycling Initial Assay Label Claim) 99.79 99.16 Assay after Freeze-thaw cycling 97.81 95.66 Label C iim) Iy 00 8a N, Any discussion of documents, acts, materials, devices, articles or the like which ;has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim 00 of this application.
0Throughout this specification the word "comprise", or variations such as 00 "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
216551 l.doc

Claims (9)

1. An oily suspension of Ceftiofur or its pharmaceutically acceptable salt, said composition comprising at least a biocompatible oil, a wetting agent, a dispersing agent and a resuspendibility enhancer, wherein the resuspendibility enhancer is not water. 00 O
2. The oily suspension as claimed in claim 1, wherein Ceftiofur or its 00 C pharmaceutically acceptable salt is present in an amount of 1% to 20% by weight of the suspension. O c N 3. The oily suspension as claimed in claim 1, wherein Ceftiofur or its pharmaceutically acceptable salt is present preferably in amount of 1% to
4. The oily suspension as claimed in any one of the preceding claims, wherein said composition comprises of 0.025% to 1.0% by weight of wetting agent, 0.05% to by weight of dispersing agent and 0.05% to 10% by weight of resuspendibility enhancer. The oily suspension as claimed in claim 4, wherein said composition preferably comprises of 0.025% to 0. 1% w/v of wetting agent, 0.05% to 0.5% w/v of dispel dug agent and 0.05% to 10% w/v of resuspendibility enhancers.
6. The oily suspension as claimed in any one of the preceding claims, wherein the pharmaceutically acceptable salt of Ceftiofur is selected from sodium, hydrochloride or hydrobromide.
7. The oily suspension as claimed in any one of the preceding claims, wherein the biocompatible oil used is selected from the group consisting of monoglyceride, diglyceride, triglyceride medium chain succinic acid triglyceride, corn oil, cottonseed oil, olive oil, sesame oil, soybean oil, safflower oil, coconut oil, sunflower oil or palm oil.
8. The oily suspension as claimed in any one of the preceding claims, wherein the wetting and dispersing agent used is selected from lecithin, fatty acid ester of sorbitan or glycerol. 216551 1.doc 00 S9. The oily suspension as claimed in any one of the preceding claims, wherein the resuspendibility enhancer used is selected from polyoxyl hydrogenated vegetable oil, polyoxyl vegetable oil, glycerol, propylene glycol or polyethylene glycol. 00 10. The oily suspension as claimed in any one of the preceding claims, which has better chemical stability due to reduced moisture content. 00 (N M 11. The oily suspension as claimed in any one of the preceding claims, wherein the suspension is administered orally, topically or parenterally.
12. A process for the preparation of an oily suspension, which comprises: i) heating a biocompatible oil to a temperature in the range of 40 0 C based on the dosage form, ii) adding a wetting agent to step liquid and allowing to cool, with stirring, iii) adding a dispersing agent and a resuspendibility enhancer to step (ii) mixture with stirring, if required iv) stirring the mixture of step (iii) at about 160 0 C up to 2 hrs v) adding Ceftiofur or its pharmaceutically acceptable salt to step (iv) mixture and mixing well with stirring, vi) homogenizing step mixture using a suitable homogenizer, vii) filling in the primary packaging components, and wherein the resuspendibility enhancer is not water.
13. An oily suspension substantially as hereinbefore described with reference to the examples and excluding, if any, comparative examples.
14. A process for the preparation of an oily suspension substantially as hereinbefore described with reference to the examples and excluding, if any, comparative examples. 216551 1.doc
AU2002328168A 2002-08-07 2002-08-07 Novel pharmaceutical composition of ceftiofur Expired AU2002328168B2 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB831096A (en) * 1956-12-20 1960-03-23 Ici Ltd Cyanacethydrazide derivatives and compositions containing them
US5736151A (en) * 1996-12-09 1998-04-07 Pharmacia & Upjohn Company Antibiotic oil suspensions
US20010048931A1 (en) * 1998-04-20 2001-12-06 Pharmaceutical Resources Inc. Flocculated suspension of megestrol acetate

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB831096A (en) * 1956-12-20 1960-03-23 Ici Ltd Cyanacethydrazide derivatives and compositions containing them
US5736151A (en) * 1996-12-09 1998-04-07 Pharmacia & Upjohn Company Antibiotic oil suspensions
US20010048931A1 (en) * 1998-04-20 2001-12-06 Pharmaceutical Resources Inc. Flocculated suspension of megestrol acetate

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