WO2000021540A1 - Compositions containing diphosphonic acids - Google Patents
Compositions containing diphosphonic acids Download PDFInfo
- Publication number
- WO2000021540A1 WO2000021540A1 PCT/EP1999/007287 EP9907287W WO0021540A1 WO 2000021540 A1 WO2000021540 A1 WO 2000021540A1 EP 9907287 W EP9907287 W EP 9907287W WO 0021540 A1 WO0021540 A1 WO 0021540A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- administration
- active substance
- stearic acid
- outer phase
- weight
- Prior art date
Links
Classifications
-
- 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
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—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
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Definitions
- the invention relates to a solid pharmaceutical form of administration containing a diphosphonic acid or a physiologically compatible salt thereof as the active substance and stearic acid as lubricant in the outer phase.
- the invention also relates to a process for preparing the said form of administration.
- diphosphonic acids are known for treatment of calcium metabolism diseases. Drugs containing these active substances are used for treating hypercalcaemia and also for treating tumour osteolysis resulting from bone metastases. They can also be successfully used for treatment of osteoporosis and resulting pain.
- Oral forms of administration are known in the case of some diphosphonic acids and salts thereof.
- EP-B 0 275 468, EP-B 0 625 355 (both Boehringer Mannheim) and WO 93/21907 (Leiras Oy) disclose pharmaceutical preparations containing clodronic acid (dichloromethylene diphosphonic acid) or salts thereof.
- WO 93/09785 discloses oral forms of administration of risedronate (the salt of 3-pyridyl- 1-hydroxyethylidene-l, 1-diphosphonic acid).
- WO 93/21907 and WO 93/09785 describe oral forms of administration provided with a coating which dissolves only at pH above 5 or 5.5. The aim is to ensure that the forms of administration travel through the stomach and the active principle is released only in the intestinal tract.
- the solid forms of administration of diphosphonic acids or salts thereof described in the prior art contain the active substance and selected pharmaceutical adjuvants, with which the active principle must be compatible, in the inner phase and selected pharmaceutical adjuvants in the outer phase, more particularly for ensuring that the preparation can be easily processed in a capsule-filling machine or tablet press.
- EP-B 0 275 468 describes clodronate-containing drugs with a high proportion of 80 - 95% active substance, a filler content of 2 - 10% and a lubricant content of 0 - 5% in the granulate, to which is added an outer phase in the form of a lubricant, preferably magnesium stearate and talcum, in a proportion of 1 - 5% .
- the selection and proportion of a suitable lubricant in the outer phase is particularly important, since it has great influence on the physical properties of the forms of administration under development.
- the choice and proportion determine whether the substance filling the capsule or tablet can be processed without difficulty on a suitable machine over a prolonged period or whether the tablets stick to the compression moulding dies in the machine. Sufficient lubricant must therefore be added to the outer phase. If however the proportion of lubricant is too high, there may be other adverse effects. For example the granulate may become so water-repellent that the resulting drug disintegrates only slowly and the desired dissolution rate (practically complete release of the active substance after 30 minutes) is not reached.
- the following known lubricants can be used in the outer phase: magnesium stearate, calcium stearate, talcum, sodium stearyl fumarate, acrogol or hydrogenated esters of fatty acids with glycerine and stearic acid.
- EP-B 0 275 468 which describes oral forms of administration for clodronate
- magnesium stearate and talcum are together used as a lubricant in the outer phase.
- EP-B 0 625 355 (Boehringer Mannheim GmbH) discloses magnesium stearate as the only lubricant in the outer phase of clodronate forms of administration.
- WO 93/21907 (Leiras Oy, clodronate) Example 1
- WO 93/09785 (Procter & Gamble, risedronate)
- Example 3 discloses stearic acid lubricant in a proportion of 5.8% by weight relative to the tablet core.
- the object of the invention therefore is to develop a pharmaceutical form of administration in which the active substances are diphosphonic acids or physiologically compatible salts thereof and which is stable enough for the active substance to be released uniformly and almost completely within 30 minutes and for no reduction in the rate of dissolution to occur even after temperature stress. This should apply both to high and low contents of active substance in the form of administration.
- solid forms of administration containing less than 5% by weight of stearic acid lubricant in the outer phase, relative to the total weight of the form of administration, e.g. 0.1 to 4.9% by weight, have dissolution rates of at least 85' after 30 minutes, and the rates do not change even after weeks of exposure to temperatures of 40 - 50°C. This applies both to low and to high contents of active substance in the form of administration.
- This aspect of the invention therefore relates to solid pharmaceutical forms of administration in v/hich the active substance is a diphosphonic acid or a physiologically compatible salt thereof, wherein the active substance in granulate form, optionally together with pharmaceutical adjuvants, is present in the inner phase and the outer phase contains a lubricant in the form of stearic acid in proportions of less than 5% by weight relative to the total weight of the form of administration .
- the outer phase preferably contains stearic acid in a proportion of 0.1 to 3%, particularly 0.9 to 3% by weight, relative to the total weight of the form of administration.
- Particularly preferably stearic acid is added in a proportion of 1.5 to 2.7% by weight relative to the total weight of the form of administration, in which case the rate of release will be at least 90% (determined by the Paddle method after the USP) .
- the granulated active substance can contain pharmaceutically acceptable adjuvants and/or additives such as lactose, starch, glucose, mannitol, calcium carbonate, calcium phosphate, microcrystalline cellulose, hydroxypropyl methyl cellulose or other substances known for this purpose in the art.
- pharmaceutically acceptable adjuvants and/or additives such as lactose, starch, glucose, mannitol, calcium carbonate, calcium phosphate, microcrystalline cellulose, hydroxypropyl methyl cellulose or other substances known for this purpose in the art.
- the form of administration according to the invention can also contain other pharmaceutical adjuvants in the outer phase, more particularly a disintegrating agent, all known disintegrating agents being usable. More particularly cross-linked polyvinyl pyrrolidone (Crospovidone USPNF) has given good service as a disintegrating agent for the purposes of the invention.
- a disintegrating agent More particularly cross-linked polyvinyl pyrrolidone (Crospovidone USPNF) has given good service as a disintegrating agent for the purposes of the invention.
- bisphosphonates are active substances which can be used according to the invention in the form of free acids or pharmaceutically compatible salts or hydrates, particularly sodium salts:
- Ibandronate, etidronate, clodronate, risedronate, pamidronate or alendronate or free acids thereof are preferred active substances according to the invention.
- the proportion of active substance in the form of administration according to the invention can be up to 95% by weight relative to the total weight of the form of administration. Active substance contents of 0.2 - 30% by weight, relative to the total weight of the form of administration, are particularly preferred.
- the method according to the invention can particularly preferably be used to make oral forms of administration containing 0.25 - 100 mg of active substance per unit dose, particularly up to 50 mg per unit dose.
- unit dose denotes the discrete form of administration, i.e. the individual tablet or capsule.
- Particularly preferred according to the invention is a form of administration in which the active substance is ibandronic acid (l-hydroxy-3- (N-methyl-N-pentyl) amino- propyl-1, 1-diphosphonic acid) or physiologically compatible salts thereof, e.g. the sodium salt.
- ibandronic acid l-hydroxy-3- (N-methyl-N-pentyl) amino- propyl-1, 1-diphosphonic acid
- physiologically compatible salts thereof e.g. the sodium salt.
- the components are mixed dry.
- the active substance preferably together with a conventional binder such as starch paste or polyvinyl pyrrolidone K25, and optionally with addition of pharmaceutically acceptable additives and adjuvants (excipients of the inner phase), is granulated wet.
- the wet granulate is then dried and screened.
- the outer phase is then added to the mixture.
- Either the components of the outer phase (stearic acid and adjuvants) are first mixed together and added to the granulate in a further step, or the stearic acid and any other adjuvants in the outer phase are added individually and directly to the granulate.
- the mixture according to the invention can easily be processed using automatic equipment and then compressed to form tablets or filled into conventional gelatine capsules. Tablets so prepared may be coated with conventional films such as described, e.g., in WO 97/39755.
- the invention also relates to a process for producing a solid pharmaceutical form of administration in which the active substance is a diphosphonic acid or a physiologically compatible salt thereof, wherein the active substance is processed by known methods with pharmaceutical adjuvants to obtain a granulate, less than 5% by weight of stearic acid lubricant is added to the resulting inner phase, and optionally further adjuvants are added to the mixture and the mixture is filled into capsules or compressed to form tablets.
- the tablets and capsule sizes are preferably so chosen as to give a concentration of active substance of 0.25 - 100 mg per unit dose. This determines the size of the form of administration according to the invention, depending on the biological potency of the active substances and any adjuvants capable of increasing it.
- the forms of administration produced according to the invention result in free-flowing, pourable compositions and do not adhere to the moulds or tools when compressed or filled into capsules.
- an in vitro release rate of 56% was found after 30 minutes. If these capsules were additionally heat-stressed at 40 - 50°C in a drying cupboard for several weeks and the rate of release was measured again, the 30-minute value fell to below 30%.
- the amount of active substance is equivalent to 5.0 mg free acid. Processing:
- a preliminary mixture was made from the active substance (Item 1) and lactose 200 (Item 2) .
- the preliminary mixture was then wet granulated with additional adjuvants such as lactose D30 (Item 3), using polyvinyl pyrrolidone binder (Item 4) .
- Additional lactose (Item 5) was then mixed with the granulate after drying and screening.
- the additives for the outer phase (Items 6 and 7) were then added individually to the mixture.
- the resulting substance was filled into capsules in suitable machines.
- the capsules were tested as part of in-process control and immediately after production had an in vitro release rate of 56% after 30 minutes.
- the release rate was determined by the Paddle method after the USP.
- the amount of active substance is equivalent to 5.0 mg free acid.
- the capsules were produced as in Comparative Example 1.
- Example 1 The capsules in Comparative Examples 1 and 2 were heat- stressed at 50°C in a drying cupboard for a number of weeks, after which the release rate was determined again. This fell to a 30-minute value below 30%.
- Example 1 The capsules in Comparative Examples 1 and 2 were heat- stressed at 50°C in a drying cupboard for a number of weeks, after which the release rate was determined again. This fell to a 30-minute value below 30%.
- Example 1 Example 1 :
- the capsule-filling material was produced as in Comparative Examples 1 and 2. As in these Examples, the additives 6 and 7 constituted the outer phase.
- the material was filled into size 0 capsules.
- Example 1 a) 90% for the batch containing 4.0 mg stearic acid and b) 101% for the batch containing 8.0 mg stearic acid.
- the capsules in the present Example 1 were also heat- stressed at 50°C in a drying oven for a number of weeks, The rates of dissolution were then determined and were the same as before heat-stressing.
- the amount of active substance is equivalent to 20.0 mg of free acid.
- the active substance was mixed with the adjuvants (Items 2, 3 and 4) and wet granulated with water.
- a mixture constituting the outer phase (Items 5 and 6) was added to the granulate after drying and screening. The material ready for compressing was then compressed to form tablets.
- the resulting tablets were tested for the in vitro release rate immediately after production. The value after 30 minutes was 102%.
- the amount of active substance is equivalent to 50.0 mg of free acid.
- the active substance was mixed with the adjuvants (Items 2, 3 and 4) and wet granulated with water.
- the constituents of the outer phase (Items 5 and 6) were individually mixed with the granulate after drying and screening. The material ready for pressing was then compressed to form tablets.
Abstract
Description
Claims
Priority Applications (19)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NZ510433A NZ510433A (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids as an inner phase and stearic acid as the outer phase |
CA002346662A CA2346662C (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids |
SI9930865T SI1117412T1 (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids |
DE69928819T DE69928819T2 (en) | 1998-10-09 | 1999-10-01 | DIPHOSPHONIC ACID CONTAINING COMPOSITIONS |
AT99952483T ATE311887T1 (en) | 1998-10-09 | 1999-10-01 | COMPOSITIONS CONTAINING DIPHOSPHONIC ACID |
PL99347243A PL194552B1 (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids |
BR9914367-4A BR9914367A (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids |
EP99952483A EP1117412B1 (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids |
HU0103931A HU226457B1 (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids |
MEP-2001-205A ME00637B (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids |
JP2000575516A JP4471498B2 (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acid |
AU64675/99A AU752532B2 (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids |
IL14191299A IL141912A0 (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids |
IL141912A IL141912A (en) | 1998-10-09 | 2001-03-08 | Pharmaceutical compositions containing diphosphonic acids and process for their preparation |
HR20010243A HRP20010243B1 (en) | 1998-10-09 | 2001-03-30 | Compositions containing diphosphonic acids |
NO20011714A NO327447B1 (en) | 1998-10-09 | 2001-04-05 | Mixtures containing diphosphonic acids and processes for their preparation. |
HK02101678.5A HK1040914B (en) | 1998-10-09 | 2002-03-05 | Compositions containing diphosphonic acids |
CY20061100267T CY1105437T1 (en) | 1998-10-09 | 2006-02-24 | DIPHOSPHONIC ACID COMPOSITIONS |
IL177940A IL177940A (en) | 1998-10-09 | 2006-09-07 | Pharmaceutical compositions containing diphosphonic acids |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98119102A EP0998932A1 (en) | 1998-10-09 | 1998-10-09 | Solid pharmaceutical dosage form containing diphosphonates or their salts and method for its production |
EP98119102.6 | 1998-10-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000021540A1 true WO2000021540A1 (en) | 2000-04-20 |
Family
ID=8232769
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1999/007287 WO2000021540A1 (en) | 1998-10-09 | 1999-10-01 | Compositions containing diphosphonic acids |
Country Status (35)
Country | Link |
---|---|
US (2) | US6294196B1 (en) |
EP (2) | EP0998932A1 (en) |
JP (2) | JP4471498B2 (en) |
KR (1) | KR100522505B1 (en) |
CN (1) | CN1150000C (en) |
AR (3) | AR014081A1 (en) |
AT (1) | ATE311887T1 (en) |
AU (1) | AU752532B2 (en) |
BR (1) | BR9914367A (en) |
CA (1) | CA2346662C (en) |
CO (1) | CO5050325A1 (en) |
CY (1) | CY1105437T1 (en) |
CZ (1) | CZ299008B6 (en) |
DE (1) | DE69928819T2 (en) |
DK (1) | DK1117412T3 (en) |
ES (1) | ES2253919T3 (en) |
HK (1) | HK1040914B (en) |
HR (1) | HRP20010243B1 (en) |
HU (1) | HU226457B1 (en) |
ID (1) | ID29876A (en) |
IL (3) | IL141912A0 (en) |
MA (1) | MA27123A1 (en) |
ME (1) | ME00637B (en) |
MY (1) | MY126625A (en) |
NO (1) | NO327447B1 (en) |
NZ (1) | NZ510433A (en) |
PE (1) | PE20001082A1 (en) |
PL (1) | PL194552B1 (en) |
RS (1) | RS49809B (en) |
RU (1) | RU2207860C2 (en) |
SI (1) | SI1117412T1 (en) |
TR (1) | TR200100889T2 (en) |
TW (1) | TW576742B (en) |
WO (1) | WO2000021540A1 (en) |
ZA (1) | ZA200102276B (en) |
Cited By (9)
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US6294196B1 (en) | 1998-10-09 | 2001-09-25 | Hoffmann-La Roche Inc. | Pharmaceutical composition containing diphosphonic acid or salt thereof |
US6719998B1 (en) | 1998-07-14 | 2004-04-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Treatment of restenosis |
JP2005522526A (en) * | 2002-05-10 | 2005-07-28 | エフ.ホフマン−ラ ロシュ アーゲー | Bisphosphonic acid for treatment and prevention of osteoporosis |
US6984400B2 (en) | 1998-07-14 | 2006-01-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Method of treating restenosis using bisphosphonate nanoparticles |
US7008645B2 (en) | 1998-07-14 | 2006-03-07 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Method of inhibiting restenosis using bisphosphonates |
EP1596870B2 (en) † | 2002-12-20 | 2011-04-06 | F. Hoffmann-La Roche AG | High dose ibandronate formulation |
US8697124B2 (en) | 2006-08-24 | 2014-04-15 | Arrow International Limited | Solid dosage form of coated bisphosphonate particles |
US9498488B2 (en) | 2003-06-27 | 2016-11-22 | Biorest Ltd. | Method of treating acute coronary syndromes |
US9993427B2 (en) | 2013-03-14 | 2018-06-12 | Biorest Ltd. | Liposome formulation and manufacture |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SK2532004A3 (en) * | 2001-12-21 | 2004-11-03 | Procter & Gamble | Method for the treatment of bone disorders |
CA2470495A1 (en) * | 2001-12-24 | 2003-07-17 | Teva Pharmaceutical Industries Ltd. | Dosage form with a core tablet of active ingredient sheathed in a compressed annular body of powder or granular material, and process and tooling for producing it |
US20040052843A1 (en) * | 2001-12-24 | 2004-03-18 | Lerner E. Itzhak | Controlled release dosage forms |
AU2006222690B2 (en) * | 2002-12-20 | 2009-04-23 | F. Hoffmann-La Roche Ag | High dose ibandronate formulation |
US7390503B1 (en) | 2003-08-22 | 2008-06-24 | Barr Laboratories, Inc. | Ondansetron orally disintegrating tablets |
EP1709968A1 (en) * | 2004-01-30 | 2006-10-11 | Astellas Pharma Inc. | P2x receptor inhibitor |
CN101022812A (en) * | 2004-08-23 | 2007-08-22 | 特瓦制药工业有限公司 | Solid and crystalline ibandronate sodium and processes for preparation thereof |
EP1802641B8 (en) * | 2004-10-08 | 2012-03-07 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods for bone resorption diseases, cancer, bone pain, immune disorders, and infectious diseases |
US8012949B2 (en) * | 2004-10-08 | 2011-09-06 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods with enhanced potency for multiple targets including FPPS, GGPPS, and DPPS |
WO2007109585A2 (en) * | 2006-03-17 | 2007-09-27 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods |
US7582789B2 (en) * | 2005-02-01 | 2009-09-01 | Hoffmann-La Roche Inc. | Ibandronate polymorph |
EP1848728B1 (en) * | 2005-02-01 | 2014-06-11 | F.Hoffmann-La Roche Ag | Ibandronate polymorph a |
US20070049557A1 (en) * | 2005-08-24 | 2007-03-01 | Hashim Ahmed | Solid pharmaceutical dosage forms comprising bisphosphonates and modified amino acid carriers |
US20070191315A1 (en) * | 2006-02-16 | 2007-08-16 | Bengt Bergstrom | Method for administering ibandronate |
US20080139514A1 (en) * | 2006-11-29 | 2008-06-12 | Subhash Pandurang Gore | Diphosphonic acid pharmaceutical compositions |
CA2570949A1 (en) * | 2006-12-12 | 2008-06-12 | Apotex Pharmachem Inc. | Ibandronate sodium propylene glycol solvate and processes for the preparation thereof |
WO2008074145A1 (en) * | 2006-12-20 | 2008-06-26 | Genpharm Ulc | Pharmaceutical composition comprising a hot-melt granulated lubricant |
EP2298286B8 (en) * | 2009-09-18 | 2017-08-09 | SiTec PharmaBio SL | Process for dewatering of product powders |
KR101244414B1 (en) * | 2010-11-05 | 2013-03-18 | 주식회사 바이오파마티스 | A composition for treating or preventing osteoporosis comprising ibandronic acid and a method of preparing the same |
EP2661262B1 (en) | 2011-01-06 | 2017-11-15 | Mahmut Bilgic | Improved bisphosphonate formulations |
JP5874545B2 (en) * | 2011-06-20 | 2016-03-02 | アステラス製薬株式会社 | Pharmaceutical composition for oral administration |
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EP0275468A1 (en) * | 1986-12-20 | 1988-07-27 | Roche Diagnostics GmbH | Pharmaceutical compositions containing clodronate, and process for their preparation |
WO1993021907A1 (en) * | 1992-04-24 | 1993-11-11 | Leiras Oy | Pharmaceutical preparation and process for its manufacture |
WO1996041618A1 (en) * | 1995-06-08 | 1996-12-27 | Sanofi | Stable pharmaceutical compositions containing tiludronate hydrates and process for producing the pharmaceutical compositions |
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DE3434667A1 (en) | 1984-09-21 | 1986-04-03 | Henkel KGaA, 4000 Düsseldorf | 4-DIMETHYLAMINO-1-HYDROXYBUTANE-1,1-DIPHOSPHONIC ACID, THEIR WATER-SOLUBLE SALTS, PROCESS FOR THEIR PRODUCTION AND THEIR USE |
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- 1999-10-01 JP JP2000575516A patent/JP4471498B2/en not_active Expired - Lifetime
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- 1999-10-01 PL PL99347243A patent/PL194552B1/en unknown
- 1999-10-01 ES ES99952483T patent/ES2253919T3/en not_active Expired - Lifetime
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- 1999-10-01 WO PCT/EP1999/007287 patent/WO2000021540A1/en active IP Right Grant
- 1999-10-01 AU AU64675/99A patent/AU752532B2/en not_active Ceased
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US6719998B1 (en) | 1998-07-14 | 2004-04-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Treatment of restenosis |
US6984400B2 (en) | 1998-07-14 | 2006-01-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Method of treating restenosis using bisphosphonate nanoparticles |
US6627221B2 (en) | 1998-10-09 | 2003-09-30 | Hoffmann-La Roche Inc. | Pharmaceutical composition containing diphosphonic acid or salt thereof |
US6294196B1 (en) | 1998-10-09 | 2001-09-25 | Hoffmann-La Roche Inc. | Pharmaceutical composition containing diphosphonic acid or salt thereof |
JP2013166773A (en) * | 2002-05-10 | 2013-08-29 | F Hoffmann La Roche Ag | Bisphosphonic acid for treatment and prevention of osteoporosis |
JP2005522526A (en) * | 2002-05-10 | 2005-07-28 | エフ.ホフマン−ラ ロシュ アーゲー | Bisphosphonic acid for treatment and prevention of osteoporosis |
US7718634B2 (en) | 2002-05-10 | 2010-05-18 | Hoffman-La Roche Inc. | Method of treatment using bisphosphonic acid |
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US8697124B2 (en) | 2006-08-24 | 2014-04-15 | Arrow International Limited | Solid dosage form of coated bisphosphonate particles |
US10420725B2 (en) | 2006-08-24 | 2019-09-24 | Allergan Pharmaceuticals International Limited | Solid dosage form of coated bisphosphonate particles |
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US11633357B2 (en) | 2013-03-14 | 2023-04-25 | Zuli Holdings, Ltd. | Liposome formulation and manufacture |
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