US4716041A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Diffusion coated multiple-units dosage form
Assignee: A/S/ ALFRED BENZON A CORP OF DENMARK
•
Filing: 1985-02-08
•
Granted: 1987-12-29
•
Expires: 2005-02-08
Abstract
Abstract In an oral pharmaceutical controlled release 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 N. Christensen
- 👤 Jens R. Jensen
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:49
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: 26
Claim 1
Independent Claim
119 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 comprising (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 coated units having been subjected to heating at a temperature at which the formation of a continuous phase of the film-forming agent of the inner film layer is accelerated to form a coating which does not substantially change its diffusion characteristics in the course of time.
Claim 2
Dependent Claim
119 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 comprising (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 coated units having been subjected to heating at a temperature at which the formation of a continuous phase of the film-forming agent of the inner film layer is accelerated to form a coating which does not substantially change its diffusion characteristics in the course of time.
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
30 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.
Claim 6
Dependent Claim
29 words
A formulation according to claim 3, in which the hydrophobic substance is present in an amount of between about 0.1 and 50% by weight of the inner film layer.
Claim 7
Dependent Claim
54 words
The formulation according to claim 2 wherein the inner film layer is a copolymer of acrylic acid ethyl ester and methacrylic acid methyl ester, the outer film layer is hydroxypropylmethylcellulose, the inner film substance which is capable of forming a continuous phase is hydroxypropylmethylcellulose, said formulation further comprising a talc anti-adhesive and potassium chloride.
Claim 8
Dependent Claim
34 words
A formulation according to claim 1 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 or mixtures thereof.
Claim 9
Dependent Claim
30 words
A formulation according to claim 7, 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 10
Dependent Claim
26 words
A formulation according to claim 7, in which the cellulose derivative is selected from hydroxypropylcellulose, carboxymethylcellulose, methylcellulose, propylcellulose, hydroxyethylcellulose, carboxyethylcellulose, carboxymethylhydroxyethylcellulose, hydroxymethylcellulose, carboxymethylethylcellulose, methylhydoxypropylcellulose or hydroxypropylmethylcellulose.
Claim 11
Dependent Claim
26 words
A formulation according to claim 1, in which the inner film layer comprises an anti-adehsive which is a finely divided, substantially water-insoluble, pharmaceutically acceptable, non-wetting powder.
Claim 12
Dependent Claim
28 words
A formulation according to claim 10, in which the anti-adhesive is present in an amount of between about 0.1 and 50% by weight of the inner film layer.
Claim 13
Dependent Claim
26 words
A formulation according to claim 1, in which the inner film layer is present in an amount of about 1-30% by weight of the uncoated units.
Claim 14
Dependent Claim
27 words
A formulation according to claim 1, in which the film-forming agent of the outer film layer is one which is anti-adhesive at temperatures above about 40° C.
Claim 15
Dependent Claim
30 words
A formulation according to claim 13, in which the film-forming agent of the outer film layer is selected from diffusion coating materials or enteric coating materials, or water-soluble coating materials.
Claim 16
Dependent Claim
26 words
A formulation according to claim 14, in which the water-soluble coating is selected from hydroxypropylcellulose, carboxymethylcellulose, methylcellulose, propylcellulose, hydroxyethylcellulose, carboxyethylcellulose, carboxymethylhydroxymethylcellulose, hyhdroxymethylcellulose, carboxymethylethylcellulose, methylhydroxypropylcellulose or hydroxypropylmethylcellulose.
Claim 17
Dependent Claim
30 words
A formulation according to claim 13, in which the film-forming agent of the outer film layer is present in an amount of about 0.1-10% by weight of the uncoated unit.
Claim 18
Dependent Claim
24 words
A formulation according to claim 13, in which the outer film coating additionally comprises a lubricant which is a finely divided pharamceutically acceptable powder.
Claim 19
Dependent Claim
20 words
A formulation according to claim 1, in which the units are crystals of a size between 0.1 and 1.5 mm.
Claim 20
Dependent Claim
22 words
A formulation according to claim 1, in which the units are cross-sectionally substantially homogeneous cores of a size of about 0.1-1.5 mm.
Claim 21
Dependent Claim
30 words
An oral pharmaceutical controlled release composition which comprises a multiplicity of units as specified in claim 1 admixed with one or more pharamceutically acceptable fillers, diluents, binders, lubricants or disintegrants.
Claim 22
Dependent Claim
26 words
A pharmaceutical composition according to claim 20 which is a tablet which disintegrates substantially immediately upon ingestion in the stomach into a multiplicity of individual units.
Claim 23
Dependent Claim
138 words
A method of preparing an oral pharmaceutical controlled release multiple-units formulation as claimed in claim 1, comprising (a) coating individual units containing an active substance 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) coating the thus coated units 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, (c) heating the coated units 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 (d) cooling the coated units to produce a coating which substantially does not change its diffusion characteristics in the course of time.
Claim 24
Dependent Claim
25 words
A method according to claim 22, in which the coating composition additionally comprises a substance which, in itself, is capable of forming a continuous phase.
Claim 25
Dependent Claim
100 words
A method according to claim 23, in which the substance is a hydrophobic substance, and the units coated according to steps (a) and (b) after which steps the hydrophobic substance is present in the inner film layer as a dispersed 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 26
Dependent Claim
20 words
A method according to claim 22, in which the coated units are heated to a temperature above about 40° C.
References Cited (Backward Citations)
US2991226A
Cited
US2928770A
Cited
US3431338A
Cited
US3437728A
Cited
GB1468172A
Cited
US4178361A
Cited
US4017647A
Cited
US4193985A
Cited
JPS53139715A
Cited
US4361546A
Cited
EP0013262A2
Cited
US4292302A
Cited
GB2066070A
Cited
US4432966A
Cited
US4259315A
Cited
EP0063014A2
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1990-12-28 | 1991-06-29 | 1991-12-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-12-28 | 1995-06-29 | 1995-12-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-12-28 | 1999-06-29 | 1999-12-29 | $7700.00 | Window Closed / Lapsed |