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WO2012093975A1 - Water soluble formulations comprising ibandronate sodium with a water content less than 11 % by weight - Google Patents

Water soluble formulations comprising ibandronate sodium with a water content less than 11 % by weight Download PDF

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Publication number
WO2012093975A1
WO2012093975A1 PCT/TR2012/000006 TR2012000006W WO2012093975A1 WO 2012093975 A1 WO2012093975 A1 WO 2012093975A1 TR 2012000006 W TR2012000006 W TR 2012000006W WO 2012093975 A1 WO2012093975 A1 WO 2012093975A1
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water soluble
formulations
sodium
weight
formulation according
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PCT/TR2012/000006
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French (fr)
Inventor
Mahmut Bilgic
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Priority claimed from TR2011/00151A external-priority patent/TR201100151A2/en
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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
    • A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
    • 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
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders

Definitions

  • the present invention relates to water soluble formulations prepared by using an active agent having less than 11% of water content by weight and production methods thereof.
  • the formulations of the present invention are used in treatment and/or prevention of bone diseases such as hypercalcaemia, osteoporosis, tumoral osteolysis, malignant hypercalcaemia, metastatic bone disease, periprostatic bone loss, Paget' s disease.
  • Bone diseases such as hypercalcaemia, osteoporosis, tumoral osteolysis, Paget' s disease are the most common diseases after cardiovascular diseases and cancer in the world.
  • Particularly osteoporosis is a stealthily progressive disease which affects postmenopausal women and arises when the bones are weakened and very susceptible to fracture because of low bone mass and deterioration of bone quality.
  • Osteoporosis is seen three times more likely in women than men; and the disease which is seen more commonly in old age is not a disease seen only in old age. Osteoporosis-related bone fractures have gradually become a serious public health concern.
  • the group of drugs frequently used in treatment of bone diseases including osteoporosis is bisphosphonates.
  • the bisphosphonate group of drugs causes decrease in number and activity of the cells called osteoclasts which are responsible for bone resorption; and by this means, they provide to preserve and even increase bone mass and strength.
  • the most common drugs of this group are alendronate, etidronate, risedronate, ibandronate and zoledronic acid.
  • Ibandronate (Formula I) is a potent third generation bisphosphonate. It is known that, when compared to placebo, ibandronate treatment wherein 2.5 mg daily ibandronate is administered to the patients with osteoporosis reduces risk for vertebral fracture in 3-year-period from approximately 10% to 5% and reduces risk for symptomatic vertebral fractures from 5.3 to 2.8%.
  • Ibandronate marketed under the trade names BONVIVA® and BONDRONAT® is in film coated tablet and intravenous forms.
  • Bisphosphonates generally have low bioavailability; therefore, it is recommended that orally used bisphosphonates are taken on an empty stomach.
  • Intravenous ibandronate is a form only used in treatment of cancer- related bone diseases.
  • the dosage used is a single dose in every 3-4 weeks though it changes according to the stage of the disease.
  • said dosage forms in the prior art cannot meet patient requirements effectively.
  • Oral ibandronate tablet form is not a good option for ibandronate which already has low bioavailability.
  • Intravenous form which was improved as an alternative to solid dosage forms is the most difficult treatment method to comply with for patients. Many patients especially, the group of patients over 50 years of age, do not want to take the drug in intravenous form which is administered with a sterile needle. Furthermore, intravenous dosage forms require an expert medical practitioner for administration and this situation is disadvantageous for the patient. Many patients do not prefer intravenous administration due to these reasons.
  • the present invention discloses water soluble pharmaceutical formulations comprising ibandronate and/or its pharmaceutically acceptable salts, hydrates, amorphous or crystalline forms or combinations thereof as active agent; production and usage areas thereof.
  • One purpose of the present invention is to develop easy to use, highly bioavailable new ibandronate formulations which can remain stable for long periods of time.
  • the water soluble formulations of the present invention can be formulated in powder or granule form and presented as filled into bottles, sachet as well as presented in tablet or capsule for obtainment of the dosage form required.
  • One characteristic feature of the formulations of the present invention is that the formulations are formulated in powder form.
  • formulations of the present invention are formulated in granule form.
  • the powder or granule formulations prepared within the scope of the present invention can be effervescent or noneffervescent; the formulations preferred are noneffervescent formulations.
  • the dosage form preferred is prepared as sachet dosage form designed to prevent active agent granules from being affected from the environmental factors such as heat, moisture, light.
  • Ibandronate or its pharmaceutically acceptable salt used in the pharmaceutical formulations of the present invention is preferably ibandronate sodium salt.
  • ibandronate sodium formulations produced in water soluble form reveal disintegration which appears as colour change (yellowing) in dosage forms under storage conditions.
  • This problem has been surprisingly solved with use of ibandronate sodium having less than 11% of water content by weight in the water soluble formulations developed within the scope of the present invention.
  • One characteristic feature of the water soluble formulations of the present invention is to use ibandronate sodium having less than 1 1% of water ratio by weight as active agent.
  • Another characteristic feature of the water soluble formulations of the present invention is to use ibandronate sodium having water content in the range of 0 to 1 1% by weight as active agent.
  • the water content of the active agent comprised in the formulations of the present invention was measured by Karl Fischer (Metrohm, 841 Titrando) device.
  • formulations of the present invention comprise at least one pharmaceutically acceptable excipient selected from a group comprising filling agents, binders, lubricants, disintegrants, diluents, stabilizing agents, sweeteners, taste regulating agents, inorganic salts, flavouring agents.
  • Another characteristic feature of the formulations of the present invention is to use suitable excipient combination and suitable amounts thereof for ibandronate formulations having sufficient stability.
  • Another characteristic feature of the formulations of the present invention is that the formulations comprise at least one filling agent, at least one sweetener and at least one inorganic salt as excipients.
  • the filling agents that can be used in the formulations of the present invention are preferably from the group of water soluble sugar alcohols and selected from sorbitol, mannitol, xylitol, erythrol, isomalt, starch hydrolyzates or combinations thereof.
  • formulations of the present invention comprise at least one filling agent minimum 50% by weight, preferably in the range of 50 to 80% by weight, more preferably in the range of 50 to 60% by weight.
  • the sweeteners that can be used in the water soluble formulations of the present invention can be selected from a group comprising aspartame, dextrose, fructose, sucralose, sodium cyclamate, mannitol, maltose, sorbitol, saccharin and/or pharmaceutically acceptable salts or combinations thereof. More than one sweetener can be used in the formulations of the present invention.
  • One characteristic feature of the formulations of the present invention is that said formulations comprise at least one sweetener in the range of 1 to 10% by weight, preferably in the range of 1 to 8% by weight, more preferably in the range of 1 to 5 % by weight.
  • the diluents that can be used in the water soluble formulations of the present invention can be selected from a group comprising calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
  • the inorganic salts that can be used in the water soluble formulations of the present invention can be selected from a group comprising sodium carbonate, sodium bicarbonate, sodium acetate, sodium chloride, potassium chloride, potassium carbonate, potassium bicarbonate.
  • the inorganic salt preferred is sodium or potassium carbonates or bicarbonates, and particularly sodium bicarbonate is used.
  • the lubricants that can be used in the water soluble formulations of the present invention can be selected from a group comprising metallic stearates (such as magnesium stearate, calcium stearate, aluminium stearate), fatty acid esters (such as sodium stearyl fumarate), fatty acids (such as stearic acid), fatty alcohols, glyceryl behenate, mineral oil, paraffins, hydrogenated vegetable oil, leucine, polyethylene glycols, metallic lauryl sulphates (such as sodium lauryl sulphate, magnesium lauryl sulphate), sodium chloride, sodium benzoate, sodium acetate and talc and/or hydrates thereof.
  • metallic stearates such as magnesium stearate, calcium stearate, aluminium stearate
  • fatty acid esters such as sodium stearyl fumarate
  • fatty acids such as stearic acid
  • fatty alcohols glyceryl behenate
  • mineral oil paraffins
  • the disintegrants that can be used in the water soluble formulations of the present invention can be selected from a group comprising highly dispersive polymers, for instance cross linked hydroxypropyl cellulose, polyvinylpyrrolidone, high-molecular weight polymers, microcrystalline cellulose, sodium starch glycolate, povidone, alginic acid, sodium alginate or combinations thereof.
  • highly dispersive polymers for instance cross linked hydroxypropyl cellulose, polyvinylpyrrolidone, high-molecular weight polymers, microcrystalline cellulose, sodium starch glycolate, povidone, alginic acid, sodium alginate or combinations thereof.
  • the water soluble formulations of the present invention can optionally comprise flavouring agents; said flavouring agents can have banana flavour, strawberry flavour, lemon flavour, orange flavour, peach flavour, vanilla flavour or a similar natural fruit flavour or an aromatic plant flavour.
  • flavouring agents can have banana flavour, strawberry flavour, lemon flavour, orange flavour, peach flavour, vanilla flavour or a similar natural fruit flavour or an aromatic plant flavour.
  • One characteristic feature of the formulations of the present invention is that the formulations comprise ibandronate sodium in the range of 50 to 300 mg, preferably in the range of 50 to 200 mg per unit dosage form.
  • Said dosage form can be used once a month or at least once a day according to the type of the disease to be treated. For instance, in the case that the disease to be treated is osteoporosis, it is recommended for use once a month; in treatment/prevention of the diseases such as the tumoral osteolysis, malignant hypercalcaemia, metastatic bone disease, it is recommended for use at least once a day.
  • the dosage forms of the present invention are preferably taken as dissolved in sufficient amount of water, preferably in 150 ml of water, preferably just before the first meal of the day.
  • Dissolution time of the formulations of the present invention is in the range of 15 to 60 seconds, preferably in the range of 15 to 45 seconds in 150 ml of water.
  • the formulations of the present invention can be produced by any methods in the prior art. These methods can be dry granulation, dry blending, direct compression or wet granulation.
  • the inventors have surprisingly seen that production of the water soluble formulations which comprise ibandronate sodium having maximum 11% of water content by weight by any dry blending methods in the prior art leads to additional improvement in the stability of the formulation.
  • the methods preferred for production of the formulations of the present invention can be dry blending method or dry granulation method; particularly the more preferred method is dry blending method.
  • a method preferred for the water soluble formulations of the present invention is as follows;
  • a method preferred for the water soluble formulations of the present invention is as follows; 1. Mixing ibadronate sodium, at least one pharmaceutically acceptable filling agent, at least one sweetener and at least one inorganic salt,
  • Example I Sachet formulation comprising ibandronate sodium having 5% of water content by weight.
  • Example II Sachet formulation comprising ibandronate sodium having 7.5% of water content by weight.
  • the method to be used for production of ibandronate sodium sachet formulations given above is dry blending method which is described in the description part in detail.
  • the pharmaceutical powder formulations obtained by dry blending and sieving steps are sent to the sachet filling machine and final product is obtained in sachet form.

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Abstract

The present invention relates to water soluble formulations prepared by using an active agent having less than 11% of water content by weight and production methods thereof. The formulations of the present invention are used in treatment and/or prevention of bone diseases such as hypercalcaemia, osteoporosis, tumoral osteolysis, malignant hypercalcaemia, metastatic bone disease, periprostatic bone loss, Paget's disease.

Description

WATER SOLUBLE FORMULATIONS COMPRISING IBANDRONATE SODIUM WITH A WATER CONTENT OF LESS THAN 11 % BY WEIGHT
The present invention relates to water soluble formulations prepared by using an active agent having less than 11% of water content by weight and production methods thereof. The formulations of the present invention are used in treatment and/or prevention of bone diseases such as hypercalcaemia, osteoporosis, tumoral osteolysis, malignant hypercalcaemia, metastatic bone disease, periprostatic bone loss, Paget' s disease.
The Prior Art
Bone diseases such as hypercalcaemia, osteoporosis, tumoral osteolysis, Paget' s disease are the most common diseases after cardiovascular diseases and cancer in the world. Particularly osteoporosis is a stealthily progressive disease which affects postmenopausal women and arises when the bones are weakened and very susceptible to fracture because of low bone mass and deterioration of bone quality. Osteoporosis is seen three times more likely in women than men; and the disease which is seen more commonly in old age is not a disease seen only in old age. Osteoporosis-related bone fractures have gradually become a serious public health concern.
The group of drugs frequently used in treatment of bone diseases including osteoporosis is bisphosphonates. The bisphosphonate group of drugs causes decrease in number and activity of the cells called osteoclasts which are responsible for bone resorption; and by this means, they provide to preserve and even increase bone mass and strength. The most common drugs of this group are alendronate, etidronate, risedronate, ibandronate and zoledronic acid.
Ibandronate (Formula I) is a potent third generation bisphosphonate. It is known that, when compared to placebo, ibandronate treatment wherein 2.5 mg daily ibandronate is administered to the patients with osteoporosis reduces risk for vertebral fracture in 3-year-period from approximately 10% to 5% and reduces risk for symptomatic vertebral fractures from 5.3 to 2.8%.
Figure imgf000003_0001
Formula (I)
Ibandronate marketed under the trade names BONVIVA® and BONDRONAT® is in film coated tablet and intravenous forms. Bisphosphonates generally have low bioavailability; therefore, it is recommended that orally used bisphosphonates are taken on an empty stomach.
Intravenous ibandronate, on the other hand, is a form only used in treatment of cancer- related bone diseases. The dosage used is a single dose in every 3-4 weeks though it changes according to the stage of the disease. However, said dosage forms in the prior art cannot meet patient requirements effectively. Oral ibandronate tablet form is not a good option for ibandronate which already has low bioavailability.
Intravenous form which was improved as an alternative to solid dosage forms is the most difficult treatment method to comply with for patients. Many patients especially, the group of patients over 50 years of age, do not want to take the drug in intravenous form which is administered with a sterile needle. Furthermore, intravenous dosage forms require an expert medical practitioner for administration and this situation is disadvantageous for the patient. Many patients do not prefer intravenous administration due to these reasons.
As seen, there is need for highly bioavailable new approaches which appeal to a wider profile of patients for pharmaceutical formulations comprising ibandronate.
The inventors have developed new water soluble ibandronate formulations in line with this requirement. However, an important problem found out in these water soluble formulations of the present invention is difficulty in ensuring the stability of the formulation.
The inventors have found that the water content of the active agent in the formulations has an important role in stability of the end product. Detailed Description of the Invention
The present invention discloses water soluble pharmaceutical formulations comprising ibandronate and/or its pharmaceutically acceptable salts, hydrates, amorphous or crystalline forms or combinations thereof as active agent; production and usage areas thereof. One purpose of the present invention is to develop easy to use, highly bioavailable new ibandronate formulations which can remain stable for long periods of time.
The water soluble formulations of the present invention can be formulated in powder or granule form and presented as filled into bottles, sachet as well as presented in tablet or capsule for obtainment of the dosage form required. One characteristic feature of the formulations of the present invention is that the formulations are formulated in powder form.
Another characteristic feature of the formulations of the present invention is that the formulations are formulated in granule form.
The powder or granule formulations prepared within the scope of the present invention can be effervescent or noneffervescent; the formulations preferred are noneffervescent formulations.
The dosage form preferred is prepared as sachet dosage form designed to prevent active agent granules from being affected from the environmental factors such as heat, moisture, light. Ibandronate or its pharmaceutically acceptable salt used in the pharmaceutical formulations of the present invention is preferably ibandronate sodium salt.
However, the studies conducted within the scope of the present invention have shown that ibandronate sodium formulations produced in water soluble form reveal disintegration which appears as colour change (yellowing) in dosage forms under storage conditions. This problem has been surprisingly solved with use of ibandronate sodium having less than 11% of water content by weight in the water soluble formulations developed within the scope of the present invention. One characteristic feature of the water soluble formulations of the present invention is to use ibandronate sodium having less than 1 1% of water ratio by weight as active agent.
Another characteristic feature of the water soluble formulations of the present invention is to use ibandronate sodium having water content in the range of 0 to 1 1% by weight as active agent.
The water content of the active agent comprised in the formulations of the present invention was measured by Karl Fischer (Metrohm, 841 Titrando) device.
Another characteristic feature of the formulations of the present invention is that said formulations comprise at least one pharmaceutically acceptable excipient selected from a group comprising filling agents, binders, lubricants, disintegrants, diluents, stabilizing agents, sweeteners, taste regulating agents, inorganic salts, flavouring agents.
Another characteristic feature of the formulations of the present invention is to use suitable excipient combination and suitable amounts thereof for ibandronate formulations having sufficient stability. Another characteristic feature of the formulations of the present invention is that the formulations comprise at least one filling agent, at least one sweetener and at least one inorganic salt as excipients.
The filling agents that can be used in the formulations of the present invention are preferably from the group of water soluble sugar alcohols and selected from sorbitol, mannitol, xylitol, erythrol, isomalt, starch hydrolyzates or combinations thereof.
Another characteristic feature of the formulations of the present invention is that said formulations comprise at least one filling agent minimum 50% by weight, preferably in the range of 50 to 80% by weight, more preferably in the range of 50 to 60% by weight.
The sweeteners that can be used in the water soluble formulations of the present invention can be selected from a group comprising aspartame, dextrose, fructose, sucralose, sodium cyclamate, mannitol, maltose, sorbitol, saccharin and/or pharmaceutically acceptable salts or combinations thereof. More than one sweetener can be used in the formulations of the present invention. One characteristic feature of the formulations of the present invention is that said formulations comprise at least one sweetener in the range of 1 to 10% by weight, preferably in the range of 1 to 8% by weight, more preferably in the range of 1 to 5 % by weight.
The diluents that can be used in the water soluble formulations of the present invention can be selected from a group comprising calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
The inorganic salts that can be used in the water soluble formulations of the present invention can be selected from a group comprising sodium carbonate, sodium bicarbonate, sodium acetate, sodium chloride, potassium chloride, potassium carbonate, potassium bicarbonate. The inorganic salt preferred is sodium or potassium carbonates or bicarbonates, and particularly sodium bicarbonate is used.
The lubricants that can be used in the water soluble formulations of the present invention can be selected from a group comprising metallic stearates (such as magnesium stearate, calcium stearate, aluminium stearate), fatty acid esters (such as sodium stearyl fumarate), fatty acids (such as stearic acid), fatty alcohols, glyceryl behenate, mineral oil, paraffins, hydrogenated vegetable oil, leucine, polyethylene glycols, metallic lauryl sulphates (such as sodium lauryl sulphate, magnesium lauryl sulphate), sodium chloride, sodium benzoate, sodium acetate and talc and/or hydrates thereof.
The disintegrants that can be used in the water soluble formulations of the present invention can be selected from a group comprising highly dispersive polymers, for instance cross linked hydroxypropyl cellulose, polyvinylpyrrolidone, high-molecular weight polymers, microcrystalline cellulose, sodium starch glycolate, povidone, alginic acid, sodium alginate or combinations thereof.
The water soluble formulations of the present invention can optionally comprise flavouring agents; said flavouring agents can have banana flavour, strawberry flavour, lemon flavour, orange flavour, peach flavour, vanilla flavour or a similar natural fruit flavour or an aromatic plant flavour. One characteristic feature of the formulations of the present invention is that the formulations comprise ibandronate sodium in the range of 50 to 300 mg, preferably in the range of 50 to 200 mg per unit dosage form.
Said dosage form can be used once a month or at least once a day according to the type of the disease to be treated. For instance, in the case that the disease to be treated is osteoporosis, it is recommended for use once a month; in treatment/prevention of the diseases such as the tumoral osteolysis, malignant hypercalcaemia, metastatic bone disease, it is recommended for use at least once a day.
The dosage forms of the present invention are preferably taken as dissolved in sufficient amount of water, preferably in 150 ml of water, preferably just before the first meal of the day. Dissolution time of the formulations of the present invention is in the range of 15 to 60 seconds, preferably in the range of 15 to 45 seconds in 150 ml of water.
The formulations of the present invention can be produced by any methods in the prior art. These methods can be dry granulation, dry blending, direct compression or wet granulation. The inventors have surprisingly seen that production of the water soluble formulations which comprise ibandronate sodium having maximum 11% of water content by weight by any dry blending methods in the prior art leads to additional improvement in the stability of the formulation.
According to this, the methods preferred for production of the formulations of the present invention can be dry blending method or dry granulation method; particularly the more preferred method is dry blending method.
A method preferred for the water soluble formulations of the present invention is as follows;
1. Mixing ibandronate sodium having maximum 11% of water content by weight and pharmaceutically acceptable excipients dryly, 2. Sieving the mixture,
3. Sending the mixture prepared to the related filling machines for obtainment of the dosage form required.
A method preferred for the water soluble formulations of the present invention is as follows; 1. Mixing ibadronate sodium, at least one pharmaceutically acceptable filling agent, at least one sweetener and at least one inorganic salt,
2. Sieving the mixture,
3. Sending the mixture obtained to the related filling machines for obtainment of the dosage form required.
The examples of the formulations of the present invention are given below. The formulations of the present invention are not limited to these examples.
EXAMPLES
Example I. Sachet formulation comprising ibandronate sodium having 5% of water content by weight.
Figure imgf000009_0001
Example II. Sachet formulation comprising ibandronate sodium having 7.5% of water content by weight.
Figure imgf000009_0002
The method to be used for production of ibandronate sodium sachet formulations given above is dry blending method which is described in the description part in detail. The pharmaceutical powder formulations obtained by dry blending and sieving steps are sent to the sachet filling machine and final product is obtained in sachet form.

Claims

1. A water soluble formulation comprising ibandronate sodium characterized in that the water content of the active agent is less than 11% by weight.
2. The water soluble pharmaceutical formulation according to claim 1 characterized in that the water content of the active agent is in the range of 0 to 11% by weight.
3. The water soluble formulation according to claims 1-2 characterized in that the formulations comprise at least one pharmaceutically acceptable excipient selected from a group comprising filling agents, binders, lubricants, disintegrants, diluents, stabilizing agents, sweeteners, taste regulating agents, inorganic salts, flavouring agents.
4. The water soluble formulation according to claim 3 characterized in that the formulations comprise at least one filling agent, at least one sweetener and at least one inorganic salt as excipients.
5. The water soluble formulation according to claim 4 characterized in that the formulations comprise at least one filling agent selected from the group of water soluble sugar alcohols.
6. The water soluble formulation according to claim 5 characterized in that the formulations comprise at least one filling agent selected from a group comprising sorbitol, mannitol, xylitol, erythrol, isomalt, starch hydrolysates or combinations thereof.
7. The water soluble formulation according to claim 4 characterized in that the formulation comprises at least one sweetener selected from a group comprising aspartame, dextrose, fructose, sucralose, sodium cyclamate, mannitol, maltose, sorbitol, saccharin and/or pharmaceutically acceptable salts or combinations thereof.
8. The water soluble formulation according to claim 4 characterized in that the formulations comprise at least one inorganic salt selected from a group comprising sodium carbonate, sodium bicarbonate, sodium acetate, sodium chloride, potassium chloride, potassium carbonate, potassium bicarbonate.
9. The water soluble formulations according to any preceding claims characterized in that the formulations are in powder or granule form.
10. The water soluble formulation according to claim 9 characterized in that the formulations are filled into bottles, capsules, sachet or compressed in tablet form.
11. The water soluble formulation according to claim 10 characterized in that the formulations are in sachet form.
12. A method for production of water soluble formulations comprising ibandronate sodium having less than 11 % of water content by weight according to any preceding claims characterized in that the method is either one of the dry granulation or dry blending methods.
13. The method for production of the water soluble formulations comprising ibandronate sodium having less than 11% of water content by weight according to claim 12 characterized in that the method is dry blending method.
14. The method for production of the water soluble formulations comprising ibandronate sodium having less than 11% of water content by weight according to claim 13 characterized in that the method comprises the steps of,
I. Mixing ibandronate sodium having less than 11% of water content by weight and the pharmaceutically acceptable excipients dryly,
II. Sieving the mixture
III. Sending the mixture obtained to the related filling machines for obtainment of the dosage form required.
15. The water soluble formulation according to claim 1 characterized in that the formulation is used in treatment and/or prevention of bone diseases such as hypercalcaemia, osteoporosis, tumoral osteolysis, malignant hypercalcaemia, metastatic bone disease, periprostatic bone loss, Paget' s disease.
PCT/TR2012/000006 2011-01-06 2012-01-06 Water soluble formulations comprising ibandronate sodium with a water content less than 11 % by weight Ceased WO2012093975A1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
TR2011/00151A TR201100151A2 (en) 2011-01-06 2011-01-06 Ibandronate formulation.
TR2011/00151 2011-01-06
TR2011/10524A TR201110524A2 (en) 2011-01-06 2011-10-24 New water-soluble formulations for use in the treatment of bone diseases.
TR2011/10524 2011-10-24

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Citations (5)

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WO2006002348A2 (en) * 2004-06-23 2006-01-05 Teva Pharmaceutical Industies Ltd. Solid and crystalline ibandronic acid
WO2007074475A2 (en) * 2005-12-27 2007-07-05 Natco Pharma Limited Novel polymorphic forms of ibandronate
WO2008131160A1 (en) * 2007-04-19 2008-10-30 Dr. Reddy's Laboratories Ltd. Ibandronate sodium polymorphs
US20090118239A1 (en) * 2007-11-05 2009-05-07 Teva Pharmaceutical Industries Ltd. Amorphous and crystalline forms of ibandronate disodium

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005063779A2 (en) * 2003-12-23 2005-07-14 Lyogen Limited A process for the preparation of alkyl- and aryl-diphosphonic acids and salts thereof
WO2006002348A2 (en) * 2004-06-23 2006-01-05 Teva Pharmaceutical Industies Ltd. Solid and crystalline ibandronic acid
WO2007074475A2 (en) * 2005-12-27 2007-07-05 Natco Pharma Limited Novel polymorphic forms of ibandronate
WO2008131160A1 (en) * 2007-04-19 2008-10-30 Dr. Reddy's Laboratories Ltd. Ibandronate sodium polymorphs
US20090118239A1 (en) * 2007-11-05 2009-05-07 Teva Pharmaceutical Industries Ltd. Amorphous and crystalline forms of ibandronate disodium

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