EP0153105A2
Expired / Lapsed
EP
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Diffusion coated multiple-units dosage form
Assignee: Takeda Pharma AS
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Filing: 1985-02-08
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Granted: —
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Expires: 2005-02-08
Abstract
Abstract In an oral pharmaceutical controlled releasable multiple-units formulation, individual units containing an active substance are coated with a substantially water-insoluble, but water-diffusible controlled release coating which includes 1) an inner film layer which causes adhesion between the units at elevated temperatures, comprising a water-dispersible film-forming agent, and 2) an outer film layer comprising a water-based film-forming agent which prevents adhesion between the units at elevated temperatures and imparts flowability to the units. <??>The inner film layer may additionally comprise a substance which is capable of forming a continuous phase. <??>By subjecting the thus coated units to heating to accelerate the formation of a continuous phase of the film-forming agent of the inner layer and optionally also of the additional substance, a coating is formed which substantially does not change its diffusion characteristics in the course of time.
Inventors
- 👤 Kim Kjornaes
- 👤 Finn Norring Christensen
- 👤 Jens Rasmus Jensen
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-07 11:14
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/5073; A61K9/20; A61K9/2072; A61K9/2077; A61K9/2081
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
73 words
An oral pharmaceutical controlled release multiple-units formulation in which individual units containing an active substance are coated with a substantially water-insoluble, but water-diffusible controlled release coating which includes 1) an inner film layer which causes adhesion between the units at elevated temperatures, comprising a water-dispersible film-forming agent, and 2) an outer film layer comprising a water-based film-forming agent which prevents adhesion between the units at elevated temperatures and imparts flowability to the units.
Claim 2
Dependent Claim
73 words
An oral pharmaceutical controlled release multiple-units formulation in which individual units containing an active substance are coated with a substantially water-insoluble, but water-diffusible controlled release coating which includes 1) an inner film layer which causes adhesion between the units at elevated temperatures, comprising a water-dispersible film-forming agent, and 2) an outer film layer comprising a water-based film-forming agent which prevents adhesion between the units at elevated temperatures and imparts flowability to the units.
Claim 3
Dependent Claim
26 words
A formulation according to claim 1, in which the inner film layer additionally comprises a substance which, in itself, is capable of forming a continuous phase.
Claim 4
Dependent Claim
36 words
A formulation according to claim 2, in which the substance is a hydrophobic substance, and the outer film layer is impermeable, at temperatures above the melting point of the hydrophobic substance, to the molten hydrophobic substance.
Claim 5
Dependent Claim
20 words
A formulation according to claim 2, in which the substance is a polymeric substance which imparts compressibility to the coating.
Claim 6
Dependent Claim
52 words
A formulation according to any of claims 1-4, in which the film-forming agent of the inner film layer is selected from cellulose derivatives, silicone polymers and copolymers, vinyl polymers and copolymers, biodegradable polymers such as polyamino acids, polylactic acid and copolymers and derivatives thereof, and acrylic polymers and copolymers, or mixtures thereof.
Claim 7
Dependent Claim
30 words
A formulation according to claim 5, in which the film-forming agent is selected from ethyl cellulose and a copolymerisate of poly(meth)-acrylic acid esters, hydroxypropylmethylcellulosephthalate, celluloseacetatephthalate, polyvinylacetatephthalate and vinylacetate-crotonic acid copolymerisates.
Claim 8
Dependent Claim
38 words
A formulation according to claim 3, in which the hydrophobic substance of the inner film layer is selected from hydrocarbons and hydrocarbon derivatives, waxes, oils and fats, and mixtures thereof, especially a waxy substance such as paraffin wax.
Claim 9
Dependent Claim
43 words
A formulation according to claims 3 or 7, in which the hydrophobic substance is present in an amount of between about 0.1 and 50%, in particular between 1 and 40%, especially between about 10 and 30%, by weight of the inner film layer.
Claim 10
Dependent Claim
43 words
A formulation according to claim 4, in which the polymeric substance in the inner film coating is selected from polyvinylpyrrolidone, polyalkylene glycols such as polyethylene glycol, and cellulose derivatives such as hydroxypropylcellulose, carboxymethylcellulose, methylcellulose, propylcellulose, hydroxyethylcellulose, carboxyethylcellulose, carboxymethylhydroxyethylcellulose, hydroxymethylcellulose, carboxymethylethylcellulose, methylhydroxypropylcellulose or hydroxypropylmethylcellulose.
Claim 11
Dependent Claim
48 words
A formulation according to claim 9, in which the polymeric substance is present in an amount between 1 and 10%, such as an amount between 2% and 8%, especially an amount of about 4% by weight relative to the amount of film-forming agent in the inner film layer.
Claim 12
Dependent Claim
29 words
A formulation according to any of the preceding claims, in which the inner film layer comprises an anti-adhesive which is a finely divided, substantially water-insoluble, pharmaceutically acceptable, non-wetting powder.
Claim 13
Dependent Claim
41 words
A formulation according to claim 11, in which the anti-adhesive is present in an amount of between about 0.1 and 50%, preferably between about 1 and 40%, especially about 10-30% such as about 15% by weight of the inner film layer.
Claim 14
Dependent Claim
35 words
A formulation according to any of claims 1-12, in which the inner film layer is present in an amount of about 1-30%, especially about 5-25%, in particular about 15%, by weight of the uncoated units.
Claim 15
Dependent Claim
43 words
A formulation according to any of claims 1-13, in which the film-forming agent of the outer film layer is one which is anti-adhesive at temperatures above about 40°C, especially temperatures above about 50°C, such as a temperature between about 60°C and about 120°C.
Claim 16
Dependent Claim
66 words
A formulation according to claim 14, in which the film-forming agent of the outer film layer is selected from diffusion coating materials such as ethylcellulose or enteric coating materials such as anionic poly(meth)acrylic acid esters, hydroxypropylmethylcellulosephthalate, celluloseacetatephthalate, polyvinylacetatephthalate, polyvinylacetatephthalate-crotonic acid copolymerisates, or mixtures thereof, or water-soluble coating materials such as water-soluble cellulose derivatives, e.g. hydroxypropylcellulose, carboxymethylcellulose, methylcellulose, propylcellulose, hydroxyethylcellulose, carboxyethylcellulose, carboxymethylhydroxyethylcellulose, hydroxymethylcellulose, carboxymethylethylcellulose, methylhydroxypropylcellulose or hydroxypropylmethylcellulose.
Claim 17
Dependent Claim
38 words
A formulation according to claim 14 or 15, in which the film-forming agent of the outer film layer is present in an amount of about 0.1-10%, especially 0.5-56, in particular about 1% by weight of the uncoated unit.
Claim 18
Dependent Claim
26 words
A formulation according to any of claims 14-16, in which the outer film coating additionally comprises a lubricant which is a finely divided pharmaceutically acceptable powder.
Claim 19
Dependent Claim
23 words
A formulation according to any of the preceding claims, in which the units are crystals of a size between 0.1 and 1.5 mm.
Claim 20
Dependent Claim
37 words
A formulation according to any of claims 1-17, in which the units are cross-sectionally substantially homogeneous cores of a size of about 0.1-1.5 mm, in particular about 0.4-1.0 mm, such as about 0.4-0.7 mm or 0.7-1.0 mm.
Claim 21
Independent Claim
144 words
A method of preparing an oral pharmaceutical controlled release multiple-units formulation as claimed in any of claims 1-19, in which a) individual units containing an active substance are coated with a coating composition comprising an aqueous dispersion of a film-forming agent to form an inner film layer which causes adhesion between the units at elevated temperatures, b) the thus coated units are provided with an outer film layer of a water-based film-forming agent which prevents adhesion between the units at elevated temperatures and imparts flowability to the coated units, and c) the coated units are subsequently heated to a temperature at which the inner film layer is tacky, and at which the formation of a continuous phase of the film-forming agent is accelerated, and subsequently cooled, whereby a coating which substantially does not change its diffusion characteristics in the course of time is formed.
Claim 22
Dependent Claim
25 words
A method according to claim 20, in which the coating composition additionally comprises a substance which, in itself, is capable of forming a continuous phase.
Claim 23
Dependent Claim
106 words
A method according to claim 21, in which the substance is a hydrophobic substance, and the units coated according to steps a) and b) in the method of claim 20, after which steps the hydrophobic substance is present in the inner film layer as a disperse phase, are heated to a temperature above the melting point of the hydrophobic substance which, on melting and subsequent cooling, forms a continuous phase in the inner film layer in homogeneous admixture with the film-forming agent, the outer film layer being one which is impermeable, at temperatures above the melting point of the hydrophobic substance, to the molten hydrophobic substance.
Claim 24
Dependent Claim
75 words
A method according to claim 21, in which the substance is a polymeric substance which, in step a) of the method of claim 20, prevents adhesion between the units and which imparts compressibility to the inner film layer, and the units coated according to steps a) and b) in the method of claim 20 are heated to a temperature at which the film-forming agent forms a continuous phase in homogeneous admixture with the polymeric substance.
Claim 25
Independent Claim
37 words
A method according to any of claims 20-23, in which the coated units are heated to a temperature above about 40°C, especially a temperature above about 50°C, such as a temperature between about 60°C and about 120°C.
Claim 26
Dependent Claim
32 words
An oral pharmaceutical controlled release composition which comprises a multiplicity of units as specified in any of claims 1-19 admixed with one or more pharmaceutically acceptable fillers, diluents, binders, lubricants or disintegrants.
Claim 27
Dependent Claim
26 words
A pharmaceutical composition according to claim 25 which is a tablet which disintegrates substantially immediately upon ingestion in the stomach into a multiplicity of individual units.
References Cited (Backward Citations)
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