WO2023126971A1 - Films oraux de médicaments anti-émétiques - Google Patents

Films oraux de médicaments anti-émétiques Download PDF

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Publication number
WO2023126971A1
WO2023126971A1 PCT/IN2022/051138 IN2022051138W WO2023126971A1 WO 2023126971 A1 WO2023126971 A1 WO 2023126971A1 IN 2022051138 W IN2022051138 W IN 2022051138W WO 2023126971 A1 WO2023126971 A1 WO 2023126971A1
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Prior art keywords
pharmaceutically acceptable
film
oral
present
oral film
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PCT/IN2022/051138
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English (en)
Inventor
Siva Ramakrishna Velaga
Siva Ramakrishna RAYALA
Srikant PIMPLE
Vamshidhar Reddy DUGGI
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Laurus Labs Limited
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Publication of WO2023126971A1 publication Critical patent/WO2023126971A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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

  • the present invention relates to new oral dosage forms of Anti-emetic drugs and its pharmaceutically acceptable salts thereof, for veterinary use, such as for oral administration to animals. More specifically the present invention relates to oral film compositions comprising Anti-emetic drugs and its pharmaceutically acceptable salts thereof and method of administering the same to the oral cavity of the animals in treating or preventing Nausea and Vomiting.
  • Emesis is caused when impulses from the chemoreceptor trigger zone (CRTZ) in the brain are sent to the vomiting centre in the medulla.
  • Motion sickness specifically occurs when signals to the CRTZ originate from the inner ear motion is sensed by the fluid of the semi-circular canals, which causes overstimulation. These signals travel to the brain’s vestibular nuclei, then to the CRTZ, and finally to the vomiting Center.
  • NK-1 receptor antagonists act by inhibiting the binding of substance P, a neuropeptide of the tachykinin family. Substance P is found in significant concentrations in the nuclei comprising the emetic centre and is considered the key neurotransmitter involved in vomiting.
  • NK-1 receptor antagonists or inhibitors that possesses unique anxiolytic, antidepressant, and antiemetic properties. By inhibiting the binding of substance P within the emetic centre, these NK- 1 receptor antagonists are effective against neural and humoral (central and peripheral) causes of vomiting or Nausea.
  • Maropitant is the only approved anti-emetic in the class neurokinin- 1 receptor inhibitor for treating or preventing vomiting or nausea for animals, specifically pets like Dogs and cats.
  • Some non-limiting examples of other USFDA approved Anti-emetic drugs for use in animals are Aminopentamide hydrogen sulfate, a cholinergic blocking agent or antispasmodic, was known to be approved in USA under the brand name of Centrine® 0.2mg Tablets.
  • Acepromazine maleate, a dopamine receptor antagonist at CRTZ in brain was approved in USA under the brand name PromAce® 5, 10, or 25 mg tablets and 50mg/ml injection.
  • Promazine Hydrochloride and Triflupromazine Hydrochloride was also known as dopamine receptor antagonist, approved in USA under the brand name Sparine® lOOmg tablets, injections and Vetame® lOmg and 25mg tablets respectively.
  • WO1992021677 publication discloses Maropitant and methane sulfonate salt of maropitant and use of the same in mammals as substance P antagonist (Substance P is a peptide composed of a chain of 11 amino acid residues; member of the tachykinin neuropeptide family) and the specification also generically discloses several possible dosage forms like, tablets, capsules, lozenges, troches, hard candies, powders, sprays, creams, salves, suppositories, jellies, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, syrups, and the like, in which maropitant can be incorporated. Further, it lists several ailments and conditions that can be prevented, of which are majorly rely on decrease in substance P mediated neurotransmission.
  • European patent EP0627221 discloses multiple compounds of NK-1 receptor antagonist which explicitly covers Maropitant for use in Emesis in mammals, which includes the treatment of Nausea and Vomiting.
  • suitable pharmaceutically acceptable salts of NK-1 antagonists i.e., salts containing pharmacologically acceptable anions, such as the hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p- toluenesulfonate and pamoate.
  • This patent also discloses wide variety of different dosage forms, i.e., tablets, capsules, lozenges, troches, hard candies, suppositories, aqueous suspensions, injectable solutions, elixirs, syrups, and the like, which may be formed by combination of various pharmaceutically acceptable inert carriers, like wise generically listed excipients suitable for oral and parenteral administration.
  • dosage forms i.e., tablets, capsules, lozenges, troches, hard candies, suppositories, aqueous suspensions, injectable solutions, elixirs, syrups, and the like, which may be formed by combination of various pharmaceutically acceptable inert carriers, like wise generically listed excipients suitable for oral and parenteral administration.
  • W02000073304 publication discloses citrate salt of Maropitant, stable and drug regulatory approved monohydrate crystalline polymorphic Form A of Maropitant citrate and process of preparing the same.
  • the specification also discloses effective dosages of crystalline maropitant citrate for oral administration in mammals i.e., 2.5mg/day to 160mg/day and preferable 5- 80mg/day of monohydrate form in a single or divided dosage administered via pills or tablets or injections.
  • U.S. patent No. 8,183,230 discloses effective Maropitant comprising specific parenteral pharmaceutical composition for systemic administration in animals.
  • Self-micro emulsifying oral quick-dissolving films for pets which comprises self-microemulsifying component, film-forming material, plasticizer, disintegrant, thickener, and flavouring agent.
  • Self-micro emulsifying components are composed of an oil phase, an emulsifier and a co-emulsifier; the oil phase can be castor oil, olive oil, oleic acid, ethyl oleate, medium chain triglycerides, a mixture of one, two or more of glyceryl oleate and isopropyl myristate; the emulsifier can be selected from polyethylene glycol glycerides, polysorbates, and polyoxyethylene castor oils.
  • the co-emulsifier can be one, two or more mixtures of ethanol, propylene glycol, glycerin, polyethylene glycol, and diethylene glycol monoethyl ether.
  • WO2016073347 patent publication discloses and refers a stable, palatable, soft chewable oral composition for increased acceptance of the medication in animals, which show resist swallowing hard tablets or capsules and chewing bitter and/or granular dosage forms.
  • Soft chew is referred to a ductile composition, where it is a supple, pliable, flexible form, i.e., is not a brittle form.
  • Specification discloses suitable non-limiting excipients of binding agent, disintegrant, wetting agent, flavorant (meat or vegetables), filler, antioxidant, colorant and taste masking agent. The flavorant is used as an admixture with filler.
  • Soft chewables are prepared by extrusion technique, where above excipients were extruded to a desired shape on a die and cut into individual units for administration. It also exemplified a soft palatable chewable composition comprising Maropitant, Microcrystalline cellulose (binding agent), disintegrant, glycerol (wetting agent), flavorant/filler and Polyvinylpyrrolidone (taste masking agent).
  • a simple method of administering but it is limited by several additional factors such as complete and sufficient chewing of the dosage form, capacity of animal or pet to chew, reluctance and compliance of the animal or pet to chew, splitting out the half chew or dogs drooling etc., which effects the release of drug and effective treatment.
  • U.S. patent publication No. 20050136096 discloses edible films for administration of medicaments to animals, wherein the edible film disclosed has an applied coating and a thin film.
  • the applied coating is a powder matrix including one or more medicaments optionally with a carrier is applied as a coating by Sifting, Screening, atomization, Static, mechanical agitation or fluidization etc.
  • the disclosure does not disclose any anti-emetic drugs or films comprising the same, such edible films are limited by animal’s oral mucosa is being directly exposed to the drugs applied over the film, that may be cause sense of irritability or drooling when administered, resulting in dosing error and reluctance to take such films from next dose onwards.
  • the coated medicament on the thin film may be eroded during the process of administration i.e., while taking out from the package and handling it while administering to the animal.
  • Parenteral dosage forms are difficult in administration, also cause pain to the animals, maximum attention while administering and pose a danger of self-administering or injury to the administrating volunteer like pet nursing staff during the process of injecting. Moreover, the administration is a like an operative procedure, which requires medical attendant and accompanying staff. Thus, there is need for an effective, pliable, easily administrable dosage form for the pet owner or any volunteer with required minimal attention. Solving the problems of pets or animal’s reluctance to swallow and poor compliance to known dosage forms has become the focus of the development of new or alternate dosage forms for oral administration of animals. Accordingly, it is also the main aim of the present inventors to provide a veterinary delivery system for effective absorption into the animal’s vascular system through gastro intestinal tract, having dose delivery accuracy, easy way to administer and shows maximum therapeutic effect.
  • novel oral film compositions comprising effective amount of Anti-emetic drugs and its pharmaceutically acceptable salts thereof and method of administering the same in treating or preventing Nausea and Vomiting in animals, which are subjected to periodic medications or occasional medications or motion sickness.
  • the major advantages of novel oral film dosage form includes reduced or no difficulty while swallowing, ease of administration, avoid scratches and bites during administration, quick disintegration in the oral cavity besides they are less prone to being spit by the animal.
  • the present invention provides oral film of Anti-emetic drugs and its pharmaceutically acceptable salts thereof for veterinary use.
  • the present invention provides composition of oral film of Antiemetic drugs and its pharmaceutically acceptable salts thereof for veterinary use, wherein the composition comprises at least one film forming polymer, plasticizer and one or more pharmaceutically acceptable excipients thereof.
  • the present invention provides process for preparing oral film of Antiemetic drugs and its pharmaceutically acceptable salts thereof for veterinary use, wherein the process may be selected from solvent casting, hot melt extrusion or printing technology.
  • the present invention provides oral films of Anti-emetic drugs and its pharmaceutically acceptable salts thereof used for the treatment or prevention of Nausea and vomiting in animals.
  • references in the specification to “one embodiment,” “an embodiment,” “another embodiment,” “a preferred embodiment,” “one aspect,” “another aspect,” “preferred aspect” and the like, indicate that the embodiment described can include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same embodiment. Further, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the knowledge of one of ordinary skill in the art to affect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described.
  • Films are classified by the site of application. Accordingly, “Oral films” can be formulated to deliver medication to the mouth such as oral hygiene products or to deliver medication to the gastrointestinal tract for absorption. “Buccal films” and “sublingual films” are formulated to facilitate absorption through the proximal mucosal membranes avoiding first pass metabolism or degradation in the gastrointestinal tract and providing a quick onset of action.
  • Oral film according to the present invention may also referred as “Oral thin film,” “OTF,” “ODF,” “oral drug strip,” “oral strip,” “veterinary oral film”, “oral disintegrating film” or “oral dissolving film”.
  • veterinary use includes prevention or treatment of veterinary medical conditions in any animal other than human for which oral films of the present invention find useful.
  • Animals herein unless otherwise specified does not limit to only domestic animals such as cats, dogs, guinea pigs, mice, horses, goats, rabbits, swine, apes, primates, hamsters, ferrets, reptiles, sheep, cows, and other non-human animals for which oral films of the present invention find useful.
  • the oral film preferably disintegrates within about five minutes and more preferably within about 180 seconds upon contact with aqueous media or saliva in oral cavity.
  • an oral film according to the present invention is "non-mucoadhesive" in nature, means that the dosage form is not designed for administration of the active pharmaceutical agent through the oral mucosa i.e. the dosage form is not designed to adhere to the mucosal surfaces of the buccal cavity as an intact film or disintegrated film residue.
  • the invention provides a non-mucoadhesive orally disintegrating film, able to disintegrate upon contact with aqueous media or saliva in oral cavity of the animal within about five minutes and more preferably within about 180 seconds.
  • film includes films, sheets and wafers, in any size and shape, including rectangular, square, or other desired shape. Preferably, they are distinct from pills, tablets, caplets or capsules and wherein the dosage from is like a thin strip of material.
  • the films are generally sufficiently flexible to allow bending or even folding without breaking.
  • the films described herein may be any desired thickness and size such that it may be placed into the oral cavity of the animal.
  • the films may have a thickness of from about 20 microns to about 300 microns. Films may be in a single layer or they may be multilayered, such as laminated or co-extruded films.
  • disintegrating is defined as a state in which any residue of the oral film remaining on the screen of the test apparatus known in the art, or in the mouth of animal, is a soft mass having no palpably film core.
  • the disintegration test does not imply complete solution of dosage unit or even of its active constituent, although a dissolved dosage unit would typically be completely disintegrated.
  • dissolution is defined by the amount of active agent released from the oral film after oral administration or by in-vitro testing known in the art.
  • An in-vitro dissolution test is to evaluate the performance of the product by measuring the amount of active agent dissolved in the dissolution medium.
  • Standardized apparatus known in the art for in-vitro dissolution testing are: USP type I apparatus (basket), USP type II apparatus (Paddle), USP type V apparatus (Paddle over disk).
  • the present invention provides oral film of Anti-emetic drugs and its pharmaceutically acceptable salt thereof for veterinary use.
  • the present invention provides composition and process for preparing oral film of Anti-emetic drugs and its pharmaceutically acceptable salt thereof for veterinary use.
  • Anti-emetic drugs according to the present invention are selected from the group comprising Maropitant, Aminopentamide, Acepromazine, Promazine and Triflupromazine or any combinations thereof and its pharmaceutically acceptable salts thereof.
  • Pharmaceutically acceptable salts of Anti-emetic drugs according to the present invention are selected from hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, hydrogen sulfate, bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate.
  • Anti-emetic drugs and its pharmaceutically acceptable salts thereof according to the present invention are may be present in an amount of about 0.1% to about 75% by weight based on total weight of the composition.
  • the present invention provides composition of oral film of Anti-emetic drugs and its pharmaceutically acceptable salt thereof, wherein the composition comprises at least one film forming polymer, plasticizer and one or more pharmaceutically acceptable excipients.
  • one or more pharmaceutically acceptable excipients are selected from suspending/thickening agents, fillers/bulking agents, disintegrating agents, stabilizers, surfactants, sweetening agents, taste masking agents, anti-foaming agents, flavoring agents and coloring agents and combinations thereof.
  • the present invention provides oral film of Anti-emetic drugs and its pharmaceutically acceptable salts thereof comprises one or more film forming polymers.
  • the term “Polymers or Film forming polymers” according to the invention are responsible for imparting adequate mechanical properties to films, and they affect the film disintegration and/or dissolution in oral cavity. Film forming polymers used according to the present invention are not limited to hydrophilic or hydrophobic polymers.
  • Suitable non-limiting hydrophilic film forming polymers according to the present invention are selected from hydroxypropyl methylcellulose or Hypromellose, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium carboxy methylcellulose, methyl cellulose, Hydroxypropyl ethylcellulose, povidone, copovidone, polydextrose, polyvinyl alcohol, polyvinyl acetate, polyethylene oxide, pullulan, sodium alginate, propylene glycol alginate, modified starch, gelatin, pectin, polyoxyethylene stearates, poly-epsilon caprolactone, polyglycolized glycerides, cyclodextrins, galactomannans, Polymerized rosin and combinations thereof.
  • Suitable non-limiting hydrophobic film forming polymers according to the present invention are selected from ethyl cellulose, Polymethacrylates, polyacrylic acid, methyl methacrylate copolymer, copolymers of acrylic acid and alkyl acrylate, carboxyvinyl copolymers and combinations thereof.
  • Polymers used according to present invention are available in various viscosity ranges. Depending on the viscosity the quantity of the polymer is chosen.
  • Film forming polymer/s according to the present invention may be present in an amount of about 10% to about 75% by weight based on total weight of the composition.
  • the present invention provides oral film of Anti-emetic drugs and its pharmaceutically acceptable salts thereof comprises plasticizers.
  • plasticizers are responsible for mechanical properties of the film, such as tensile strength and decrease the fragility of film by decreasing the glass transition temperature of polymer.
  • Suitable non-limiting plasticizers according to the present invention are selected from polyethylene glycol, propylene glycol, polyethylene-propylene glycol, glycerol/glycerin, glycerol monoacetate, glycerol diacetate, glycerol triacetate, triacetin, polysorbate, cetyl alcohol, sorbitol, sodium diethylsulfosuccinate, triethyl citrate, tributyl citrate, phthalate derivatives such as dimethyl, diethyl and dibutyl phthalate, citrate derivatives and combinations thereof.
  • Plasticizers according to the present invention may be present in an amount of about 1% to about 30% by weight based on total weight of the composition.
  • Suitable suspending/thickening agents according to the present invention are responsible for improving the viscosity of the drug and excipient dispersion preparation and consistency of the oral film.
  • Suitable non-limiting suspending/thickening agents according to the present invention are selected from maltodextrin, natural gums like xanthan gum, carrageen, locust bean gum, cellulose derivatives, dextrin, modified starch and combinations thereof.
  • Suspending/thickening agents according to the present invention may be present in an amount of about 1% to about 50% by weight based on total weight of the composition.
  • Suitable filler/bulking agents according to the present invention are selected from Starches, anhydrous lactose, mannitol, Maltodextrin, dicalcium phosphate, calcium sulfate, cellulose, kaolin, sodium chloride, sorbitol, sucrose and combinations thereof.
  • Disintegrating agents according to the present invention are responsible for quick disintegration of oral film upon contact with aqueous media or saliva in oral cavity.
  • Suitable non-limiting disintegrating agents according to the present invention are selected from Starch, Colloidal silicon dioxide, microcrystalline cellulose, Crospovidone, Sodium Starch glycolate, Croscarmellose sodium and combinations thereof.
  • “Sweetening agent or Sweetener” enhances the palatable/taste and pleasurable factor, which makes the film relatively acceptable or agreeable to the patient.
  • Suitable non-limiting sweeteners according to the present invention are selected from glucose (corn syrup), dextrose, invert sugar, fructose, and combinations thereof; saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Ammonium Glycyrrhizinate, Stevia Rebaudiana (Stevioside); chloro derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol, mannitol, maltodextrin, xylitol, and the like, hydrogenated starch hydrolysates and the synthetic sweetener 3 ,6-dihydro-6-methyl- 1-1-1 ,2,3-oxathiazin-4-one-2,2-dioxide
  • taste masking agents are responsible for blocking or diminishing the bitter taste of drug substance or excipients present in the film.
  • Suitable nonlimiting taste masking agents according to the present invention are selected from ion exchange resins, cyclodextrins and its derivatives, ready made available mixtures of taste mask enhancers and combinations thereof.
  • Suitable non-limiting buffering agents are selected from sodium carbonate, sodium bicarbonate, Citric Acid, Sodium Citrate, potassium carbonate, potassium bicarbonate, Ammonium Phosphate Dibasic, Sodium Phosphate Dibasic, sodium phosphate tribasic, potassium phosphate dibasic, potassium phosphate tribasic, Borate, calcium carbonate, magnesium carbonate, sodium hydroxide, magnesium hydroxide, potassium hydroxide, aluminium hydroxide, and combinations thereof.
  • Stabilizers according to the present invention are responsible for improving the shelf life by preventing the degradation of active agents.
  • Suitable non-limiting stabilizers according to the present invention may be selected from Tocopherol, Ascorbic acid, Citric acid, sodium bisulfite, sodium metabisulfite, propyl gallate, Potassium Metabisulfite, butylated hydroxytoluene and butylated hydroxyanisole and combinations thereof.
  • Suitable non-limiting surfactants according to the present invention are selected from cetyl alcohol, sodium lauryl sulfate, Polyoxyl 40, Polyoxyl 40 hydrogenated castor oil, Polyoxyl 15 hydroxystearate Polysorbate 80, Macrogol stearate, Hydrogenated Castor Oil, Spans®, Tweens®, Ethoxylated oils, poloxamers and combinations thereof.
  • Suitable anti-foaming agents according to the present invention are selected from simethicone or dimethicone or any agent that removes air bubbles/entrapped air/void from film-forming compositions.
  • “Flavors” in the present invention are responsible for masking the bitter or nauseating taste of incorporated drug.
  • Suitable non-limiting veterinary acceptable flavoring agents according to the present invention selected from chicken, turkey, beef, pork, lamb, fish, egg, cheese, edible yeast, dairy products which are of either artificially available or naturally available or extracted from meat or organs of animals.
  • Other non-limiting flavoring agents according to the present invention are selected from the group comprising of natural and synthetic flavoring liquids such agents includes volatile oils, synthetic flavor oils, flavoring aromatics, oils, liquids, oleoresins or extracts derived from plants, leaves, flowers, fruits, stems and combinations thereof.
  • a non-limiting representative list of examples includes mint oils, cocoa, pea nuts and citrus oils such as lemon, orange, grape, lime and grapefruit and fruit essences including apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot or other fruit flavors.
  • aldehydes and esters such as benzaldehyde (cherry, almond), citral i.e., alphacitral (lemon, lime), neral, i.e., beta-citral (lemon, lime), decanal (orange, lemon), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), tolyl aldehyde (cherry, almond), 2,6-dimethyloctanol (green fruit), and 2-dodecenal (citrus, mandarin), and combinations thereof.
  • aldehydes and esters such as benzaldehyde (cherry, almond), citral i.e., alphacitral (lemon, lime), neral, i.e., beta-citral (lemon, lime), decanal (orange, lemon), aldehyde C-8 (citrus fruits), aldehyde
  • Suitable coloring agents according to the present invention are selected from the group comprising of food, drug and cosmetic colors (FD and C), drug and cosmetic colors (D and C), or external drug and cosmetic colors (Ext. D and C). These colors are dyes, their corresponding lakes, and certain natural and derived colorants. Other non-limiting examples of coloring agents according to present invention are selected from known azo dyes, organic or inorganic pigments, or coloring agents of natural origin and combinations thereof.
  • excipients used in the oral film of the present invention may have one or more functions i.e. an excipient used in oral fi Im of the present invention may have multi-function like starch and modified starch used in the present invention may also act as a bulking agent and/or disintegrating agent; Maltodextrin used in the present invention may act as a sweetener and/or suspending/thickening agent and/or filler/bulking agent; Mannitol used in the present invention may act as a sweetener and/or as a filler/bulking agent; cellulose derivatives used in the present invention may act as a film forming polymer and/or suspending/thickening agent.
  • a skilled person should not construe the limit of an excipient stated or illustrated in any aspect or embodiment or an example of oral film in the present invention to a single function.
  • the present invention provides composition of oral film of Anti-emetic drug(s) and its pharmaceutically acceptable salts thereof for veterinary use, wherein the composition comprises from about 0.1% to about 75% by weight of Anti-emetic drug(s) and its pharmaceutically acceptable salts thereof.
  • the present invention provides composition of oral film of Antiemetic drug(s) and its pharmaceutically acceptable salts thereof for veterinary use, wherein the composition comprises: i. from about 0.1% to about 75% by weight of Anti-emetic drug(s) and its pharmaceutically acceptable salts; ii. from about 10% to about 75% by weight of at least one film forming polymer; iii. from about 1% to about 30% by weight of plasticizer; and iv. one or more pharmaceutically acceptable excipients; wherein the percentage (%) by weight is relative to the total weight of the composition.
  • the present invention provides process for preparing oral film of Anti-emetic drugs and its pharmaceutically acceptable salts thereof for veterinary use, wherein the process may be selected from solvent casting, hot melt extrusion or printing technology.
  • Solvents used according to the present invention in the process for preparing oral film of Antiemetic drugs or its pharmaceutically acceptable salts thereof may be selected from purified water, a polar organic solvent including, but not limited to ethanol, dichloromethane, isopropanol, acetone, methylene chloride, or any combination thereof.
  • the present invention provides oral film of Maropitant and its pharmaceutically acceptable salt thereof.
  • the present invention provides composition of oral film of Maropitant and its pharmaceutically acceptable salt thereof, wherein the composition comprises at least one film forming polymer, plasticizer and one or more pharmaceutically acceptable excipients.
  • the present invention provides process for preparing oral film of Maropitant and its pharmaceutically acceptable salt thereof, wherein the process may be selected from solvent casting, hot melt extrusion or printing technology.
  • the present invention provides composition of oral film of Maropitant and its pharmaceutically acceptable salts thereof for veterinary use, wherein the composition comprises from about 0.1% to about 75% by weight of Maropitant and its pharmaceutically acceptable salts thereof.
  • the present invention provides composition of oral film of Maropitant and its pharmaceutically acceptable salt thereof, wherein the composition comprises: i. from about 0.1% to about 75% by weight of Maropitant and its pharmaceutically acceptable salts; ii. from about 10% to about 75% by weight of at least one film forming polymer; iii. from about 1% to about 30% by weight of plasticizer; and iv. one or more pharmaceutically acceptable excipients; wherein the percentage (%) by weight is relative to the total weight of the composition.
  • the present invention provides composition of oral film of Acepromazine and its pharmaceutically acceptable salt thereof.
  • the present invention provides composition of oral film of Acepromazine and its pharmaceutically acceptable salt thereof, wherein the composition comprises at least one film forming polymer, plasticizer and one or more pharmaceutically acceptable excipients.
  • the present invention provides process for preparing oral film of Acepromazine and its pharmaceutically acceptable salt thereof, wherein the process may be selected from solvent casting, hot melt extrusion or printing technology.
  • the present invention provides composition of oral film of Acepromazine and its pharmaceutically acceptable salts thereof for veterinary use, wherein the composition comprises from about 0.1% to about 75% by weight of Acepromazine and its pharmaceutically acceptable salts thereof.
  • the present invention provides composition of oral film of Acepromazine and its pharmaceutically acceptable salt thereof, wherein the composition comprises: i. from about 0.1 % to about 75% by weight of Acepromazine and its pharmaceutically acceptable salt; ii. from about 10% to about 75% by weight of at least one film forming polymer; iii. from about 1% to about 30% by weight of plasticizer; and iv. one or more pharmaceutically acceptable excipients; wherein the percentage (%) by weight is relative to the total weight of the composition.
  • the present invention provides oral film of Aminopentamide and its pharmaceutically acceptable salt thereof.
  • the present invention provides composition of oral film of Aminopentamide and its pharmaceutically acceptable salt thereof, wherein the composition comprises at least one film forming polymer, plasticizer and one or more pharmaceutically acceptable excipients.
  • the present invention provides process for preparing oral film of Aminopentamide and its pharmaceutically acceptable salt thereof, wherein the process may be selected from solvent casting, hot melt extrusion or printing technology.
  • the present invention provides composition of oral film of Aminopentamide and its pharmaceutically acceptable salts thereof for veterinary use, wherein the composition comprises from about 0.1% to about 75% by weight of Aminopentamide and its pharmaceutically acceptable salt thereof.
  • the present invention provides composition of oral film of Aminopentamide and its pharmaceutically acceptable salt thereof, wherein the composition comprises: i. from about 0.1% to about 75% by weight of Aminopentamide and its pharmaceutically acceptable salt; ii. from about 10% to about 75% by weight of at least one film forming polymer; iii. from about 1% to about 30% by weight of plasticizer; and iv. one or more pharmaceutically acceptable excipients; wherein the percentage (%) by weight is relative to the total weight of the composition.
  • the present invention provides oral film compositions comprising one or more Anti-emetic drugs and its pharmaceutically acceptable salt thereof used for the treatment or prevention of Nausea and vomiting in animals.
  • the present invention provides oral film compositions comprising Maropitant and its pharmaceutically acceptable salts thereof used for the treatment or prevention of Nausea and vomiting in animals.
  • the present invention provides oral film compositions comprising Acepromazine and its pharmaceutically acceptable salt thereof used for the treatment or prevention of Nausea and vomiting in animals.
  • the present invention provides oral film compositions comprising Aminopentamide and its pharmaceutically acceptable salt thereof used for the treatment or prevention of Nausea and vomiting in animals.
  • step 3 Add Hydroxypropyl methylcellulose and/or Hydroxypropyl cellulose to step 2 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 4 Add Maropitant citrate to the dispersion of step 3 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 5 Add Microcrystalline Cellulose to dispersion of step 4 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 6 Add Polyethylene glycol to dispersion of step 5 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 7 Optionally add Glycerin to dispersion of step 6 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 8 Add flavor to dispersion of step 8 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 9 Homogenize the dispersion of step 9 using a homogenizer to obtain a homogenous dispersion.
  • step 10/11 is casted using a film casting machine where the dispersion is spreaded on a backing film to form a thin wet film which passed through a drying zone.
  • the dried film is cut into a desired size by using slitter. 14. Pack the film into suitable pouches/sachets
  • step 3 Add Hydroxypropyl methylcellulose to step 2 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 4 Add modified starch to step 3 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 4 Add Acepromazine maleate to step 4 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 7 Add Microcrystalline Cellulose to dispersion of step 6 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 8 Add Polyethylene glycol to dispersion of step 7 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 8 optionally add Glycerin to dispersion of step 8 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 8/9 Add colorant to dispersion of step 8/9 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 11 Add flavor to dispersion of step 10 under stirring and continue stirring till a homogenous dispersion is obtained. 12. Homogenize the dispersion of step 11 using a homogenizer to obtain a homogenous dispersion.
  • step 12/13 The dispersion of step 12/13 is casted using a film casting machine where the dispersion is spreaded on a backing film to form a thin wet film which passed through a drying zone.
  • the dried film is cut into a desired size by using slitter.
  • step 3 Add Hydroxypropyl methylcellulose to step 2 under stirring and continue stirring till a homogenous dispersion is obtained. 4. Optionally add modified starch to step 3 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 5 Add Aminopentamide hydrogen sulfate to step 4 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 8 optionally add Glycerin to dispersion of step 8 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 8/9 Add colorant to dispersion of step 8/9 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 11 Add, flavor to dispersion of step 10 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 11 Homogenize the dispersion of step 11 using a homogenizer to obtain a homogenous dispersion.
  • step 12/13 The dispersion of step 12/13 is casted using a film casting machine where the dispersion is spreaded on a backing film to form a thin wet film which passed through a drying zone.
  • the dried film is cut into a desired size by using slitter.
  • step 2 Added Maropitant Citrate to the solution of step 1 and stirred with a suitable stirrer to get a homogenous dispersion.
  • step 6 Added Microcrystalline cellulose to step 5 under stirring and continue stirring till a homogenous dispersion is obtained.
  • step 7 Added flavor to dispersion of step 6 under stirring and continue stirring till a homogenous dispersion is obtained.
  • the suspension was homogenized using a homogenizer to obtain a homogenous dispersion.
  • the dispersion is casted using a film casting machine where the dispersion is spreaded on a backing film to form a thin wet film which passed through a drying zone.
  • the dried film is cut into a desired size by using slitter.
  • Disintegration study The obtained oral film of Example 4 is tested for disintegration test using static method, where the oral film is placed in a petri dish containing water and the time taken for disintegration is observed.
  • Example 4 Dissolution: Also the obtained film of Example 4 is tested for dissolution in USP type 5 (Paddle over Disc) apparatus, 900ml volume, 75rpm using pH 7.2 Phosphate buffer as dissolution medium and the results are given below:
  • the oral film of present invention has shown more than 90% of drug is released within 15 minutes.
  • oral films of the present invention formulated according to an embodiment has shown quick disintegration and dissolution of drug, which solves the problems mentioned above like difficulty of administration, swallowing, dosing errors etc in animals.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Otolaryngology (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Inorganic Chemistry (AREA)
  • Nutrition Science (AREA)
  • Zoology (AREA)
  • Hospice & Palliative Care (AREA)
  • Physiology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne de nouvelles formes posologiques orales de médicaments Anti-émétiques et leurs sels pharmaceutiquement acceptables pour une utilisation vétérinaire, par exemple pour une administration orale à des animaux. Plus spécifiquement, la présente invention concerne des compositions et un procédé de préparation d'un film oral comprenant des médicaments Anti-émétiques et ses sels pharmaceutiquement acceptables.
PCT/IN2022/051138 2021-12-30 2022-12-29 Films oraux de médicaments anti-émétiques WO2023126971A1 (fr)

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IN202141062001 2021-12-30

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3215120A1 (fr) * 2014-11-03 2017-09-13 Zoetis Services LLC Composition vétérinaire à mâcher appétissante
CA3142445A1 (fr) * 2019-06-10 2020-12-17 Poly-Med, Inc. Procedes, dispositifs et compositions pour une administration locale

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3215120A1 (fr) * 2014-11-03 2017-09-13 Zoetis Services LLC Composition vétérinaire à mâcher appétissante
CA3142445A1 (fr) * 2019-06-10 2020-12-17 Poly-Med, Inc. Procedes, dispositifs et compositions pour une administration locale

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