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WO2008134819A1 - Forme posologique améliorée et procédé associé - Google Patents

Forme posologique améliorée et procédé associé Download PDF

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Publication number
WO2008134819A1
WO2008134819A1 PCT/AU2008/000633 AU2008000633W WO2008134819A1 WO 2008134819 A1 WO2008134819 A1 WO 2008134819A1 AU 2008000633 W AU2008000633 W AU 2008000633W WO 2008134819 A1 WO2008134819 A1 WO 2008134819A1
Authority
WO
WIPO (PCT)
Prior art keywords
dosage form
optionally
functional protein
gelatinised
range
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/AU2008/000633
Other languages
English (en)
Inventor
Benjamin Sauer
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.)
Jurox Pty Ltd
Original Assignee
Jurox Pty 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
Priority claimed from AU2007902407A external-priority patent/AU2007902407A0/en
Application filed by Jurox Pty Ltd filed Critical Jurox Pty Ltd
Priority to AU2008247327A priority Critical patent/AU2008247327B2/en
Priority to NZ580357A priority patent/NZ580357A/en
Publication of WO2008134819A1 publication Critical patent/WO2008134819A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/25—Shaping or working-up of animal feeding-stuffs by extrusion
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/111—Aromatic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/116—Heterocyclic compounds
    • A23K20/137—Heterocyclic compounds containing two hetero atoms, of which at least one is nitrogen
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/195—Antibiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/30—Shaping or working-up of animal feeding-stuffs by encapsulating; by coating
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
    • A23K50/45—Semi-moist feed
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals

Definitions

  • This invention relates to an improved dosage form for veterinary medicines, particularly to an improved chewable, semi moist, stable animal dosage form containing oral veterinary medicines, and to a process for producing such a dosage form.
  • Small omnivores and carnivores such as cats and dogs, often need to be treated with a veterinary medicine to treat a condition or to ward off a disease.
  • medicines such as antibiotics, non-steroidal anti-inflammatory drugs, drugs for cardiovascular disease and/or parasiticides will need to be administered to an animal at some stage during its life.
  • the means for administering such medicine will depend on the nature of the condition to be treated.
  • direct oral administration of a veterinary medicine to an animal is considered a quick and easy way to administer the medicine.
  • there are relatively few products on the market which are palatable to the animal and therefore oral administration is often not a desirable mode of administration due to the unreliability of administering the correct dose of medicine to the animal.
  • the present inventor have found an improved chewable dosage form for delivering a range of veterinary medicines including heat and pH sensitive actives, to an animal together with a process for making such a dosage form.
  • the improved chewable dosage form is stable and palatable and comprises a unique combination of active ingredients, humectants and plasticisers in a gelatinised functional protein matrix having a specified moisture content and water activity.
  • the present inventor have found that the improved chewable dosage form may be manufactured using a combination of protein gelatinisation and cold extrusion techniques under low temperatures and neutral pH.
  • the conditions required by the process of the present invention allow temperature and pH sensitive materials to be employed and in particular allows a greater range of active ingredients to be used than previously possible in prior art processes for producing palatable, chewable and stable animal dosage forms.
  • a chewable, stable dosage form for animals comprising: a) about 20.0- 70.0% w/w of gelatinised functional protein matrix; b) about 0.001 - 40.000% w/w of one or more active ingredients; c) about 0.5 - 40.0% w/w of one or more plasticisers which includes one or more oils and/or water; d) about 0.5 - 20.0% w/w of one or more humectants; e) optionally about 0.05 - 5.00% w/w of one or more anti-microbials; f) optionally about 0.05 - 5.00% w/w of one or more extrusion aids; g) optionally about 0.05 - 50.00% w/w of one or more flavouring agents; wherein c) - g) are incorporated in the gelatinised functional protein matrix and b) is incorporated in (i) the gelatinised functional protein matrix, (ii) a coating of the dosage
  • the dosage form of the present invention comprises a gelatinised functional protein matrix in an amount of about 20.0 - 70.0% w/w.
  • the gelatinised functional protein is present in an amount of about 25.0 - 65.0 % w/w, more preferably about 30.0 - 60.0 % w/w.
  • the gelatinised functional protein matrix is formed from the gelatinisation of about 20.0 - 70.0% w/w of one or more functional proteins, preferably about 25.0 - 65.0 % w/w and more preferably about 30.0 - 60.0 % w/w.
  • the one or more functional proteins include but are not limited to vital wheat gluten, defatted soy flour, soy protein concentrate, soy protein isolate, corn gluten meal, mung beans, yeast by-products and mixtures thereof.
  • the functional protein is vital wheat gluten.
  • the term "functional protein” refers to a protein that has a high level, usually greater then about 65%, preferably greater then about 75%, more preferably about 80% or more of intact protein i.e. wherein the tertiary and quaternary structure of the protein has undergone minimal denaturation. Preparation of a functional protein is achieved largely through mechanical processing in a way so as to preserve the tertiary and quaternary structure.
  • the present inventor have found that the presence of one or more functional proteins in the protein matrix has an important effect on the quality of the binding and solid structure formation of the dosage form of the present invention.
  • gelatinisation of the functional protein involves breaking of the tertiary and quaternary structure of the functional protein, by a means that includes but is not limited to hydration, to form a denatured functional protein followed by realignment of the protein, by a means that includes but is not limited to re-hydration.
  • functional proteins such as wheat gluten, possess a special visco-elastic property when re-hydrated which contributes to the above noted rheological features of the dosage form product of the present invention.
  • the improved binding properties formed at low to moderate temperatures and neutral pH allows the utilisation of non-binding materials for modifying product features including but not limited to the addition of active ingredients, humectants, flavouring agents etc.
  • starches are not required in the formation of the dosage form of the invention.
  • to cause starches to gelatinise requires substantially higher temperatures than that envisaged in the present invention. Therefore, it is desirable that starches be excluded although it is recognised that small amounts may be included, for example, as carriers or additives in relation to other ingredients.
  • the level of inclusion will not contribute to the working of the invention and will certainly not detract from achieving the dosage form through a process of gelatinisation of a functional protein. In the dosage form of the invention, there would be less then about 0.1% w/w of gelatinised starch.
  • the dosage form of the present invention includes one or more active ingredients in an amount of about 0.001 - 40.000 % w/w.
  • the one or more active ingredients is present in an amount of about 0.005 - 35.000 % w/w, more preferably about 0.01 - 30.00 % w/w.
  • the one or more active ingredients is included only within the functional protein matrix. In another embodiment, the one or more active ingredients is incorporated within the functional protein matrix and a coating of the dosage form of the present invention.
  • the one or more actives is incorporated only within a coating of the dosage form.
  • one or more process sensitive actives is incorporated only within a coating of the dosage form.
  • An example of a process sensitive active is one that does not tolerate the moisture content and/or mechanical energy used in the formation of the dosage product form.
  • the dosage form of the present invention allows the simple oral administration of veterinary medicines to animals, preferably small omnivores and carnivores, such as cats and dogs.
  • the present inventor have been able to incorporate temperature and/or pH sensitive and/or process sensitive active ingredients into the dosage form of the present invention.
  • the one or more actives include but are not limited to the group consisting of antibiotics such as penicillins including penicillin- V, penicillin-G, amoxicillin, ampicillin and cloxacillin; cephalosporin's including cefalexin, cefuroxime and cefprozil; fluoroquinolones including flumequine, enrofloxacin, orbifloxacin and marbofloxacin; tetracycline's including oxytetracycline and doxycycline; macrolides including erythromycin and azithromycin; non-steroidal anti-inflammatories including carprofen, meioxicam, aspirin, phenylbutazone and etodolac; drugs for treating cardiovascular disease including benazepril, enalapril, pimobendan, millophyline and etar
  • the dosage form of the present invention includes one or more plasticisers which includes one or more oils and/or water in an amount of about 0.5 - 40.0% w/w.
  • the one or more plasticisers is present in an amount of about 5.0 - 35.0 % w/w, more preferably about 10.0 -30.0 % w/w.
  • the one or more plasticisers include one or more oils and/or water and may additionally include one or more other plasticisers.
  • the oils include but are not limited to vegetable oil, olive oil, castor oil, sesame oil, soy bean oil, sunflower oil, paraffin oil, fractionated coconut oil, cod liver oil and mixtures thereof.
  • Other plasticisers include but are not limited to glycerol, propylene glycol, sorbitol, ethylene glycol, and mixtures thereof.
  • the plasticiser is a combination of vegetable oil and water.
  • the inventor has found that the inclusion of one or more plasticisers is important in a) ensuring that the dosage form product of the present invention retains a rubbery, pliable texture, thereby making it chewable and b) reducing friability such that the dosage form has a low friability, even during the chewing process.
  • This has the advantage of allowing the one or more active ingredients to remain in the dosage form product until it has been chewed and then digested by the animal.
  • the dosage form of the present invention includes one or more humectants in an amount of about 0.5 - 20.0% w/w.
  • the humectant is present in an amount of about 1.0 - 17.5 % w/w, more preferably about 2.5 - 15.0 % w/w.
  • the one or more humectants traps water, making it unavailable for microbial growth.
  • the one or more humectants include but are not limited to salts such as sodium chloride, potassium chloride and lithium chloride; glycerol; sugars such as glucose, fructose, sucrose and lactose; propylene glycol; polyols such as sorbitol, xylitol and maltitol, polymeric polyols such as polydextrose; natural extracts such as quilaia; urea; lactic acid and mixtures thereof.
  • Preferred sugars include but are not limited to glucose, sucrose, fructose, and mixtures thereof.
  • Preferred salts include but are not limited to sodium chloride, potassium chloride, and mixtures thereof.
  • the humectants are sucrose and/or sodium chloride or glycerol and/or propylene glycol.
  • the dosage form of the present invention has a total moisture content in the range of about 0.5-40.0 % w/w, and may be classed as a semi-moist product or as a product having an intermediate moisture content.
  • the present inventor have found that the presence of one or more humectants is important in protecting the semi-moist dosage form from microbial growth.
  • the dosage form of the present invention has a water activity in the range of about 0.60 - 0.80, preferably in the range of about 0.60 - 0.78, more preferably in the range of about 0.60 - 0.75.
  • a water activity below 0.80 inhibits the microbial growth and also the dependence on antimicrobials.
  • the pH of the dosage form of the present invention is in the range of about 5.0 - 7.5, preferably about 5.5 - 7.5.
  • the present inventor have found that the pH and the water activity of the dosage form product of the present invention are important in determining the shelf life and hence stability of the product.
  • the dosage form of the present invention optionally comprises about 0.05 - 5.00% w/w of one or more anti-microbial agents. Preferably, in an amount of about 0.1 - 3.0% w/w, more preferably about 0.25 - 2.50% w/w.
  • the inclusion of one or more anti-microbial agents serves to inhibit possible microbial growth.
  • the one or more anti-microbials include but are not limited to sorbate salts such as sodium or potassium sorbate; sorbic acid; citric salts such as sodium or potassium citrate; citric acid; propionate salts such as sodium or potassium propionate; propionic acid; methyl, ethyl, propyl, paraben; pH modifiers such as phosphoric acid; and mixtures thereof.
  • the dosage form of the present invention optionally comprises about 0.05 - 5.00% w/w of one or more extrusion aids.
  • the one or more extrusion aids is present in an amount of about 0.075 - 4.000% w/w, more preferably 0.1 - 2.5 % w/w.
  • the one or more extrusion aids include but are not limited to elemental sulphur; sulphur containing amino acids; polysaccharides such as alginate; guar gum; gelatine; carrageenan; and emulsifiers such as lecithin; and mixtures thereof.
  • the present inventor have found that the utilisation of one or more extrusion aids enhances the binding characteristics of the chosen functional proteins.
  • the dosage form of the present invention optionally comprises about 0.05 - 50.00% w/w of one or more flavouring agents.
  • the one or more flavouring agents is present in an amount of about 1.0 - 45.0 % w/w, more preferably about 10.0 - 40.0 % w/w.
  • the one or more flavouring agents enhance the palatability of the dosage form product of the present invention.
  • the one or more flavouring agents include but are not limited to meat meals; meat by-product meals; poultry meals; poultry by-product meals; fish meals; fish by-product meals; digests; and mixtures thereof.
  • the dosage form of the present invention may additionally comprise one or more other ingredients such as: colouring agents including but not limited to iron oxide; non-binding fillers including but not limited to grain flour and anti-oxidants, preferably in an amount of 0.01 - 0.10 % w/w including but not limited to butylated hydroxy toluene and butylated hydroxyanisole.
  • colouring agents including but not limited to iron oxide
  • non-binding fillers including but not limited to grain flour and anti-oxidants, preferably in an amount of 0.01 - 0.10 % w/w including but not limited to butylated hydroxy toluene and butylated hydroxyanisole.
  • the dosage form of the present invention may optionally be coated to an amount of 0.1 — 5.0% w/w.
  • the coating may be selected from any coating for pet food known in the art and includes but is not limited to protective coatings such as povidone and methyl cellulose, etc.
  • the coating may further include other ingredients including but not limited to microbial inhibitors, vitamins, minerals, flavour enhancers and active ingredients, particularly those that are process sensitive. Accordingly, the coating may be used to add a barrier against moisture, to add microbial inhibitors, vitamins and minerals, flavour enhancers and/or include actives into the formulation, particularly process sensitive actives.
  • a chewable, stable dosage form for animals comprising: a) about 20.0 - 70.0% w/w of gelatinised functional protein matrix; b) about 0.001 - 40.000% w/w of one or more active ingredients; c) about 0.5 - 40.0% w/w of one or more plasticisers which includes one or more oils and/or water; d) about 0.5 - 20.0% w/w of one or more humectants; e) optionally about 0.05 - 5.00% w/w of one or more anti-microbials; f) optionally about 0.05 - 5.00% w/w of one or more extrusion aids; g) optionally about 0.05 - 50.00% w/w of one or more flavouring agents; wherein b) - g) are incorporated in the gelatinised functional protein matrix and the dosage form has a total moisture content in the range of about 0.5 - 4
  • a chewable, stable dosage form for animals comprising: a) about 30.0 - 60.0% w/w of gelatinised functional protein matrix preferably formed from gelatinisation of one or more functional proteins selected from the group consisting of: vital wheat gluten, defatted soy flour, soy protein concentrate, soy protein isolate, corn gluten meal, mung beans, yeast by-products and mixtures thereof.
  • a process for preparing a chewable, stable animal dosage form comprising the steps of: i) combining: a) about 20 - 70% w/w of one or more functional proteins; b) optionally about 0.001 - 40.000% w/w of one or more active ingredients; c) optionally about 0.5 - 40.0% w/w of one or more plasticisers which includes one or more oils and/or water; d) about 0.5 - 20.0% w/w of one or more humectants; e) optionally about 0.05 - 5.0% w/w of one or more anti-microbials; f) optionally about 0.05 - 5.00% w/w of one or more extrusion aids; g) optionally about 0.05 - 50.00% w/w of one or more flavouring agents; and mixing for a time sufficient to form a premix in which a) - g) are dispersed therein; i ⁇ ) adding to
  • a dosage form having a total moisture content in the range of about 0.5 - 40.0 % w/w and a water activity in the range of about 0.60 - 0.80; wherein the one or more plasticisers is added at step i), step ii) or at both steps i) and ii) and the one or more active ingredients is added at step i), in the coating at step vii), or at both steps i) and vii); and wherein steps i) - v) are carried out at a temperature in the range of from about 3O 0 C up to a maximum of 7O 0 C and at a pH in the range of about 5.0 - 7.5.
  • a chewable, stable animal dosage form produced according to the process defined in the second aspect of the invention.
  • the one or more functional proteins, one or more active ingredients; one or more plasticisers; one or more hurnectants; one or more anti-microbials; one or more extrusion aids; one or more flavouring agents and coating are as described above in the first aspect of the invention.
  • ingredients c) - g) and optionally b) are incorporated within the functional gelatinised matrix, while in the second aspect the functionalised gelatinised matrix has ingredients b) - i) incorporated therein.
  • ingredients c) - g) and optionally b) in the first aspect and ingredients b) - i) in the second aspect are dispersed throughout the functional gelatinised matrix, more preferably uniformly dispersed throughout the matrix.
  • the process for preparing a chewable semi-moist animal dosage form according to the present invention is a new low temperature protein extrusion process for the formation of a protein based structure that includes one or more active ingredients.
  • Step i) of the process of the invention requires combining ingredients a) - g) of the formulation and mixing for a time sufficient to form a premix in which a) - g) are dispersed.
  • the ingredients are uniformly dispersed in the premix.
  • the premix is a dry blend. The present inventor have found that adequate mixing prior to processing is important, particularly with respect to the one or more active ingredients.
  • the b) one or more active ingredients is added at step i), in the coating at step vii), or at both steps i) and vii). It will be understood, that the total amount of the one or more active ingredients added in the process is in the amount of about 0.001 - 40.000% w/w. In cases where the one or more actives is added in step i) and the concentration of the one or more actives is low, such as below a concentration of 1%, then pre-dispersion of the active with another excipient prior to addition to the premix is preferable in order to assist in obtaining a uniform premix.
  • Mixing may be carried out in batch or continuous mixing modes. Mixing may be carried out in any suitable vessel. Examples of suitable mixing vessels for batch mixing include but are not limited to ribbon blenders, cone blenders, vertical mixers and auger mixers. Examples of suitable mixing vessels for continuous mixing include but are not limited to vertical mixers and ribbon blenders.
  • step (ii) of the process Hydration of the one or more functional proteins to form a hydrated protein premix occurs in step (ii) of the process.
  • this step may be referred to as the pre-conditioning step.
  • step ii) of the process of the invention requires that h) about 0.5 - 40.0% w/w water is added to the premix.
  • the hydration time is in the range of 40 - 110 seconds, more preferably 50 - 100 seconds.
  • the hydration step breaks up the 3 -dimensional structure of the one or more functional proteins.
  • the present inventor have found that the provision of sufficient hydration time to allow wetting of the functional protein in the dry blend to form a hydrated protein blend is an important factor of the process.
  • a sufficiently long process time of greater than 40 seconds and less than about 100 seconds desirably leads to uniform hydration of the protein substrates.
  • wetting it is meant that sufficient hydration has occurred to allow a suitable granule of the hydrated protein premix to be formed with adequate mechanical force.
  • the one or more proteins are completely hydrated, it will be appreciated that partial hydration of the one or more proteins is also possible according to the invention.
  • the one or more plasticisers may be added at step i), step u) or at both steps i) and ii). It will be understood that the total amount of one or more plasticisers added in the process is in the amount of about 0.5 - 40.0% w/w. Preferably, one or more of the plasticisers is added at step ii).
  • step ii) further comprises the addition of one or more oxidants, preferably in an amount of 0.01 - 0.1 % w/w.
  • the ingredients in step ii) of the process are homogenised.
  • Step ii) preferably takes place in a pre-conditioner vessel such as a ribbon blender, or any variation thereof.
  • Step iii) of the process of the invention requires sufficient mechanical work input to the hydrated protein premix so as to form a gelatinised functional protein matrix containing b) - i).
  • the mechanical work forces the hydrated protein blend from step (ii), wherein the one or more proteins is in a denatured form, to realign.
  • mechanical work input refers to the specific mechanical energy (SME) needed to mix and/or knead the hydrated protein blend to form the gelatinised functional protein matrix having the desired texture and consistency required to hold the final dosage form together.
  • the specific mechanical energy (SME) is in the range of about 0.03 - 0.06 kW/h/kg, more preferably, about 0.035 - 0.055 kW/h/kg.
  • the heating and/or cooling may occur during step (iii) to aid in achieving the desired consistency and/or texture.
  • the present inventor have found that it is very important to ensure that the maximum exposure temperature within the vessel during step iii) is no greater than 7O 0 C and that the maximum exposure time to the elevated temperature of 7O 0 C within the vessel is preferably very short in the range of 20 - 40 seconds, i.e. it is important that the dry blend containing the hydrated protein premix and the forming gelatinised functional protein are exposed to a temperature of no greater than 70 0 C.
  • the temperature is in the range of from about 3O 0 C up to a maximum of 7O 0 C, more preferably about 35- 65 0 C and even more preferably about 37.5 - 62.5 0 C.
  • step iii) takes place in an extrusion vessel.
  • Extruders include but are not limited to single, double (co- or counter-rotating) extruders or any variation thereof.
  • Step iv) of the process involves extruding the gelatinised functional protein matrix into a dosage form. This includes sizing and shaping the gelatinised functional protein matrix into the desired size and shape.
  • the dosage form may or may not be necessary to dry and/or cool the dosage form. For instance, if the water content is too high, further drying may be required.
  • Step v) of the process involves optionally drying the dosage form. Drying may be achieved using continuous or batch style drying, including but limited to the use of a tray dryer or fluid bed.
  • Step vi) involves optionally cooling the dosage form. Cooling may be achieved using a continuous or batch styled cooler, including but not limited to the use of a tray cooler. Preferably cooling takes place at temperature in the range of about 2 - 3O 0 C.
  • Step vii) involves optionally coating the dosage form. This may be carried out according to standard procedures. Other ingredients as indicated above in the first aspect of the invention may be included in the coating at this stage.
  • the process of the present invention provides a dosage form having a total moisture content of about 0.5-40 % w/w, preferably about 5 - 30 % w/w, more preferably about 10 - 25% w/w.
  • a moisture content in this range has been found by the inventor to form a semi-moist chewable and pliable product.
  • the process of the present invention provides a dosage form having a water activity of about 0.60 - 0.8.
  • a water activity below 0.8 inhibits the microbial growth and also the dependence on antimicrobials.
  • steps i) - v) are carried out at a temperature in the range of from about 3O 0 C up to a maximum of 7O 0 C, preferably about 35 - 65 0 C, and more preferably about 37.5 - 62.5 0 C. Carrying out the process in this temperature range allows the use of temperature sensitive ingredients, such as temperature sensitive active ingredients.
  • Steps i), ii) and v) of the process of the present invention are preferably carried out at ambient pressure.
  • steps iii) and iv ) of the process are carried out at elevated pressures, preferably for short periods of time such as 50 - 60 seconds.
  • a further advantage of the process of the present invention is the fact that it is carried at close to neutral pH, specifically in the pH range of about 5.0 - 7.5, preferably about 5.5 - 7.0. This again allows a range of ingredients to be used in the process, specifically pH sensitive ingredients.
  • the process of the present invention may further comprise the addition of one or more other ingredients such as: colouring agents including but not limited to iron oxide; non-binding fillers including but not limited to grain flour and anti-oxidants including but not limited to butylated hydroxy toluene and butylated hydroxyanisole.
  • colouring agents including but not limited to iron oxide
  • non-binding fillers including but not limited to grain flour
  • anti-oxidants including but not limited to butylated hydroxy toluene and butylated hydroxyanisole.
  • the process of the invention may further include the optional step of coating the dosage form.
  • the dosage form may optionally be coated to an amount of 0.1 - 5.0% w/w.
  • the coating is as described above in relation to the first and second aspects of the invention.
  • a process for preparing a chewable, stable animal dosage form comprising the steps of: i) combining: a) about 20.0 - 70.0% w/w of one or more functional proteins; b) about 0.001 - 40.000% w/w of one or more active ingredients; c) about 0.5 - 20.0% w/w of one or more humectants; d) optionally about 0.05 - 5.00% w/w of one or more anti-microbials; e) optionally about 0.05 - 5.00% w/w of one or more extrusion aids; f) optionally about 0.05 - 50.00% w/w of one or more flavouring agents; and mixing for a time sufficient to form a premix in which a) - f) are dispersed therein; ii) adding to the premix: g) 0.05 - 40.00% w/w water; h) about 0.5 - 40.0% of one
  • a process for preparing a chewable, stable animal dosage form comprising the steps of: i) combining in a vessel, preferably selected from the group consisting of ribbon blenders, cone blenders, vertical mixers and auger mixers: a) 20 - 70% w/w one or more functional proteins, preferably selected from the group consisting of vital wheat gluten, defatted soy flour, soy protein concentrate, soy protein isolate, corn gluten meal, mung beans, yeast by-products and mixtures thereof; b) 0.001 - 40% w/w one or more active ingredients, preferably selected from the group consisting of penicillins; cephalosporin's; fluoroquinolones; tetracycline's; macrolides; non-steroidal antiinflammatories; drugs for cardiovascular disease, preferably benazepril; parasiticides; macrocyclic lactones and mixtures thereof; c) 0.5 - 20 % w/w one or more humectant
  • a process for preparing a chewable, stable animal dosage form comprising the steps of: i) combining in a vessel a ribbon blender: a) 20 - 70 % w/w vital wheat gluten; b) 0.001 - 40% w/w one or more active ingredients, preferably selected from the group consisting of penicillins; cephalosporin's; fluoroquinolones; tetracycline's; macrolides; non-steroidal anti-inflammatory drugs; drugs for cardiovascular disease, preferably benazepril; parasiticides; macrocyclic lactones and mixtures thereof; c) 0.5 - 20 % w/w mixture of sugar and salt; d) 0.5 - 5 % w/w potassium sorbate; e) 0.05 - 50% w/w mixture of meat meal and poultry meal; and batch mixing in the ribbon blender for a time sufficient to form a dry premix in which a) - e) are uniformly dispersed
  • the dosage form of the present invention is able to be chewed by an animal in need of administration of a veterinary medicine. Whilst the dosage form is applicable to all animals able to effectively chew a pliable structure it is particularly suited to small omnivores and carnivores such as cats and dogs.
  • stable means chemical and physical stability of the active ingredients of the dosage form over at least a 3 month period, preferably 6 months, when stored at about 30°C/60% relative humidity.
  • chemical stability it is intended to mean that the concentration of the active ingredients, remains within about ⁇ 10%w/w of the stated concentration of the active ingredients and the pH of the dosage form remains in the range of about 5.0 - 7.5.
  • physical stability it is intended to mean that the appearance and texture of the formulation is semi- moist and pliable, such that the moisture content remains in the range of about 10 - 30 %w/w.
  • a chewable, stable dosage form according to the invention has the ingredients as listed in Table 7.
  • the dosage form has a surface pH of about 6.01, a water content of about 13% w/w and a water activity of about 0.71.
  • a chewable, stable dosage form according to the invention has the ingredients as listed in Table 8, wherein the active ingredient is a combination of pyrantel, febantel and praziquantel. Table 8
  • the dosage form has a surface pH of about 6.01, a water content of about 13% w/w and a water activity of about 0.71.
  • the preconditioned mix was transferred to the extruder, and a specific mechanical energy in the order of 0.035 — 0.055 kW/h/kg applied at a temperature in the order of 30-70°C. v.
  • the extrudate was sized and cut accordingly, and dried to a total moisture content of 16% using a continues oven drier/cooler at a temperature ⁇ 60°C for 20 minutes to form a dosage form according to the invention.
  • the resulting dosage form has a pH of about 6.01 and a water activity of about 0.71.

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Zoology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Animal Husbandry (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Animal Behavior & Ethology (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Inorganic Chemistry (AREA)
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Abstract

L'invention concerne une forme posologique pouvant être mâchée, qui est destinée à l'administration d'une variété de médicaments vétérinaires à des animaux. La forme posologique de l'invention est particulièrement adaptée à l'administration de médicaments sensibles à la chaleur et au pH. L'invention fait appel à la gélatinisation d'une protéine fonctionnelle, telle que le gluten de blé vital, pour incorporer le médicament à la forme posologique. La gélatinisation s'effectue dans des conditions de température, pression et pH relativement clémentes. L'invention porte également sur un procédé de préparation de ladite forme posologique, selon lequel les étapes clés du traitement sont conduites dans une plage de températures comprise entre 30 °C et 70 °C maximum, à un pH compris entre environ 5,0 et 7,5.
PCT/AU2008/000633 2007-05-07 2008-05-06 Forme posologique améliorée et procédé associé Ceased WO2008134819A1 (fr)

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AU2008247327A AU2008247327B2 (en) 2007-05-07 2008-05-06 Improved dosage form and process
NZ580357A NZ580357A (en) 2007-05-07 2008-05-06 Chewable gelatinised protein dosage form and process

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US9374997B2 (en) 2009-04-30 2016-06-28 Dow Agrosciences Llc Pesticide compositions exhibiting enhanced activity
WO2010126583A1 (fr) * 2009-04-30 2010-11-04 Dow Agrosciences, Llc Compositions pesticides présentant une activité accrue et leurs procédés de préparation
US8765697B2 (en) 2009-04-30 2014-07-01 Dow Agrosciences, Llc. Pesticide compositions exhibiting enhanced activity
US8785379B2 (en) 2009-04-30 2014-07-22 Dow Agrosciences, Llc. Pesticide compositions exhibiting enhanced activity
US8796476B2 (en) 2009-04-30 2014-08-05 Dow Agrosciences, Llc Pesticide compositions exhibiting enhanced activity and methods for preparing same
US9247730B2 (en) 2009-04-30 2016-02-02 Dow Agrosciences Llc Pesticide compositions exhibiting enhanced activity and methods for preparing same
US20130197006A1 (en) * 2010-10-12 2013-08-01 Bayer Animal Health Gmbh Non-Starch Based Soft Chewables
US9744127B2 (en) * 2010-10-12 2017-08-29 Bayer Intellectual Property Gmbh Non-starch based soft chewables
JP2016175936A (ja) * 2010-10-12 2016-10-06 バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ 非澱粉を基にしたソフトチュアブル
US9931320B2 (en) 2012-02-06 2018-04-03 Merial Inc. Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof
US9233100B2 (en) 2012-02-06 2016-01-12 Merial, Inc. Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof
US9259417B2 (en) 2012-02-06 2016-02-16 Merial, Inc. Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof
US10596156B2 (en) 2012-02-06 2020-03-24 Boehringer Ingelheim Animal Health USA Inc. Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof
US11337917B2 (en) 2012-04-04 2022-05-24 Intervet Inc. Soft chewable pharmaceutical products
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US12396945B2 (en) 2012-04-04 2025-08-26 Intervet Inc. Soft chewable pharmaceutical products
WO2013150052A1 (fr) * 2012-04-04 2013-10-10 Intervet International B.V. Produits pharmaceutiques mous pouvant être mâchés
AU2014229179B2 (en) * 2013-03-15 2017-09-14 Argenta Innovation Limited Chewable formulation
US9314478B2 (en) 2013-03-15 2016-04-19 Argenta Manufacturing Limited Method of making an anhydrous, fat soluble, chewable drug delivery formulation
CN105451771A (zh) * 2013-03-15 2016-03-30 阿根塔制造有限公司 可咀嚼配制物
EP2968569A4 (fr) * 2013-03-15 2016-11-02 Argenta Mfg Ltd Formulation à mâcher
JP2016512229A (ja) * 2013-03-15 2016-04-25 アルジェンタ マニュファクチャリング リミティド チュアブル製剤
AU2014229179C1 (en) * 2013-03-15 2018-09-27 Argenta Innovation Limited Chewable formulation
WO2014141223A1 (fr) * 2013-03-15 2014-09-18 Argenta Manufacturing Limited Formulation à mâcher
CN105451771B (zh) * 2013-03-15 2020-05-19 阿根塔创新有限公司 可咀嚼配制物
CN111803465A (zh) * 2013-03-15 2020-10-23 阿根塔创新有限公司 可咀嚼配制物
JP2017520273A (ja) * 2014-05-19 2017-07-27 ハンス−ユルゲン・ドイアラー 肉食動物用のセミモイスト飼料製品を製造するための方法およびセミモイスト飼料製品
JP2016002057A (ja) * 2014-06-18 2016-01-12 ユニ・チャーム株式会社 ペットフード用粒体およびペットフード
CN106470555A (zh) * 2014-06-18 2017-03-01 尤妮佳股份有限公司 宠物食品用粒体及宠物食品
JP2020500898A (ja) * 2016-12-09 2020-01-16 バイエル・アニマル・ヘルス・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ａｎｉｍａｌ Ｈｅａｌｔｈ Ｇｍｂｈ 医薬製剤およびその製造方法
US11382865B2 (en) 2016-12-09 2022-07-12 Bayer Animal Health Gmbh Pharmaceutical preparation and method for its manufacture
JP2020528919A (ja) * 2017-07-26 2020-10-01 ティージーエックス ソフト チュー エルエルシー 獣医用途のためのデンプン不含のソフトチュー
WO2019021191A1 (fr) * 2017-07-26 2019-01-31 Tgx Soft Chew, Llc Produit à mâcher mou exempt d'amidon pour applications vétérinaires
US11478421B2 (en) 2017-07-26 2022-10-25 Tgx Soft Chew, Llc Starch-free soft chew for veterinary applications
JP7223744B2 (ja) 2017-07-26 2023-02-16 ティージーエックス ソフト チュー エルエルシー 獣医用途のためのデンプン不含のソフトチュー
US11559491B2 (en) 2017-08-17 2023-01-24 Ceva Sante Animale Oral compositions and the preparation methods thereof
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JP7403001B2 (ja) 2020-05-06 2023-12-21 マース インコーポレーテッド 医薬品の投与のための嗜好性支持体組成物
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