Patent US4574080A successfully refreshed from Google Patents.
US4574080A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Combination formulation
Assignee: BENZON PHARMA A DANISH Ltd Co
•
Filing: 1983-08-15
•
Granted: 1986-03-04
•
Expires: 2003-08-15
Abstract
Abstract A pharmaceutical oral controlled release multiple-units formulation is prepared by mixing units containing an active substance and coated with a substantially water-insoluble, but water diffusable controlled release coating with particles of an active substance, the mean size of which is at least one power of 10 smaller than the coated units under conditions which will result in adherence of the smaller particles to the surface of the controlled release coating in a substantially uniform layer. The coated units have a mean size of between about 0.1 and 1.5 mm, in particular about 0.4 to 1.2 mm, and the fine particles have a mean particle size of from about 1 to about 50 μm and are present in the composition in an amount of at the most 25 percent by weight, in particular at the most 5 percent by weight and preferably not more than 1 percent by weight, calculated on the weight of the coated units. The mixing is performed in the presence of an anti-adhesive which counteracts undesired electrostatic charging such as talc or colloidal silicon dioxide. The active substance which is subject to controlled release may be potassium chloride, and the active substance of the small particles may be a diuretic. The controlled release coating contains a film-forming polymer such as ethyl cellulose, a plasticizer and a hydrophobic substance. In this manner, it is possible to combine an active substance which it is preferred to administer in a controlled release multiple-units composition, for example because it has an irritating effect on the gastric mucosa or because it has a short half life, with an instantly releasing active substance to obtain a combination composition which simplifies the dosing regimen and thus improves patient compliance.
Inventors
- 👤 Stig Roswall
- 👤 Lene B. Thorhus
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 12:15
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/20; A61K9/2072; A61K9/2077; A61K9/2081; A61K9/48; A61K9/50; A61K9/5073
Claims Analysis
Total Claims: 31
Claim 1
Independent Claim
67 words
A pharmaceutical oral controlled release multiple-unit dosage form containing a multiplicity of individual coated units, each unit containing an active substance coated with a water-insoluble, but water diffusible controlled release coating, each unit additionally comprising particles of active substance adhered to the surface of the controlled release coating in a substantially uniform layer, the particles being at least one power of ten smaller than the coated unit.
Claim 2
Dependent Claim
67 words
A pharmaceutical oral controlled release multiple-unit dosage form containing a multiplicity of individual coated units, each unit containing an active substance coated with a water-insoluble, but water diffusible controlled release coating, each unit additionally comprising particles of active substance adhered to the surface of the controlled release coating in a substantially uniform layer, the particles being at least one power of ten smaller than the coated unit.
Claim 3
Dependent Claim
34 words
A dosage form according to claim 1 in which the active substance adhered to the surface of the controlled release coating is present in an amount of no more than about 25% by weight.
Claim 4
Dependent Claim
40 words
A dosage form according to claim 2, wherein the active substance adhered to the surface of the controlled release coating is present in an amount of no more than 10% by weight, calculated on the weight of the coated units.
Claim 5
Dependent Claim
16 words
A dosage form according to claim 1, additionally comprising an anti-adhesive adhered to the coated units.
Claim 6
Dependent Claim
19 words
A dosage form according to claim 4, wherein the anti-adhesive is a fine particle powder which counteracts electrostatic charging.
Claim 7
Dependent Claim
23 words
A dosage form according to claim 1 in which the controlled release coating contains a film-forming substance, a plasticizer, and a hydrophobic substance.
Claim 8
Dependent Claim
43 words
A dosage form according to claim 6, wherein the plasticizer is selected from triacetin, acetylated monoglyceride, rape oil, olive oil, sesame oil, acetyltributylcitrate, acetyltriethylcitrate, glycerin, sorbitol, diethyloxyalate, diethylmalate, diethylfumarate, diethylsuccinate, diethylmalonate, dioctylphthalate, dibutylsebacate, triethylcitrate, tributylcitrate, glyceroltributyrate, polyethyleneglycol, propyleneglycol, and mixtures of the above.
Claim 9
Dependent Claim
34 words
A dosage form according to claim 6, wherein the hydrophobic substance is present in an amount of between about 1 and 25% calculated on the weight of the dry matter of the coating suspension.
Claim 10
Dependent Claim
32 words
A dosage form according to claim 8, wherein the hydrophobic substance is present in an amount of between 3 and 20%, calculated on the weight of dry matter of the coating suspension.
Claim 11
Dependent Claim
25 words
A dosage form according to claim 6, wherein the hydrophobic substance is selected from hydrocarbons and hydrocarbon derivatives, waxes, oils and fats, and mixtures thereof.
Claim 12
Dependent Claim
34 words
A dosage form according to claim 10, wherein the hydrophobic substance is a wax-like substance selected from beef tallow, whale wax, beeswax, paraffin wax and castor wax, and higher fatty acids and esters thereof.
Claim 13
Dependent Claim
26 words
A dosage form according to claim 1, wherein the film-forming substance is selected from cellulose derivatives, acrylic polymers, vinyl polymers, and other high molecular synthetic polymers.
Claim 14
Dependent Claim
12 words
A dosage form according to claim 1, wherein the units are crystals.
Claim 15
Dependent Claim
17 words
A dosage form according to claim 1, wherein the active substance in the units is potassium chloride.
Claim 16
Dependent Claim
25 words
A dosage form according to claim 14, wherein the potassium chloride is in the form of potassium chloride crystals, each unit substantially comprising one crystal.
Claim 17
Dependent Claim
22 words
A dosage form according to claim 1, in which the coated units are of a size between about 0.1 and 1.5 mm.
Claim 18
Dependent Claim
20 words
A dosage form according to claim 16, wherein the coated units are of a size between 0.4 and 1.0 mm.
Claim 19
Dependent Claim
27 words
A dosage form according to claim 1, in which the active substance which is present on the surface of the coating is present substantially as a monolayer.
Claim 20
Dependent Claim
37 words
A dosage form according to claim 1, in which the active substance in the coated units is potassium chloride and the active substance which is adhered to the surface of the controlled release coating is a diuretic.
Claim 21
Dependent Claim
26 words
A dosage form according to claim 1 which is a tablet which disintegrates substantially immediately upon ingestion in the stomach into a multiplicity of individual units.
Claim 22
Dependent Claim
37 words
A dosage form according to claim 1, wherein the active substance adhered to the surface of the controlled release coating is present in an amount of 0.5-1% by weight, calculated on the weight of the coated units.
Claim 23
Independent Claim
85 words
A method for preparing a pharmaceutical oral controlled release multiple-unit dosage form, comprising mixing a multiplicity of individual units, each of which contains an active substance and is coated with a substantially water-insoluble, but water diffusible controlled release coating, with particles of an active substance the mean size of which is at least one power of 10 smaller than the coated units, under conditions which result in adherence of the smaller particles to the surface of the controlled release coating in a substantially uniform layer.
Claim 24
Independent Claim
85 words
A method for preparing a pharmaceutical oral controlled release multiple-unit dosage form, comprising mixing a multiplicity of individual units, each of which contains an active substance and is coated with a substantially water-insoluble, but water diffusible controlled release coating, with particles of an active substance the mean size of which is at least one power of 10 smaller than the coated units, under conditions which result in adherence of the smaller particles to the surface of the controlled release coating in a substantially uniform layer.
Claim 25
Dependent Claim
41 words
A method according to claim 22 in which the proportion of the smaller particles which are adhered to the controlled release coating in the mixing process is no more than about 25% by weight, calculated on the weight of coated units.
Claim 26
Dependent Claim
35 words
A method according to claim 23 in which the mixing is performed in the presence of an anti-adhesive which counteracts undesired attraction between the small particles and between the small particles and the mixing equipment.
Claim 27
Dependent Claim
22 words
A method according to claim 24 in which the anti-adhesive is a fine particle powder of a kind which counteracts static charging.
Claim 28
Dependent Claim
37 words
A method according to claim 23, wherein the proportion of the smaller particles which are adhered to the controlled release coating in the mixing process is 0.5-1% by weight, calculated on the weight of the coated units.
Claim 29
Dependent Claim
44 words
A method according to claim 22 in which the coated units are of a mean size of between about 0.1 and 1.5 mm, and the fine particles have a mean particle size as measured by microscopy, of from about 1 to about 50 μm.
Claim 30
Dependent Claim
20 words
A method according to claim 22 in which the mixing is performed in low shear mixing equipment or cube mixers.
Claim 31
Dependent Claim
29 words
A method according to claim 22 in which the units with applied small particles adhering to the controlled release coating are combined with excipients and compressed into disintegratable tablets.
References Cited (Backward Citations)
US3873346A
Cited
US3909444A
Cited
GB1468172A
Cited
US4322449A
Cited
US4173626A
Cited
US4316884A
Cited
US4353887A
Cited
US4359483A
Cited
US4411933A
Cited
US4259315A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1989-03-03 | 1989-09-02 | 1990-03-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-03-03 | 1993-09-02 | 1994-03-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-03-03 | 1997-09-02 | 1998-03-04 | $7700.00 | Window Closed / Lapsed |