US4882167A
Expired / Lapsed
US
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Dry direct compression compositions for controlled release dosage forms
Assignee: Individual
•
Filing: 1987-11-24
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Granted: 1989-11-21
•
Expires: 2007-11-24
Abstract
Abstract The selection of: a hydrophobic carbohydrate polymer, e.g. ethyl cellulose; and, generally at least one digestive-difficulty soluble component, i.e. a wax, e.g. carnauba wax, fatty acid material or neutral lipid provides upon dry direct compression a controlled and continuous release matrix for tablets or implants of biologically active agents. Preferred for producing dry direct compressed products is the combination of: a hydrophobic cellulose derivative; a wax, and, a fatty acid material and/or a neutral lipid since it provides upon dry direct compression a controlled and continuous release tablet or implant of improved structurally integrity against externally imposed forces.
Inventors
- 👤 Choong-Gook Jang
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 02:33
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/20; A61K9/2004; A61K9/2013; A61K9/2022; A61K9/205; A61K9/2054
Claims Analysis
Total Claims: 39
Claim 1
Independent Claim
250 words
A dry, direct compressed product containing controlled release dosage forms of therapeutically active particulate agents produced without heat or solvents by the steps comprising: (a) dry blending blend particles, all of which have particle sizes smaller than 20 mesh, consisting essentially of from 0.01 to 95 weight parts of biologically active particulate solids with from 5 to 99.99 weight parts of a matrix blend combination consisting essentially of from 1 to 96 parts by weight of a hydrophobic carbohydrate polymer of the class of ethyl cellulose, propyl cellulose, cellulose acetate, cellulose propionate, cellulose acetatebutryate and cellulose acetate-propionate and from 4 to 99 parts by weight of a digestive-difficulty soluble component of the class consisting of a wax of the class consisting of carnauba wax, spermceti, beeswax, candelilla wax, esparto and paraffins; a fatty acid material of the class consisting of fatty acids having from 12 to 28 carbon atoms, fatty monoalchols having 12 to 28 carbon atoms, fatty amines and amides having from 12 to 28 carbon atoms; a neutral lipid of the class consisting of stearin, palmitin, castorwax, phospholipids, glycolipids, glycerides, hydrogenated cottonseed oil, hydrogenated cottonseed oil, hydrogenated tallow and metal and organic salts of C 11 -C 28 fatty acids: and, mixtures thereof; (b) compressing said blended solids and blend under a pressure of 1.5 to 20 tons per square inch; and (c) thereafter, recovering said compressed product having a hardness of 4 to 25 kg and excellent resistance to delamination when subjected to an external longitudinal force.
Claim 2
Dependent Claim
250 words
A dry, direct compressed product containing controlled release dosage forms of therapeutically active particulate agents produced without heat or solvents by the steps comprising: (a) dry blending blend particles, all of which have particle sizes smaller than 20 mesh, consisting essentially of from 0.01 to 95 weight parts of biologically active particulate solids with from 5 to 99.99 weight parts of a matrix blend combination consisting essentially of from 1 to 96 parts by weight of a hydrophobic carbohydrate polymer of the class of ethyl cellulose, propyl cellulose, cellulose acetate, cellulose propionate, cellulose acetatebutryate and cellulose acetate-propionate and from 4 to 99 parts by weight of a digestive-difficulty soluble component of the class consisting of a wax of the class consisting of carnauba wax, spermceti, beeswax, candelilla wax, esparto and paraffins; a fatty acid material of the class consisting of fatty acids having from 12 to 28 carbon atoms, fatty monoalchols having 12 to 28 carbon atoms, fatty amines and amides having from 12 to 28 carbon atoms; a neutral lipid of the class consisting of stearin, palmitin, castorwax, phospholipids, glycolipids, glycerides, hydrogenated cottonseed oil, hydrogenated cottonseed oil, hydrogenated tallow and metal and organic salts of C 11 -C 28 fatty acids: and, mixtures thereof; (b) compressing said blended solids and blend under a pressure of 1.5 to 20 tons per square inch; and (c) thereafter, recovering said compressed product having a hardness of 4 to 25 kg and excellent resistance to delamination when subjected to an external longitudinal force.
Claim 3
Dependent Claim
50 words
A dry, direct compressed product according to claim 1 wherein said hydrophobic polymer is ethyl cellulose present in from 5 to 30 weight parts and the balance of said combination being selected from carnauba wax, hydrogenated cottonseed oil, a fatty acid having from 12 to 28 carbons or mixtures thereof.
Claim 4
Dependent Claim
79 words
A matrix composition according to claim 1 wherein: said hydrophobic cellulose polymer is ethyl cellulose present in from 3 to 50 parts by weight; said wax is carnauba wax present in from 5 to 70 parts by weight; said fatty acid material is a mixture of stearic acid and palmitic acid; said neutral lipid is hydrogenated cottonseed oil; and, said fatty acid material or said neutral lipid or both is present in from 5 to 80 parts by weight.
Claim 5
Dependent Claim
38 words
A product according to claim 1 wherein said compressing is followed by the further steps (c) of granulating said tablets and blending them with additional excipients and (d) finally, compressing said blend into tablets with desired release rates.
Claim 6
Dependent Claim
46 words
A product according to claim 1 wherein said mixture of said digestive-difficulty soluble component comprises from 2 to 97 parts by weight of said wax and from 2 to 97 parts by weight of said fatty acid material, of said neutral lipid and of mixtures thereof.
Claim 7
Dependent Claim
59 words
A product according to claim 1 wherein: said polymer is present in from 5 to 30 parts by weight; said wax is present in from 10 to 40 parts by weight; said fatty acid material is present in from 10 to 70 parts by weight; and, said neutral lipid is present in from 10 to 70 parts by weight.
Claim 8
Dependent Claim
32 words
A product according to claim 1 wherein said blended particles of step (a) additionally contains from 0.01 to 10 weight parts of hydrophobic fumed silica whereby the dissolution release rate is reduced.
Claim 9
Dependent Claim
17 words
A product according to claim 7 wherein said silica amounts to from 0.05 to 3 weight parts.
Claim 10
Independent Claim
40 words
A method for reducing the controlled release rate of tablets containing both a biologically active agent and a lipid controlled release excipient comprising the step of dispersing from 0.05 to 3 weight percent of hydrophobic fumed silica throughout said tablet.
Claim 11
Independent Claim
40 words
A method for reducing the controlled release rate of tablets containing both a biologically active agent and a lipid controlled release excipient comprising the step of dispersing from 0.05 to 3 weight percent of hydrophobic fumed silica throughout said tablet.
Claim 12
Dependent Claim
68 words
A dry, direct compression tablet comprising at least one particulate biologically active agent evenly dispersed within a controlled release excipient binder matrix characterized in that the tablet has a hardness of 3 to 25 kilograms and the absence of: a derivative of said agent resulting from its degradation by heat and/or solvent; solvent residue; interlinked excipient skeletal structures; and, solid solutions and eutectic mixtures of the tablet components.
Claim 13
Dependent Claim
68 words
A dry, direct compression tablet comprising at least one particulate biologically active agent evenly dispersed within a controlled release excipient binder matrix characterized in that the tablet has a hardness of 3 to 25 kilograms and the absence of: a derivative of said agent resulting from its degradation by heat and/or solvent; solvent residue; interlinked excipient skeletal structures; and, solid solutions and eutectic mixtures of the tablet components.
Claim 14
Dependent Claim
18 words
The tablet of claim 10 wherein said binder matrix contains as an essential ingredient a hydrophobic carbohydrate polymer.
Claim 15
Dependent Claim
52 words
The tablet of claim 11 wherein said agent is from 0.01 to 95 wt. % and said matrix is from 99.99 to 5 wt. % of said tablet and said matrix contains from 1 to 100 wt. % of said polymer and up to 99 wt. % of a difficulty soluble component.
Claim 16
Independent Claim
67 words
A method of preparing a controlled release tablet comprising the steps of: (a) dry blending a desired level of biologically active particulate agent into an excipient binder having as an essential ingredient a hydrophobic carbohydrate polymer, said blend having a particle size smaller than 10 mesh; and (b) compressing said blend into tablets of from 3 to 25 kg hardness as measured on a Pfizer hardness tester.
Claim 17
Independent Claim
67 words
A method of preparing a controlled release tablet comprising the steps of: (a) dry blending a desired level of biologically active particulate agent into an excipient binder having as an essential ingredient a hydrophobic carbohydrate polymer, said blend having a particle size smaller than 10 mesh; and (b) compressing said blend into tablets of from 3 to 25 kg hardness as measured on a Pfizer hardness tester.
Claim 18
Dependent Claim
38 words
A method according to claim 13 wherein said compressing is followed by the further steps (c) of granulating said tablets and blending them with additional excipients and (d) finally, compressing said blend into tablets with desired release rates.
Claim 19
Dependent Claim
52 words
The method according to claim 13 wherein said desired level ranged from 0.01 to 95 wt. %, said binder comprising at least one difficulty soluble component and said polymer is ethyl cellulose and present in about 10 to 30 wt. %, said wt. % based on the total weight of said blend.
Claim 20
Dependent Claim
33 words
A dry direct compression tablet comprising at least one particulate biologically active agent dispersed throughout a matrix of hydrophobic carbohydrate polymer, said polymer constituting from 5 to 99.99 wt. % of said tablet.
Claim 21
Dependent Claim
33 words
A dry direct compression tablet comprising at least one particulate biologically active agent dispersed throughout a matrix of hydrophobic carbohydrate polymer, said polymer constituting from 5 to 99.99 wt. % of said tablet.
Claim 22
Dependent Claim
14 words
A tablet according to claim 16 wherein said matrix consists essentially of ethyl cellulose.
Claim 23
Dependent Claim
21 words
A tablet according to claim 16 wherein said matrix additionally contains from 0.01 to 10 weight parts of hydrophobic fumed silica.
Claim 24
Independent Claim
226 words
A method comprising (a) dry blend particles, all of which have particle sizes smaller than 20 mesh, consisting essentially of from 0.01 to 95 weight parts of biologically active particulate solids with from 5 to 9.99 weight parts of a matrix blend combination consisting essentially of from 1 to 96 parts by weight of a hydrophobic carbohydrate polymer of the class of ethyl cellulose, propyl cellulose, cellulose acetate, cellulose propionate, cellulose acetate-butyrate and cellulose acetate-propionate anf from 4 to 99 parts by weight of a digestive-difficulty soluble component of the class consisting of a wax of the class consisting of a wax of the class consisting of carnauba wax, spermaceti, beeswax, candelilla wax, esparto and paraffins; a fatty acid material of the class consisting of fatty acids having from 12 to 28 carbons, fatty mono-alcohols having 12 to 28 carbons, fatty amines and amides having 12 to 28 carbons; a neutral libid of the class consisting of stearin, palmitin, castorwax, phospholipids, glycolipids, glycerides, hydrogenated cottonseed oil, hydrogenated tallow and metal salts of C 11 -C 28 fattu acods' and, mixtures thereof; (b) compressing said blended solids and blend under a pressure of 1.5 to 20 tons per square inch; and (c) thereafter, recovering said compressed product having a hardness of 4 to 25 kg and excellent resistance to delamination when subjected to an external longitudinal force.
Claim 25
Independent Claim
226 words
A method comprising (a) dry blend particles, all of which have particle sizes smaller than 20 mesh, consisting essentially of from 0.01 to 95 weight parts of biologically active particulate solids with from 5 to 9.99 weight parts of a matrix blend combination consisting essentially of from 1 to 96 parts by weight of a hydrophobic carbohydrate polymer of the class of ethyl cellulose, propyl cellulose, cellulose acetate, cellulose propionate, cellulose acetate-butyrate and cellulose acetate-propionate anf from 4 to 99 parts by weight of a digestive-difficulty soluble component of the class consisting of a wax of the class consisting of a wax of the class consisting of carnauba wax, spermaceti, beeswax, candelilla wax, esparto and paraffins; a fatty acid material of the class consisting of fatty acids having from 12 to 28 carbons, fatty mono-alcohols having 12 to 28 carbons, fatty amines and amides having 12 to 28 carbons; a neutral libid of the class consisting of stearin, palmitin, castorwax, phospholipids, glycolipids, glycerides, hydrogenated cottonseed oil, hydrogenated tallow and metal salts of C 11 -C 28 fattu acods' and, mixtures thereof; (b) compressing said blended solids and blend under a pressure of 1.5 to 20 tons per square inch; and (c) thereafter, recovering said compressed product having a hardness of 4 to 25 kg and excellent resistance to delamination when subjected to an external longitudinal force.
Claim 26
Dependent Claim
48 words
A method according to claim 19 wherein said hydrophobic carbohydrated polymer is ethyl cellulose present in from 5 to 30 weight parts and the balance of said combination being selected from carnauba wax, hydrogenated cottonseed oil, a fatty acid having from 12 to 28 carbons or mixtures thereof.
Claim 27
Dependent Claim
78 words
A method according to claim 19 wherein said hydrophobic cellulose polymer is ethyl cellulose present in from 3 to 50 parts by weight; said wax is carnauba wax present in from 5 to 70 parts by weight; said fatty acid material is a mixture of stearic acid and palmitic acid; said neutral lipid is hydrogenated cottonseed oil; and, said fatty acid material or said neutral lipid or both is present in from 5 to 80 parts by weight.
Claim 28
Dependent Claim
38 words
A method according to claim 19 wherein said compressing is followed by the further steps (c) of granulating said tablets and blending them with additional excipients and (d) finally, compressing said blend into tablets with desired release rates.
Claim 29
Dependent Claim
46 words
A method according to claim 19 wherein said mixture of said digestive-difficulty soluble component comprises from 2 to 97 parts by weight of said wax and from 2 to 97 parts by weight of said fatty acid material, of said neutral lipid and of mixtures thereof.
Claim 30
Dependent Claim
45 words
A method according to claim 19 wherein said polymer is present in from 5 to 30 parts by weight; said wax is present in from 10 to 70 parts by weight; and, said neutral lipid is present in from 10 to 70 parts by weight.
Claim 31
Dependent Claim
32 words
A method according to claim 19 wherein said blended particles of step (a) additionally contains from 0.01 to 10 weight parts of hydrophobic fumed silica whereby the dissolution release rate is reduced.
Claim 32
Dependent Claim
17 words
A method according to claim 25 wherein said silica amounts to from 0.05 to 3 weight parts.
Claim 33
Independent Claim
15 words
A method comprising the steps of dispersing at least one particulate biologically active agent evenly
Claim 34
Independent Claim
15 words
A method comprising the steps of dispersing at least one particulate biologically active agent evenly
Claim 35
Dependent Claim
53 words
A method according to claim 27 wherein said agent is from 0.01 to 95 wt. % and said matrix is from 99.99 to 5 wt. % of said tablet and said matrix contains from 1 to 100 wt. % of said polymer and up to 99 wt. % of a difficulty soluble component.
Claim 36
Dependent Claim
21 words
A method according to claim 28 wherein said component is a fatty acid, a neutral lipid, a wax or mixtures thereof.
Claim 37
Dependent Claim
20 words
The method of preparing controlled release tablets according to compositions in claim 16 by dry blending and dry direct compression.
Claim 38
Dependent Claim
19 words
The method of preparing controlled release tablets according to compositions in claim 17 by dry blending dry direct compression.
Claim 39
Dependent Claim
24 words
A method according to claim 19 wherein said matrix blend combination is ethyl cellulose and a fatty acid material having 12 to 28 carbons.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1992-11-20 | 1993-05-22 | 1993-11-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-11-20 | 1997-05-22 | 1997-11-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-11-20 | 2001-05-22 | 2001-11-21 | $7700.00 | Window Closed / Lapsed |