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WO2005065640A1 - Nouvelles compositions pour formes posologiques orales, et procede de preparation de telles compositions - Google Patents

Nouvelles compositions pour formes posologiques orales, et procede de preparation de telles compositions Download PDF

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Publication number
WO2005065640A1
WO2005065640A1 PCT/IN2005/000003 IN2005000003W WO2005065640A1 WO 2005065640 A1 WO2005065640 A1 WO 2005065640A1 IN 2005000003 W IN2005000003 W IN 2005000003W WO 2005065640 A1 WO2005065640 A1 WO 2005065640A1
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Prior art keywords
indion
composition according
group
process according
acid
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PCT/IN2005/000003
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WO2005065640A8 (fr
Inventor
Rajesh Jain
Kour Chand Jindal
Sukhjeet Singh
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Panacea Biotec Ltd
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Panacea Biotec Ltd
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Priority to YUP-2005/0835A priority Critical patent/RS20050835A/sr
Publication of WO2005065640A1 publication Critical patent/WO2005065640A1/fr
Publication of WO2005065640A8 publication Critical patent/WO2005065640A8/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • 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
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Definitions

  • the present invention relates to novel buccal dosage form compositions of preferably poorly bioavailable drug(s), or drug(s) which undergo extensive presystemic metabolism, to provide extended release of the drug, and process of preparation thereof.
  • the compositions of the present invention are preferably in the taste masked form.
  • Migraine is a significant disorder, due to its high prevalence and disabling severity. The total sum of suffering caused by migraine is probably higher than that with any other kind of headache. Nearly 15% of the population suffer from this recurrent debilitating 12 attacks of headache associated with anorexia, nausea, vomiting and photo/ or phonophobia (Dechant, K.L. et al.; Drugs 43(5) 776 - 798, 1992). Migraine had not been clearly defined or classified until 1988, and its subforms had not been studied individually until very recently.
  • Migraine could be two types namely, migraine without aura (common migraine) and migraine with aura (classic migraine), respectively.
  • migraine without aura is characterised by headache attacks lasting 4 to 72 hours. This headache is usually severe, unilateral pulsating aggravated by physical activity and accompanied by nausea, 20 vomiting, photophobia and phonophobia.
  • the attacks are initiated by neurological symptoms called aura (visual, sensory, speech or motor symptoms).
  • 5-HT serotonin
  • 5-HT1D receptors located on cerebral blood vessels which are dilated and distended during migraine headache (Dechant, K.L. et al.; Drugs 43(5) 776 - 798, 1992).
  • 5-HT1D agonists are potent cerebral vasoconstrictors able to close arteriovenous anastomoses (AVAs) and also inhibit release of neurotransmitter acting on presynaptic 5-HT ID receptors.
  • AZAs arteriovenous anastomoses
  • 5-HT1D receptors mediate vasconstriction and platelet aggregation but also depolarize serotonergic neurons of brain stem.
  • Sumatriptan is a novel 5-HT ID receptor agonist which is effective in the acute treatment of migraine headache.
  • the antimigraine activity has been attributed to the selective vasoconstriction of cranial blood vessels which are dilated and distended during migraine headache and/or from inhibition of neurogenically mediated inflammation in dura mater.
  • Sumatriptan is also reported to have affinity for 5-HT1A and 5-HT1B receptors (Dechant, K.L. et al. ; Drugs 43(5) 776 - 798, 1992, Ghelardini et al., J, Pharmacol. Exp. Ther 279: 884 - 890, 1996).
  • Peak plasma concentration of Sumatriptan reached at a median of 10 min (range 5 to 20 min) after 6 mg subcutaneous dose and median of 1.5 hour (range 0.5 to 4.5 hours) after a 100 mg oral dose.
  • the mean bioavailability of Sumatriptan was 96% after subcutaneous administration but only 14% after oral, due to extensive presystemic metabolism (metabolized predominantly by the A' isoenzyme of monoamine oxidase). Protein binding is approximately 14 to 21%.
  • the terminal elimination half life is 2 hours.
  • zolmitriptan Like Sumatriptan, newer congeners zolmitriptan, avitriptan and naratriptan have affinity for both 5-HT1B and 5-HT1D receptor. Zolmitriptan showed similar pharmacology as compared to Sumatriptan with better potency, oral bioavailability and increased lipophilicity with central as well as peripheral synapses.
  • U.S. Pat. No. 4,948,580 describes a bioadhesive composition which may be employed as an oral drug delivery system and includes a freeze-dried polymer mixture formed of the copolymer poly(methyl vinyl ether/maleic anhydride) and gelatin dispersed in an ointment base. This composition is said to be useful to deliver active ingredients such as steroids, antifungal agents, and antibacterial agents, to the oral mucosa.
  • U.S. Pat. No. 4,915,948 describes a tablet which is said to have improved adhesion to mucous membranes.
  • the tablet includes a water soluble biopolymer selected from xanthan gum, a pectin and mixtures thereof, and a solid polyol having a solubility at room temperature in water greater than about 20 g/100 g solution.
  • U.S. Pat. Nos. 4,994,276, 5,128,143, and 5,135,757 describe a controlled . release excipient comprised of synergistic heterodisperse polysaccharides (e.g., a heteropolysaccharide, such as xanthan gum in combination with a polysaccharide gum capable of cross-linking with the heteropolysaccharide, such as locust bean gum) that is capable of processing into oral solid dosage forms using either direct compression, following addition of drug and lubricant powder, conventional wet granulation, or a combination of the two. Release of the medicament from the formulations is reported to proceed according to zero-order or first-order mechanisms.
  • synergistic heterodisperse polysaccharides e.g., a heteropolysaccharide, such as xanthan gum in combination with a polysaccharide gum capable of cross-linking with the heteropolysaccharide, such as locust bean gum
  • U.S. Pat. No. 4,059,686 describes a pharmaceutical preparation for oral cavity administration characterized by being a mixture of a pharmacologically active agent, a pharmaceutical carrier, and sodium polyacrylate in conventional dosage form. It adheres strongly to a local site and dissolves gradually over a prolonged period of time, releasing appropriate amounts of the active agent. The preparation is designed to adhere to mucosal membranes.
  • U.S. Pat. No. 3,972,995 describes a dosage form for buccal administration of a drug, and which is directly applicable to the interior surfaces of the mouth.
  • the dosage form is comprised of a support member which is water-insoluble, waterproof and flexible, a moisture-activated adhesive precursor applied to one surface of the support member, and an active ingredient applied to the central portion of the support member, either directly or dispersed in a matrix.
  • the dosage form is applied directly to the interior surface of the mouth.
  • Contact with saliva activates the adhesive and causes the support member to adhere to the interior surface of the mouth, thereby exposing the active ingredient to a limited area of the oral mucosa while isolating the active ingredient from the remainder of the oral environment.
  • U.S. Pat. No. 5,330,761 describes a controlled release bioadhesive tablet which includes a locally active agent, a heterodisperse gum matrix, and a pharmaceutically acceptable diluent. The final product adheres to mucous membranes and releases the locally active agent over a desired period of time.
  • U.S. Pat. No. 4,900,554 describes an adhesive device for application to body tissue having an adhesive layer and a backing layer positioned over one side of the adhesive layer.
  • the adhesive layer includes one or more acrylic acid polymers having adhesive properties upon dissolution or swelling in water and at least one water-insoluble cellulose derivative.
  • the backing layer is water-insoluble or sparingly water-soluble.
  • This patent discloses a composition comprising the active agent in an admixture that also includes a bioadhesive. Further, it includes a backing layer so that the adhesive does not adhere to adjacent areas. Further, the patent does not teach the use of a sustained release composition which can be attached to a tooth or other dental surface by a separate adhesive.
  • Oral controlled release delivery systems should ideally be adaptable so that release rates and profiles can be matched to physiological and chronotherapeutic requirements.
  • free forms such as sublingual tablets, troches, and buccal dosage forms.
  • other forms are designed to adhere to the oral mucosa and deliver an active pharmaceutical agent either directly into the oral mucosa, or into the saliva. Ointments and other sticky adhering compositions also have been used. The active ingredient in all these forms can act locally or systemically.
  • each of the above-cited references further discusses sustained release compositions, many of which can be used to release a pharmaceutically active agent in the oral cavity.
  • sustained release compositions many of which can be used to release a pharmaceutically active agent in the oral cavity.
  • a major problem is providing prolonged release at effective concentrations. For example, fungal infections beginning in the mouth and then entering other parts of the body are life-threatening to immuno-compromised patients. It is thus desirable to release antifungal agents on an ongoing basis. However, it is very difficult to achieve the same.
  • Buccal tablets and sublingual tablets are pharmaceutical preparations primarily intended for systemic effect. These tablets are placed between the cheek and gingival or under the tongue and allowed to dissolve slowly. The drugs absorbed through the oral mucous membrane enter directly, not through the portal circulation but through the systemic circulation. An advantage of these tablets is in the efficient absorption of the drug, because the drug is not decomposed by the liver. However, if the disintegration and dissolution of the tablet are too rapid, the object of this method of administration is not achieved.
  • a problem with these sustained release devices involves the area of comfort coupled with taste. Patients often reject these oral sustained release devices because they have a "foreign" feeling or, the composition has a bitter or unpleasant taste. As a result, these devices are often dislodged by the patient. Hence the bitter taste of such buccal compositions arising essentially due to the bitter taste of the active ingredient(s) present therein needs to be properly masked in order to make it patient compliant.
  • novel extended release buccal dosage form composition comprising at least one active agent or its tautomeric forms, analogues, isomers, polymorphs, solvates, or salts thereof; one or more ion exchange resin(s); one or more sustaining material(s); one or more release modifying agent(s); optionally with other pharmaceutically acceptable excipients.
  • poorly bioavailable drugs preferably triptan(s), its salts, esters or hydrates, more preferably Sumatriptan succinate, which provides extended release of the active ingredient.
  • It is yet another objective of the present invention to provide process for preparation of a composition which comprises of the following steps: i) complexation of active agent with ion exchange resin(s), ii) addition of one or more release modifying agent(s), and one or more sustaining material(s), iii) formulation of the mixture into a suitable dosage form.
  • the present invention relates to novel extended release buccal dosage form composition
  • novel extended release buccal dosage form composition comprising at least one active agent or its tautomeric forms, analogues, isomers, polymorphs, solvates, or salts thereof; one or more ion exchange resin(s); one or more sustaining material(s); one or more release modifying agent(s); optionally with other pharmaceutically acceptable excipients.
  • the present invention relates to novel extended release buccal dosage form composition
  • at least one active agent preferably triptan(s), its tautomeric forms, analogues, isomers, polymorphs, solvates, or salts, more preferably Sumatriptan succinate; one or more ion exchange resin(s), one or more sustaining material(s), one or more release modifying agent(s), optionally with other pharmaceutically acceptable excipients.
  • the active ingredient is selected from but not limited to a group comprising carvedilol, olanzapine, ondansetron, L-cardinipine, zolpidem, fluoxetine, etc. or its tautomeric forms, analogues, isomers, polymorphs, solvates, or salts thereof.
  • Sumatriptan succinate is bitter tasting drug and is expected to provide unpleasant taste when formulated as extended release buccal dosage form. It was however surprisingly found that when the drug was formulated as extended release buccal tablet composition according to the present invention, the bitter taste of Sumatriptan succinate was not evident.
  • the novel extended release buccal dosage form composition of the present invention comprises Domperidone or its salts, esters or hydrates thereof as the active ingredient.
  • the ion exchange resin(s) of the present invention is selected from a group comprising cross-linked polyacrylic copolymer resins (manufactured by Ion Exchange (India) Ltd.) such as Indion® 204, Indion® 214, Indion® 224, Indion® 234; Amberlite resins such as IRP-64®, Polacrilin potassium, and the like, or mixtures thereof.
  • the sustaining materials are selected from the group including cellulose and cellulose derivatives, waxes, carbomers, polyalkylene polyols, polycarbophils, methacrylate derivatives, gelatins, gums, polyethylene oxides, and the like.
  • the sustaining materials comprise materials which are non-toxic and pharmaceutically acceptable. These may be natural, semi-synthetic, synthetic or man-modified. Suitable materials include cellulose and cellulose derivatives like microcrystalline cellulose, methyl cellulose, ethyl cellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, cellulose acetate phthalate, cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate, cellulose acetate trimellitate, cellulose carboxymethyl ethers and their salts, hydroxypropyl methylcellulose phthalate , hydroxypropyl methylcellulose acetate succinate, Polyethylene; Polyquaternium-1; Poly vinyl acetate (homopolymer); Polyvinyl acetate phthalate; Propylene glycol alginate; PVM/MA (polyvinylmethylether/maleic anhydride) copolymer; Polyvinyl pyrrolidone (PVP)/ dimethiconylacrylate/pol
  • the ion exchange resin(s) is used as a sustaining material.
  • the release modifying agent(s) of the present invention is selected from the group comprising pore formers, pH modifiers and tonicity adjusting agents, or mixtures thereof.
  • Such release modifying agents are selected from the group including pore formers, pH modifiers and tonicity adjusting agents.
  • pH modifiers include citric acid, tartaric acid, fumaric acid, malic acid, maleic acid, ascorbic acid, and the like.
  • pore forming agents include sodium chloride, potassium chloride and the like.
  • tonicity adjusting agents include sodium chloride, potassium chloride, dextrose, lactose, povidone, and the like.
  • the release modifying agent(s) preferably are hydrophilic in nature and present in a blend of fast and slow hydrating polymers.
  • Pharmaceutically acceptable excipients as used in the composition are selected from the group of excipients generally used by persons skilled in the art e.g. diluents, disintegrants, binders, fillers, bulking agent, organic acid(s), colorants, stabilizers, preservatives, lubricants, glidants, chelating agents and the like.
  • the composition further comprises of a taste masking agent selected from but not limited to a group comprising Ion exchange resins, Acrylic and methacrylic acid polymers, Carbopols, and the like.
  • the ion exchange resin(s) functions as a taste masking agent.
  • compositions of the present invention may be formulated as an oral dosage form such on tablets, capsules, patches and the like.
  • the compositions may be in the form of compressed tablets, moulded tablets, products prepared by extrusion or film cast technique, and the like.
  • the composition of the present invention is in the form of tablets.
  • the tablets can be prepared by either direct compression, dry compression (slugging), or by granulation.
  • the granulation technique is either aqueous or non-aqueous.
  • the tablets of the present invention are prepared by non-aqueous granulation technique.
  • the non-aqueous solvent used is selected from a group comprising ethanol or isopropyl alcohol.
  • a process for preparation of a composition which comprises complexation of active agent with ion exchange resin(s), addition of one or more release modifying agent(s), and one or more sustaining material(s), and formulation of the mixture into a suitable dosage form.
  • the process of preparation of the composition of the present invention involves complexation of sumatriptan succinate with ion exchange resin(s), addition of release modifying agent such as an organic acid to break the complex and sustaining material to provide for gradual release of the drug into oral cavity primarily by erosion process; addition of one or more pharmaceutically acceptable excipients as described herein, and formulating into tablets.
  • release modifying agent such as an organic acid
  • the active ingredient is primarily released by erosion or diffusion process.
  • the said compositions provide a taste masked dosage form, which can be retained in the oral cavity for long period of time. Moreover the said composition is not expected to compromise the absorption of the poorly bioavailable drug, such as Sumatriptan from the oral cavity.
  • sumatriptan succinate was complexed with ion exchange resin(s), the process being reversible under acidic conditions. Such complexation. would result in liberation of free drug in the stomach resulting in reduced bioavailability due to first pass metabolism.
  • an organic acid is added to the composition, the release of the drug from the taste masked formulation increases significantly at pH of the oral cavity. Moreover, this release is not accompanied by increase in bitter taste of the drug.
  • the organic acid added to the formulation alters the pH in the microenvironment of the complex resulting in the gradual breakdown of the complex. The uncomplexed drug is then slowly released into the oral cavity.
  • the release rate of the drug from the dosage form can be modified using one or more sustaining materials as described herein.
  • the sumatriptan succinate complex along with organic acid is embedded in a matrix of sustaining materials such as controlled release polymers which form a diffusion layer around the tablet when it comes in contact with the fluid of oral cavity.
  • This diffusion layer controls the penetration of fluid into the tablet which, in turn controls the gradual breakdown of the complex. It also controls the release of the uncomplexed drug out of the tablet and into the oral cavity.
  • Example 1 Ingredients mg/tablet i) Sumatriptan succinate 25.0 ii) Ion exchange resin (Cross-linked polyacrylic copolymer resin; Indion® 204) 75.0
  • step 2 Filter the slurry of step 1 and dry. Sift the dried mass.
  • Example 2 Ingredient mg/tablet i) Sumatriptan succinate 25.0 ii) Ion exchange resin (Cross-linked polyacrylic copolymer resin; Indion® 204) 75.0
  • step 2 Filter the slurry of step 1 and dry. Sift the dried mass.
  • Example 3 Ingredients mg/tablet i) Domperidone maleate (equivalent to Domperidone 10 mg) 12.72 ii) Ion exchange resin (Cross-linked polyacrylic copolymer resin; Indion® 204) 75.00 iii) Maltodextrin 48.00 iv) Sucrose 30.00 v) Carboxymethyl cellulose 18.00 vi) Hydroxypropyl methyl cellulose 8.00 vii) Hydroxypropyl cellulose 8.00 viii) Citric acid 15.00 ix) Sodium chloride 5.00 x) Povidone 3.00 xi) Isopropyl alcohol Lost in processing
  • step 2 Filter the slurry of step 1 and dry. Sift the dried mass.
  • Example 4 Ingredient mg/tablet i) Domperidone maleate (equivalent to Domperidone 10 mg) 12.72 ⁇ ) Ion exchange resin (Cross -linked polyacrylic copolymer resin; Indion® 204) 75.00 iii) Lactose 48.00 iv) Locust bean gum 10.00 v) Xanthan gum 8.00 vi) Povidone 3.00 vii) Isopropyl alcohol Lost in processing
  • Example 5 Ingredients mg/tablet i) Olanzapine 10.00 ii) Ion exchange resin (Cross-linked polyacrylic copolymer resin; Indion® 214) 75.00 iii) Maltodextrin 48.00 iv) Sucrose 30.00 v) Carboxymethyl cellulose 18.00 vi) Hydroxypropyl methyl cellulose 8.00 vii) Hydroxypropyl cellulose 8.00 viii) Citric acid 15.00 ix) Sodium chloride 5.00 x) Povidone 3.00 xi) Isopropyl alcohol Lost in processing
  • step 2 Filter the slurry of step 1 and dry. Sift the dried mass.
  • step 2 Filter the slurry of step 1 and dry. Sift the dried mass.
  • Example 7 Ingredients mg/tablet i) Zolpidem tartrate 10.0 ii) Ion exchange resin (Cross-linked polyacrylic copolymer resin; Indion® 234) 75.0 iii) Maltodextrin 48.0 iv) Sucrose 30.0 v) Carboxymethyl cellulose . 18.0 vi) Hydroxypropyl methyl cellulose 8.0 vii) Hydroxypropyl cellulose 8.0 viii) Citric acid 15.0 ix) Sodium chloride 5.0 x) Povidone 3.0 xi) Isopropyl alcohol Lost in processing xii) Magnesium stearate 3.0 xiii) Water Lost in processing

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  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention se rapporte à de nouvelles compositions pour formes posologiques orales, qui contiennent de préférence un ou plusieurs médicaments à faible biodisponibilité, ou un ou plusieurs médicaments faisant l'objet d'une biotransformation hépatique présystémique importante. Les compositions selon l'invention permettent une libération prolongée du médicament dans la cavité buccale, et se présentent de préférence sous forme de compositions au goût masqué. L'invention concerne également un procédé de préparation de telles compositions.
PCT/IN2005/000003 2004-01-06 2005-01-05 Nouvelles compositions pour formes posologiques orales, et procede de preparation de telles compositions Ceased WO2005065640A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
YUP-2005/0835A RS20050835A (sr) 2004-01-06 2005-01-05 Sastavi bukalnih doznih oblika za produženo otpuštanje leka i postupak za njihovo dobijanje

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN24/DEL/2004 2004-01-06
IN26/DEL/2004 2004-01-06
IN26DE2004 2004-01-06
IN24DE2004 2004-01-06

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WO2005065640A1 true WO2005065640A1 (fr) 2005-07-21
WO2005065640A8 WO2005065640A8 (fr) 2005-12-08

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007096906A3 (fr) * 2006-02-27 2007-10-18 Panacea Biotec Ltd Nouvelles compositions bucco-adhésives et procédé d'élaboration desdites compositions
WO2008155620A1 (fr) * 2007-06-20 2008-12-24 Develco Pharma Schweiz Ag Forme posologique contenant une matrice dispersible de granulés à libération entretenue
CN100450548C (zh) * 2006-12-22 2009-01-14 江苏奥赛康药业有限公司 一种波拉克林树脂组合物的口腔贴片及其制备方法
US8133506B2 (en) 2008-03-12 2012-03-13 Aptalis Pharmatech, Inc. Drug delivery systems comprising weakly basic drugs and organic acids
WO2013056159A1 (fr) * 2011-10-13 2013-04-18 Jaleva Pharmaceuticals, Llc Procédés et compositions pour administration rapide d'agents actifs par la bouche
CN105232502A (zh) * 2015-02-10 2016-01-13 万全万特制药江苏有限公司 含波拉克林钾和盐酸氟西汀复合物的口崩片及其制备方法
EP2906210A4 (fr) * 2012-10-12 2016-06-08 Jaleva Pharmaceuticals Llc Procédé de préparation de teintures de résine
US10220194B2 (en) 2012-11-28 2019-03-05 Advanced Resin Therapeutics, Inc. Dual chamber applicator
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CN114344241A (zh) * 2021-12-15 2022-04-15 悦康药业集团安徽天然制药有限公司 一种聚丙烯酸树脂改性吸附药物载体及其制备方法

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WO2007096906A3 (fr) * 2006-02-27 2007-10-18 Panacea Biotec Ltd Nouvelles compositions bucco-adhésives et procédé d'élaboration desdites compositions
CN100450548C (zh) * 2006-12-22 2009-01-14 江苏奥赛康药业有限公司 一种波拉克林树脂组合物的口腔贴片及其制备方法
WO2008155620A1 (fr) * 2007-06-20 2008-12-24 Develco Pharma Schweiz Ag Forme posologique contenant une matrice dispersible de granulés à libération entretenue
US8133506B2 (en) 2008-03-12 2012-03-13 Aptalis Pharmatech, Inc. Drug delivery systems comprising weakly basic drugs and organic acids
WO2013056159A1 (fr) * 2011-10-13 2013-04-18 Jaleva Pharmaceuticals, Llc Procédés et compositions pour administration rapide d'agents actifs par la bouche
EP2906210A4 (fr) * 2012-10-12 2016-06-08 Jaleva Pharmaceuticals Llc Procédé de préparation de teintures de résine
US10220194B2 (en) 2012-11-28 2019-03-05 Advanced Resin Therapeutics, Inc. Dual chamber applicator
CN105232502A (zh) * 2015-02-10 2016-01-13 万全万特制药江苏有限公司 含波拉克林钾和盐酸氟西汀复合物的口崩片及其制备方法
RU2690159C1 (ru) * 2015-07-23 2019-05-31 Атена Драг Деливери Солюшнз Пвт Лтд. Композиция золпидема и способ ее получения
CN114344241A (zh) * 2021-12-15 2022-04-15 悦康药业集团安徽天然制药有限公司 一种聚丙烯酸树脂改性吸附药物载体及其制备方法
CN114344241B (zh) * 2021-12-15 2024-01-30 悦康药业集团安徽天然制药有限公司 一种聚丙烯酸树脂改性吸附药物载体及其制备方法

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