[go: up one dir, main page]

WO1992009271A1 - Composition for solid pharmaceutical preparations containing active vitamins d3 and process for preparation thereof - Google Patents

Composition for solid pharmaceutical preparations containing active vitamins d3 and process for preparation thereof Download PDF

Info

Publication number
WO1992009271A1
WO1992009271A1 PCT/US1991/002846 US9102846W WO9209271A1 WO 1992009271 A1 WO1992009271 A1 WO 1992009271A1 US 9102846 W US9102846 W US 9102846W WO 9209271 A1 WO9209271 A1 WO 9209271A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
vitamins
pharmaceutical preparations
solid pharmaceutical
active vitamins
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1991/002846
Other languages
French (fr)
Inventor
Motonari Okumura
Masahiro Ariyoshi
Takeshi Noguchi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Taisho Pharmaceutical Co Ltd
Sumitomo Pharma Co Ltd
Wisconsin Alumni Research Foundation
Original Assignee
Sumitomo Pharmaceuticals Co Ltd
Taisho Pharmaceutical Co Ltd
Wisconsin Alumni Research Foundation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sumitomo Pharmaceuticals Co Ltd, Taisho Pharmaceutical Co Ltd, Wisconsin Alumni Research Foundation filed Critical Sumitomo Pharmaceuticals Co Ltd
Publication of WO1992009271A1 publication Critical patent/WO1992009271A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin

Definitions

  • This invention relates to a composition for solid pharmaceutical preparations containing active vitamins D 3 and a process for the preparation thereof, and more particularly to a composition for solid pharmaceutical preparations containing active vitamins D 3 in which hydroxypropyl methyl cellulose is used as an excipient.
  • active vitamins D 3 are labile and sensitive to heat and light and apt to be readily oxidized, so that the formation of pharmaceutical preparations containing active vitamins D 3 requires to stabilize them.
  • the preparations are obtained by dissolving active vitamins D 3 together with bile acids, cholesterols or polyvinyl pyrrolidone in an alcoholic solvent such as ethanol, methanol, propanol or the like which permits both to be dissolved therein, followed by removal of the solvent under reduced pressure.
  • an alcoholic solvent such as ethanol, methanol, propanol or the like which permits both to be dissolved therein.
  • each of the proposed methods exhibits a disadvantage of causing the composition to be partially resinified during the removal of the solvent under reduced pressure.
  • each of the conventional methods proposed causes the composition to be rendered non-uniform in grain size when it is pulverized.
  • composition for solid pharmaceutical preparations of active vitamins D 3 as disclosed in Japanese Patent Application Laid-Open Publication No. 155309/1984.
  • the present invention has been made in view of the foregoing disadvantage of the prior art.
  • the inventors have made a careful study for the purpose of preparing a composition for solid pharmaceutical preparations which is capable of stabilizing active vitamins D 3 , having a uniform content and facilitating the handling.
  • a composition for solid pharmaceutical preparations containing active vitamins D 3 which comprises hydroxypropylmethyl cellulose (hereinafter referred to as
  • HPMC HPMC
  • an active vitamins D 3 and a polymer which is readily soluble in an organic solvent each attached to HPMC meets such requirements.
  • composition for solid pharmaceutical preparations containing active vitamins D 3 which is capable of permitting the active vitamins D 3 to be significantly thermally stabilized and being improved in handling.
  • compositions containing active vitamins D 3 which is capable of highly facilitating the preparation while ensuring thermal stability of the vitamins D 3 .
  • a composition for solid pharmaceutical preparations containing active vitamins D 3 comprises hydroxypropyl methyl cellulose, and an active vitamin D 3 and a polymer which is readily soluble in an organic solvent each attached to the hydroxypropyl methyl cellulose.
  • a process for preparing such a composition as described above uses an alcoholic solvent.
  • the polymer which is readily soluble in an organic solvent includes polyvinyl pyrrolidone (hereinafter referred to as "PVP"), HMPC and the like.
  • the active vitamins D 3 of the present invention include vitamins D 3 of which positions 1 ⁇ and/or 25 are subject to hydroxidation, such as, for example, 1 ⁇ - hydroxycholecalciferol; 25-hydroxycholecalciferol; 1 ⁇ , 25- dihydroxycholecalciferol; 26, 26, 26, 27, 27, 27-hexafluoro-1 ⁇ , 25-dihydroxycholecalciferol (hereinafter referred to as "ST- 630); 1 ⁇ , 25-dihydroxycholecalciferol; 24, 25- dihydroxycholecalciferol, 1 ⁇ -dihydroxycholecalciferol; 1 ⁇ , 25- dihydroxy-26, 27-dimethylcholecalciferol; 1 ⁇ -hydroxy-26, 27- dimethylcholecalciferol; 25-hydroxy-26, 27- dimethylcholecalciferol; 1 ⁇ , 25-dihydroxy-24, 24-difluoro-26, 27-dimethylcholecalciferol; 1 ⁇ , 25-dihydroxy-26,
  • the polymer which is readily soluble in an organic solvent is loaded in an amount of from 0.1% to 50% by weight and preferably from 0.1% to 35% by weight in the composition.
  • composition of the present invention is obtained by preparing HPMC using an alcoholic solution in which the active vitamins D 3 and the polymer which is readily soluble in an organic solvent are dissolved.
  • the alcoholic solvent suitable for use for this purpose includes, for example, ethanol
  • HPMC acts as an excipient. Any prior art is silent concerning the use of HPMC as a sole excipient in wet granulation as in the present
  • HPMC highly exhibits a film forming property, therefore, the granulation of a composition using a solvent in which HPMC is dissolved causes removal and subsequent pulverization of the composition to be rendered difficult or troublesome.
  • the composition of the present invention is prepared using the alcoholic solvent in which HPMC is dissolved.
  • the use of the alcoholic solvent permits the surface of HPMC particles acting as a nucleus of the composition to be dissolved in the solvent, so that the active vitamins D 3 are taken in HPMC, resulting in being substantially stabilized.
  • composition thus obtained may be formed into pharmaceutical preparations as it is or, if necessary, while being mixed with at least one of any suitable additives known in the art such as an excipient, a degradative agent, a binder, a lubricant, an anti-oxidant, a coating agent, a coloring agent, a corrigent, a surface active agent and the like.
  • suitable additives known in the art such as an excipient, a degradative agent, a binder, a lubricant, an anti-oxidant, a coating agent, a coloring agent, a corrigent, a surface active agent and the like.
  • the excipient includes, for example, lactose, starch, crystalline cellulose, calcium hydrogenphosphate, light silica, titanium oxide, magnesium metasilicate aluminate, polyethylene glycol and the like.
  • the degradative agent includes, for example,
  • carboxymethyl cellulose calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium.
  • the binder includes, for example, hydroxypropyl cellulose, gelatin, gum arabic, ethyl cellulose, polyvinyl
  • the lubricant includes, for example, stearic acid, magnesium stearate, calcium stearate, talc, hardened oil, fatty saccharide and the like.
  • the anti-oxidant includes, for example, dibutyl hydroxytoluene (BHT), gallic propyl, butylhydroxy anisole (BHA), ⁇ -tocopherol, citric acid and the like.
  • BHT dibutyl hydroxytoluene
  • BHA butylhydroxy anisole
  • ⁇ -tocopherol citric acid and the like.
  • the coating agent includes, for example, HPMC,
  • diethylaminoacetate aminoalkyl methacrylate copolymer, hydroxypropylmethyl cellulose acetate succinate, methacrylic acid coplymer, cellulose acetate trimellitate (CAT), polyvinyl acetate phthalate, and the like.
  • the coloring agent includes, for example, a tar pigment, titanium oxide and the like.
  • the corrigent includes, for example, citric acid, adipic acid, ascorbic acid, menthol and the like.
  • the surface active agent includes, for example, glycerin monostearate, polysorbates, sodium lauryl sulfate,
  • composition for solid pharmaceutical preparations according to the present invention may be prepared according to a conventional wet granulation process.
  • the a conventional wet granulation process may be used.
  • composition is preferably prepared using an apparatus
  • the apparatus includes, for example, a fluidized bed type apparatus, a rolling and flowing type apparatus, a centrifugal flowing type apparatus, a vacuum type apparatus.
  • TC-5R 500g of HPMC 2910 (hereinafter referred to as "TC-5R") was subject to stirring granulation using a solution prepared by dissolving 5mg of ST-630, 12.5g of BHT and 125g of PVP-K30 in 187.5g of 90% ethanol and then pulverized after drying, to thereby provide a composition of the present invention.
  • the composition was sealedly put in a glass bottle and stored at 40°C to examine the stability.
  • a variation in residual rate of ST-630 with time was as indicated in Table 1.
  • a composition for reference was prepared by adding 5ml of an ethanol solution containing ST-63 of 100 ⁇ g/ml in
  • Table 1 clearly reveals that in the reference, decomposition of ST-630 occurred rapidly, whereas ST-630 in the composition of the present invention was stabilized for a long period of time.
  • 500g of TC-5R was subject to stirring granulation using a solution prepared by dissolving 5mg of ST-630, 12.5g of BHT and 125g of TC-5R in 187.5g of 90% ethanol and then pulverized after drying, to thereby provide a composition of the present invention.
  • 500g of TC-5R was subject to agitating granulation using a solution prepared by dissolving 5mg of ST- 630, 12.5g of BHT and 125g of PVP-K30 in 500g of ethanol and then pulverized after drying, to thereby provide a composition of the present invention.
  • Table 2 clearly indicates that in each of the tablets prepared using the composition of the present invention, ST-630 was kept stabilized for a long period of time.

Landscapes

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

Abstract

A composition for solid pharmaceutical preparations containing active vitamins D3 capable of permitting the active vitamins D3 to be significantly stabilized and being improved in handling. The composition includes hydroxypropylmethyl cellulose. To the cellulose are attached active vitamins D3 and a polymer which is readily soluble in an organic solvent.

Description

TITLE OF THE INVENTION
COMPOSITION FOR SOLID PHARMACEUTICAL
PREPARATIONS CONTAINING ACTIVE VITAMINS D3
AND PROCESS FOR PREPARATION THEREOF
BACKGROUND OF THE INVENTION
This invention relates to a composition for solid pharmaceutical preparations containing active vitamins D3 and a process for the preparation thereof, and more particularly to a composition for solid pharmaceutical preparations containing active vitamins D3 in which hydroxypropyl methyl cellulose is used as an excipient.
In general, active vitamins D3 are labile and sensitive to heat and light and apt to be readily oxidized, so that the formation of pharmaceutical preparations containing active vitamins D3 requires to stabilize them.
In order to stabilize active vitamins D3, some techniques were proposed such as a method for forming an
inclusion compound between the vitamins and bile acids as disclosed in Japanese Patent Application Laid-Open Publication No. 69562/1980, a method for forming a complex between the vitamins and cholesterols as disclosed in Japanese Patent
Application Laid-Open Publication No. 40461/1982, a method for dispersing the vitamins in polyvinyl pyrrolidone as disclosed in Japanese Patent Application Laid-Open Publication No.
206533/1983 and the like.
In the proposed methods, the preparations are obtained by dissolving active vitamins D3 together with bile acids, cholesterols or polyvinyl pyrrolidone in an alcoholic solvent such as ethanol, methanol, propanol or the like which permits both to be dissolved therein, followed by removal of the solvent under reduced pressure. Unfortunately, each of the proposed methods exhibits a disadvantage of causing the composition to be partially resinified during the removal of the solvent under reduced pressure. Also, each of the conventional methods proposed causes the composition to be rendered non-uniform in grain size when it is pulverized.
In view of the above, a method was proposed wherein an excipient which is slightly soluble in an organic solvent is suspended in a solution in which active vitamins D3 are
dissolved and then a solvent of the solution is removed
according to a suitable procedure, to thereby obtain a
composition for solid pharmaceutical preparations of active vitamins D3, as disclosed in Japanese Patent Application Laid-Open Publication No. 155309/1984.
However, restrictions in preparation of the composition cause a core material for the composition to be limited to an excipient which is slightly soluble in an organic solvent.
Also, a large volume of organic solvent must be used to form an outer layer for the composition of an excipient which is readily soluble in an organic solvent, so that much energy is required to remove the organic solvent by drying.
SUMMARY OF THE INVENTION
The present invention has been made in view of the foregoing disadvantage of the prior art. The inventors have made a careful study for the purpose of preparing a composition for solid pharmaceutical preparations which is capable of stabilizing active vitamins D3, having a uniform content and facilitating the handling. As a result, it has been found that a composition for solid pharmaceutical preparations containing active vitamins D3 which comprises hydroxypropylmethyl cellulose (hereinafter referred to as
"HPMC"), and an active vitamins D3 and a polymer which is readily soluble in an organic solvent each attached to HPMC meets such requirements.
Accordingly, it is an object of the present invention to provide a composition for solid pharmaceutical preparations containing active vitamins D3 which is capable of permitting the active vitamins D3 to be significantly thermally stabilized and being improved in handling.
It is another object of the present invention to provide a process for preparing a composition for solid
pharmaceutical preparations containing active vitamins D3 which is capable of highly facilitating the preparation while ensuring thermal stability of the vitamins D3.
In accordance with one aspect of the present invention, a composition for solid pharmaceutical preparations containing active vitamins D3 is provided. The composition comprises hydroxypropyl methyl cellulose, and an active vitamin D3 and a polymer which is readily soluble in an organic solvent each attached to the hydroxypropyl methyl cellulose.
In accordance with another aspect of the present invention, a process for preparing such a composition as described above is provided. The method uses an alcoholic solvent.
DETAILED DESCRIPTION OF THE INVENTION
The polymer which is readily soluble in an organic solvent includes polyvinyl pyrrolidone (hereinafter referred to as "PVP"), HMPC and the like.
The active vitamins D3 of the present invention include vitamins D3 of which positions 1α and/or 25 are subject to hydroxidation, such as, for example, 1α - hydroxycholecalciferol; 25-hydroxycholecalciferol; 1α, 25- dihydroxycholecalciferol; 26, 26, 26, 27, 27, 27-hexafluoro-1α, 25-dihydroxycholecalciferol (hereinafter referred to as "ST- 630); 1α, 25-dihydroxycholecalciferol; 24, 25- dihydroxycholecalciferol, 1α-dihydroxycholecalciferol; 1α , 25- dihydroxy-26, 27-dimethylcholecalciferol; 1α-hydroxy-26, 27- dimethylcholecalciferol; 25-hydroxy-26, 27- dimethylcholecalciferol; 1α, 25-dihydroxy-24, 24-difluoro-26, 27-dimethylcholecalciferol; 1α, 25-dihydroxy-26, 27-diethylcholecalciferol; 25-hydroxy-26, 27-dimethylcholecalciferol;; 25-hydroxy-26, 26, 26, 27, 27, 27-hexafluorocalciferol; 25-hydroxy-26, 26, 26, 27, 27, 27-hexafluoroepicalciferol; 1α, 25-dihydroxy-24, 24-difluorohomocholecalciferol; 1α, 25-dihydroxycholecalciferol-26, 23-lactone; 1α, 25-dihydroxy-22-oxacholecalciferol; 1α-hydroxy-22-oxacholecalciferol; and ergocalciferols corresponding to the above. HPMC used as an excipient in the composition of the present invention is loaded in an amount of from 50% to 99.9% by weight and preferably from 65% to 99.9% by weight in the
composition. The polymer which is readily soluble in an organic solvent is loaded in an amount of from 0.1% to 50% by weight and preferably from 0.1% to 35% by weight in the composition.
The composition of the present invention is obtained by preparing HPMC using an alcoholic solution in which the active vitamins D3 and the polymer which is readily soluble in an organic solvent are dissolved. The alcoholic solvent suitable for use for this purpose includes, for example, ethanol
containing 20% or less water.
In the preparation of the composition, HPMC acts as an excipient. Any prior art is silent concerning the use of HPMC as a sole excipient in wet granulation as in the present
invention. The reason would be that HPMC highly exhibits a film forming property, therefore, the granulation of a composition using a solvent in which HPMC is dissolved causes removal and subsequent pulverization of the composition to be rendered difficult or troublesome.
As described above, the composition of the present invention is prepared using the alcoholic solvent in which HPMC is dissolved. The use of the alcoholic solvent permits the surface of HPMC particles acting as a nucleus of the composition to be dissolved in the solvent, so that the active vitamins D3 are taken in HPMC, resulting in being substantially stabilized.
The composition thus obtained may be formed into pharmaceutical preparations as it is or, if necessary, while being mixed with at least one of any suitable additives known in the art such as an excipient, a degradative agent, a binder, a lubricant, an anti-oxidant, a coating agent, a coloring agent, a corrigent, a surface active agent and the like.
The excipient includes, for example, lactose, starch, crystalline cellulose, calcium hydrogenphosphate, light silica, titanium oxide, magnesium metasilicate aluminate, polyethylene glycol and the like.
The degradative agent includes, for example,
carboxymethyl cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium. Type A (Ac-Di-Sol®) starch, crystalline cellulose, hydroxypropyl starch, starch of which a part is modified into α-starch and the like.
The binder includes, for example, hydroxypropyl cellulose, gelatin, gum arabic, ethyl cellulose, polyvinyl
alcohol, pullulan and the like.
The lubricant includes, for example, stearic acid, magnesium stearate, calcium stearate, talc, hardened oil, fatty saccharide and the like.
The anti-oxidant includes, for example, dibutyl hydroxytoluene (BHT), gallic propyl, butylhydroxy anisole (BHA), α-tocopherol, citric acid and the like.
The coating agent includes, for example, HPMC,
hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropylmethyl cellulose phthalate, polyvinylacetal
diethylaminoacetate, aminoalkyl methacrylate copolymer, hydroxypropylmethyl cellulose acetate succinate, methacrylic acid coplymer, cellulose acetate trimellitate (CAT), polyvinyl acetate phthalate, and the like.
The coloring agent includes, for example, a tar pigment, titanium oxide and the like.
The corrigent includes, for example, citric acid, adipic acid, ascorbic acid, menthol and the like.
The surface active agent includes, for example, glycerin monostearate, polysorbates, sodium lauryl sulfate,
lauromacrogol, fatty saccharide, and the like.
The composition for solid pharmaceutical preparations according to the present invention may be prepared according to a conventional wet granulation process. However, the
composition is preferably prepared using an apparatus
constructed so as to concurrently dry the alcoholic solution in which the active vitamins D3 and polymer are dissolved while spraying it. The apparatus includes, for example, a fluidized bed type apparatus, a rolling and flowing type apparatus, a centrifugal flowing type apparatus, a vacuum type apparatus.
The present invention will be described in detail with reference to the following examples.
Example 1
500g of HPMC 2910 (hereinafter referred to as "TC-5R") was subject to stirring granulation using a solution prepared by dissolving 5mg of ST-630, 12.5g of BHT and 125g of PVP-K30 in 187.5g of 90% ethanol and then pulverized after drying, to thereby provide a composition of the present invention. The composition was sealedly put in a glass bottle and stored at 40°C to examine the stability. A variation in residual rate of ST-630 with time was as indicated in Table 1.
A composition for reference was prepared by adding 5ml of an ethanol solution containing ST-63 of 100μg/ml in
concentration to 50g of lactose in a mortar and mixing them, followed by drying.
Table 1
Samples Residual Rate of ST-630 (%)
Storage Temperature: 40°C
One Month Two Months Three Months Present Invention 97 95 98
Reference 64 46 38
Table 1 clearly reveals that in the reference, decomposition of ST-630 occurred rapidly, whereas ST-630 in the composition of the present invention was stabilized for a long period of time.
Example 2
500g of TC-5R was subject to stirring granulation using a solution prepared by dissolving 5mg of ST-630, 12.5g of BHT and 125g of TC-5R in 187.5g of 90% ethanol and then pulverized after drying, to thereby provide a composition of the present invention.
Example 3
500g of TC-5R was subject to agitating granulation using a solution prepared by dissolving 5mg of ST- 630, 12.5g of BHT and 125g of PVP-K30 in 500g of ethanol and then pulverized after drying, to thereby provide a composition of the present invention.
127.5g of the so-obtained composition, 867.5g of mannitol and 200g of hydroxypropyl cellulose having a low degree of substitution were fully mixed together to prepare a mixture and then 450g of purified water was added to the mixture, followed by stirring granulation and pulverization after drying , resulting in a powder for preparation of tablets. Then, 5g of magnesium stearate was added to the powder, which was then formed into tablets of 7mm in diameter and 120mg in weight and containing ST-630 in an amount of about 0.1ug.
Subsequently, the tablets each were sealedly put in a glass bottle and stored at 40°C to examine the stability. A variation in residual rate of ST-630 with time was as indicated in Table 2.
Table 2
Sample Residual Rate of ST-630 (%)
Storage Temperature: 40°C
One Month Two Months Three Months Present Invention 100 98 95
Table 2 clearly indicates that in each of the tablets prepared using the composition of the present invention, ST-630 was kept stabilized for a long period of time.

Claims

What is Claimed is:
1. A composition for solid pharmaceutical preparations containing active-type vitamins D3, comprising
hydroxypropylmethyl cellulose, and an active vitamins D3 and a polymer which is readily soluble in an organic solvent each attached to said hydroxypropyl methyl cellulose.
2. A composition as defined in Claim 1, wherein said polymer is selected from the group consisting of polyvinyl pyrrolidone and hydroxypropylmethyl cellulose.
3. A composition as defined in Claim 1 or 2, wherein said active vitamin D3 is 26, 26, 26, 27, 27, 27-hexafluoro-1 , 25-dihydroxycholecalciferol.
4. A process for preparing a composition defined in any one of Claims 1 to 3, wherein an alcoholic solvent is used.
5. A process as defined in Claim 4, wherein said alcoholic solvent comprises ethanol containing 20% or less water.
PCT/US1991/002846 1990-11-28 1991-04-25 Composition for solid pharmaceutical preparations containing active vitamins d3 and process for preparation thereof Ceased WO1992009271A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2332013A JPH04198129A (en) 1990-11-28 1990-11-28 Composition containing active vitamin D↓3 types
JP2/332013 1990-11-28

Publications (1)

Publication Number Publication Date
WO1992009271A1 true WO1992009271A1 (en) 1992-06-11

Family

ID=18250168

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1991/002846 Ceased WO1992009271A1 (en) 1990-11-28 1991-04-25 Composition for solid pharmaceutical preparations containing active vitamins d3 and process for preparation thereof

Country Status (4)

Country Link
EP (1) EP0559645A1 (en)
JP (1) JPH04198129A (en)
AU (1) AU8096591A (en)
WO (1) WO1992009271A1 (en)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994000128A1 (en) * 1992-06-22 1994-01-06 Lunar Corporation ORAL 1α-HYDROXYPREVITAMIN D
EP0588539A1 (en) * 1992-09-18 1994-03-23 Teva Pharmaceutical Industries, Ltd. Stabilized pharmaceutical compositions containing derivatives of vitamins D2 and D3
EP0508756B1 (en) * 1991-04-09 1996-10-23 Takeda Chemical Industries, Ltd. Stabilized vitamin D preparation
US5795882A (en) * 1992-06-22 1998-08-18 Bone Care International, Inc. Method of treating prostatic diseases using delayed and/or sustained release vitamin D formulations
US6004996A (en) * 1997-02-05 1999-12-21 Hoffman-La Roche Inc. Tetrahydrolipstatin containing compositions
KR100688618B1 (en) * 2001-09-12 2007-03-09 주식회사 유유 Sustained-release pharmaceutical composition for vitamin D oral administration
WO2007068287A1 (en) * 2005-12-15 2007-06-21 Laboratoria Qualiphar Sustained release vitamin preparation
EP2468265A3 (en) * 2010-12-04 2013-01-02 DEEF Pharmaceutical Industries Co. Homogeneous preparations containing vitamin D
US8703187B2 (en) 2007-04-25 2014-04-22 Warner Chilcott Company, Llc Vitamin D content uniformity in pharmaceutical dosage forms
US10300078B2 (en) 2013-03-15 2019-05-28 Opko Ireland Global Holdings, Ltd. Stabilized modified release vitamin D formulation and method of administering same
US10493084B2 (en) 2014-08-07 2019-12-03 Opko Ireland Global Holdings, Ltd. Adjunctive therapy with 25-hydroxyvitamin D and articles therefor
US10668089B2 (en) 2006-06-21 2020-06-02 Opko Ireland Global Holdings, Ltd. Method of treating and preventing secondary hyperparathyroidism
US11007204B2 (en) 2006-02-03 2021-05-18 Opko Renal, Llc Treating vitamin D insufficiency and deficiency with 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3
US11154509B2 (en) 2007-04-25 2021-10-26 Eirgen Pharma Ltd. Methods for controlled release oral dosage of a vitamin D compound
US11173168B2 (en) 2016-03-28 2021-11-16 Eirgen Pharma Ltd. Methods of treating vitamin D insufficiency in chronic kidney disease
US11672809B2 (en) 2010-03-29 2023-06-13 Eirgen Pharma Ltd. Methods and compositions for reducing parathyroid levels
US11752158B2 (en) 2007-04-25 2023-09-12 Eirgen Pharma Ltd. Method of treating vitamin D insufficiency and deficiency

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7034595B2 (en) * 2016-03-23 2022-03-14 株式会社ファンケル Vitamin D3 stabilizing composition
AU2019329905B2 (en) 2018-08-31 2024-02-01 Opko Ireland Global Holdings, Ltd. Vitamin D pediatric dosage forms, methods of making and using

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0116755A1 (en) * 1983-02-22 1984-08-29 Teijin Limited Composition for solid pharmaceutical preparations of active vitamins D3 and process for preparation thereof
EP0215596A2 (en) * 1985-09-05 1987-03-25 Teijin Limited Composition for injection of active type vitamins D3
EP0387808A2 (en) * 1989-03-13 1990-09-19 Ss Pharmaceutical Co., Ltd. Compositions for the preparation of dosage-form active vitamins D3 and process for preparing stable dosage-form active vitamins D3 by using the same
EP0413727A1 (en) * 1988-04-26 1991-02-27 Ellco Food Ab Blood platelet lysate, method of its preparation and a cell culture medium containing said blood platelet lysate.

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0116755A1 (en) * 1983-02-22 1984-08-29 Teijin Limited Composition for solid pharmaceutical preparations of active vitamins D3 and process for preparation thereof
EP0215596A2 (en) * 1985-09-05 1987-03-25 Teijin Limited Composition for injection of active type vitamins D3
EP0413727A1 (en) * 1988-04-26 1991-02-27 Ellco Food Ab Blood platelet lysate, method of its preparation and a cell culture medium containing said blood platelet lysate.
EP0387808A2 (en) * 1989-03-13 1990-09-19 Ss Pharmaceutical Co., Ltd. Compositions for the preparation of dosage-form active vitamins D3 and process for preparing stable dosage-form active vitamins D3 by using the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
STN International Information Services, Data Base: Chemical Abstracts, Accession Number: 100(12): 91354r; & JP-A-58206533 (TEIJIN LTD) 1 December 1983 *

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0508756B1 (en) * 1991-04-09 1996-10-23 Takeda Chemical Industries, Ltd. Stabilized vitamin D preparation
US6147064A (en) * 1992-06-22 2000-11-14 Bone Care International, Inc. Oral 1α-hydroxyprevitamin D in composition and method for treating psoriasis
US5795882A (en) * 1992-06-22 1998-08-18 Bone Care International, Inc. Method of treating prostatic diseases using delayed and/or sustained release vitamin D formulations
US5529991A (en) * 1992-06-22 1996-06-25 Lunar Corporation Oral 1α-hydroxyprevitamin D
US6150346A (en) * 1992-06-22 2000-11-21 Bone Care International, Inc. Method and composition for treating or preventing osteoporosis
WO1994000128A1 (en) * 1992-06-22 1994-01-06 Lunar Corporation ORAL 1α-HYDROXYPREVITAMIN D
US5614513A (en) * 1992-06-22 1997-03-25 Bone Care International, Inc. Oral 1α-hydroxyprevitamin D
US5622941A (en) * 1992-06-22 1997-04-22 Lunar Corporation Oral 1 α-hydroxyprevitamin D
US6133250A (en) * 1992-06-22 2000-10-17 Bone Care International, Inc. Oral 1α-hydroxyprevitamin D in methods for increasing blood level of activated vitamin D
AU667742B2 (en) * 1992-09-18 1996-04-04 Teva Pharmaceutical Industries Ltd. Stabilized pharmaceutical compositions containing derivatives of vitamins D2 and D3
US5804573A (en) * 1992-09-18 1998-09-08 Teva Pharmaceutical Industries Ltd. Stabilized pharmaceutical composition containing derivative of vitamins D2 and D3
EP0588539A1 (en) * 1992-09-18 1994-03-23 Teva Pharmaceutical Industries, Ltd. Stabilized pharmaceutical compositions containing derivatives of vitamins D2 and D3
US5565442A (en) * 1992-09-18 1996-10-15 Teva Pharmaceutical Industries Ltd. Stabilized pharmaceutical compositions containing derivatives of vitamins D2 and D3
US6004996A (en) * 1997-02-05 1999-12-21 Hoffman-La Roche Inc. Tetrahydrolipstatin containing compositions
KR100688618B1 (en) * 2001-09-12 2007-03-09 주식회사 유유 Sustained-release pharmaceutical composition for vitamin D oral administration
WO2007068287A1 (en) * 2005-12-15 2007-06-21 Laboratoria Qualiphar Sustained release vitamin preparation
US11007204B2 (en) 2006-02-03 2021-05-18 Opko Renal, Llc Treating vitamin D insufficiency and deficiency with 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3
US11911398B2 (en) 2006-02-03 2024-02-27 Opko Renal, Llc Treating Vitamin D insufficiency and deficiency with 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3
US10668089B2 (en) 2006-06-21 2020-06-02 Opko Ireland Global Holdings, Ltd. Method of treating and preventing secondary hyperparathyroidism
US8703187B2 (en) 2007-04-25 2014-04-22 Warner Chilcott Company, Llc Vitamin D content uniformity in pharmaceutical dosage forms
US11752158B2 (en) 2007-04-25 2023-09-12 Eirgen Pharma Ltd. Method of treating vitamin D insufficiency and deficiency
US11154509B2 (en) 2007-04-25 2021-10-26 Eirgen Pharma Ltd. Methods for controlled release oral dosage of a vitamin D compound
US11672809B2 (en) 2010-03-29 2023-06-13 Eirgen Pharma Ltd. Methods and compositions for reducing parathyroid levels
EP2468265A3 (en) * 2010-12-04 2013-01-02 DEEF Pharmaceutical Industries Co. Homogeneous preparations containing vitamin D
US11253528B2 (en) 2013-03-15 2022-02-22 Eirgen Pharma Ltd. Stabilized modified release Vitamin D formulation and method of administering same
EP3650016B1 (en) 2013-03-15 2021-05-05 EirGen Pharma Ltd. Stabilized modified release vitamin d formulation and method of administering same
EP2968172B1 (en) 2013-03-15 2020-07-22 EirGen Pharma Ltd. Stabilized modified release vitamin d formulation and method of administring same
EP3332773B1 (en) 2013-03-15 2020-08-26 OPKO Ireland Global Holdings, Limited Stabilized modified release vitamin d formulation and method of administering same
US10357502B2 (en) 2013-03-15 2019-07-23 Opko Ireland Global Holdings, Ltd. Stabilized modified release vitamin D formulation and method of administering same
US10350224B2 (en) 2013-03-15 2019-07-16 Opko Ireland Global Holdings, Ltd. Stabilized modified release vitamin D formulation and method of administering same
US10300078B2 (en) 2013-03-15 2019-05-28 Opko Ireland Global Holdings, Ltd. Stabilized modified release vitamin D formulation and method of administering same
US12478631B2 (en) 2013-03-15 2025-11-25 Eirgen Pharma Ltd. Stabilized modified release vitamin D formulation and method of administering same
US11007205B2 (en) 2014-08-07 2021-05-18 Eirgen Pharma Ltd. Adjunctive therapy with 25-hydroxyvitamin D and articles therefor
US10493084B2 (en) 2014-08-07 2019-12-03 Opko Ireland Global Holdings, Ltd. Adjunctive therapy with 25-hydroxyvitamin D and articles therefor
US11738033B2 (en) 2014-08-07 2023-08-29 Eirgen Pharma Ltd. Adjunctive therapy with 25-hydroxyvitamin D and articles therefor
US11173168B2 (en) 2016-03-28 2021-11-16 Eirgen Pharma Ltd. Methods of treating vitamin D insufficiency in chronic kidney disease
US12208106B2 (en) 2016-03-28 2025-01-28 Eirgen Pharma Ltd. Methods of vitamin D treatment

Also Published As

Publication number Publication date
JPH04198129A (en) 1992-07-17
EP0559645A1 (en) 1993-09-15
AU8096591A (en) 1992-06-25

Similar Documents

Publication Publication Date Title
WO1992009271A1 (en) Composition for solid pharmaceutical preparations containing active vitamins d3 and process for preparation thereof
US5328903A (en) Composition for solid pharmaceutical preparations containing vitamin D3 derivative
US4729895A (en) Composition for solid pharmaceutical preparations of active vitamins D.sub.3
DE69832621T2 (en) New pharmaceutical formulations with controlled release of active ingredients
RU2095054C1 (en) Solid medicinal formula for oral administration
US5126145A (en) Controlled release tablet containing water soluble medicament
RU2103995C1 (en) Omeprazol microgranules and a method of their preparing
EP1267844B2 (en) Sustained release vitamin composition
DE69808670T2 (en) PRODUCTION METHOD AND COMPOSITION OF AN ORAL PREPARATION OF ITRACONAZOLE
US5487900A (en) Stabilized vitamin D preparation
US4904699A (en) Nifedipine concentrate stabilized against the influence of light and a process for its preparation
JPH07196513A (en) Pharmaceutical granules
JP4540092B2 (en) Pharmaceutical composition containing bioactive compound unstable to acid and process for producing the same
US20050163846A1 (en) Preparation composition containing acid-unstable physiologically active compound, and process for producing same
KR0172134B1 (en) Solid preparation
JP2914690B2 (en) Formulation containing stable vitamin D
JP2963718B2 (en) Preparations containing vitamin D
JPH10298074A (en) Vitamin-containing composition
JPH0848632A (en) Solid composition containing etoposide and solid preparation
JPH0536413B2 (en)
HK1068271A (en) Preparation compositions containing acid-unstable physiologically active compounds and process for producing the same
MXPA00006574A (en) Method and composition of an oral preparation of itraconazole
HK1070289A (en) Fenofibrate pharmaceutical composition with a higher bioavailability and its manufacturing process

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AT AU BB BG BR CA CH DE DK ES FI GB HU KP KR LK LU MC MG MW NL NO RO SD SE SU

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE BF BJ CF CG CH CM DE DK ES FR GA GB GR IT LU ML MR NL SE SN TD TG

WWE Wipo information: entry into national phase

Ref document number: 1991910918

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1991910918

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 1991910918

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: CA