[go: up one dir, main page]

WO2007102038A1 - Formulations de ziprasidone - Google Patents

Formulations de ziprasidone Download PDF

Info

Publication number
WO2007102038A1
WO2007102038A1 PCT/IB2005/003754 IB2005003754W WO2007102038A1 WO 2007102038 A1 WO2007102038 A1 WO 2007102038A1 IB 2005003754 W IB2005003754 W IB 2005003754W WO 2007102038 A1 WO2007102038 A1 WO 2007102038A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
particle size
mean particle
range
pharmaceutical composition
Prior art date
Application number
PCT/IB2005/003754
Other languages
English (en)
Inventor
Girish Kumar Jain
Mohan Kumar Kondapaturu
Original Assignee
Wockhardt Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Wockhardt Limited filed Critical Wockhardt Limited
Priority to PCT/IB2005/003754 priority Critical patent/WO2007102038A1/fr
Publication of WO2007102038A1 publication Critical patent/WO2007102038A1/fr

Links

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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin

Definitions

  • the present invention relates to an oral pharmaceutical formulation of antipsychotic such as Ziprasidone, in particular, ziprasidone hydrochloride hydrate particles having a maximum size cutoff, and to a method of treating psychosis and related disorders with such formulation.
  • antipsychotic such as Ziprasidone
  • ziprasidone hydrochloride hydrate particles having a maximum size cutoff
  • the most important attribute of drug substance that determines its performance in formulation is its particle characteristics. This is particularly true in those cases where the drug is poorly soluble or a free acid form with poor solubility at low pH values. Such drugs are likely to exhibit dissolution-rate-limited absorption, and if dissolution does not take place rapidly enough, a therapeutic concentration in body fluids may never be achieved, the peak plasma concentration may be significantly delayed, or much of the drug may bypass that region of the gastrointestinal tract where absorption is best. Particle size reduction (e.g. Micronization) is often utilized to enhance dissolution rate. Small particles present a larger surface area per unit weight to the dissolution media and hence dissolve more rapidly than large particles.
  • Particle size reduction e.g. Micronization
  • Particle size and surface area are two of the most important properties determining the solubility rate of a drug and thus potentially its bioavailability.
  • bioavailability problems and bioequivalence due to inappropriate particle size of the drug substance There are numerous examples of bioavailability problems and bioequivalence due to inappropriate particle size of the drug substance.
  • Most drugs are passively absorbed and their rates of absorption are dependent upon the concentration gradients in each case; by increasing the dissolution rate in the GI tract, the absorption rate is necessarily increased so long as the dissolution rate is still the limiting step. If a drug is not absorbed enough to be systemically active and if the drug is not soluble enough to be used for its local action in the gut, the reduction of particle size may improve its therapeutic efficacy.
  • Particle size and shape also play an extremely important role in the homogeneity of powder blend and the unblending of powders in a mixer. Segregation in handling or during the compaction process has a significant effect on the content uniformity of the finished products. Particle size can also affect the stability of a drug substance in that it governs the surface area available for oxidation and hydrolysis. Surface area is critical for interaction with excipients in tablet dosage forms and can greatly affect stability.
  • Ziprasidone is an antipsychotic agent with the following chemical name: 5-[2-[4-(l,2- benzisothiazol-3-yl)-l-pi ⁇ erazinyl] ethyl]-6- chloro-l,3-dihydro-2 H -indol-2-one.
  • Ziprasidone is disclosed in U.S. Patent no. 4,831,031 and 5,312,925 (assigned to Pfizer). Ziprasidone inhibits synaptic reuptake of serotonin and norepinephrine. No appreciable affinity was exhibited for other receptor/binding sites tested, including the cholinergic muscarinic receptor.
  • ziprasidone as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug's efficacy in schizophrenia is mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2 (5HT 2 ) antagonism. Ziprasidone's antagonism of histamine H ] receptors may explain the somnolence observed with this drug.
  • D 2 dopamine type 2
  • 5HT 2 serotonin type 2
  • Ziprasidone is typically administered as the hydrochloride acid addition salt.
  • Ziprasidone is well absorbed after oral administration, reaching peak plasma concentrations in 6 to 8 hours.
  • the absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%.
  • the absorption of ziprasidone is increased up to two-fold in the presence of food.
  • the hydrochloride salt possesses relatively poor aqueous solubility, a factor that affects bioavailability.
  • US 5,312,925 (Pfizer Inc.) describes a process for the synthesis of monohydrate of 5-(2- (4-l,2-benzisothiazol-3-yl)piperazinyl)ethyl)-6-chloro-l,3-dihydro-2H-indol-2-one hydrochloride and its characterization based on IR, XRD and moisture content.
  • the '925 patent also discloses that the hemihydrate may be obtained by the process described in Example 16 of US Patent No. 4,831,031 and their characterization by IR, XRD and moisture content. It also discloses the IR, XRD and moisture content of anhydrous Ziprasidone hydrochloride.
  • the monohydrate of Ziprasidone hydrochloride was prepared by reacting anhydrous 5- (2-(4-l,2-benzisothiazol-3-yl)piperazinyl)ethyl)-6-chloro-l,3-dihydro-2H-indol-2-one with aqueous hydrochloric acid.
  • the temperature range of the reaction was maintained between 60 to 65 °C and aqueous hydrochloride used for salt formation was around 0.7 M.
  • the reaction times were set around 3 to 24 hours.
  • the final product thus obtained was dried carefully monitored conditions to make certain that water content was from about 3.8 % to about 4.5 % to obtain the stable monohydrate.
  • step (3) cooling the solution resulting from step (3) and crystals were collected by filtration and drying.
  • the patent also describes ziprasidone composition comprising ziprasidone free base or crystalline ziprasidone hydrochloride particles having a mean particle size equal to or less than about 85 ⁇ m alongwith a diluent or carrier.
  • the prosecution file history of the '366 patent describes the significance of particle size of ziprasidone as mentioned below. As known in the prior art, with increase in particle size, surface area decreases and consequently dissolution and bioequivalence are also expected to decrease. This can be applied easily to drugs falling under BCS classification II (poorly soluble, highly permeable).
  • Ziprasidone belongs to this class so it is anticipated that formulations using higher particle size will show poor solubility and hence poor availability.
  • the invention as claimed in the '366 patent shows that ziprasidone with mean particle size of equal to or less than about 85 ⁇ m show same solubility (in contrast, to what is anticipated theoretically) and hence are bioequivalent with a formulation having a particle size of about 20 ⁇ m.
  • a perusal of file wrapper reveals that, though a composition is claimed, what it transcends to is the bioequivalence of a capsule formulation made with ziprasidone of mean particle size about 20 ⁇ m is equivalent to a capsule formulation made with ziprasidone of mean particle size of 85 ⁇ m.
  • micronised drug powders are extremely cohesive due to high energy milling processes causing significant dislocation of cystal structure on the particle surface. These particles tend to agglomerate during the solid state processing and unless properly formulated can lead to poor dissolution performance.
  • WO 04050655A1 (Dr. Reddy's Laboratories, Inc.) describes amorphous form of ziprasidone hydrochloride and a composition comprising the same.
  • WO 2005/020929 (Ahmed et. al) describes a sustained release solid oral dosage form comprising ziprasidone alongwith suitable pharmaceutically acceptable carrier.
  • the said dosage form releases ziprasidone from about 4 to about 24 hours.
  • the said dosage form further comprises of bi or multiplayer tablets comprising one active layer and the other layer comprised of swelleble material.
  • Micronised Ziprasidone is used in this sustained release dosage form i.e. having a mean particle size of less than about 5 ⁇ m. Jet milling is done to micronize the drug.
  • US application no. 2005/0163858 assigned to Alpharma describe a formulation of ziprasidone or its pharmaceutically acceptable salts having a mean particle size greater than 85 ⁇ m alongwith a pharmaceutical carrier.
  • a pharmaceutical composition for ziprasidone hydrochloride hydrate according to the present invention provides good therapeutic effect in the treatment of psychotropic and related disorders.
  • the said composition exhibits good dissolution properties at physiological pH.
  • the invention is surprising in this respect, however in that the rate of dissolution in vitro does not correlate with particle size. i.e. ziprasidone dissolution rate in aqueous media (from the composition according to present invention) does not vary substantially with particle size, and therefore appears to be largely independent of it.
  • ziprasidone free base or ziprasidone hydrochloride hydrate or its salt or pharmaceutically acceptable derivative thereof can be formulated in a composition having a reasonable particle size (which is easily manageable using conventional formulations methodology and equipment). Therefore, surprisingly, the invention provides a formulation of ziprasidone providing enhanced invitro and invivo performance independent of particle size of ziprasidone or it's salt or solvate or derivatives thereof.
  • the said composition is made up of ziprasidone hydrochloride hydrate salt with specific particle size together with suitable pharmaceutical excipients.
  • the said composition is prepared using dry granulation process and therefore provides a stable composition with homogeneity of drug content in the formulation.
  • the present invention provides an oral pharmaceutical composition comprising therapeutically effective amount of ziprasidone hydrochloride hydrate or it's salt or pharmaceutically acceptable derivative thereof having a mean particle size in the range of 100 - 300 ⁇ m alongwith other suitable pharmaceutical excipients such as diluents, binders, disintegrants, surfactants, solubilizers, glidants, lubricants and the like to enhance stability and dissolution properties at physiologic pH.
  • suitable pharmaceutical excipients such as diluents, binders, disintegrants, surfactants, solubilizers, glidants, lubricants and the like to enhance stability and dissolution properties at physiologic pH.
  • the said oral composition comprising ziprasidone can be prepared by simple manufacturing process for solid orals known in the art.
  • the present invention yields a stable oral composition comprising ziprasidone hydrochloride hydrate or it's salt or pharmaceutically acceptable derivative thereof having a mean particle size in the range of 100 - 300 ⁇ m
  • an object of the present invention to provide an oral pharmaceutical composition comprising ziprasidone of mean particle size in the range of 100-300 ⁇ m and a process for preparing the same for administration of ziprasidone to patients suffering from psychotropic and related disorders.
  • the present invention therefore also provides a pharmaceutical composition
  • a pharmaceutical composition comprising ziprasidone hydrochloride hydrate or it's salt or pharmaceutically acceptable derivative thereof having a mean particle size in the range of 100-300 ⁇ m along with suitable excipients.
  • Another aspect of the present invention is a solid pharmaceutical composition adapted for oral administration.
  • the said composition comprises ziprasidone, particularly, ziprasidone hydrochloride hydrate of mean particle size in the range of 100-300 ⁇ m alongwith suitable pharmaceutical excipients. It is still further object of the present invention to provide an orally deliverable solid formulation of ziprasidone hydrochloride hydrate that exhibit good stability and dissolution properties at physiological pH.
  • the present invention further provides a method of administering to a subject in need of treatment a pharmaceutical product or formulation substantially as hereinbefore described and in particular a solid composition which can be administered orally and as such is particularly suited for the treatment of depression and other related psychotropic disorders.
  • the present invention further provides use of ziprasidone in the manufacture of a medicament for the treatment of psychotropic and other related disorders.
  • a medicament according to the present invention comprises a formulation substantially as herein described, and in particular a solid formulation, typically a capsule formulation substantially as hereinafter described.
  • the present formulation provides noticeable benefits being simple operational process of manufacturing said stable oral solid pharmaceutical composition.
  • Yet another object of this present invention is to provide for an oral solid composition comprising an antipsychotic, that is bioequivalent to the reference composition.
  • Figure 1 illustrates comparative dissolution profile of Ziprasidone from ziprasidone capsules (Example- 1) in pH 7.5 Buffer
  • Figure 2 illustrates comparative dissolution profile of Ziprasidone from ziprasidone capsules (Example-2) in pH 7.5 Buffer
  • Figure 3 illustrates comparative dissolution profile of Ziprasidone from ziprasidone capsules (Example-3) in pH 7.5 Buffer DETAILED DESCRIPTION OF THE INVENTION
  • the present invention provides an oral pharmaceutical composition comprising therapeutically effective amount of ziprasidone hydrochloride hydrate or it's salt or pharmaceutically acceptable derivative having a mean particle size in the range of 100 - 300 ⁇ m alongwith other suitable pharmaceutical excipients such as diluents, binders, disintegrants, surfactants, solubilizers, glidants, lubricants and the like to enhance stability and dissolution properties at physiologic pH.
  • suitable pharmaceutical excipients such as diluents, binders, disintegrants, surfactants, solubilizers, glidants, lubricants and the like to enhance stability and dissolution properties at physiologic pH.
  • the said oral composition comprising ziprasidone can be prepared by simple manufacturing process for solid orals known in the art.
  • the present invention yields a stable oral composition comprising ziprasidone hydrochloride hydrate or it's salt or pharmaceutically acceptable derivative thereof having a mean particle size in the range of 100 - 300 ⁇ m along
  • pharmaceutically acceptable derivative means various pharmaceutical equivalent isomers, enantiomers, complexes, hydrates, polymorphs, etc of ziprasidone hydrochloride hydrate.
  • composition includes but not limited to solutions and/or suspensions, dispersions, concentrates, ready mix, powders, granules, tablets, micro-tablets, capsules, pellets, comprising ziprasidone hydrochloride hydrate or its pharmaceutically acceptable derivative thereof in a core constituted by drug having a mean particle size in the range of 100-300 ⁇ m alongwith suitable pharmaceutical excipients.
  • terapéuticaally effective amount means an amount of the drug, which is capable of eliciting a physiological response in a human patient. More specifically, the term “therapeutically effective amount” means the amount of drug, which is capable of treating depression and related psychotropic disorders.
  • the said medicament according to the present invention comprises a formulation substantially as herein described, and in particular a capsule or a tablet or micro-tablets or granules or pellets filled in capsule formulation, typically an oral capsule formulation substantially as hereinafter further described.
  • a formulation according to the present invention provides a novel capsule dosage form comprising ziprasidone hydrochloride hydrate or its pharmaceutically acceptable derivatives thereof having a mean particle size of 100-300 ⁇ m alongwith suitable pharmaceutical excipients.
  • ziprasidone hydrochloride hydrate or its salts or pharmaceutically acceptable derivatives thereof may be prepared as crystalline particles of various sizes as described under the our original PCT application no. WO05054235, filed on 28 th November 2003.
  • the particles have a mean particle size greater than 100 m, preferably having a mean particle size about 100 m to about 300 m, and more preferably about 100 m to about 250 m and most preferably about 100 to about 200 m.
  • the term "particles" refers to individual particles regardless of whether the particles exist singly or are agglomerated.
  • Reference to ziprasidone or ziprasidone hydrochloride hydrate particles having "a mean particle size” is defined herein as "volume mean diameter” based on the assumption that the particles are of a spherical shape.
  • Particle size distribution can be measured by techniques known in the art, such as Malvern light scattering.
  • the active is preferably ziprasidone hydrochloride hydrate.
  • the particles may be combined with pharmaceutically acceptable carriers to provide pharmaceutical formulations, particularly formulations that provide bioequivalence with that of the reference product Geodon R Capsules. Suitable carriers are described further herein.
  • the particles having a mean particle size of greater than 100 ⁇ m is combined with a pharmaceutically acceptable carrier or other excipients resulting in formulation that provides an AUC that is greater than 80% and less than 120% of the mean AUC observed for an equivalent formulation of Geodon R .
  • a formulation comprising particles having mean particle size of 100 ⁇ m to 300 ⁇ m provides a maximum ziprasidone plasma concentration (Cmax) that is greater than 80 % and less than 120% of the Cmax observed for an equivalent formulation of Geodon R .
  • an oral pharmaceutical capsule dosage form may be formulated by mixing the active agent with suitable diluents, binders, disintegrants, wetting agents, surfactants, lubricants and the like and compacting it using suitable roller compactor. Excipients are usually added in a specified order to increase the rate of dissolution and to facilitate a rapid approach to equilibrium. The slugs such produced, are milled to the required particle size, mixed with glidants and lubricants and filled into the suitable size capsules.
  • the present invention provides a pharmaceutical product manufactured by using suitable process and comprising of active agent with specific particle size distribution as hereinbefore described.
  • Another aspect of the present invention relates to oral capsule composition of antidepressant such as ziprasidone hydrochloride hydrate or its salt or pharmaceutically acceptable derivative thereof comprising ziprasidone hydrochloride hydrate or its salt or pharmaceutically acceptable derivative thereof as pharmaceutically active agent having a mean particle size of 100-300 ⁇ m and having been made with the simple manufacturing process.
  • the capsule composition contains a pharmaceutically effective amount of ziprasidone hydrochloride hydrate or its salt or pharmaceutically acceptable derivative thereof, for treating psychotropic and other related disorders.
  • the oral capsule composition is comprised of pharmaceutically effective amount of at least one antidepressant such as ziprasidone hydrochloride hydrate or its salt or pharmaceutically acceptable derivative thereof mixed together with other pharmaceutically acceptable excipients for treating depression and other related psychotropic disorders.
  • at least one antidepressant such as ziprasidone hydrochloride hydrate or its salt or pharmaceutically acceptable derivative thereof mixed together with other pharmaceutically acceptable excipients for treating depression and other related psychotropic disorders.
  • “Pharmaceutically acceptable excipient,” as used herein means a pharmacologically inactive ingredient which is used to formulate a drug product and which is readily known and available in the pharmaceutical arts. Examples of such excipients are given below:
  • Suitable excipients employed in a pharmaceutical formulation according to the present invention may include commonly used pharmaceutical excipients such as diluents, binders, disintegrants, wetting agents, surfactants, glidants, lubricants and the like.
  • Wetting agents and/or surfactants are used to improve the solubility of the active agent in the solution. The artisan can select appropriate wetting agents and/or surfactants in order to get good solubility of active agents.
  • any one of the foregoing ziprasidone particle- containing formulations preferably provides a mean maximum plasma concentration of ziprasidone of about 120 ng/ml in the fed mode. Furthermore, the formulations preferably provide a mean time to maximum plasma concentration of ziprasidone of about 3-9 hours in the fed mode.
  • Formulations prepared from the foregoing particle-size distributions preferably provide a dissolution profile such that at least 70% of the ziprasidone therein dissolves within 45 minutes using a USP-II apparatus containing 900 ml of aqueous sodium phosphate buffer, pH 7.5, containing 2 % (w/v) sodium lauryl sulphate, and equipped with paddles stirring at 75 rpm.
  • the present invention further comprises a process of preparing a pharmaceutical product, or a pharmaceutical formulation, or a medicament as substantially as hereinbefore described.
  • a process of preparing a pharmaceutical product, or a pharmaceutical formulation, or a medicament as substantially as hereinbefore described comprises providing at least one antipsychotic along with suitable pharmaceutical excipients, wherein preferably the formulation comprises an orally deliverable pharmaceutical formulation, typically in capsule form.
  • a capsule formulation was prepared using the following excipients:
  • Sift ingredients 1,2,3 and 4 through sieve of suitable mesh size. Mix and blend the contents in a suitable blender. The blend is then compacted using suitable roll compactor. The resultant slugs are milled to suitable size and blended with talc in a suitable blender. The resultant granules are filled in suitable size capsule shells.
  • Figure - 1 shows the comparative dissolution profiles of the said invented capsule formulation and the reference formulation (Geodon R Capsules).
  • Example-2 shows the comparative dissolution profiles of the said invented capsule formulation and the reference formulation (Geodon R Capsules).
  • a capsule formulation was prepared using the following excipients:
  • Sift ingredients 1,2,3 and 4 through sieve of suitable mesh size. Mix and blend the contents in a suitable blender. The blend is then compacted using suitable roll compactor. The resultant slugs are milled to suitable size and blended with talc in a suitable blender. The resultant granules are filled in suitable size capsule shells.
  • Figure - 2 shows the comparative dissolution profiles of the said invented capsule formulation and the reference formulation (Geodon R Capsules).
  • a capsule formulation was prepared using the following excipients:
  • Sift ingredients 1,2,3 and 4 through sieve of suitable mesh size. Mix and blend the contents in a suitable blender. The blend is then compacted using suitable roll compactor. The resultant slugs are milled to suitable size and blended with talc in a suitable blender. The resultant granules are filled in suitable size capsule shells.
  • Figure - 3 shows the comparative dissolution profiles of the said invented capsule formulation and the reference formulation (Geodon R Capsules).
  • a randomized, two period, two treatment, single dose crossover comparative bioavailability study was performed between the test ziprasidone hydrochloride hydrate capsules with reference product (Geodon R capsules) in healthy, adult human subjects under fed conditions. A total of 12 subjects were enrolled in the study and all of them completed the study. The investigations included two treatment phases and were separated by washout period of three days between the treatments. All the treatment phases were of 24 hours duration each.
  • a randomized three-period, three treatment, three sequence single dose crossover comparative bioavailability study was also performed between the test ziprasidone hydrochloride hydrate capsules with reference product (Geodon R capsules) in healthy, adult human subjects under fasting conditions. A total of 12 subjects were enrolled in the study and all of them completed the study. The investigations included three treatment phases and were separated by washout period of three days between the treatments
  • the area under the time curve concentrations (AUC 0-t ) following test formulation was found to be comparable to the AUC following reference ziprasidone capsule formulation.
  • AUC area under the time curve concentrations
  • oral capsule formulation was found to be bioequivalent to the Reference ziprasidone capsule formulation.

Landscapes

  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition pharmaceutique orale qui comprend une quantité thérapeutiquement efficace d'hydrate d'hydrochlorure de ziprasidone ou son sel ou encore un dérivé pharmaceutiquement acceptable de ce dernier et qui présente une granulométrie moyenne comprise entre 100 et 300 gm ainsi que d'autres excipients pharmaceutiques appropriés tels que des diluants, des liants, des délitants, des tensioactifs, des agents de solubilisation, des agents de glissement, des lubrifiants et autres. La composition orale comprenant de la ziprasidone peut être préparée au moyen d'un processus de fabrication simple.
PCT/IB2005/003754 2005-12-05 2005-12-05 Formulations de ziprasidone WO2007102038A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/IB2005/003754 WO2007102038A1 (fr) 2005-12-05 2005-12-05 Formulations de ziprasidone

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2005/003754 WO2007102038A1 (fr) 2005-12-05 2005-12-05 Formulations de ziprasidone

Publications (1)

Publication Number Publication Date
WO2007102038A1 true WO2007102038A1 (fr) 2007-09-13

Family

ID=38474626

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2005/003754 WO2007102038A1 (fr) 2005-12-05 2005-12-05 Formulations de ziprasidone

Country Status (1)

Country Link
WO (1) WO2007102038A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102008045854A1 (de) 2008-09-05 2010-03-11 Tiefenbacher Pharmachemikalien Alfred E. Tiefenbacher Gmbh & Co. Kg Partikel aus Ziprasidone und einem Sprengmittel enthaltende Pharmazeutische Zusammensetzung
EP2340834A1 (fr) 2009-12-30 2011-07-06 Abdi Ibrahim Ilac Sanayi Ve Ticaret Anonim Sirketi Solubilité améliorée de la ziprasidone
WO2011148253A2 (fr) 2010-05-25 2011-12-01 Aurobindo Pharma Limited Formes posologiques solides d'antipsychotiques

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050163858A1 (en) * 2003-12-31 2005-07-28 Garth Boehm Ziprasidone formulations

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050163858A1 (en) * 2003-12-31 2005-07-28 Garth Boehm Ziprasidone formulations

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102008045854A1 (de) 2008-09-05 2010-03-11 Tiefenbacher Pharmachemikalien Alfred E. Tiefenbacher Gmbh & Co. Kg Partikel aus Ziprasidone und einem Sprengmittel enthaltende Pharmazeutische Zusammensetzung
EP2340834A1 (fr) 2009-12-30 2011-07-06 Abdi Ibrahim Ilac Sanayi Ve Ticaret Anonim Sirketi Solubilité améliorée de la ziprasidone
WO2011080706A1 (fr) 2009-12-30 2011-07-07 Abdi Ibrahim Ilac Sanayi Ve Ticaret Anonim Sirketi Solubilité améliorée de la ziprasidone
WO2011148253A2 (fr) 2010-05-25 2011-12-01 Aurobindo Pharma Limited Formes posologiques solides d'antipsychotiques

Similar Documents

Publication Publication Date Title
JP6577980B2 (ja) アピキサバン製剤
TWI778983B (zh) 包含2-羥基-6-((2-(1-異丙基-1h-吡唑-5-基)吡啶-3-基)甲氧基)-苯甲醛之片劑
TWI635863B (zh) 帕博西里之固態劑型
HK1243947A1 (en) Apixaban formulations
HK1243945A1 (en) Apixaban formulations
CA2811634C (fr) Compositions pharmaceutiques solides antidiabetiques
EP2050436A1 (fr) Composition pharmaceutique qui comporte de la dutastéride
CN109963565B (zh) 一种药物组合物及其制备方法
JP3037393B2 (ja) 経口投与用固形薬剤の製造方法
WO2007102038A1 (fr) Formulations de ziprasidone
TWI597063B (zh) 藥物組成物及其製備方法
AU2017228681B2 (en) Apixaban formulations
CN114848646A (zh) 包含取代的2-氨基吡啶衍生物的药物组合物及其制备方法
HK40031930A (en) Apixaban formulations
CN116782888A (zh) 药物组合物
HK40029900A (en) Apixaban formulations
HK1180248B (en) Apixaban formulations

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 05857345

Country of ref document: EP

Kind code of ref document: A1