GB2329124A - A method of forming dose units of active agents - Google Patents
A method of forming dose units of active agents Download PDFInfo
- Publication number
- GB2329124A GB2329124A GB9719457A GB9719457A GB2329124A GB 2329124 A GB2329124 A GB 2329124A GB 9719457 A GB9719457 A GB 9719457A GB 9719457 A GB9719457 A GB 9719457A GB 2329124 A GB2329124 A GB 2329124A
- Authority
- GB
- United Kingdom
- Prior art keywords
- agent
- particles
- composition
- coating material
- droplets
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 47
- 239000013543 active substance Substances 0.000 title claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 83
- 239000000203 mixture Substances 0.000 claims abstract description 50
- 239000002245 particle Substances 0.000 claims abstract description 34
- 239000007788 liquid Substances 0.000 claims abstract description 24
- 238000000576 coating method Methods 0.000 claims abstract description 20
- 239000011248 coating agent Substances 0.000 claims abstract description 19
- 239000012876 carrier material Substances 0.000 claims abstract description 18
- 239000000463 material Substances 0.000 claims abstract description 13
- 239000007787 solid Substances 0.000 claims abstract description 9
- 238000005507 spraying Methods 0.000 claims abstract description 8
- 238000001035 drying Methods 0.000 claims abstract description 6
- 239000011782 vitamin Substances 0.000 claims abstract description 3
- 229940088594 vitamin Drugs 0.000 claims abstract description 3
- 229930003231 vitamin Natural products 0.000 claims abstract description 3
- 235000013343 vitamin Nutrition 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims description 19
- 229940079593 drug Drugs 0.000 claims description 19
- 238000004108 freeze drying Methods 0.000 claims description 16
- 238000007710 freezing Methods 0.000 claims description 10
- 230000008014 freezing Effects 0.000 claims description 10
- 229920000642 polymer Polymers 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000013078 crystal Substances 0.000 claims description 6
- 150000002632 lipids Chemical class 0.000 claims description 6
- 108090000623 proteins and genes Proteins 0.000 claims description 6
- 102000004169 proteins and genes Human genes 0.000 claims description 6
- 150000001720 carbohydrates Chemical class 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000001828 Gelatine Substances 0.000 claims description 4
- 239000002158 endotoxin Substances 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 150000004676 glycans Chemical class 0.000 claims description 4
- 229920006008 lipopolysaccharide Polymers 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 3
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 2
- 229920001817 Agar Polymers 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 108010038807 Oligopeptides Proteins 0.000 claims description 2
- 102000015636 Oligopeptides Human genes 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 239000008272 agar Substances 0.000 claims description 2
- 229940072056 alginate Drugs 0.000 claims description 2
- 235000010443 alginic acid Nutrition 0.000 claims description 2
- 229920000615 alginic acid Polymers 0.000 claims description 2
- 239000012620 biological material Substances 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229920001525 carrageenan Polymers 0.000 claims description 2
- 238000007906 compression Methods 0.000 claims description 2
- 230000006835 compression Effects 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 239000005556 hormone Substances 0.000 claims description 2
- 229940088597 hormone Drugs 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 244000005700 microbiome Species 0.000 claims description 2
- 108020004707 nucleic acids Proteins 0.000 claims description 2
- 102000039446 nucleic acids Human genes 0.000 claims description 2
- 150000007523 nucleic acids Chemical class 0.000 claims description 2
- 229920002401 polyacrylamide Polymers 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 150000004804 polysaccharides Polymers 0.000 claims description 2
- 230000002459 sustained effect Effects 0.000 claims description 2
- 229960005486 vaccine Drugs 0.000 claims description 2
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims 2
- 230000001580 bacterial effect Effects 0.000 claims 1
- 229960000074 biopharmaceutical Drugs 0.000 abstract description 4
- 238000013268 sustained release Methods 0.000 abstract 2
- 239000012730 sustained-release form Substances 0.000 abstract 2
- 238000001816 cooling Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 4
- 239000011344 liquid material Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 230000003019 stabilising effect Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 239000011247 coating layer Substances 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 239000008240 homogeneous mixture Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000011369 resultant mixture Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- -1 flavouring Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1658—Proteins, e.g. albumin, gelatin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
A method of producing agent forms by dispersing an agent composition in a solution of a coating material in a liquid carrier material and spraying the resultant dispersed mixture to form fine droplets which are frozen. Drying the said frozen particles to produce a plurality of individual solid particles comprising of the agent composition coated with the coating material. The coated particles have sustained release properties of the agent and the method is useful for producing sustained release unit dose delivery systems of process sensitive materials such as bio-pharmaceuticals, as well as other agents such as vitamins.
Description
METHOD OF FORMING DOSE UNITS OF ACTIVE AGENTS
The present invention relates to vehicles for the delivery of agents to the human or animal body.
Specifically the invention relates to the formation of particles containing active agent, and further relates to a method of coating such particles.
Recently there has been an expansion in the number and type of delivery systems available for delivering drugs or other agents. Liquid injection and tablets have been known for hundreds of years. In more recent times alternative drug delivery systems have increasingly come to the fore. These include capsules, powder inhalations, parenteral delivery systems such as injectable forms which Pare sterile and filled into sealed ampoules or vials, transdermal delivery devices and trans-mucous membrane systems such as anal or vaginal suppositories.
More recently drug delivery devices have been developed which permit the controlled and sustained or intermittent release of drugs into biological systems.
It has now been discovered however that many conventional methods of production are frequently not suitable for producing delivery units containing agents which are physically or chemically unstable or heat sensitive. This particularly applies to the bio-pharmaceuticals that are arising from the emerging bio-technology industry.
For example, one conventional process is spray drying.
This makes use of high temperature drying steps involving the use of chemically aggressive organic solvents. Both the temperature and solvents can be deleterious to the properties of unstable active agents.
It is an object of the present invention to provide a new method for processing agents into a form acceptable for delivery to biological systems, which method is capable of application, inter alia, with unstable drugs and other agents.
It is a particular object of the present invention to provide a low temperature process for the production of particulate dose forms comprising agent.
According one aspect of the present invention there is provided a method of producing agent forms, which method comprises: providing an agent composition, contacting said composition with a liquid carrier material, spraying the resultant mixture to form droplets thereof, freezing said droplets to produce frozen particles, and freeze drying said particles, thereby to produce a plurality of solid particles comprising the agent composition.
In this way agent forms may be produced from a loose starting composition at a low temperature and without the need for solvent/heat treatment. Thus chemically, physically or temperature unstable agents may be formed into a suitable form for incorporation into an gent delivery device without fear of damaging the agent by the processing method.
In the contacting step, the agent composition and carrier liquid material may form an emulsion of liquid agent dispersed in the carrier liquid. In this case the freeze dried particles may comprise agent coated in carrier material.
Alternatively the agent composition may form a suspension of solid or semi-solid agent, such as gel, dispersed in the liquid carrier material. In this case the freeze dried particles may comprise agent coated in carrier material.
Alternatively the agent composition may be dissolved in the carrier liquid to form a solution of agent in the liquid carrier material. In this case the freeze dried particles may comprise an homogenous mixture of agent and carrier.
The foregoing alternatives are not mutually exclusive, and depending upon the nature of the agent composition, the resultant mixture may be made up one or more of each alternative.
The agent composition may comprise an active agent or agents per se. Alternatively, the composition may comprise an active agent or agents along one or more excipients or additives.
The agent composition may comprise an agent absorbed into another element such as a polymer. Suitable elements include polyacrylamides, agar, lipids, proteins, carbohydrates and the like.
The agent may comprises a long chain molecule such as a polymer.
The agent may comprises a liposome which forms a suspension in the carrier liquid.
Other agent compositions include small tablets, or other small particles which are mixed to form a dispersion in the carrier liquid.
For example, in one embodiment the agent composition comprises a crystalline powder of the agent.
The agent may comprise a drug or other pharmaceutically active substance, such as a peptide, an oligopeptide, a protein, a hormone, a nucleic acid, a polysaccharide, a peptide with polysaccharide side chains, a lipid, a lipopolysaccharide, a vaccine, a vitamin.
Excipients which may be included in the agent composition may comprise one or more of mannitol, microcrystalline cellulose, flavouring, preservative, surfactant.
The agent composition may comprise a food flavouring, and the food flavouring particles formed in the method may be incorporated into a foodstuff.
The method of the present invention is particularly useful for forming agent forms comprising delicate agents. Hence the agent may comprise biological material, for example a micro-organism such as a useful bacteria or a virus.
In particular the agent may comprise a genetically engineered virus for therapeutic or other useful application.
The agent composition may comprise an agent form produced according to the method as hereinbefore described, which agent form is contacted with the carrier liquid to form a dispersion therein. The agent form is thereby coated in carrier material by the method of the present invention. The process may be repeated to produce multiple coating layers, of the same or different compositions of carrier material.
Where an agent would tend to dissolve in the carrier liquid it may be included in a stabilising formulation which substantially prevents dissolution thereof in the carrier liquid material. In this way agents which would normally dissolve in the carrier liquid may be coated with carrier material. By way of example the stabilising composition may comprise one or more of a carbohydrate, a lipid, a lipopolysaccharide, a protein, a surfactant.
The carrier liquid material may comprises water. Frozen water (ice) will be removed during the freeze drying process. Water has the advantage when present in the carrier liquid material of requiring only a small degree of cooling from ambient temperature, say 20 degrees centigrade, to below the freezing point; 0 degrees centigrade. Hence little energy is required to produce the required cooling in the freeze drying and spray cooling steps.
The carrier material may comprise a polymer. The carrier material may comprise one or more of gelatine, carageenan, alginate, carbopol, carboxymethyl cellulose, or ethyl cellulose. The polymer may be rendered liquid andfor sprayable by the addition of water or another suitable solvent or liquid removable by freeze drying.
The spraying step preferably forms an aerosol of droplets, thereby facilitating the freezing of the droplets while still airborne.
The droplets may be cooled by contacting said droplets with a gas cooled to below the freezing point of the mixture. Preferably cooling is effected by contacting said droplets with a stream of cooled gas. The droplets may freeze as frozen droplets, or flakes or other shapes depending upon the nature of the material frozen and the conditions of freezing. The cooled particles may be stored in a chilled enviroment and mixed with other substances as desired, or otherwise treated when chilled.
Subsequently the particles may be freeze dried to render the particles stable at room temperature.
The freeze drying may be by one of the known methods of which the person skilled in the art will be capable of carrying out. Typically freeze drying involves sublimation of the frozen n liquidz in a vacuum.
In another aspect of the invention the method may comprise storing the frozen droplets in a chilled environment prior to freeze drying.
In yet another aspect of the invention the frozen droplets may be mixed with a composition for tablet manufacture and tabletted by compression before freeze drying.
In a further aspect of the invention the method is adapted to produce particles of between about a micron and about a thousand microns. The temperature to which the gas is cooled may be chosen to produce a desired droplet size. Alternatively, or in addition, the spray droplets may be formed by an adjustable spray nozzle, adjustment of which nozzle permits variation of the droplet size.
In another aspect of the invention, there is provided a method of coating agent forms comprising spraying a liquid carrier material as hereinbefore described onto a plurality of agent forms, and cooling said sprayed agent forms to solidify the carrier material, and freeze drying the resultant particles to leave an agent form coated in carrier material.
The agent forms coated may be coated as freeze dried particles, or as solidified droplets formed before freeze drying.
The coating preferably fully encapsulates the agent forms, but partial coating may occur in certain embodiments.
The coating procedure may be repeated on the coated agent forms to build up multi-layer coatings. The coatings may comprise the same coating material or different coating materials. Agents may be included in the carrier liquid to produce one or more agent containing layers.
The coating layers and/or agent forms produced by the present invention may rendered porous after freeze drying the pores corresponding to the sublimed matter.
Following is a description by way of example only of examples demonstrating application of the present invention.
Example 1
A bio-pharmaceutical which has a relatively low solubility is chosen to be coated. A coating solution of a carrier polymer, such as gelatine, in water is formed.
To this solution is added crystalline powdered drug, and mixed to form a uniform suspension of drug crystals in the solution. The liquid mixture thereby formed is then sprayed from a nozzle by means of compressed air into which the suspension is entrained as droplets. The droplets disperse from the nozzle to form an aerosol. The nozzle is sprayed into a moving stream of air cooled to well below the freezing point of the liquid mixture. The frozen, solidified droplets are then collected as they fall under the influence of gravity. The droplets are maintained in a cool atmosphere until it is desired to freeze dry the frozen droplets. Freeze drying is carried out by the known methods to remove the ice from the droplets, leaving solid particles of drug crystals coated in porous polymeric gelatine. The pores correspond to previous disposition of the removed ice.
The solid particles are then incorporated into a drug delivery device, for example a capsule, and may then be administered to a patient. The polymeric coating layer provides a protective coating, which also serves to control the rate at which agent is dissolved into a system to which the capsule is administered. The control function may be altered by changing the coating thickness, and by varying the fraction of solvent (water) in the liquid mixture before spraying. If it is desired to produce multiple coatings, then the procedure can be repeated, this time substituting the particles to be recoated for the drug crystals.
Example 2
A bio-pharmaceutical is chosen which is relatively soluble in water, to the extent that it dissolves almost immediately on contact therewith at room temperature. A stabilizing formulation is formed consisting of water and a carbohydrate and surfactant. The drug is added to the stabilising formulation to form a mixture. The mixture thereby formed is then sprayed from a nozzle by means of compressed air into which the mixture is entrained as droplets. The droplets disperse from the nozzle of a spray gun to form an aerosol. The nozzle is sprayed into a moving stream of air cooled to well below the freezing point of the mixture. The frozen, solidified droplets are then collected as they fall under the influence of gravity. The droplets are maintained in a cool atmosphere until it is desired to freeze dry the frozen droplets.
Freeze drying is carried out by the known methods to remove the ice from the droplets, leaving particles consisting of an homogeneous mixture of drug and stabilising formulation. The agent form can be now be coated in the same way as the drug crystals were coated in example one, either before freeze drying, or after freeze drying.
The present invention provides a low temperature method of forming particulate drug forms from a wide range of starting points. Solid drug compositions can be formed without the need for damaging solvent processing or high temperatures. The method allows the production of multilayer particles, the layers of which can consist of flavourings, drugs, excipients as required.
Claims (20)
1. A method of producing agent forms, which method comprises: providing an agent composition comprising an agent, dispersing said agent composition in a solution of a coating material in a liquid carrier material, spraying the resultant dispersed mixture to form droplets thereof, freezing said droplets to produce frozen particles and drying said particles, thereby to produce a plurality of solid, individual particles comprising the agent composition coated with said coating material.
2. A method as claimed in claim 1, wherein said agent composition comprises a carrier for said agent.
3. A method as claimed in claim 2, wherein said carrier comprises a polymer, such for example as polyacrylamide, agar, lipid, protein or carbohydrate, which polymer is adapted to absorb said agent.
4. A method as claimed in claim 2, wherein said carrier comprises a liposome which carries said agent.
5. A method as claimed in any preceding claim, wherein said agent comprises a drug.
6. A method as claimed in any preceding claim, wherein said agent comprises a pharmaceutically active substance, such, for example, as a peptide, an oligopeptide, a protein, a hormone, a nucleic acid, a polysaccharide, a peptide with polysaccharide side chains, a lipid, a lipopolysaccharide, a vaccine, or a vitamin.
7. A method as claimed in any preceding claim, wherein said agent comprises biological material such as a microorganism such as a useful bacterial strain or a virus.
8. A method as claimed in any preceding claim, wherein said agent composition further comprises one or more excipients or additives.
9. A method as claimed in any preceding claim, wherein said agent composition further comprises a stabilising agent for preventing said agent from dissolving when contacted by said liquid carrier material.
10. A method as claimed in claim 12, which stabilising agent comprises one or more of a carbohydrate, a lipid, a lipopolysaccharide, a protein, and a surfactant.
11. A method as claimed in any preceding claim, characterised in that said dispersed mixture is viscous.
12. A method as claimed in any preceding claim, wherein said liquid carrier material comprises water.
13. A method as claimed in any preceding claim, wherein said coating material comprises a polymer.
14. A method as claimed in claim 13, wherein said polymer is selected from one or more of gelatine, carageenan, alginate, carbopol, carboxymethyl cellulose, and ethyl cellulose.
15. A method as claimed in any preceding claim, wherein said drying of the particles comprises freeze-drying.
16. A method as claimed in claim 15, wherein said frozen particles are mixed with a composition for tablet manufacture and tabletted by compression prior to being freeze-dried.
17. Apparatus for producing agent forms in accordance with the method of any preceding claim, which apparatus comprises dispersing means for dispersing an agent composition comprising an agent in a solution of coating material in a liquid carrier material, spraying means for spraying the resultant dispersed mixture to form droplets thereof, freezing means for freezing said droplets to produce frozen particles and drying means for drying said frozen particles, thereby to produce a plurality of solid, individual particles of said agent composition coated with said coating material.
18. An agent form comprising a plurality of dried particles of an agent composition, which agent form is produced in accordance with the method of any of claims 1 - 16.
19. An agent form as claimed in claim 18, which agent form comprises a drug composition for administration to a patient.
20. An agent form as claimed in claim 19, wherein said particulate drug composition comprises a plurality of particles comprising drug crystals coated in one or more layers of a coating material, which drug crystals are adapted to be released through said one or more layers of coating material over a sustained period of time.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9719457A GB2329124B (en) | 1997-09-12 | 1997-09-12 | Method of forming dose units of active agents |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9719457A GB2329124B (en) | 1997-09-12 | 1997-09-12 | Method of forming dose units of active agents |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| GB9719457D0 GB9719457D0 (en) | 1997-11-12 |
| GB2329124A true GB2329124A (en) | 1999-03-17 |
| GB2329124A8 GB2329124A8 (en) | 1999-08-24 |
| GB2329124B GB2329124B (en) | 2002-05-08 |
Family
ID=10818995
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB9719457A Expired - Fee Related GB2329124B (en) | 1997-09-12 | 1997-09-12 | Method of forming dose units of active agents |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2329124B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001019345A1 (en) * | 1999-09-10 | 2001-03-22 | Astrazeneca Ab | Method to obtain microparticles |
| WO2002072070A1 (en) * | 2001-03-09 | 2002-09-19 | Astrazeneca Ab | Method to obtain microparticles containing a h+, k+-atp-ase inhibitor |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1316522A (en) * | 1970-08-14 | 1973-05-09 | Du Pont | Method of preparing particulate blends |
| EP0081913B1 (en) * | 1981-12-11 | 1985-06-26 | JOHN WYETH & BROTHER LIMITED | Process and apparatus for freezing a liquid medium |
| WO1988001150A1 (en) * | 1986-08-18 | 1988-02-25 | Physio-Control Corporation | Method and apparatus for the automatic calibration of signals employed in oximetry |
| EP0413865A1 (en) * | 1989-08-22 | 1991-02-27 | Taisho Pharmaceutical Co. Ltd | Process to prepare coated particles |
| EP0668013A2 (en) * | 1994-02-22 | 1995-08-23 | Nippon Telegraph And Telephone Corporation | Freeze-dried blood cells, stem cells and platelets and manufacturing method for the same |
| US5611973A (en) * | 1994-06-03 | 1997-03-18 | L'oreal | Process of producing a starting material in the form of granules |
| US5656597A (en) * | 1993-04-28 | 1997-08-12 | Akzo Nobel N.V. | Lyospheres comprising gonadotropin |
-
1997
- 1997-09-12 GB GB9719457A patent/GB2329124B/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1316522A (en) * | 1970-08-14 | 1973-05-09 | Du Pont | Method of preparing particulate blends |
| EP0081913B1 (en) * | 1981-12-11 | 1985-06-26 | JOHN WYETH & BROTHER LIMITED | Process and apparatus for freezing a liquid medium |
| WO1988001150A1 (en) * | 1986-08-18 | 1988-02-25 | Physio-Control Corporation | Method and apparatus for the automatic calibration of signals employed in oximetry |
| EP0413865A1 (en) * | 1989-08-22 | 1991-02-27 | Taisho Pharmaceutical Co. Ltd | Process to prepare coated particles |
| US5656597A (en) * | 1993-04-28 | 1997-08-12 | Akzo Nobel N.V. | Lyospheres comprising gonadotropin |
| EP0668013A2 (en) * | 1994-02-22 | 1995-08-23 | Nippon Telegraph And Telephone Corporation | Freeze-dried blood cells, stem cells and platelets and manufacturing method for the same |
| US5611973A (en) * | 1994-06-03 | 1997-03-18 | L'oreal | Process of producing a starting material in the form of granules |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001019345A1 (en) * | 1999-09-10 | 2001-03-22 | Astrazeneca Ab | Method to obtain microparticles |
| US6753014B1 (en) | 1999-09-10 | 2004-06-22 | Astrazeneca Ab | Method to obtain microparticles |
| WO2002072070A1 (en) * | 2001-03-09 | 2002-09-19 | Astrazeneca Ab | Method to obtain microparticles containing a h+, k+-atp-ase inhibitor |
Also Published As
| Publication number | Publication date |
|---|---|
| GB2329124B (en) | 2002-05-08 |
| GB2329124A8 (en) | 1999-08-24 |
| GB9719457D0 (en) | 1997-11-12 |
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| Date | Code | Title | Description |
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| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 20040912 |