CA2227272C - Use of lipids as aids in the production of solid drug forms by melt extrusion - Google Patents
Use of lipids as aids in the production of solid drug forms by melt extrusion Download PDFInfo
- Publication number
- CA2227272C CA2227272C CA002227272A CA2227272A CA2227272C CA 2227272 C CA2227272 C CA 2227272C CA 002227272 A CA002227272 A CA 002227272A CA 2227272 A CA2227272 A CA 2227272A CA 2227272 C CA2227272 C CA 2227272C
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- melt
- lipid
- lipids
- melt extrusion
- production
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Use of lipids as adjuvents in the production of solid medicinal forms by the melt extrusion process.
Description
BASF Aktiengesellschaft 950168 O.Z. 0050/46347 Use of lipids as aids in the production of solid drug forms by melt extrusion The present invention relates to the use of lipids as aids in the production of solid drug forms by melt extrusion.
The production of solid drug forms by melt extrusion is dis-closed, :Eor example, in US-A 4880585, wherein the drug form is produced from the melt, which contains active ingredient and is still plastic, with the aid of a molding calender which directly molds tablets from the melt.
It has long been known that, in almost all cases when tablets are made from granules, satisfactory results are achieved only if a small amount of a lubricant is added to the formulations, after the granulation but before the tabletting, and this is deposited as a fine film on the outsides of the granule particles and thus prevents adhesion of the granules to the tabletting punches. The effect of these lubricants is very great although it is necessary to add only very small amounts to the granules (generally about 0.1 to 1$ by weight; cf. H. Sucker, P. Fuchs. P. Speiser: Phar-mazeutische Technologie; Georg Thieme Verlag, Stuttgart (1991), pages 259-260).
Known mold release agents for conventional processes are, for ex-ample, fatty acid esters or fatty acid salts, with only magnesium stearate normally being used in practice. Magnesium stearate is normally added to the granules which contain active ingredient and are ready before tabletting.
In the production of drug forms by melt extrusion in conjunction with a tabletting process such as calendering, it is crucial that the melt: does not adhere to the surfaces of the calender rolls because, otherwise, there is no release from the molds. It also has to be taken into account in calendering to produce tablets that thE: compression process in the calender results in tablets which have a typical fin which is formed at the interface of the pairs of'. molding rolls which are in contact only at the surface.
Followirig the calendering, this fin must be removed mechanically, generally after cooling/hardening of the melt tablets, in order to provide the tablets with a homogeneous surface structure. The success of this deflashing depends crucially on the consistency of the cooled melt containing active ingredient. This means that despite the calendering being satisfactory (no adhesion of the melt in the calender), deflashing of the resulting tablets is not necessarily possible. Many polymers form thermoplastic melts even in the presence of large amounts of active ingredients and/or an-cillary substances, and these are highly flexible after cooling and can be flexed over wide ranges without breakage. In these cases, removal of the fins is very difficult and often completely impossible, although there are no problems with the extrusion and the calendering too.
Thus, it is crucial for the use of a formulation for producing tablets by melt extrusion/calendering that, besides the complete mixture having good thermoplasticity, in particular it is also possible to reduce the tendency to adhere during the calendering and control the plasticity of the cooled melt in order to ensure deflashing of the tablets.
Melt-processable cellulose derivatives such as hydroxypropyl-cellulose are, as water-soluble polymers, very suitable for pro-ducing tablets by solvent-free melt extrusion/calendering. It is possible by admixture of other ancillary substances, eg. HPMC
(hydroxypropylmethylcellulose) polymers which are swellable in water, to control the dissolution times of such tablets in the gastrointestinal tract, as is disclosed, for example, in DE-A 4226753.
However, it has now been found that, in many cases when hydroxy-propylcelluloses are used as water-soluble, thermoplastic polymer component,, although the resulting melts can be extruded satisfac-torily, they a) in many cases showed an extreme tendency to adhere during the calendering, b) did not permit removal of the fin because of excessive plas-ticity of the cooled melts (containing active ingredient) in the case of the calendered tablets, and c) caused considerable problems in cleaning the extruders be-cause of the great tendency of the melt to adhere.
It is an object of the present invention to find aids which make it possible, especially when hydroxypropylcelluloses are used as matrix polymers in the production of drug forms by melt extru-sion, to solve the abovementioned problems.
The production of solid drug forms by melt extrusion is dis-closed, :Eor example, in US-A 4880585, wherein the drug form is produced from the melt, which contains active ingredient and is still plastic, with the aid of a molding calender which directly molds tablets from the melt.
It has long been known that, in almost all cases when tablets are made from granules, satisfactory results are achieved only if a small amount of a lubricant is added to the formulations, after the granulation but before the tabletting, and this is deposited as a fine film on the outsides of the granule particles and thus prevents adhesion of the granules to the tabletting punches. The effect of these lubricants is very great although it is necessary to add only very small amounts to the granules (generally about 0.1 to 1$ by weight; cf. H. Sucker, P. Fuchs. P. Speiser: Phar-mazeutische Technologie; Georg Thieme Verlag, Stuttgart (1991), pages 259-260).
Known mold release agents for conventional processes are, for ex-ample, fatty acid esters or fatty acid salts, with only magnesium stearate normally being used in practice. Magnesium stearate is normally added to the granules which contain active ingredient and are ready before tabletting.
In the production of drug forms by melt extrusion in conjunction with a tabletting process such as calendering, it is crucial that the melt: does not adhere to the surfaces of the calender rolls because, otherwise, there is no release from the molds. It also has to be taken into account in calendering to produce tablets that thE: compression process in the calender results in tablets which have a typical fin which is formed at the interface of the pairs of'. molding rolls which are in contact only at the surface.
Followirig the calendering, this fin must be removed mechanically, generally after cooling/hardening of the melt tablets, in order to provide the tablets with a homogeneous surface structure. The success of this deflashing depends crucially on the consistency of the cooled melt containing active ingredient. This means that despite the calendering being satisfactory (no adhesion of the melt in the calender), deflashing of the resulting tablets is not necessarily possible. Many polymers form thermoplastic melts even in the presence of large amounts of active ingredients and/or an-cillary substances, and these are highly flexible after cooling and can be flexed over wide ranges without breakage. In these cases, removal of the fins is very difficult and often completely impossible, although there are no problems with the extrusion and the calendering too.
Thus, it is crucial for the use of a formulation for producing tablets by melt extrusion/calendering that, besides the complete mixture having good thermoplasticity, in particular it is also possible to reduce the tendency to adhere during the calendering and control the plasticity of the cooled melt in order to ensure deflashing of the tablets.
Melt-processable cellulose derivatives such as hydroxypropyl-cellulose are, as water-soluble polymers, very suitable for pro-ducing tablets by solvent-free melt extrusion/calendering. It is possible by admixture of other ancillary substances, eg. HPMC
(hydroxypropylmethylcellulose) polymers which are swellable in water, to control the dissolution times of such tablets in the gastrointestinal tract, as is disclosed, for example, in DE-A 4226753.
However, it has now been found that, in many cases when hydroxy-propylcelluloses are used as water-soluble, thermoplastic polymer component,, although the resulting melts can be extruded satisfac-torily, they a) in many cases showed an extreme tendency to adhere during the calendering, b) did not permit removal of the fin because of excessive plas-ticity of the cooled melts (containing active ingredient) in the case of the calendered tablets, and c) caused considerable problems in cleaning the extruders be-cause of the great tendency of the melt to adhere.
It is an object of the present invention to find aids which make it possible, especially when hydroxypropylcelluloses are used as matrix polymers in the production of drug forms by melt extru-sion, to solve the abovementioned problems.
It has been found that this object is achieved by using lipids as mold release agents and lubricants in the production of drug forms by melt extrusion.
The invention as claimed in thus directed to a process for producing a solid pharmaceutical composition in tablet form by melt extrusion, which process consists essentially of:
mixing an active ingredient, a water-soluble thermoplastic matrix polymer and a lipid;
heating the mixture until a solvent-free, polymer melt is formed;
extruding the melt into a tabletting molding calender;
allowing the melt to cool; and removing the formed solid pharmaceutical composition in the form of a tablet from the molding calender;
wherein the lipid is used in amounts of 1 to 5% of the total weight of the composition and functions as a mold release agent and lubricant.
The lipids which are suitable according to the invention are mono-, di- and triglycerides of naturally occurring fatty acids, for example glycerol monostearate, glycerol distearate, glycerol tristearate, glycerol tripalmitate, glycerol trimyristate, glyc-erol tribehenate, glycerol palmitate stearate or glyceride mix-tures occurring in natural oils, preferably hydrogenated castor oil.
Ceramides are furthermore also suitable for this purpose.
Preferred lipids are, in particular, phospholipids, with phospho-glycerides such as lecithins being particularly preferred. Hydro-genated lecithins such as soybean and egg lecithins are very par-ticularly preferred.
The lipids are used in amounts 1 to 5% of the total weight of the preparations containing active ingredient.
3a The preparations containing active ingredient can contain as ma-trix polymers melt-processable polymers, for example - polyvinylpyrrolidone, - copolymers of N-vinylpyrrolidone and vinyl acetate with up to 50 % by weight of vinyl acetate, - carboxyalkylcelluloses such as carboxymethylcelluloses, alkylcelluloses such as methylcellulose, - hydroxyalkylcelluloses such as hydroxymethyl-, hydroxyethyl-, hydroxypropyl- and hydroxybutylcellulose, - hydroxyalkylcelluloses such as hydroxyethylmethyl- and hydroxypropylmethylcellulose, or mixtures thereof.
Preferred polymers are hydroxypropylcelluloses and polymers based on vinylpyrrolidone.
Suitable active ingredients are all active ingredients which do not decompose under the conditions of melt extrusion.
The amount of the active component in the complete preparation can vary within wide limits depending on the activity and release rate. Thus, the content of active ingredient can be in the range from 0.1 to 90 %, preferably from 0.5 to 60 %, of the total BASF Aktiengesellschaft 950168 O.Z. 0050/46347 weight of the preparation. The only condition is that the prepa-ration is still melt-processable.
The preparations may furthermore contain conventional pharmaceu-tical ancillary substances such as bulking agents, colorants, disintegrants or stabilizers in conventional amounts.
Otherwise, the components are processed in a conventional way in extruders, preferably in single or twin screw extruders at a tem-perature in the range from 50 to 200 C. The shaping of the polymer melt which contains active ingredient and is free of solvent to give the preparations according to the invention can take place, for example, by calendering the extrudate and by converting the extrudate with rotating knives into pellets which have identical volumes and have a solidified surface but are still moldable, and subsequently compressing to tablets in conventional tabletting machines.
It is possible to mix the ancillary substances into the melt or solution of active ingredients and polymers. It is furthermore possible to incorporate the ancillary substances together with the active ingredient into the polymer melt. In addition, mix-tures of ancillary substances, the active ingredient and the polymers can be directly melted. It is generally customary for a physical mixture of ancillary substances, active ingredients and the polymers to be melted together.
It has been found, surprisingly, that addition of even small amounts of lipids is able to prevent adhesion of the melts con-taining active ingredient.
Addition of only 3 % by weight of lecithin reduces the melt adhe-sion of the extruded composition so much that the formulations can be calendered without restrictions. The cleaning of the ex-truder to remove the otherwise viscous, highly adhesive melt res-idues is considerably simplified because lecithin-containing for-mulas show scarcely any adhesion to metal and can be removed en bloc from the metal parts of the extruder which are still hot after completion of the extrusion. The plasticity of the cooled melt is also beneficially affected so that deflashing of the tab-lets (removal of fins) takes place considerably better.
Examples 1 to 20 All the tests were carried out in a twin screw extruder (ZSK-40 extruder from Werner und Pfleiderer, Stuttgart). The extruder comprised 4 heatable sections, and it was possible to heat the BASF Aktiengesellschaft 950168 O.Z. 0050/46347 extruder head and the slit die separately. The temperature set-tings are to be found in the table. The extruded melt was dis-charged in the form of a strip 12-14 cm wide through a slit die and subsequently directly compressed to tablets in a molding cal-5 ender consisting of a pair of counter-rotating molding rolls (coolable). The tablets had an elongate, rod-like shape (oblong tablets without bar). The raw materials listed in the table have previously been mixed in a gyro-wheel mixer and fed as mixture into the extruder via a weigh feeder delivering 20 to 30 kg/h.
The extruder conveyor was operated in all cases at 100 to 150 rpm.
For comparison purposes, formulations in which no lipid was used were processed. Although extrusion was possible in all these cases, calendering was not, because it was impossible to remove the tablets from the pairs of molding rolls in the calender. In additio:n, cleaning of the parts of the extruder coming into con-tact with the product was considerably more difficult in these cases (composition strongly adherent to metal surfaces) than with lipid-aontaining formulations.
BASF Aktiengesellschaft 950168 O.Z. 0050/46347 q o 0 0 0 0 0tn o 0 0 0 0 0 0 0 0W) o O ~ -- ~ -+ ~~ ~ N N M M N N ~ N =--~ ~ ~+
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The invention as claimed in thus directed to a process for producing a solid pharmaceutical composition in tablet form by melt extrusion, which process consists essentially of:
mixing an active ingredient, a water-soluble thermoplastic matrix polymer and a lipid;
heating the mixture until a solvent-free, polymer melt is formed;
extruding the melt into a tabletting molding calender;
allowing the melt to cool; and removing the formed solid pharmaceutical composition in the form of a tablet from the molding calender;
wherein the lipid is used in amounts of 1 to 5% of the total weight of the composition and functions as a mold release agent and lubricant.
The lipids which are suitable according to the invention are mono-, di- and triglycerides of naturally occurring fatty acids, for example glycerol monostearate, glycerol distearate, glycerol tristearate, glycerol tripalmitate, glycerol trimyristate, glyc-erol tribehenate, glycerol palmitate stearate or glyceride mix-tures occurring in natural oils, preferably hydrogenated castor oil.
Ceramides are furthermore also suitable for this purpose.
Preferred lipids are, in particular, phospholipids, with phospho-glycerides such as lecithins being particularly preferred. Hydro-genated lecithins such as soybean and egg lecithins are very par-ticularly preferred.
The lipids are used in amounts 1 to 5% of the total weight of the preparations containing active ingredient.
3a The preparations containing active ingredient can contain as ma-trix polymers melt-processable polymers, for example - polyvinylpyrrolidone, - copolymers of N-vinylpyrrolidone and vinyl acetate with up to 50 % by weight of vinyl acetate, - carboxyalkylcelluloses such as carboxymethylcelluloses, alkylcelluloses such as methylcellulose, - hydroxyalkylcelluloses such as hydroxymethyl-, hydroxyethyl-, hydroxypropyl- and hydroxybutylcellulose, - hydroxyalkylcelluloses such as hydroxyethylmethyl- and hydroxypropylmethylcellulose, or mixtures thereof.
Preferred polymers are hydroxypropylcelluloses and polymers based on vinylpyrrolidone.
Suitable active ingredients are all active ingredients which do not decompose under the conditions of melt extrusion.
The amount of the active component in the complete preparation can vary within wide limits depending on the activity and release rate. Thus, the content of active ingredient can be in the range from 0.1 to 90 %, preferably from 0.5 to 60 %, of the total BASF Aktiengesellschaft 950168 O.Z. 0050/46347 weight of the preparation. The only condition is that the prepa-ration is still melt-processable.
The preparations may furthermore contain conventional pharmaceu-tical ancillary substances such as bulking agents, colorants, disintegrants or stabilizers in conventional amounts.
Otherwise, the components are processed in a conventional way in extruders, preferably in single or twin screw extruders at a tem-perature in the range from 50 to 200 C. The shaping of the polymer melt which contains active ingredient and is free of solvent to give the preparations according to the invention can take place, for example, by calendering the extrudate and by converting the extrudate with rotating knives into pellets which have identical volumes and have a solidified surface but are still moldable, and subsequently compressing to tablets in conventional tabletting machines.
It is possible to mix the ancillary substances into the melt or solution of active ingredients and polymers. It is furthermore possible to incorporate the ancillary substances together with the active ingredient into the polymer melt. In addition, mix-tures of ancillary substances, the active ingredient and the polymers can be directly melted. It is generally customary for a physical mixture of ancillary substances, active ingredients and the polymers to be melted together.
It has been found, surprisingly, that addition of even small amounts of lipids is able to prevent adhesion of the melts con-taining active ingredient.
Addition of only 3 % by weight of lecithin reduces the melt adhe-sion of the extruded composition so much that the formulations can be calendered without restrictions. The cleaning of the ex-truder to remove the otherwise viscous, highly adhesive melt res-idues is considerably simplified because lecithin-containing for-mulas show scarcely any adhesion to metal and can be removed en bloc from the metal parts of the extruder which are still hot after completion of the extrusion. The plasticity of the cooled melt is also beneficially affected so that deflashing of the tab-lets (removal of fins) takes place considerably better.
Examples 1 to 20 All the tests were carried out in a twin screw extruder (ZSK-40 extruder from Werner und Pfleiderer, Stuttgart). The extruder comprised 4 heatable sections, and it was possible to heat the BASF Aktiengesellschaft 950168 O.Z. 0050/46347 extruder head and the slit die separately. The temperature set-tings are to be found in the table. The extruded melt was dis-charged in the form of a strip 12-14 cm wide through a slit die and subsequently directly compressed to tablets in a molding cal-5 ender consisting of a pair of counter-rotating molding rolls (coolable). The tablets had an elongate, rod-like shape (oblong tablets without bar). The raw materials listed in the table have previously been mixed in a gyro-wheel mixer and fed as mixture into the extruder via a weigh feeder delivering 20 to 30 kg/h.
The extruder conveyor was operated in all cases at 100 to 150 rpm.
For comparison purposes, formulations in which no lipid was used were processed. Although extrusion was possible in all these cases, calendering was not, because it was impossible to remove the tablets from the pairs of molding rolls in the calender. In additio:n, cleaning of the parts of the extruder coming into con-tact with the product was considerably more difficult in these cases (composition strongly adherent to metal surfaces) than with lipid-aontaining formulations.
BASF Aktiengesellschaft 950168 O.Z. 0050/46347 q o 0 0 0 0 0tn o 0 0 0 0 0 0 0 0W) o O ~ -- ~ -+ ~~ ~ N N M M N N ~ N =--~ ~ ~+
OO O O O O O O N N ~ '-T N o o N o O o OO o 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ~ .- .-+ -- .-+ --. .-+ -+ N o N o 0 o r. .-+
M oG O O O O ~/1 O O O O O O O o 0 0 0 0 'RT o =--~ o 0 0 o .--~ ..+ ..-. .-~ ,--~ ~ .-r .-. ~ .--i .~ .-. .-.~ ... .-.. .-. .-. r..
~y O O O O O O o 0 0 0 0 0 0 0 0 0 0 0 o 0 0 0 0 0 --~ --+ '~ d N N N N N r-+ --~
.--~ ~+ ..-~ ... .--~ ~ .-.. .... .-+ .--~ .-, .-. r.+ .-.. .-w .-. r.. .-.
~ O O O o 0 0 0 0 0 ~a o o 0 o M o E..~ 00 00 00 00 00 00 O, C\ Q, ,..~ ON C" C~ ,~ O,~
V1 O O o O O OO
~ M v~1 ~1 V\1 0 y o 0 0 o v~i o O o O O
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O~ 0~0 N ~ ~ M ~ v'1 tn It N M M M M M --~ m O', o o N h D ~
O~ 00 O O O M M O n O
et er et V1 v1 v1 t~ N N N N o o ~+ O ~ -+ o a 'G ~ ~ ~ y ~ N CV ~ E~ ~ N
~+ V O O O O O o o _ _ _ o 0 U U U U U U U U U " s s U U
xxxxxxx x U U U U U U U U U U U U U U U U U U
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> > > > > > f+ F-z ~ Qr a ar 1264 .-r H M'~T Yl [- 00 ~~
CA 02227272 1998-02-16 =
BASF Aktiengesellschaft 950168 O.Z. 0050/46347 A ~ M
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Claims (4)
1. A process for producing a solid pharmaceutical composition in tablet form by melt extrusion, which process consists essentially of:
mixing an active ingredient, a water-soluble thermoplastic matrix polymer and a lipid;
heating the mixture until a solvent-free, polymer melt is formed;
extruding the melt into a tabletting molding calender;
allowing the melt to cool; and removing the formed solid pharmaceutical composition in the form of a tablet from the molding calender;
wherein the lipid is used in amounts of 1 to 5% of the total weight of the composition and functions as a mold release agent and lubricant.
mixing an active ingredient, a water-soluble thermoplastic matrix polymer and a lipid;
heating the mixture until a solvent-free, polymer melt is formed;
extruding the melt into a tabletting molding calender;
allowing the melt to cool; and removing the formed solid pharmaceutical composition in the form of a tablet from the molding calender;
wherein the lipid is used in amounts of 1 to 5% of the total weight of the composition and functions as a mold release agent and lubricant.
2. The process of claim 1, wherein the lipid is a phosphoglyceride.
3. The process of claim 1, wherein the lipid is a lecithin.
4. The process of any one of claims 1 to 3, wherein the thermoplastic matrix polymer is selected from the group consisting of hydroxy propylcelluloses and vinylpyrrolidone-based polymers.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19531277.5 | 1995-08-25 | ||
| DE19531277A DE19531277A1 (en) | 1995-08-25 | 1995-08-25 | Use of lipids as an aid in the production of solid dosage forms by the melt extrusion process |
| PCT/EP1996/003667 WO1997007786A2 (en) | 1995-08-25 | 1996-08-21 | Use of lipids as adjuvents in the production of solid medicinal forms by the melt extrusion process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2227272A1 CA2227272A1 (en) | 1997-03-06 |
| CA2227272C true CA2227272C (en) | 2007-12-11 |
Family
ID=7770352
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002227272A Expired - Lifetime CA2227272C (en) | 1995-08-25 | 1996-08-21 | Use of lipids as aids in the production of solid drug forms by melt extrusion |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US6387401B2 (en) |
| EP (1) | EP0845982B1 (en) |
| AR (1) | AR003345A1 (en) |
| AT (1) | ATE210970T1 (en) |
| AU (1) | AU6875396A (en) |
| BR (1) | BR9610234A (en) |
| CA (1) | CA2227272C (en) |
| DE (2) | DE19531277A1 (en) |
| DK (1) | DK0845982T3 (en) |
| ES (1) | ES2170259T3 (en) |
| HR (1) | HRP960381A2 (en) |
| WO (1) | WO1997007786A2 (en) |
| ZA (1) | ZA967170B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8025899B2 (en) | 2003-08-28 | 2011-09-27 | Abbott Laboratories | Solid pharmaceutical dosage form |
| US9107830B2 (en) | 1999-11-12 | 2015-08-18 | Abbvie, Inc. | Inhibitors of crystallization in a solid dispersion |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000033817A1 (en) * | 1998-12-08 | 2000-06-15 | Phares Pharmaceutical Research N.V. | Phospholipid compositions |
| DE19916383A1 (en) * | 1999-03-31 | 2000-10-05 | Schering Ag | Pharmaceutical composition with an extrusion |
| EP1204410B1 (en) * | 1999-07-30 | 2012-09-12 | Capsugel Belgium NV | Multi-component pharmaceutical dosage form |
| US7364752B1 (en) | 1999-11-12 | 2008-04-29 | Abbott Laboratories | Solid dispersion pharamaceutical formulations |
| DE10026698A1 (en) * | 2000-05-30 | 2001-12-06 | Basf Ag | Self-emulsifying active ingredient formulation and use of this formulation |
| DE10026699A1 (en) * | 2000-05-30 | 2001-12-06 | Basf Ag | Formulation based on heparin, glycosaminoglycan or heparinoid and use of the formulation and the formulation base |
| GB0102342D0 (en) | 2001-01-30 | 2001-03-14 | Smithkline Beecham Plc | Pharmaceutical formulation |
| US7883721B2 (en) | 2001-01-30 | 2011-02-08 | Smithkline Beecham Limited | Pharmaceutical formulation |
| US7842308B2 (en) * | 2001-01-30 | 2010-11-30 | Smithkline Beecham Limited | Pharmaceutical formulation |
| US20050175687A1 (en) * | 2001-01-30 | 2005-08-11 | Mcallister Stephen M. | Pharmaceutical formulations |
| TW200526274A (en) | 2003-07-21 | 2005-08-16 | Smithkline Beecham Plc | Pharmaceutical formulations |
| US8377952B2 (en) * | 2003-08-28 | 2013-02-19 | Abbott Laboratories | Solid pharmaceutical dosage formulation |
| ES2600577T3 (en) * | 2003-12-04 | 2017-02-09 | Bend Research, Inc. | Spray-solidification process using an extruder to prepare multiparticulate compositions of crystalline drugs |
| PE20060003A1 (en) * | 2004-03-12 | 2006-03-01 | Smithkline Beecham Plc | POLYMERIC PHARMACEUTICAL FORMULATION FOR INJECTION MOLDING |
| WO2005105039A1 (en) * | 2004-05-04 | 2005-11-10 | Boehringer Ingelheim International Gmbh | Solid pharmaceutical form comprising an ltb4 antagonist |
| EP1693045A1 (en) | 2005-02-17 | 2006-08-23 | Abbott GmbH & Co. KG | Production of dosage forms from active molten substances |
| DK2200588T3 (en) * | 2007-09-25 | 2019-07-01 | Solubest Ltd | COMPOSITIONS CONCERNING LIPOFILE ACTIVE RELATIONS AND METHOD OF PRODUCTION THEREOF |
| EP2219624A2 (en) | 2007-11-08 | 2010-08-25 | Glaxo Group Limited | Pharmaceutical formulations |
| AU2009256572A1 (en) * | 2008-06-13 | 2009-12-17 | Capsugel Belgium Nv | Hydroxypropyl cellulose capsule shell |
| MX2013003288A (en) | 2010-09-22 | 2013-05-22 | Mcneil Ppc Inc | Manufacture of tablets from energy-applied powder blend. |
| AT511581A1 (en) * | 2011-05-26 | 2012-12-15 | G L Pharma Gmbh | ORAL RETARDANT FORMULATION |
| US9511028B2 (en) | 2012-05-01 | 2016-12-06 | Johnson & Johnson Consumer Inc. | Orally disintegrating tablet |
| DE102017106216A1 (en) * | 2017-03-22 | 2018-09-27 | Amw Gmbh | Extruded depot form for sustained release of active ingredient |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2581541B1 (en) | 1985-05-09 | 1988-05-20 | Rhone Poulenc Sante | NOVEL PHARMACEUTICAL COMPOSITIONS FOR THE EXTENDED RELEASE OF AN ACTIVE INGREDIENT AND THEIR PREPARATION METHOD |
| DE4226753A1 (en) | 1992-08-13 | 1994-02-17 | Basf Ag | Preparations containing active substances in the form of solid particles |
| MX9603480A (en) * | 1994-02-16 | 1997-12-31 | Abbott Lab | Process for preparing fine particle pharmaceutical formulations. |
| DE4413350A1 (en) * | 1994-04-18 | 1995-10-19 | Basf Ag | Retard matrix pellets and process for their production |
| US5965161A (en) | 1994-11-04 | 1999-10-12 | Euro-Celtique, S.A. | Extruded multi-particulates |
| DE19504832A1 (en) * | 1995-02-14 | 1996-08-22 | Basf Ag | Solid drug preparations |
-
1995
- 1995-08-25 DE DE19531277A patent/DE19531277A1/en not_active Withdrawn
-
1996
- 1996-08-20 HR HR19531277.5A patent/HRP960381A2/en not_active Application Discontinuation
- 1996-08-21 AT AT96929292T patent/ATE210970T1/en not_active IP Right Cessation
- 1996-08-21 ES ES96929292T patent/ES2170259T3/en not_active Expired - Lifetime
- 1996-08-21 BR BR9610234A patent/BR9610234A/en not_active Application Discontinuation
- 1996-08-21 US US09/000,389 patent/US6387401B2/en not_active Expired - Lifetime
- 1996-08-21 AU AU68753/96A patent/AU6875396A/en not_active Abandoned
- 1996-08-21 DE DE59608516T patent/DE59608516D1/en not_active Expired - Lifetime
- 1996-08-21 EP EP96929292A patent/EP0845982B1/en not_active Expired - Lifetime
- 1996-08-21 CA CA002227272A patent/CA2227272C/en not_active Expired - Lifetime
- 1996-08-21 WO PCT/EP1996/003667 patent/WO1997007786A2/en not_active Ceased
- 1996-08-21 DK DK96929292T patent/DK0845982T3/en active
- 1996-08-23 ZA ZA9607170A patent/ZA967170B/en unknown
- 1996-08-23 AR ARP960104102A patent/AR003345A1/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9107830B2 (en) | 1999-11-12 | 2015-08-18 | Abbvie, Inc. | Inhibitors of crystallization in a solid dispersion |
| US8025899B2 (en) | 2003-08-28 | 2011-09-27 | Abbott Laboratories | Solid pharmaceutical dosage form |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE210970T1 (en) | 2002-01-15 |
| WO1997007786A3 (en) | 1997-04-03 |
| DE59608516D1 (en) | 2002-01-31 |
| AR003345A1 (en) | 1998-07-08 |
| HRP960381A2 (en) | 1998-02-28 |
| US20010007664A1 (en) | 2001-07-12 |
| EP0845982A2 (en) | 1998-06-10 |
| ES2170259T3 (en) | 2002-08-01 |
| BR9610234A (en) | 1999-06-29 |
| WO1997007786A2 (en) | 1997-03-06 |
| CA2227272A1 (en) | 1997-03-06 |
| AU6875396A (en) | 1997-03-19 |
| DE19531277A1 (en) | 1997-02-27 |
| ZA967170B (en) | 1998-03-02 |
| US6387401B2 (en) | 2002-05-14 |
| EP0845982B1 (en) | 2001-12-19 |
| DK0845982T3 (en) | 2002-03-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20160822 |