WO2013100878A1 - Pharmaceutical formulations comprising aripiprazole - Google Patents
Pharmaceutical formulations comprising aripiprazole Download PDFInfo
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- WO2013100878A1 WO2013100878A1 PCT/TR2012/000234 TR2012000234W WO2013100878A1 WO 2013100878 A1 WO2013100878 A1 WO 2013100878A1 TR 2012000234 W TR2012000234 W TR 2012000234W WO 2013100878 A1 WO2013100878 A1 WO 2013100878A1
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- aripiprazole
- pharmaceutical formulation
- diluent
- formulation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—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
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
-
- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Definitions
- the present invention relates to pharmaceutical formulations comprising aripiprazole so as to be used in the treatment of irritability associated with schizophrenia, bipolar disorder, major depression and autistic disorder.
- Aripiprazole was firstly disclosed in the application numbered EP367141. In said document, it was explained that aripiprazole is effective in the treatment of schizophrenia.
- Aripiprazole is available in the form of 1 mg/ml oral solution and 5 mg, 10 mg, 15 mg, 20 mg and 30 mg tablets on the market.
- the excipients and their amounts used in the preparation of the formulations are important for the formulations comprising aripiprazole to be in desired weight and size and to have the optimum physical properties. Failure of the obtained tablets to reach the desired mass due to use of low doses of aripiprazole as active agent in the preparation of formulations comprising aripiprazole leads to the result that the final product does not have the desired tablet weight and size.
- the inventors have observed that the substances in the formulation are easily combined, weight uniformity is obtained by providing smooth flow and an effective treatment is obtained with the tablet forms having desired physical properties in the case that the formulations comprising aripiprazole and formulated in the form of orodispersible tablet comprise diluent in the range of 55 to 90% and have a ratio of diluent: disintegrant in the range of 1 :1 to 20:1.
- the present invention relates to pharmaceutical formulations comprising aripiprazole.
- the inventors have observed that the substances in the formulation are easily combined, weight uniformity is obtained by providing smooth flow, and an effective treatment is obtained with the tablet forms having desired physical properties; in the case that the formulations comprising aripiprazole and formulated in the form of orodispersible tablet comprise diluent in the range of 55 to 90% and have a ratio of diluent: disintegrant in the range of 1 :1 to 20:1.
- the first constituent of the invention is formulations comprising aripiprazole and formulated in the form of orodispersible tablet, characterized in that said formulation comprises diluent in the range of 55 to 90% and has a ratio of diluent: disintegrant in the range of 1 : 1 to 20: 1.
- the ratio of diluent: disintegrant is preferably in the range of 3:1 to 5:1 by weight.
- the diluent used according to the invention was selected from a group comprising D- mannitol, xylitol, microcrystalline cellulose, crospovidone, dibasic calcium phosphate anhydrose, lactose, starch, maltose, dextrin, maltodextrin, magnesium carbonate, talc and combinations thereof.
- a pharmaceutical composition comprising aripiprazole, characterized in that the diluent used is selected from a group comprising D-mannitol, xylitol, microcrystalline cellulose, crospovidone, dibasic calcium phosphate anhydrose and combinations thereof.
- a pharmaceutical composition comprising aripiprazole, characterized in that the diluent used is more preferably a mixture comprising D-mannitol, xylitol, microcrystalline cellulose, crospovidone and dibasic calcium phosphate anhydrose.
- Dissolution rate of the pharmaceutical composition comprising aripiprazole formulated in orodispersible tablet form is a considerably important parameter for the bioavailability of the drug and the effectiveness of the treatment. Accordingly, the inventors have observed that the weight of each diluent agent used in the diluent mixture has an influence on the dissolution rate of the obtained tablet form.
- the obtained aripiprazol tablet forms can dissolve more rapidly and a high bioavailability can be obtained.
- the present invention relates to the pharmaceutical composition
- aripiprazol formulated in the form of orodispersible tablet form wherein said composition comprises a diluent mixture comprising D-mannitol in the range of 40-80%), xylitol in the range of 1-15%, microcrystalline cellulose in the range of 5-30%, crospovidone in the range of 3-15% and dibasic calcium phosphate anhydrous in the range of 1-20% in proportion to the total weight of the mixture.
- the ratio of aripiprazol active agent to the diluent mixture by weight also has an effect on the solubility and the dispersion rate of the orodispersible aripiprazol tablet in the mouth. It has been seen that when the ratio of aripiprazol to the diluent mixture is in the range of 1 :15 to 5:1, preferably 1 :12 to 1 :1, more preferably 1:10 to 1 :2 by weight, a high solubility and rapid dispersion can be obtained.
- the present invention relates to the pharmaceutical compositions comprising aripiprazol formulated in the form of orodispersible tablet form wherein the ratio of aripiprazol active agent to the diluent mixture is in the range of 1 :15 to 5:1, preferably 1 :12 to 1 : 1 , more preferably 1 : 10 to 1 :2 by weight.
- the disintegrant used within the scope of the present invention can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, silicone dioxide, croscarmellose sodium, crospovidone, hydroxypropylcellulose, methylcellulose, povidone, magnesium aluminium silicate, starch or combinations thereof.
- a pharmaceutical composition comprising aripiprazole, characterized in that said composition preferably comprises povidone as disintegrant.
- the formulations of the invention can comprise at least one pharmaceutically acceptable excipient in addition to the active agent aripiprazole, diluent and disintegrant.
- the pharmaceutically acceptable excipients to be used in addition to aripiprazole, diluent and disintegrant in the present invention can be selected from a group comprising lubricant, binder, coloring agent, sweetener and flavoring agent.
- the lubricant that can be used in the formulations of the invention comprising aripiprazole, diluent and disintegrant can be selected from a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
- the binder that can be used in the formulations of the invention comprising aripiprazole, diluent and disintegrant can be selected from a group comprising ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, methylcellulose, povidone.
- the sweetener that can be used in the formulations of the invention comprising aripiprazole, diluent and disintegrant can be selected from a group comprising acesulfame, aspartame, fructose, maltitol, xylitol, saccharine, sodium cyclamate, sucralose, sucrose.
- the flavoring agent that can be used in the formulations of the invention comprising aripiprazole, diluent and disintegrant can be selected from a group comprising menthol, menthane, anetol, methyl salicylate, eucalyptol, cinnamon, 1 -methyl acetate, sage, eugenol, oxanone, lemon, orange, strawberry, blackberry or combinations thereof.
- the coloring agent that can be used in the formulations of the invention comprising aripiprazole, diluent and disintegrant can be selected from a group comprising carotenoids, chlorophyll and yellow iron oxide or combinations thereof.
- a pharmaceutical formulation comprising aripiprazole according to a preferred embodiment of the invention, characterized in that the coloring agent used in it is preferably yellow iron oxide.
- aripiprazole in the formulations of the invention comprising aripiprazole, diluent and disintegrant, aripiprazole can be in the range of 0.1 to 75%, preferably in the range of 2 to 60%, more preferably in the range of 3 to 50% by weight.
- aripiprazole active agent is an important criteria for obtaining homogeneous and highly dispersible tablet formulations comprising aripiprazole.
- the inventors have studied on the dispersion rate of the formulation by using aripiprazole having different average particle size. Based on the study, they have observed that when aripiprazol having average particle size in the range of 50-350 ⁇ , preferably 75- 300 ⁇ and more preferably 100- 250 ⁇ is used as active agent, the obtained aripiprazole tablets can disperse more rapidly and homogeneously.
- the present invention relates to pharmaceutical compositions comprising aripiprazol formulated in the form of orodispersible tablet form wherein aripiprazol having average particle size in the range of 50-350 ⁇ , preferably 75-300 ⁇ and more preferably 100- 250 ⁇ is used as active agent.
- the formulations prepared according to the present invention can comprise diluent in the range of 10 to 99%, preferably in the range of 30 to 95%, more preferably in the range of 55 to 90% in proportion to the total weight of the unit dosage form.
- the formulations prepared according to the present invention can comprise disintegrant in the range of 1 to 20%, sweetener in the range of 0.1 to 15%», flavoring agent in the range of 0.1 to 10%, lubricant in the range of 0.1 to 5%, coloring agent in the range of 0.1 to 10% in proportion to the total weight of the unit dosage form.
- disintegrant in the range of 1 to 20%
- sweetener in the range of 0.1 to 15%
- flavoring agent in the range of 0.1 to 10%
- lubricant in the range of 0.1 to 5%
- coloring agent in the range of 0.1 to 10% in proportion to the total weight of the unit dosage form.
- Another characteristic of the present invention is that compacting is performed twice during the production of the formulations and the obtained orodispersible aripiprazole tablets have the property of fast dispersibility.
- the production method for the preparation of pharmaceutical formulations of the invention comprises the following steps:
- the pharmaceutical formulation of the invention can be used in the treatment of irritability associated with schizophrenia, bipolar disorder, major depression and autistic disorder.
- aripiprazole, diluent, coloring agent, flavoring agent, sweetener and povidone are mixed together and sieved.
- Lubricant is added into this mixture and mixed again.
- the obtained mixture is taken into the compacting machine, compacted, sieved; and the same process is applied again.
- the mixture sieved again after the 2 nd compacting process is compressed into tablets.
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Description
PHARMACEUTICAL FORMULATIONS COMPRISING ARIPIPRAZOLE
The present invention relates to pharmaceutical formulations comprising aripiprazole so as to be used in the treatment of irritability associated with schizophrenia, bipolar disorder, major depression and autistic disorder. Aripiprazole was firstly disclosed in the application numbered EP367141. In said document, it was explained that aripiprazole is effective in the treatment of schizophrenia.
Aripiprazole is available in the form of 1 mg/ml oral solution and 5 mg, 10 mg, 15 mg, 20 mg and 30 mg tablets on the market. The excipients and their amounts used in the preparation of the formulations are important for the formulations comprising aripiprazole to be in desired weight and size and to have the optimum physical properties. Failure of the obtained tablets to reach the desired mass due to use of low doses of aripiprazole as active agent in the preparation of formulations comprising aripiprazole leads to the result that the final product does not have the desired tablet weight and size. Besides, there are also some difficulties experienced in combining the dry mixture of active agent and excipients in a desired form and providing a smooth flow of the mixture obtained by direct compacting while compressing the formulations comprising aripiprazole into tablets. Failure to enable smooth flow leads to failure to provide weight and dose uniformity in the tablets obtained. This case causes problems for the producer in the production and quality control phases; and also makes the patient unable to take same amounts of doses during the treatment due to the deficiency of weight and dose uniformity in the obtained dosage forms. As a result, these problems seen in the prior art leads to a decrease in the efficiency of the treatment.
As can be seen, there is still need for developing new approaches to obtain aripiprazole formulations with optimum physical characteristics in order to combine the active agent and
the excipients effectively in the formulations that can be prepared by direct compacting; and to obtain smooth flow and provide weight uniformity enabling the product in tablet form to be in desired weight and sizes.
Surprisingly, the inventors have observed that the substances in the formulation are easily combined, weight uniformity is obtained by providing smooth flow and an effective treatment is obtained with the tablet forms having desired physical properties in the case that the formulations comprising aripiprazole and formulated in the form of orodispersible tablet comprise diluent in the range of 55 to 90% and have a ratio of diluent: disintegrant in the range of 1 :1 to 20:1. Description of the Invention
The present invention relates to pharmaceutical formulations comprising aripiprazole. As a result of the studies conducted for this need, the inventors have observed that the substances in the formulation are easily combined, weight uniformity is obtained by providing smooth flow, and an effective treatment is obtained with the tablet forms having desired physical properties; in the case that the formulations comprising aripiprazole and formulated in the form of orodispersible tablet comprise diluent in the range of 55 to 90% and have a ratio of diluent: disintegrant in the range of 1 :1 to 20:1.
According to this, the first constituent of the invention is formulations comprising aripiprazole and formulated in the form of orodispersible tablet, characterized in that said formulation comprises diluent in the range of 55 to 90% and has a ratio of diluent: disintegrant in the range of 1 : 1 to 20: 1.
In a preferred embodiment of the invention, the ratio of diluent: disintegrant is preferably in the range of 3:1 to 5:1 by weight.
The diluent used according to the invention was selected from a group comprising D- mannitol, xylitol, microcrystalline cellulose, crospovidone, dibasic calcium phosphate anhydrose, lactose, starch, maltose, dextrin, maltodextrin, magnesium carbonate, talc and combinations thereof.
According to a preferred embodiment of the invention, a pharmaceutical composition comprising aripiprazole, characterized in that the diluent used is selected from a group
comprising D-mannitol, xylitol, microcrystalline cellulose, crospovidone, dibasic calcium phosphate anhydrose and combinations thereof.
According to a preferred embodiment of the invention, a pharmaceutical composition comprising aripiprazole, characterized in that the diluent used is more preferably a mixture comprising D-mannitol, xylitol, microcrystalline cellulose, crospovidone and dibasic calcium phosphate anhydrose.
Dissolution rate of the pharmaceutical composition comprising aripiprazole formulated in orodispersible tablet form is a considerably important parameter for the bioavailability of the drug and the effectiveness of the treatment. Accordingly, the inventors have observed that the weight of each diluent agent used in the diluent mixture has an influence on the dissolution rate of the obtained tablet form. They have seen that when the diluent mixture comprises D- mannitol in the range of 40-80%, xylitol in the range of 1-15%, microcrystalline cellulose in the range of 5-30%, crospovidone in the range of 3-15% and dibasic calcium phosphate anhydrous in the range of 1-20% in proportion to the total weight of the mixture, the obtained aripiprazol tablet forms can dissolve more rapidly and a high bioavailability can be obtained.
In another aspect, the present invention relates to the pharmaceutical composition comprising aripiprazol formulated in the form of orodispersible tablet form wherein said composition comprises a diluent mixture comprising D-mannitol in the range of 40-80%), xylitol in the range of 1-15%, microcrystalline cellulose in the range of 5-30%, crospovidone in the range of 3-15% and dibasic calcium phosphate anhydrous in the range of 1-20% in proportion to the total weight of the mixture.
The inventors have also observed that the ratio of aripiprazol active agent to the diluent mixture by weight also has an effect on the solubility and the dispersion rate of the orodispersible aripiprazol tablet in the mouth. It has been seen that when the ratio of aripiprazol to the diluent mixture is in the range of 1 :15 to 5:1, preferably 1 :12 to 1 :1, more preferably 1:10 to 1 :2 by weight, a high solubility and rapid dispersion can be obtained.
In another aspect, the present invention relates to the pharmaceutical compositions comprising aripiprazol formulated in the form of orodispersible tablet form wherein the ratio of aripiprazol active agent to the diluent mixture is in the range of 1 :15 to 5:1, preferably 1 :12 to 1 : 1 , more preferably 1 : 10 to 1 :2 by weight.
The disintegrant used within the scope of the present invention can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, silicone dioxide, croscarmellose sodium, crospovidone, hydroxypropylcellulose, methylcellulose, povidone, magnesium aluminium silicate, starch or combinations thereof.
According to a preferred embodiment of the invention, a pharmaceutical composition comprising aripiprazole, characterized in that said composition preferably comprises povidone as disintegrant.
The formulations of the invention can comprise at least one pharmaceutically acceptable excipient in addition to the active agent aripiprazole, diluent and disintegrant.
According to this, the pharmaceutically acceptable excipients to be used in addition to aripiprazole, diluent and disintegrant in the present invention can be selected from a group comprising lubricant, binder, coloring agent, sweetener and flavoring agent.
The lubricant that can be used in the formulations of the invention comprising aripiprazole, diluent and disintegrant can be selected from a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
The binder that can be used in the formulations of the invention comprising aripiprazole, diluent and disintegrant can be selected from a group comprising ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, methylcellulose, povidone.
The sweetener that can be used in the formulations of the invention comprising aripiprazole, diluent and disintegrant can be selected from a group comprising acesulfame, aspartame, fructose, maltitol, xylitol, saccharine, sodium cyclamate, sucralose, sucrose. The flavoring agent that can be used in the formulations of the invention comprising aripiprazole, diluent and disintegrant can be selected from a group comprising menthol, menthane, anetol, methyl salicylate, eucalyptol, cinnamon, 1 -methyl acetate, sage, eugenol, oxanone, lemon, orange, strawberry, blackberry or combinations thereof.
The coloring agent that can be used in the formulations of the invention comprising aripiprazole, diluent and disintegrant can be selected from a group comprising carotenoids, chlorophyll and yellow iron oxide or combinations thereof.
A pharmaceutical formulation comprising aripiprazole according to a preferred embodiment of the invention, characterized in that the coloring agent used in it is preferably yellow iron oxide.
The % amount values given within the scope of the invention were calculated in proportion to the unit dosage weight.
In the formulations of the invention comprising aripiprazole, diluent and disintegrant, aripiprazole can be in the range of 0.1 to 75%, preferably in the range of 2 to 60%, more preferably in the range of 3 to 50% by weight.
It is known that the average particle size of aripiprazole active agent is an important criteria for obtaining homogeneous and highly dispersible tablet formulations comprising aripiprazole. The inventors have studied on the dispersion rate of the formulation by using aripiprazole having different average particle size. Based on the study, they have observed that when aripiprazol having average particle size in the range of 50-350 μπι, preferably 75- 300 μιη and more preferably 100- 250 μιη is used as active agent, the obtained aripiprazole tablets can disperse more rapidly and homogeneously.
In another aspect, the present invention relates to pharmaceutical compositions comprising aripiprazol formulated in the form of orodispersible tablet form wherein aripiprazol having average particle size in the range of 50-350 μιη, preferably 75-300 μηι and more preferably 100- 250 μιη is used as active agent.
The formulations prepared according to the present invention can comprise diluent in the range of 10 to 99%, preferably in the range of 30 to 95%, more preferably in the range of 55 to 90% in proportion to the total weight of the unit dosage form.
The formulations prepared according to the present invention can comprise disintegrant in the range of 1 to 20%, sweetener in the range of 0.1 to 15%», flavoring agent in the range of 0.1 to 10%, lubricant in the range of 0.1 to 5%, coloring agent in the range of 0.1 to 10% in proportion to the total weight of the unit dosage form.
One of the problems faced during the preparation of tablets comprising aripiprazole is that tablets do not disperse fast and effectively in the mouth after they are compressed. As a result of the studies conducted for this need, the inventors obtained aripiprazole tablets that can disperse faster and more effectively by the method of compacting twice.
According to this, another characteristic of the present invention is that compacting is performed twice during the production of the formulations and the obtained orodispersible aripiprazole tablets have the property of fast dispersibility.
The production method for the preparation of pharmaceutical formulations of the invention comprises the following steps:
• Mixing the active agent aripiprazole with diluent, disintegrant, coloring agent, sweetener and flavoring agent; and sieving this mixture
• Adding lubricant into the mixture and mixing it again
• Compacting the obtained mixture once and sieving it
• Compacting the mixture for the second time and sieving it again
• And compressing the final mixture obtained into tablets.
The pharmaceutical formulation of the invention can be used in the treatment of irritability associated with schizophrenia, bipolar disorder, major depression and autistic disorder.
EXAMPLE: Formulation and process for preparation of orodispersible tablets comprising aripiprazole
To obtain the formulation to be used within the scope of said invention; aripiprazole, diluent, coloring agent, flavoring agent, sweetener and povidone are mixed together and sieved. Lubricant is added into this mixture and mixed again. The obtained mixture is taken into the compacting machine, compacted, sieved; and the same process is applied again. The mixture sieved again after the 2nd compacting process is compressed into tablets.
Claims
1. Orodispersible tablet formulation comprising aripiprazole, characterized in that said formulation comprises diluent in the range of 55 to 90% by weight and the ratio of diluent: disintegrant is in the range of 1 :1 to 20:1 by weight.
2. The pharmaceutical formulation comprising aripiprazole according to claim 1, characterized in that the ratio of diluent: disintegrant is in the range of 3:1 to 15:1 by weight.
3. The pharmaceutical formulation according to claims 1 and 2, characterized in that the diluent is selected from a group comprising D-mannitol, xylitol, microcrystalline cellulose, crospovidone, dibasic calcium phosphate anhydrose, lactose, starch, maltose, dextrin, maltodextrin, magnesium carbonate, talc and combinations thereof.
4. The pharmaceutical formulation according to claim 3, characterized in that the diluent is selected from a group comprising D-mannitol, xylitol, microcrystalline cellulose, crospovidone, dibasic calcium phosphate anhydrose and combinations thereof.
5. The pharmaceutical formulation according to claim 4, characterized in that the diluent is preferably a combination comprising xylitol, microcrystalline cellulose, crospovidone, dibasic calcium phosphate anhydrose.
6. The pharmaceutical formulation according to claims 1-5, characterized in that said formulation comprises a diluent mixture comprising D-mannitol in the range of 40- 80%, xylitol in the range of 1-15%, microcrystalline cellulose in the range of 5-30%, crospovidone in the range of 3-15% and dibasic calcium phosphate anhydrous in the range of 1 -20% in proportion to the total weight of the mixture.
7. The pharmaceutical formulation according to claims 1-6, characterized in that the ratio of aripiprazol active agent to the diluent mixture is in the range of 1 : 15 to 5: 1 ,
8. The pharmaceutical formulation according to claim 7, characterized in that the ratio of aripiprazol active agent to the diluent mixture is in the range of l :12 to 1 : 1.
9. The pharmaceutical formulation according to claim 8, characterized in that the ratio of aripiprazol active agent to the diluent mixture is in the range of 1 : 10 to 1 :2 by weight.
10. The pharmaceutical formulation according to claims 1 to 9, characterized in that the disintegrant is selected from a group comprising carboxymethyl cellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, silicone dioxide, croscarmellose sodium, crospovidone, hydroxypropylcellulose, methylcellulose, povidone, magnesium aluminium silicate, starch or combinations thereof.
11. The pharmaceutical formulation according to claim 10, characterized in that said formulation comprises povidone as disintegrant.
12. The pharmaceutical formulation according to claims 1 to 11, characterized in that said formulation comprises at least one pharmaceutically acceptable excipient in addition to aripiprazole, diluent and disintegrant.
13. The pharmaceutical formulation according to claim 12, characterized in that the pharmaceutically acceptable excipients that can be used in addition to aripiprazole, diluent and disintegrant are selected from a group comprising lubricant, binder, coloring agent, sweetener and flavoring agent.
14. The pharmaceutical formulation according to claim 13, characterized in that the lubricant is selected from a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
15. The pharmaceutical formulation according to claim 13, characterized in that the binder is selected from a group comprising ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, methylcellulose, povidone.
16. The pharmaceutical formulation according to claim 13, characterized in that the sweetener is selected from a group comprising acesulfame, aspartame, fructose, maltitol, xylitol, saccharine, sodium cyclamate, sucralose, sucrose.
17. The pharmaceutical formulation according to claim 13, characterized in that the flavoring agent is selected from a group comprising menthol, menthane, anetol, methyl salicylate, eucalyptol, cinnamon, 1 -methyl acetate, sage, eugenol, oxanone, lemon, orange, strawberry, blackberry or combinations thereof.
18. The pharmaceutical formulation according to claim 13, characterized in that the coloring agent is selected from a group comprising carotenoids, chlorophyll and yellow iron oxide or a combination thereof.
19. The pharmaceutical formulation according to claim 18, characterized in that said formulation comprises yellow iron oxide as coloring agent.
20. The pharmaceutical formulation comprising aripiprazole according to any one of the preceding claims, characterized in that said formulation comprises aripiprazole in the range of 0.1 to 75% by weight.
21. The pharmaceutical formulation comprising aripiprazole according to any one of the preceding claims, characterized in that said formulation comprises aripiprazol having average particle size in the range of 50-350 μπι.
22. The pharmaceutical formulation comprising aripiprazole according to claim 21 , characterized in that said formulation comprises aripiprazol having average particle size in the range of 75-300 μπι.
23. The pharmaceutical formulation comprising aripiprazole according to claim 22, characterized in that said formulation comprises aripiprazol having average particle size in the range of 100- 250 μπι is used as active agent.
24. The formulation according to claim 23, characterized in that said formulation comprises aripiprazole in the range of 2 to 60% by weight.
25. The formulation according to claim 24, characterized in that said formulation comprises aripiprazole in the range of 3 to 50% by weight.
26. The formulation according to any one of the preceding claims, characterized in that said formulation comprises diluent in the range of 10 to 99% in proportion to the total weight of the unit dose amount.
27. The formulation according to claim 26, characterized in that said formulation comprises diluent in the range of 30 to 95% by weight.
28. The formulation according to claim 27, characterized in that said formulation comprises diluent in the range of 55 to 90% by weight.
29. The pharmaceutical formulation comprising aripiprazole according to any one of the preceding claims, characterized in that said formulation comprises disintegrant in the range of 1 to 20% by weight.
30. The formulation according to any one of the preceding claims, characterized in that said formulation comprises lubricant in the range of 1 to 20% by weight.
31. The pharmaceutical formulation comprising aripiprazole according to any one of the preceding claims, characterized in that said formulation comprises sweetener in the range of 0.1 to 15% by weight.
32. The pharmaceutical formulation comprising aripiprazole according to any one of the preceding claims, characterized in that said formulation comprises flavoring agent in the range of 0.1 to 10% by weight.
33. The pharmaceutical formulation comprising aripiprazole according to any one of the preceding claims, characterized in that said formulation comprises coloring agent in the range of 0.1 to 10%.
34. The process for preparation of the pharmaceutical formulation comprising aripiprazole according o any one of the preceding claims, characterized in that it is obtained by a method comprising the steps of:
• Mixing the active agent aripiprazole with diluent, disintegrant, coloring agent, sweetener and flavoring agent; and sieving this mixture
• Adding lubricant into the mixture and mixing it again
• Compacting the obtained mixture once and sieving it
• Compacting the mixture for the second time and sieving it again
• And compressing the final mixture obtained into tablets.
35. The pharmaceutical formulation comprising aripiprazole according to any one of the preceding claims, wherein said formulation is used in the treatment of irritability associated with schizophrenia, bipolar disorder, major depression and autistic disorder.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2011/12993 | 2011-12-27 | ||
| TR201112993 | 2011-12-27 | ||
| TR201203834 | 2012-04-04 | ||
| TR2012/03834 | 2012-04-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2013100878A1 true WO2013100878A1 (en) | 2013-07-04 |
Family
ID=47684009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2012/000234 Ceased WO2013100878A1 (en) | 2011-12-27 | 2012-12-27 | Pharmaceutical formulations comprising aripiprazole |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2013100878A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103860494A (en) * | 2014-01-24 | 2014-06-18 | 浙江美华鼎昌医药科技有限公司 | Aripiprazole tablet and preparation method of aripiprazole tablet |
| WO2014173515A1 (en) * | 2013-04-22 | 2014-10-30 | Pharmathen S.A. | Pharmaceutical composition comprising an atypical antipsychotic agent and method for the preparation thereof |
| WO2015067313A1 (en) | 2013-11-07 | 2015-05-14 | Synthon B.V. | Orodispersible pharmaceutical compositions comprising aripiprazole |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0367141A2 (en) | 1988-10-31 | 1990-05-09 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives |
| US20050019398A1 (en) * | 2000-04-12 | 2005-01-27 | Sanjeev Kotharl | Flashmelt oral dosage formulation |
| WO2006097344A1 (en) * | 2005-03-17 | 2006-09-21 | Synthon B.V. | Pharmaceutical tablets of crystalline type ii aripiprazole |
| US20070154544A1 (en) * | 2006-01-05 | 2007-07-05 | Julia Hrakovsky | Wet formulations of aripiprazole |
| WO2008020820A2 (en) * | 2006-08-15 | 2008-02-21 | Nobel Ilac Sanayii Ve Ticaret A.S. | Pharmaceutical compositions comprising aripiprazole |
| WO2008034628A1 (en) * | 2006-09-22 | 2008-03-27 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Aripiprazole hemifumarate and process for its preparation |
| WO2010079506A2 (en) * | 2008-06-23 | 2010-07-15 | Torrent Pharmaceuticals Ltd. | Pharmaceutical composition of aripiprazole |
| WO2011032882A1 (en) * | 2009-09-15 | 2011-03-24 | Ratiopharm Gmbh | Orally disintegrating pharmaceutical dosage form containing aripiprazole |
| EP2359816A1 (en) * | 2010-02-09 | 2011-08-24 | Sanovel Ilac Sanayi ve Ticaret A.S. | Aripiprazole formulations |
| DE102010019416A1 (en) * | 2010-05-04 | 2011-11-10 | Stada Arzneimittel Ag | Orodispersible tablet comprising a triptan or an atypical neuroleptic |
-
2012
- 2012-12-27 WO PCT/TR2012/000234 patent/WO2013100878A1/en not_active Ceased
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0367141A2 (en) | 1988-10-31 | 1990-05-09 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives |
| US20050019398A1 (en) * | 2000-04-12 | 2005-01-27 | Sanjeev Kotharl | Flashmelt oral dosage formulation |
| WO2006097344A1 (en) * | 2005-03-17 | 2006-09-21 | Synthon B.V. | Pharmaceutical tablets of crystalline type ii aripiprazole |
| US20070154544A1 (en) * | 2006-01-05 | 2007-07-05 | Julia Hrakovsky | Wet formulations of aripiprazole |
| WO2008020820A2 (en) * | 2006-08-15 | 2008-02-21 | Nobel Ilac Sanayii Ve Ticaret A.S. | Pharmaceutical compositions comprising aripiprazole |
| WO2008034628A1 (en) * | 2006-09-22 | 2008-03-27 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Aripiprazole hemifumarate and process for its preparation |
| WO2010079506A2 (en) * | 2008-06-23 | 2010-07-15 | Torrent Pharmaceuticals Ltd. | Pharmaceutical composition of aripiprazole |
| WO2011032882A1 (en) * | 2009-09-15 | 2011-03-24 | Ratiopharm Gmbh | Orally disintegrating pharmaceutical dosage form containing aripiprazole |
| EP2359816A1 (en) * | 2010-02-09 | 2011-08-24 | Sanovel Ilac Sanayi ve Ticaret A.S. | Aripiprazole formulations |
| DE102010019416A1 (en) * | 2010-05-04 | 2011-11-10 | Stada Arzneimittel Ag | Orodispersible tablet comprising a triptan or an atypical neuroleptic |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014173515A1 (en) * | 2013-04-22 | 2014-10-30 | Pharmathen S.A. | Pharmaceutical composition comprising an atypical antipsychotic agent and method for the preparation thereof |
| WO2015067313A1 (en) | 2013-11-07 | 2015-05-14 | Synthon B.V. | Orodispersible pharmaceutical compositions comprising aripiprazole |
| CN103860494A (en) * | 2014-01-24 | 2014-06-18 | 浙江美华鼎昌医药科技有限公司 | Aripiprazole tablet and preparation method of aripiprazole tablet |
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