CA2380596A1 - Metering and packaging of controlled release medication - Google Patents
Metering and packaging of controlled release medication Download PDFInfo
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- CA2380596A1 CA2380596A1 CA002380596A CA2380596A CA2380596A1 CA 2380596 A1 CA2380596 A1 CA 2380596A1 CA 002380596 A CA002380596 A CA 002380596A CA 2380596 A CA2380596 A CA 2380596A CA 2380596 A1 CA2380596 A1 CA 2380596A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
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- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Controlled quantities of powdered medication are formed in controlled release packages using electrostating metering. Also provided are combination medication therapy delivery packages comprising two or more active pharmaceuticals segregated from one another in a single delivery package.
Description
3 The present invention relates to the packaging of dry powders and particularly 4 to the metering and packaging of precise quantities of pharmaceuticals and drugs for medical uses. The invention has particular utility in the metering and packaging of 6 dry powders, particularly precise amounts of dry powder pharmaceuticals and drugs, 7 and will be described in connection with such utility, although other utilities are 8 contemplated.
9 The convenience of administering a single dose of a medication which releases multiple active ingredients in a controlled fashion and in a chosen location 11 over an extended period of time, as opposed to the administration of a number of 12 single doses at regular intervals, has long been recognized in the pharmaceutical arts.
13 The advantage to the patient and clinician in having consistent and uniform blood 14 levels of medication over an extended period of time are likewise recognized. The advantages of a variety of controlled-release dosage forms are well known.
Among 16 the most important advantages are: ( 1 ) increased contact time for the drug to allow for 17 local activity in the stomach, small intestine, colon, or other locus of activity; (2) 18 increased and more efficient absorption for drugs which have specific absorption 19 sites; (3) the ability to reduce the number of dosages per period of time;
(4) employment of less total drug; (5) minimization or elimination of local and/or 21 systemic side effects; (6) minimization of drug accumulation associated with chronic 22 dosing; (7) improved efficiency and safety of treatment; (8) reduced fluctuation of 23 drug level; and (9) better patient compliance with overall disease management.
24 Additionally, many experts believe controlled release drug delivery has many important non-therapeutic ramifications as well, including a financial saving to the 26 patient in terms of fewer lost work days, reduced hospitalization and fewer visits to 27 the physician.
28 It i5 known that certain design parameters are critical to proper drug delivery.
29 Typically, they are: ( I ) delivering the drug to the target tissue; (2) supplying the drug for a predetermined period of time; and (3) fabricating a delivery system that provides 31 drug in the desired spatial and temporal pattern. Controlled release drug delivery 1 systems are intended to utilize these parameters to achieve the aforementioned 2 advantages as compared to conventional pharmaceutical dosing.
3 Previously direct placement of medication onto a substrate generally was 4 limited to medical placement of large doses or required technology where the active pharmaceutical was mixed with the substrate or matrix to provide differential 6 delivery, or coated with a material with desired release characteristics.
7 As used herein "controlled-release" is used to describe a system, i.e.
method 8 and materials for making an active ingredient available to the patient in accordance 9 with a preselected condition, i.e. time, site, etc.. Controlled-release includes the use of instantaneous release, delayed release and sustained release.
"Instantaneous 11 release"' refers to immediate release to the patient. "Delayed release"
means the 12 active ingredient is not made available until some time delay after administration.
13 Typically, dosages are administered by oral ingestion, although other forms of 14 administration are contemplated in accordance with the present invention.
"Sustained release" refers to release of active ingredient whereby the level of active ingredient 16 available to the patient is maintained at some level over a period of time.
The method 17 of effecting each type of release can be varied. For example, the active-ingredient can 18 be placed on a semi-permeable membrane having predetermined diffusion, 19 dissolution, erosion or breakdown characteristics.
Alternatively, the active ingredient can be masked by a coating, a laminate, 21 etc. Regardless of the method of providing the desired release pattern, the present 22 invention contemplates delivery of a controlled-release system which utilizes one or 23 more of the "release" methods and materials. Moreover, the present invention 24 advantageously can be employed in the development of multiple different release system(s).
26 The patent and scientific literature is replete with various sustained release 27 (SR) methods and materials. For connnon methods of obtaining SR systems, see 28 "Sustained and Controlled Release Drug Delivery Systems,'' Robinson, Joseph R., 29 Ed., PP 138-171, 1978, Marcel Dekker, Inc. New York, NY. For example it is known to fill polymeric capsules with a solid, liquid, suspension or gel containing a 31 therapeutic agent which is slowly released by difftision through the capsule walls.
32 Heterogeneous matrices, for example, compressed tablets, control the release of their 1 therapeutic agents either by diffusion, erosion of the matrix or a combination of both.
2 Other SR systems focus on the fabrication of laminates of polymeric material and 3 therapeutic agent which are then formed into a sandwich, relying on different 4 diffusion or erosion rates to control release of the therapeutic agent.
Liquid-liquid encapsulation in a viscous syrup-like solution of polymer also has been lmown to be 6 useful in controlling release of the therapeutic agent. Additionally, it is generally 7 known that heterogeneous dispersions or solutions of therapeutic agents in water-8 swellable hydrogen matrices are useful in controlling the release of the agent by slow 9 surface-to-center swelling of the matrix and subsequent diffusion of the agent from the water-swollen part of the matrix.
11 During dissolution of a controlled-release matrix tablet, the dosage form 12 generally remains as a non-disintegrating, slowly eroding entity from which the 13 therapeutic agent leaches out, through a diffusion controlled process.
Conventional 14 SR formulations are generally designed to release their active ingredients over an extended period of time, usually 8-24 hours. Conventional SR formulations use 16 waxes or hydrophilic gums as the primary drug carriers to prolong the release of the 17 active ingredients.
18 Starch USP (potato or corn) is commonly used as a component in conventional 19 tablet or hard shell capsule formulations.
The existing sustained release technologies generally involve relatively 21 complicated formulations and manufacturing processes which often are difficult and 22 expensive to precisely control. For example, one well known SR delivery system, 23 OROS, marketed by the Alza Corporation, involves laser drilling through a tablet to 24 create passages for the release of the drug from the tablet core. In controlled release technologies, it is desirable to be able to incorporate the active ingredient in its 26 controlled-release pattern in a single dosage unit without deteriorating the active 27 ingredient. Moreover, the dosage unit should be able to deliver the system without 28 interfering with its release pattern.
29 Various methods have been devised to enable controlled-release systems to be delivered to a patient without destruction of the delivery system during 31 manufacturing, handling and distribution. For example, controlled-release systems 32 have been provided in the form of beads or particles which are packaged in a gelatin 1 capsule for oral dosage. This method of delivery of the controlled-release system 2 prevents damage to the coating on the beads.
3 Furthermore, when controlled-release active ingredients are incorporated in 4 compression tablets, it may be difficult for many people to swallow such tablets.
Moreover, dissolution of high compression tablets often initially is slow and erratic 6 and may result in localized hot spots of alimentary tract irritation where disintegration 7 and release of the active ingredient finally occurs. And, present systems do not allow 8 for the accurate deposition of doses of powdered medication onto different substrates 9 either in single packets, layered packet, or multipackets on the same plane of the base substrate. The present invention overcomes the disadvantages of the prior art by 11 offering a simple and inexpensive means of incorporating active ingredient (the drug) 12 with a multitude of controlled-release systems.
13 In our earlier U.S. Patent 5,699,649, granted December 23, 1997, we describe 14 a method and apparatus for packaging microgram quantities of fine powders such as pharmaceuticals using electrostatic phototechnology techniques. More particularly, as 16 described in our aforesaid U.S. Patent 5,699,649, the ability of powders to acquire an 17 electrical charge advantageously is utilized for precisely measuring exact microgram 18 quantities of the powder, whereupon these exact microgram quantities are then placed 19 in individual containers, and the containers sealed.
Electrostatic charge has been employed to attract a given quantity of powder 21 to a surface. An example of this is the laser printer or the electrostatic copy device 22 where a drum is charged and toner particles are attracted and held in position by the 23 charge. The charge on the drum is neutralized by the attracted toner powder, thus 24 limiting the amount of toner in accordance with the charge image on the drum. The charged powder on the printer drum is then transferred to a sheet of paper or other 26 carrier to give a final image. In our U.S. Patent 5,699,649, electrostatic charge 27 technology is employed for transfernng a predetermined amount of a finely powdered 28 pharmaceutical or drug to a carrier or an intermediate such as a drum, carrying a 29 charge of predetermined intensity and area, rotating the charged drum surface, carrying the predeternlined amount of powdered pharmaceutical or drug on its 31 surface, to a transfer station where the charge is overcome and the dry powder is 32 transferred to a package which is then sealed. In lieu of a drum, a belt, or other 1 movable surface is charged to a given potential in a localized area.
Alternatively, a 2 predetermined amount of powdered pharmaceutical or dmg may be deposited directly 3 in a package using electrostatic charge technology.
4 When a given amount of a powdered pharmaceutical or drug is to be packaged, the charge and area of charge can be determined experimentally for each 6 dose of pharmaceutical or drug and each particle size distribution. This can be done 7 by controlling either the charged area for a given charge density or the total 8 electrostatic charge on any individual charged area. These conditions can be adjusted 9 to provide essentially the exact desired amount of the particular pharniaceutical or drug to be transferred at the transfer station.
11 Ln our U.S. Application Serial No. 09/097, I 04, we describe another 12 electrostatic charge technology which may be adopted to be used for measuring and 13 packaging unit doses of a pharmaceutical or drug in a readily ingestible form, i.e. as a 14 tablet or capsule. The technology thus described also permits reproducible precise measurement and packaging of a pharmaceutical or drug, and which may be scaled 16 from laboratory to pilot plant to full scale production without the need for 17 recertification.
18 In accordance with one aspect of the present invention, controlled quantities of 19 powdered medication are formed in controlled release packages using electrostatic metering technology. The present invention also provides, in another aspect, 21 combination medication delivery systems in which the active ingredients are 22 segregated from one another 23 Further features and objects of the present invention will become clear from 24 the following detailed description taken in conjunction with the accompanying drawings, wherein like numerals depict like parts, and wherein:
26 Fig. l is a schematic flow diagram showing the various steps involved in 27 practicing the present invention;
28 Fig. 2 is an enlarged cross-sectional view of one embodiment of a controlled 29 release tablet made in accordance with the present invention;
Fig. 3 is a view, similar to Fig. l, and showing alternative steps involved ui 31 practicing the present invention;
9 The convenience of administering a single dose of a medication which releases multiple active ingredients in a controlled fashion and in a chosen location 11 over an extended period of time, as opposed to the administration of a number of 12 single doses at regular intervals, has long been recognized in the pharmaceutical arts.
13 The advantage to the patient and clinician in having consistent and uniform blood 14 levels of medication over an extended period of time are likewise recognized. The advantages of a variety of controlled-release dosage forms are well known.
Among 16 the most important advantages are: ( 1 ) increased contact time for the drug to allow for 17 local activity in the stomach, small intestine, colon, or other locus of activity; (2) 18 increased and more efficient absorption for drugs which have specific absorption 19 sites; (3) the ability to reduce the number of dosages per period of time;
(4) employment of less total drug; (5) minimization or elimination of local and/or 21 systemic side effects; (6) minimization of drug accumulation associated with chronic 22 dosing; (7) improved efficiency and safety of treatment; (8) reduced fluctuation of 23 drug level; and (9) better patient compliance with overall disease management.
24 Additionally, many experts believe controlled release drug delivery has many important non-therapeutic ramifications as well, including a financial saving to the 26 patient in terms of fewer lost work days, reduced hospitalization and fewer visits to 27 the physician.
28 It i5 known that certain design parameters are critical to proper drug delivery.
29 Typically, they are: ( I ) delivering the drug to the target tissue; (2) supplying the drug for a predetermined period of time; and (3) fabricating a delivery system that provides 31 drug in the desired spatial and temporal pattern. Controlled release drug delivery 1 systems are intended to utilize these parameters to achieve the aforementioned 2 advantages as compared to conventional pharmaceutical dosing.
3 Previously direct placement of medication onto a substrate generally was 4 limited to medical placement of large doses or required technology where the active pharmaceutical was mixed with the substrate or matrix to provide differential 6 delivery, or coated with a material with desired release characteristics.
7 As used herein "controlled-release" is used to describe a system, i.e.
method 8 and materials for making an active ingredient available to the patient in accordance 9 with a preselected condition, i.e. time, site, etc.. Controlled-release includes the use of instantaneous release, delayed release and sustained release.
"Instantaneous 11 release"' refers to immediate release to the patient. "Delayed release"
means the 12 active ingredient is not made available until some time delay after administration.
13 Typically, dosages are administered by oral ingestion, although other forms of 14 administration are contemplated in accordance with the present invention.
"Sustained release" refers to release of active ingredient whereby the level of active ingredient 16 available to the patient is maintained at some level over a period of time.
The method 17 of effecting each type of release can be varied. For example, the active-ingredient can 18 be placed on a semi-permeable membrane having predetermined diffusion, 19 dissolution, erosion or breakdown characteristics.
Alternatively, the active ingredient can be masked by a coating, a laminate, 21 etc. Regardless of the method of providing the desired release pattern, the present 22 invention contemplates delivery of a controlled-release system which utilizes one or 23 more of the "release" methods and materials. Moreover, the present invention 24 advantageously can be employed in the development of multiple different release system(s).
26 The patent and scientific literature is replete with various sustained release 27 (SR) methods and materials. For connnon methods of obtaining SR systems, see 28 "Sustained and Controlled Release Drug Delivery Systems,'' Robinson, Joseph R., 29 Ed., PP 138-171, 1978, Marcel Dekker, Inc. New York, NY. For example it is known to fill polymeric capsules with a solid, liquid, suspension or gel containing a 31 therapeutic agent which is slowly released by difftision through the capsule walls.
32 Heterogeneous matrices, for example, compressed tablets, control the release of their 1 therapeutic agents either by diffusion, erosion of the matrix or a combination of both.
2 Other SR systems focus on the fabrication of laminates of polymeric material and 3 therapeutic agent which are then formed into a sandwich, relying on different 4 diffusion or erosion rates to control release of the therapeutic agent.
Liquid-liquid encapsulation in a viscous syrup-like solution of polymer also has been lmown to be 6 useful in controlling release of the therapeutic agent. Additionally, it is generally 7 known that heterogeneous dispersions or solutions of therapeutic agents in water-8 swellable hydrogen matrices are useful in controlling the release of the agent by slow 9 surface-to-center swelling of the matrix and subsequent diffusion of the agent from the water-swollen part of the matrix.
11 During dissolution of a controlled-release matrix tablet, the dosage form 12 generally remains as a non-disintegrating, slowly eroding entity from which the 13 therapeutic agent leaches out, through a diffusion controlled process.
Conventional 14 SR formulations are generally designed to release their active ingredients over an extended period of time, usually 8-24 hours. Conventional SR formulations use 16 waxes or hydrophilic gums as the primary drug carriers to prolong the release of the 17 active ingredients.
18 Starch USP (potato or corn) is commonly used as a component in conventional 19 tablet or hard shell capsule formulations.
The existing sustained release technologies generally involve relatively 21 complicated formulations and manufacturing processes which often are difficult and 22 expensive to precisely control. For example, one well known SR delivery system, 23 OROS, marketed by the Alza Corporation, involves laser drilling through a tablet to 24 create passages for the release of the drug from the tablet core. In controlled release technologies, it is desirable to be able to incorporate the active ingredient in its 26 controlled-release pattern in a single dosage unit without deteriorating the active 27 ingredient. Moreover, the dosage unit should be able to deliver the system without 28 interfering with its release pattern.
29 Various methods have been devised to enable controlled-release systems to be delivered to a patient without destruction of the delivery system during 31 manufacturing, handling and distribution. For example, controlled-release systems 32 have been provided in the form of beads or particles which are packaged in a gelatin 1 capsule for oral dosage. This method of delivery of the controlled-release system 2 prevents damage to the coating on the beads.
3 Furthermore, when controlled-release active ingredients are incorporated in 4 compression tablets, it may be difficult for many people to swallow such tablets.
Moreover, dissolution of high compression tablets often initially is slow and erratic 6 and may result in localized hot spots of alimentary tract irritation where disintegration 7 and release of the active ingredient finally occurs. And, present systems do not allow 8 for the accurate deposition of doses of powdered medication onto different substrates 9 either in single packets, layered packet, or multipackets on the same plane of the base substrate. The present invention overcomes the disadvantages of the prior art by 11 offering a simple and inexpensive means of incorporating active ingredient (the drug) 12 with a multitude of controlled-release systems.
13 In our earlier U.S. Patent 5,699,649, granted December 23, 1997, we describe 14 a method and apparatus for packaging microgram quantities of fine powders such as pharmaceuticals using electrostatic phototechnology techniques. More particularly, as 16 described in our aforesaid U.S. Patent 5,699,649, the ability of powders to acquire an 17 electrical charge advantageously is utilized for precisely measuring exact microgram 18 quantities of the powder, whereupon these exact microgram quantities are then placed 19 in individual containers, and the containers sealed.
Electrostatic charge has been employed to attract a given quantity of powder 21 to a surface. An example of this is the laser printer or the electrostatic copy device 22 where a drum is charged and toner particles are attracted and held in position by the 23 charge. The charge on the drum is neutralized by the attracted toner powder, thus 24 limiting the amount of toner in accordance with the charge image on the drum. The charged powder on the printer drum is then transferred to a sheet of paper or other 26 carrier to give a final image. In our U.S. Patent 5,699,649, electrostatic charge 27 technology is employed for transfernng a predetermined amount of a finely powdered 28 pharmaceutical or drug to a carrier or an intermediate such as a drum, carrying a 29 charge of predetermined intensity and area, rotating the charged drum surface, carrying the predeternlined amount of powdered pharmaceutical or drug on its 31 surface, to a transfer station where the charge is overcome and the dry powder is 32 transferred to a package which is then sealed. In lieu of a drum, a belt, or other 1 movable surface is charged to a given potential in a localized area.
Alternatively, a 2 predetermined amount of powdered pharmaceutical or dmg may be deposited directly 3 in a package using electrostatic charge technology.
4 When a given amount of a powdered pharmaceutical or drug is to be packaged, the charge and area of charge can be determined experimentally for each 6 dose of pharmaceutical or drug and each particle size distribution. This can be done 7 by controlling either the charged area for a given charge density or the total 8 electrostatic charge on any individual charged area. These conditions can be adjusted 9 to provide essentially the exact desired amount of the particular pharniaceutical or drug to be transferred at the transfer station.
11 Ln our U.S. Application Serial No. 09/097, I 04, we describe another 12 electrostatic charge technology which may be adopted to be used for measuring and 13 packaging unit doses of a pharmaceutical or drug in a readily ingestible form, i.e. as a 14 tablet or capsule. The technology thus described also permits reproducible precise measurement and packaging of a pharmaceutical or drug, and which may be scaled 16 from laboratory to pilot plant to full scale production without the need for 17 recertification.
18 In accordance with one aspect of the present invention, controlled quantities of 19 powdered medication are formed in controlled release packages using electrostatic metering technology. The present invention also provides, in another aspect, 21 combination medication delivery systems in which the active ingredients are 22 segregated from one another 23 Further features and objects of the present invention will become clear from 24 the following detailed description taken in conjunction with the accompanying drawings, wherein like numerals depict like parts, and wherein:
26 Fig. l is a schematic flow diagram showing the various steps involved in 27 practicing the present invention;
28 Fig. 2 is an enlarged cross-sectional view of one embodiment of a controlled 29 release tablet made in accordance with the present invention;
Fig. 3 is a view, similar to Fig. l, and showing alternative steps involved ui 31 practicing the present invention;
1 Fig. 4 is a view, similar to Fig. 2, and showing an alternative form of a 2 controlled release tablet made in accordance with the present invention;
3 Fig. 5 is a view similar to Fig. 2, and showing yet another alternative 4 embodiment of the present invention;
$ Fig. 6 is a view, similar to Fig. 2, and showing yet another embodiment of the 6 invention; and '7 Figs. 7 - 9 are views similar to Fig. 2, and showing yet other embodiments of 8 the present invention.
9 Referring now to Fig. 1, there is a schematic flow diagram of the various pieces of equipment needed to perform in the total process from powder supply to 11 packaged pharmaceutical or drug. i.e. in controlled release tablet form, containing a 12 specified amount of pharmaceutical or drug powder in the tablet or package.
At 16 is 13 indicated the pharmaceutical or drug powder supply which is fed into a device 18 for 14 creating an aerosol of the powder. Next the powder particles are ionized at 20. As will be indicated later, a number of these steps and pieces of equipment can be 16 combined. At 24 is indicated a earner surface capable of maintaining a space charge 17 on its surface. This can be a plastic belt, for example, or a selenium drum of the type 18 used in Xerox T~~ photocopiers. This earner surface 24 is passed through a charging 19 station 2~ where a predetermined electrostatic charge 25A (an electrostatic "image") is created on a predetermined area of the transfer surface. This charged surface 25A
21 then passes through a step 26 wherein powder is deposited on the earner surface in a 22 sufficient amount 26.A to neutralize the charge carried by the carrier surface.
23 Thereafter, the carrier surface, carrying the predetermined amount 26A of powder on 24 its surface, is passed to a powder discharging device 30 which discharges the powder 26A from the surface 24 onto a membrane 29. Alternatively, the powder may be 26 placed directly onto the membrane 29. The membrane 29 containing its charge of 27 powder 26A, then passes through a sealing step 32 wherein a second membrane 28 which may be porous, permeable or semi-permeable covers and seals the discharged 29 powder 26A on the membrane 29. There is thus produced an aliquot of powdered medicine 26A sandwiched between semi-pernieable or permeable membranes 29 and 31 34.
fi 1 This sandwiched material is then passed to a cutting station 38 wherein the 2 sandwich is cut into individual tablets or loafers 36.
3 As mentioned previously in discussing Fig. 1, the carrier surface with the 4 electrostatic charge carries a known amount of charge on its surface and the polarity of this charge is apposite to that of the powder particles suspended in the chamber.
6 The charged particles migrate to the charged surface because of the attraction by the 7 opposite nature of the charges. This migration of the particles continues until the 8 charge on the carrier surface is neutralized.
3 Fig. 5 is a view similar to Fig. 2, and showing yet another alternative 4 embodiment of the present invention;
$ Fig. 6 is a view, similar to Fig. 2, and showing yet another embodiment of the 6 invention; and '7 Figs. 7 - 9 are views similar to Fig. 2, and showing yet other embodiments of 8 the present invention.
9 Referring now to Fig. 1, there is a schematic flow diagram of the various pieces of equipment needed to perform in the total process from powder supply to 11 packaged pharmaceutical or drug. i.e. in controlled release tablet form, containing a 12 specified amount of pharmaceutical or drug powder in the tablet or package.
At 16 is 13 indicated the pharmaceutical or drug powder supply which is fed into a device 18 for 14 creating an aerosol of the powder. Next the powder particles are ionized at 20. As will be indicated later, a number of these steps and pieces of equipment can be 16 combined. At 24 is indicated a earner surface capable of maintaining a space charge 17 on its surface. This can be a plastic belt, for example, or a selenium drum of the type 18 used in Xerox T~~ photocopiers. This earner surface 24 is passed through a charging 19 station 2~ where a predetermined electrostatic charge 25A (an electrostatic "image") is created on a predetermined area of the transfer surface. This charged surface 25A
21 then passes through a step 26 wherein powder is deposited on the earner surface in a 22 sufficient amount 26.A to neutralize the charge carried by the carrier surface.
23 Thereafter, the carrier surface, carrying the predetermined amount 26A of powder on 24 its surface, is passed to a powder discharging device 30 which discharges the powder 26A from the surface 24 onto a membrane 29. Alternatively, the powder may be 26 placed directly onto the membrane 29. The membrane 29 containing its charge of 27 powder 26A, then passes through a sealing step 32 wherein a second membrane 28 which may be porous, permeable or semi-permeable covers and seals the discharged 29 powder 26A on the membrane 29. There is thus produced an aliquot of powdered medicine 26A sandwiched between semi-pernieable or permeable membranes 29 and 31 34.
fi 1 This sandwiched material is then passed to a cutting station 38 wherein the 2 sandwich is cut into individual tablets or loafers 36.
3 As mentioned previously in discussing Fig. 1, the carrier surface with the 4 electrostatic charge carries a known amount of charge on its surface and the polarity of this charge is apposite to that of the powder particles suspended in the chamber.
6 The charged particles migrate to the charged surface because of the attraction by the 7 opposite nature of the charges. This migration of the particles continues until the 8 charge on the carrier surface is neutralized.
9 The actual amount of powder mass transferred to the earner surface is a function of the mass-to-charge ratio of the charged particles. Although it is difficult 11 to achieve a linear relationship between the mass and the actual charge, it is possible 12 to establish a fixed relationship bet<veen the surface area of the powder particles and 13 the charge the powder particle is carrying at charge saturation. However, the surface 14 area of a mixed group of powder particles of different sizes and shapes can be extremely difficult to calculate mathematically, particularly when the shapes are 16 irregular, (e.g. non-spherical, microcrystalline, etc.) As mentioned earlier, the 17 simplest method of determining the amount and area of charge to attract a given 18 weight of particles is to estimate the correct area and charge and then apply the 19 estimated charge to the estimated area on the carrier surface 24 and expose this selectively charged area to a mass of powder which has been ionized in the ionizing 21 step. The amount of powder deposited can then be readily measured at the discharge 22 step. Thereafter, either the size of the charged area or the amount of charge applied to 23 the area at the charging station 2~ can be adjusted upwardly or downwardly to provide 24 the correct amount of charge, both in area and charge intensity, for picking up a desired weight of oppositely charged powder. Likewise, using the technology of our 26 co-pending application Serial No. 09/097,104, larger quantities of medication may be 27 deposited.
28 A feature and advantage of the present invention is to produce carefully 29 controlled doses of controlled release medication. Electrostatic metering and packagiilg as above described permits exact dosiilg. And, by employing selected 31 porous, permeable or semi-permeable membranes for encapsulating the powdered 1 medicine aliquots, drug release rate and also site of drug release can be determined by 2 adjusting membrane material and/or membrane thickness.
3 The membranes should be formed of ingestible materials having a selected 4 permeability porosity to fluids at a selected site or sites within the alimentary canal, so as to permit controlled release of the medication. By way of example, one or both 6 membranes 29, 34 may comprise acid-dissolvable materials when it is desired to 7 release the medication into the stomach or the membranes 29, 34 may be alkaline 8 dissolvable materials at differing pH"s to release into chosen locations within the 9 intestine. Porosity, membrane thickness, etc., may be selected to provide desired rate of dissolution at the site of interest.
11 The invention is susceptible to modification. For example, referring to Figs. 3 12 and 4 by adding a second powdered medicine supply and discharge station (shown 13 generally at 40), a two-component controlled release tablet 48 may be formed (see 14 Fig. 4) incorporating two different powdered medicines 50, 52, encapsulated between 1 S membranes 29 and 34 for simultaneous controlled release.
16 Alternatively, as shown in Fig. 5, two different drugs 60, 62 may be layered on 17 one another, separated by a membrane 64 so the two medications may be delivered 18 sequentially either in the same location, or in different locations within the alimentary 19 canal. Another feature and advantage of the mufti-drug tablet of Fig. 4 and Fig. 5, as will be discussed in detail herein below, is that two normally incompatible drugs may 21 be to be safely packaged in a single tablet.
22 The invention is susceptible to modification. For example, individual doses 23 may be formed by electrostatic deposition in accordance with U.S. Patent No.
24 5,714,007.
Other possibilities are possible. For example, referring to Fig. 6, the tablet 26 may incorporate an adhesive layer 72 such as a mucosal adhesive, which in turn is 27 covered by an acid or alkaline dissolvable protective membrane 74, which dissolves at 28 a selected site allowing the adhesive to adhere, for example, to the intestinal wall, 29 thereby increasing residence time of the medication in a chosen location.
Alternatively, an acid or alkaline activatable adhesive may be applied to the outer 31 surface of the tablet. In yet another possibility, the membrane may be a material 32 which expands on contact with the acid or alkaline in the alimentary canal and 1 becomes more porous whereby to slowly release medication in a chosen location 2 within the alimentary canal.
3 As mentioned above, a particular feature and advantage of the present 4 invention is that it permits packaging, within a single tablet of two or more different drugs normally considered to be incompatible. Certain drugs are known to cause 6 undesirable side effects which need to be countered by a second drug. For example, 7 Omeprazole~ which fords substantial utility as an oral antiulcer agent, also is known to 8 block the release of B 12 from its protein binding site in food. This can lead to 9 pernicious anemia. The present invention permits packaging of time-release Omeprazole with Vitamin B12 in an appropriate dosage of, e.g. 25~gm - I mg.
After 11 taking the medication, one membrane will dissolve allowing absorption of the B12, 12 while the remaining membrane package carrying the Omeprazole will pass into the 13 small intestine where the drug is released and absorbed.
14 The invention is susceptible to modification. For example, while the membranes have been described as being preformed, permeable, semipermeable or 16 porous material, one or both membranes could be formed in place from a gel or 17 liquid.
18 The ability to accurately place the dose of medication onto a plurality of substrates 19 and seal the dose with other membranes in accordance with the present invention, allows for the fabrication of many different dosage forms; by altering the substrates 21 and encapsulating material a single unit dose form can be fabricated with a plurality 22 of different drugs in different coverings, membranes and barriers. This will provide a 23 single dosage form with multiple active ingredients each being delivered to the 24 appropriate site for absorption. Alternatively, two or more active medicaments may be combined in a single delivery container, i.e. pill, capsule or caplet without actually 26 mixing the two or more ingredients. For example, referring to Fig. 7, the active 27 ingredients are segregated from one another in a compartmentalized capsule 100.
28 Alternatively, two or more tablets 102, 104 each containing only one active 29 ingredient, could be placed in a larger absorbable capsule or encased in a larger tablet 106. Or, as shown in Fig. 9, two or more active ingredients could each be formulated 31 as encapsulated particles 108A, 108B, and the encapsulated mixed particles placed in 32 a capsule 110 where the only contact is bettveen the particle inert coatings, etc.
1 There are many drugs which could benefit from combinations to improve 2 patient benefit. However, with many active ingredients, there is a question of 3 chemical interaction. Thus, several drugs are normally prescribed as separate tablets 4 or capsules which presents a problem iil terms of patient compliance, e.g.
TB triple therapy, AIDS mufti-drug therapy, anti-infectives, etc. Also, delivery of two or more 6 active medicaments could reduce side effects, and~'or improve therapeutic response 7 which may in turn permit a decrease in the required dosage. By way of example, we 8 provide the following combinations:
9 ( 1 ) Omeprazole ~ and analogs and isomers - As noted above Omeprazole is an inhibitor of gastric secretion and also inhibits the absorption of certain 11 drugs/compounds that require stomach acid such as Vitamin B I 2, the def cit of which 12 results in pernicious anemia. A combination of B 12 with Omeprazole would 13 eliminate the potential problem.
14 (2) Valacyclovir~ and analogs and is used to treat Herpes Zostcr. It is well known that two d'°~' Cimetidine' and Probenecid'~ both increase the AUC
(area under 16 curve) and Cmax. A combination drug can be constructed with a combination of 17 either one or more of these components to provide more efficacy.
18 (3) Enalaprils and analogs and isomers is an ACE inhibitor used for the 19 treatment of hypertension. This drug has been used with the following and analogs and isomers beta adrenegic-blocking agents, methyldopa, nitrate, calcium blocking 21 agents, hydrazine, Prazosin~' and Digoxin' without clinically significant side effects.
22 One or more of these agents may be combined with Enalapril to improve the 23 compliance of patient with hypertension and hypertension and other cardiac diseases.
24 (4) Ketoconazolek and analogs and isomers is used to treat fungal infections. One of the side effects is the reduction of Testosterone. This side effect 26 could be helped by the combination of Testosterone or one of its isomers or analogs to 27 overcome the side effect.
28 (5) Omeprazole~ and analogs and isomers is also used in combination with 29 Clarithoromycin' for ulcer treatment. These two drugs may be combined as a single dose for patient compliance.
31 (6) Tamoxifen~° and analogs and isomers used in treatment of breast 32 cancer has a +/- 30% incident of water retention with weight gain > 5%.
This can be 1 a disturbing consequence for patients with an even more disturbing disease.
The 2 addition of a diuretic or combination diuretic to form a single dosage form for 3 reduction in side effect and compliance.
4 (7) Isotretinoiin ~ and analogs and isomers used for the treatment of postular acne has a severe danger if taken by a woman who is pregnant. The 6 incorporation of oral contraceptive medication would eliminate the potential for 7 pregnancy while medicated.
8 (8) Metfonnin NCI' and analogs and isomers are hypoglycemic agents 9 which have been used in combination with Solfonylurea' 3 and analogs and isomers to treat Type 2 Diabetes. These t~~o agents act in different ways on reducing glucose 11 levels. A combination would be helpful for those patients requiring more aggressive 12 oral therapy for their diabetes.
13 It should be noted that certain combination drugs, including some of the 14 above-listed combination drugs, also may be blended and packaged in a single tablet or capsule, when chemical interaction is not a problem.
16 The present invention also allows for the rapid production of different dosage 17 medications using the same active ingredient, and allows for the development of 18 medications with longer resident time.
1.2
28 A feature and advantage of the present invention is to produce carefully 29 controlled doses of controlled release medication. Electrostatic metering and packagiilg as above described permits exact dosiilg. And, by employing selected 31 porous, permeable or semi-permeable membranes for encapsulating the powdered 1 medicine aliquots, drug release rate and also site of drug release can be determined by 2 adjusting membrane material and/or membrane thickness.
3 The membranes should be formed of ingestible materials having a selected 4 permeability porosity to fluids at a selected site or sites within the alimentary canal, so as to permit controlled release of the medication. By way of example, one or both 6 membranes 29, 34 may comprise acid-dissolvable materials when it is desired to 7 release the medication into the stomach or the membranes 29, 34 may be alkaline 8 dissolvable materials at differing pH"s to release into chosen locations within the 9 intestine. Porosity, membrane thickness, etc., may be selected to provide desired rate of dissolution at the site of interest.
11 The invention is susceptible to modification. For example, referring to Figs. 3 12 and 4 by adding a second powdered medicine supply and discharge station (shown 13 generally at 40), a two-component controlled release tablet 48 may be formed (see 14 Fig. 4) incorporating two different powdered medicines 50, 52, encapsulated between 1 S membranes 29 and 34 for simultaneous controlled release.
16 Alternatively, as shown in Fig. 5, two different drugs 60, 62 may be layered on 17 one another, separated by a membrane 64 so the two medications may be delivered 18 sequentially either in the same location, or in different locations within the alimentary 19 canal. Another feature and advantage of the mufti-drug tablet of Fig. 4 and Fig. 5, as will be discussed in detail herein below, is that two normally incompatible drugs may 21 be to be safely packaged in a single tablet.
22 The invention is susceptible to modification. For example, individual doses 23 may be formed by electrostatic deposition in accordance with U.S. Patent No.
24 5,714,007.
Other possibilities are possible. For example, referring to Fig. 6, the tablet 26 may incorporate an adhesive layer 72 such as a mucosal adhesive, which in turn is 27 covered by an acid or alkaline dissolvable protective membrane 74, which dissolves at 28 a selected site allowing the adhesive to adhere, for example, to the intestinal wall, 29 thereby increasing residence time of the medication in a chosen location.
Alternatively, an acid or alkaline activatable adhesive may be applied to the outer 31 surface of the tablet. In yet another possibility, the membrane may be a material 32 which expands on contact with the acid or alkaline in the alimentary canal and 1 becomes more porous whereby to slowly release medication in a chosen location 2 within the alimentary canal.
3 As mentioned above, a particular feature and advantage of the present 4 invention is that it permits packaging, within a single tablet of two or more different drugs normally considered to be incompatible. Certain drugs are known to cause 6 undesirable side effects which need to be countered by a second drug. For example, 7 Omeprazole~ which fords substantial utility as an oral antiulcer agent, also is known to 8 block the release of B 12 from its protein binding site in food. This can lead to 9 pernicious anemia. The present invention permits packaging of time-release Omeprazole with Vitamin B12 in an appropriate dosage of, e.g. 25~gm - I mg.
After 11 taking the medication, one membrane will dissolve allowing absorption of the B12, 12 while the remaining membrane package carrying the Omeprazole will pass into the 13 small intestine where the drug is released and absorbed.
14 The invention is susceptible to modification. For example, while the membranes have been described as being preformed, permeable, semipermeable or 16 porous material, one or both membranes could be formed in place from a gel or 17 liquid.
18 The ability to accurately place the dose of medication onto a plurality of substrates 19 and seal the dose with other membranes in accordance with the present invention, allows for the fabrication of many different dosage forms; by altering the substrates 21 and encapsulating material a single unit dose form can be fabricated with a plurality 22 of different drugs in different coverings, membranes and barriers. This will provide a 23 single dosage form with multiple active ingredients each being delivered to the 24 appropriate site for absorption. Alternatively, two or more active medicaments may be combined in a single delivery container, i.e. pill, capsule or caplet without actually 26 mixing the two or more ingredients. For example, referring to Fig. 7, the active 27 ingredients are segregated from one another in a compartmentalized capsule 100.
28 Alternatively, two or more tablets 102, 104 each containing only one active 29 ingredient, could be placed in a larger absorbable capsule or encased in a larger tablet 106. Or, as shown in Fig. 9, two or more active ingredients could each be formulated 31 as encapsulated particles 108A, 108B, and the encapsulated mixed particles placed in 32 a capsule 110 where the only contact is bettveen the particle inert coatings, etc.
1 There are many drugs which could benefit from combinations to improve 2 patient benefit. However, with many active ingredients, there is a question of 3 chemical interaction. Thus, several drugs are normally prescribed as separate tablets 4 or capsules which presents a problem iil terms of patient compliance, e.g.
TB triple therapy, AIDS mufti-drug therapy, anti-infectives, etc. Also, delivery of two or more 6 active medicaments could reduce side effects, and~'or improve therapeutic response 7 which may in turn permit a decrease in the required dosage. By way of example, we 8 provide the following combinations:
9 ( 1 ) Omeprazole ~ and analogs and isomers - As noted above Omeprazole is an inhibitor of gastric secretion and also inhibits the absorption of certain 11 drugs/compounds that require stomach acid such as Vitamin B I 2, the def cit of which 12 results in pernicious anemia. A combination of B 12 with Omeprazole would 13 eliminate the potential problem.
14 (2) Valacyclovir~ and analogs and is used to treat Herpes Zostcr. It is well known that two d'°~' Cimetidine' and Probenecid'~ both increase the AUC
(area under 16 curve) and Cmax. A combination drug can be constructed with a combination of 17 either one or more of these components to provide more efficacy.
18 (3) Enalaprils and analogs and isomers is an ACE inhibitor used for the 19 treatment of hypertension. This drug has been used with the following and analogs and isomers beta adrenegic-blocking agents, methyldopa, nitrate, calcium blocking 21 agents, hydrazine, Prazosin~' and Digoxin' without clinically significant side effects.
22 One or more of these agents may be combined with Enalapril to improve the 23 compliance of patient with hypertension and hypertension and other cardiac diseases.
24 (4) Ketoconazolek and analogs and isomers is used to treat fungal infections. One of the side effects is the reduction of Testosterone. This side effect 26 could be helped by the combination of Testosterone or one of its isomers or analogs to 27 overcome the side effect.
28 (5) Omeprazole~ and analogs and isomers is also used in combination with 29 Clarithoromycin' for ulcer treatment. These two drugs may be combined as a single dose for patient compliance.
31 (6) Tamoxifen~° and analogs and isomers used in treatment of breast 32 cancer has a +/- 30% incident of water retention with weight gain > 5%.
This can be 1 a disturbing consequence for patients with an even more disturbing disease.
The 2 addition of a diuretic or combination diuretic to form a single dosage form for 3 reduction in side effect and compliance.
4 (7) Isotretinoiin ~ and analogs and isomers used for the treatment of postular acne has a severe danger if taken by a woman who is pregnant. The 6 incorporation of oral contraceptive medication would eliminate the potential for 7 pregnancy while medicated.
8 (8) Metfonnin NCI' and analogs and isomers are hypoglycemic agents 9 which have been used in combination with Solfonylurea' 3 and analogs and isomers to treat Type 2 Diabetes. These t~~o agents act in different ways on reducing glucose 11 levels. A combination would be helpful for those patients requiring more aggressive 12 oral therapy for their diabetes.
13 It should be noted that certain combination drugs, including some of the 14 above-listed combination drugs, also may be blended and packaged in a single tablet or capsule, when chemical interaction is not a problem.
16 The present invention also allows for the rapid production of different dosage 17 medications using the same active ingredient, and allows for the development of 18 medications with longer resident time.
1.2
Claims (20)
1. A controlled release pharmaceutical delivery package comprising a unit aliquot dose of a pharmaceutical electricstatically deposited on a porous, permeable or semi-permeable ingestible membrane.
2. A pharmaceutical delivery package according to claim 1, wherein said membrane comprises an acid-dissolvable material.
3. A pharmaceutical delivery package according to claim 1, wherein said membrane comprises an alkali-dissolvable material.
4. A pharmaceutical delivery package according to claim 1, and comprising two or more pharmaceuticals deposited on said membrane, and separated by one another by one or more barriers or membranes.
5. A pharmaceutical delivery package according to claim 1, according to claim 1, and further comprising an adhesive on the outer surface of the membrane.
6. A pharmaceutical delivery package according to claim 5, wherein the adhesive is acid or alkylene activatable.
7. A pharmaceutical delivery package according to claim 5, and further comprising an alkali or acid dissolvable membrane covering the adhesive.
8. A pharmaceutical delivery package according to claim 1, wherein said membrane comprises a material which expands upon contact with acid or alkaline in the alimentary canal, whereby to become more porous.
9. A pharmaceutical delivery package comprising two or more active pharmaceuticals (a) combined in a single delivery package, and (b) segregated from one another.
10. A pharmaceutical delivery package according to claim 9, wherein said active ingredients are segregated from one another in a compartmentalized capsule.
11. A pharmaceutical delivery package according to claim 9, wherein said pharmaceuticals are segregated from one another in a tablet.
12. A pharmaceutical delivery package according to claim 9, wherein said pharmaceuticals are encapsulated within inert coatings.
13. A pharmaceutical delivery package comprising a mixture of Ketoconazole and testosterone.
14. A pharmaceutical delivery package comprising a mixture of Valacylovir and one or both of Cimetidine and Probenecid.
15. A pharmaceutical delivery package comprising a mixture of Enalapril and a beta adrenegic-blocking agent, methyldopa, nitrate, a calcium blocking agent, hydrazine, Prazosin or Digoxin.
16. A pharmaceutical delivery package comprising a mixture of Omeprazole and B12.
17. A pharmaceutical delivery package comprising a mixture of Omeprazole and Clarithoromycin.
18. A pharmaceutical delivery package comprising a mixture of Tamoxifen and a diuretic.
19. A pharmaceutical delivery package comprising a mixture of Isotretinoin and an oral contraceptive.
20. A pharmaceutical delivery package comprising a mixture of Metformin HCl and Solfonylurea.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US09/376,619 US6428809B1 (en) | 1999-08-18 | 1999-08-18 | Metering and packaging of controlled release medication |
US09/376,619 | 1999-08-18 | ||
PCT/US2000/022468 WO2001012103A1 (en) | 1999-08-18 | 2000-08-16 | Metering and packaging of controlled release medication |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2380596A1 true CA2380596A1 (en) | 2001-02-22 |
Family
ID=23485760
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002380596A Abandoned CA2380596A1 (en) | 1999-08-18 | 2000-08-16 | Metering and packaging of controlled release medication |
Country Status (11)
Country | Link |
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US (3) | US6428809B1 (en) |
EP (2) | EP1207809B1 (en) |
JP (1) | JP2003517351A (en) |
AT (1) | ATE429190T1 (en) |
AU (1) | AU6909800A (en) |
CA (1) | CA2380596A1 (en) |
DE (1) | DE60042076D1 (en) |
DK (1) | DK1207809T3 (en) |
ES (1) | ES2323846T3 (en) |
PT (1) | PT1207809E (en) |
WO (1) | WO2001012103A1 (en) |
Families Citing this family (103)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6642236B1 (en) * | 1998-12-14 | 2003-11-04 | Cortendo Ab | Methods for prophylactic treatment of cardiovascular disease with inhibitor of cortisol synthesis |
US6428809B1 (en) * | 1999-08-18 | 2002-08-06 | Microdose Technologies, Inc. | Metering and packaging of controlled release medication |
AU3289301A (en) | 2000-01-20 | 2001-07-31 | Delsys Pharmaceutical Corporation | Multi-step drug dosage forms |
GB0001449D0 (en) * | 2000-01-21 | 2000-03-08 | Cortendo Ab | Compositions |
FR2816840B1 (en) * | 2000-11-17 | 2004-04-09 | Flamel Tech Sa | MEDICINE BASED ON SUSTAINED RELEASE ANTI-HYPERCLYCEMIA MICROCAPSULES AND METHOD FOR PREPARING THE SAME |
FR2825023B1 (en) * | 2001-05-23 | 2005-04-15 | Flamel Tech Sa | ANTIDIABETIC ORAL PHARMACEUTICAL FORM "ONE TAKEN PER DAY" INCLUDING BIGUANIDE AND AT LEAST ONE OTHER ACTIVE INGREDIENT |
US20040156903A1 (en) * | 2002-05-22 | 2004-08-12 | Abrams Andrew L.. | Metering and packaging of controlled release medication |
US20070087048A1 (en) * | 2001-05-31 | 2007-04-19 | Abrams Andrew L | Oral dosage combination pharmaceutical packaging |
BRPI0209720A2 (en) * | 2001-05-31 | 2017-06-13 | Microdose Tech Inc | dosage and packaging of controlled release medication |
US6844048B2 (en) * | 2001-07-11 | 2005-01-18 | Sarnoff Corporation | Substrates for powder deposition containing conductive domains |
GB0118300D0 (en) * | 2001-07-26 | 2001-09-19 | Cortendo Ab | Formulations |
US8101209B2 (en) | 2001-10-09 | 2012-01-24 | Flamel Technologies | Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles |
US7670612B2 (en) * | 2002-04-10 | 2010-03-02 | Innercap Technologies, Inc. | Multi-phase, multi-compartment capsular delivery apparatus and methods for using same |
US20040185119A1 (en) * | 2003-02-26 | 2004-09-23 | Theuer Richard C. | Method and compositions for treating gastric hyperacidity while diminishing the likelihood of producing vitamin deficiency |
US20040265323A1 (en) * | 2003-05-16 | 2004-12-30 | Mccormick Beth A. | Compositions comprising pathogen elicited epithelial chemoattractant (eicosanoid hepoxilin A3), inhibitors thereof and methods of use thereof |
WO2005041848A2 (en) * | 2003-10-27 | 2005-05-12 | Oriel Therapeutics, Inc. | Dry powder drug containment system packages with tabs, inhalers and associated methods |
US7377277B2 (en) * | 2003-10-27 | 2008-05-27 | Oriel Therapeutics, Inc. | Blister packages with frames and associated methods of fabricating dry powder drug containment systems |
US8210171B2 (en) * | 2004-09-13 | 2012-07-03 | Oriel Therapeutics, Inc. | Tubular dry powder drug containment systems, associated inhalers and methods |
DK1836665T3 (en) | 2004-11-19 | 2013-04-15 | Glaxosmithkline Llc | PROCEDURE FOR SPECIAL CUSTOMIZED DELIVERY OF VARIABLE DOSAGE MEDICINE COMBINATION PRODUCTS FOR INDIVIDUALIZATION OF THERAPIES |
US7286149B2 (en) * | 2004-12-14 | 2007-10-23 | Palo Alto Research Center Incorporated | Direct xerography system |
US7325987B2 (en) * | 2004-12-14 | 2008-02-05 | Palo Alto Research Center Incorporated | Printing method using quill-jet |
US7325903B2 (en) * | 2004-12-14 | 2008-02-05 | Palo Alto Research Center Incorporated | Quill-jet printer |
US7342596B2 (en) * | 2004-12-14 | 2008-03-11 | Palo Alto Research Center Incorporated | Method for direct xerography |
US8912908B2 (en) | 2005-04-28 | 2014-12-16 | Proteus Digital Health, Inc. | Communication system with remote activation |
US8730031B2 (en) | 2005-04-28 | 2014-05-20 | Proteus Digital Health, Inc. | Communication system using an implantable device |
US8836513B2 (en) | 2006-04-28 | 2014-09-16 | Proteus Digital Health, Inc. | Communication system incorporated in an ingestible product |
EP2392258B1 (en) | 2005-04-28 | 2014-10-08 | Proteus Digital Health, Inc. | Pharma-informatics system |
US9198608B2 (en) | 2005-04-28 | 2015-12-01 | Proteus Digital Health, Inc. | Communication system incorporated in a container |
US8802183B2 (en) | 2005-04-28 | 2014-08-12 | Proteus Digital Health, Inc. | Communication system with enhanced partial power source and method of manufacturing same |
WO2007028035A2 (en) | 2005-09-01 | 2007-03-08 | Proteus Biomedical, Inc. | Implantable zero-wire communications system |
CA2625776A1 (en) * | 2005-10-14 | 2007-04-26 | Microdose Technologies, Inc. | Pharmaceutical packaging of an oral dosage combination |
EP1965774A2 (en) * | 2005-12-30 | 2008-09-10 | Cogentus Pharmaceuticals, Inc. | Oral pharmaceutical formulations containing non-steroidal anti-inflammatory drugs and acid inhibitors |
US8349120B2 (en) * | 2006-03-07 | 2013-01-08 | Ora Health Corporation | Multi-layer patch made on a sheet and enclosed in a blister |
US20070254858A1 (en) * | 2006-04-27 | 2007-11-01 | Cronk Peter J | Contraceptive and Acne Medication Combination and Treatment of Acne and Other Diseases with Reduced Side Effects |
US20070254025A1 (en) * | 2006-04-27 | 2007-11-01 | Cronk Peter J | Oral contraceptive and acne medication combination and treatment of acne with reduced side effects |
CN105468895A (en) | 2006-05-02 | 2016-04-06 | 普罗透斯数字保健公司 | Patient customized therapeutic regimens |
US20100297226A1 (en) * | 2006-06-01 | 2010-11-25 | Dexcel Pharma Technologies Ltd. | Multiple unit pharmaceutical formulation |
SG174026A1 (en) | 2006-08-03 | 2011-09-29 | Nitec Pharma Ag | Delayed-release glucocorticoid treatment of rheumatoid disease |
WO2008066617A2 (en) | 2006-10-17 | 2008-06-05 | Proteus Biomedical, Inc. | Low voltage oscillator for medical devices |
EP2083680B1 (en) | 2006-10-25 | 2016-08-10 | Proteus Digital Health, Inc. | Controlled activation ingestible identifier |
EP2069004A4 (en) | 2006-11-20 | 2014-07-09 | Proteus Digital Health Inc | Active signal processing personal health signal receivers |
MY165532A (en) | 2007-02-01 | 2018-04-02 | Proteus Digital Health Inc | Ingestible event marker systems |
CA2676280C (en) | 2007-02-14 | 2018-05-22 | Proteus Biomedical, Inc. | In-body power source having high surface area electrode |
US9270025B2 (en) | 2007-03-09 | 2016-02-23 | Proteus Digital Health, Inc. | In-body device having deployable antenna |
EP2124725A1 (en) | 2007-03-09 | 2009-12-02 | Proteus Biomedical, Inc. | In-body device having a multi-directional transmitter |
US8540632B2 (en) | 2007-05-24 | 2013-09-24 | Proteus Digital Health, Inc. | Low profile antenna for in body device |
US9763989B2 (en) | 2007-08-03 | 2017-09-19 | Shaklee Corporation | Nutritional supplement system |
CN101815509A (en) | 2007-08-03 | 2010-08-25 | 沙克利公司 | Nutritional dosage unit |
DK2192946T3 (en) | 2007-09-25 | 2022-11-21 | Otsuka Pharma Co Ltd | In-body device with virtual dipole signal amplification |
US20090087483A1 (en) * | 2007-09-27 | 2009-04-02 | Sison Raymundo A | Oral dosage combination pharmaceutical packaging |
US8439033B2 (en) | 2007-10-09 | 2013-05-14 | Microdose Therapeutx, Inc. | Inhalation device |
MY161533A (en) | 2008-03-05 | 2017-04-28 | Proteus Digital Health Inc | Multi-mode communication ingestible event markers and systems, and methods of using the same |
US20090325999A1 (en) * | 2008-06-27 | 2009-12-31 | Jie Du | Personalized pharmaceutical kits, packaging and compositions for the treatment of allergic conditions |
SG195535A1 (en) | 2008-07-08 | 2013-12-30 | Proteus Digital Health Inc | Ingestible event marker data framework |
KR101214453B1 (en) * | 2008-08-13 | 2012-12-24 | 프로테우스 디지털 헬스, 인코포레이티드 | Ingestible circuitry |
WO2010057049A2 (en) | 2008-11-13 | 2010-05-20 | Proteus Biomedical, Inc. | Ingestible therapy activator system and method |
CN102271578B (en) | 2008-12-11 | 2013-12-04 | 普罗秋斯数字健康公司 | Evaluation of gastrointestinal function using portable electroviscerography systems and methods of using the same |
US9439566B2 (en) | 2008-12-15 | 2016-09-13 | Proteus Digital Health, Inc. | Re-wearable wireless device |
TWI424832B (en) | 2008-12-15 | 2014-02-01 | Proteus Digital Health Inc | Body-associated receiver and method |
US9659423B2 (en) | 2008-12-15 | 2017-05-23 | Proteus Digital Health, Inc. | Personal authentication apparatus system and method |
TWI602561B (en) | 2009-01-06 | 2017-10-21 | 波提亞斯數位康健公司 | Pharmaceutical dosages delivery system |
AU2010203625A1 (en) | 2009-01-06 | 2011-07-21 | Proteus Digital Health, Inc. | Ingestion-related biofeedback and personalized medical therapy method and system |
CA2749646A1 (en) * | 2009-01-26 | 2010-07-29 | Nitec Pharma Ag | Delayed-release glucocorticoid treatment of asthma |
NZ582836A (en) * | 2009-01-30 | 2011-06-30 | Nitec Pharma Ag | Delayed-release glucocorticoid treatment of rheumatoid arthritis by improving signs and symptoms, showing major or complete clinical response and by preventing from joint damage |
WO2010111403A2 (en) | 2009-03-25 | 2010-09-30 | Proteus Biomedical, Inc. | Probablistic pharmacokinetic and pharmacodynamic modeling |
CN102458236B (en) * | 2009-04-28 | 2016-01-27 | 普罗秋斯数字健康公司 | The Ingestible event marker of high reliability and using method thereof |
WO2010132331A2 (en) | 2009-05-12 | 2010-11-18 | Proteus Biomedical, Inc. | Ingestible event markers comprising an ingestible component |
US8558563B2 (en) | 2009-08-21 | 2013-10-15 | Proteus Digital Health, Inc. | Apparatus and method for measuring biochemical parameters |
TWI517050B (en) | 2009-11-04 | 2016-01-11 | 普羅托斯數位健康公司 | System for supply chain management |
UA109424C2 (en) | 2009-12-02 | 2015-08-25 | PHARMACEUTICAL PRODUCT, PHARMACEUTICAL TABLE WITH ELECTRONIC MARKER AND METHOD OF MANUFACTURING PHARMACEUTICAL TABLETS | |
WO2011085022A1 (en) | 2010-01-05 | 2011-07-14 | Microdose Therapeutx, Inc. | Inhalation device and method |
JP5841951B2 (en) | 2010-02-01 | 2016-01-13 | プロテウス デジタル ヘルス, インコーポレイテッド | Data collection system |
WO2011127252A2 (en) | 2010-04-07 | 2011-10-13 | Proteus Biomedical, Inc. | Miniature ingestible device |
TWI557672B (en) | 2010-05-19 | 2016-11-11 | 波提亞斯數位康健公司 | Computer system and computer-implemented method to track medication from manufacturer to a patient, apparatus and method for confirming delivery of medication to a patient, patient interface device |
JP2013535756A (en) | 2010-08-13 | 2013-09-12 | インテリメディシン インコーポレイテッド | System and method for the production of personalized pharmaceuticals |
JP2014504902A (en) | 2010-11-22 | 2014-02-27 | プロテウス デジタル ヘルス, インコーポレイテッド | Ingestible device with medicinal product |
EP2654658A4 (en) | 2010-12-23 | 2016-04-06 | Tailorpill Technologies Llc | System and methods for personalized pill compounding |
US9439599B2 (en) | 2011-03-11 | 2016-09-13 | Proteus Digital Health, Inc. | Wearable personal body associated device with various physical configurations |
US8834411B2 (en) | 2011-04-06 | 2014-09-16 | Mystic Pharmaceuticals, Inc. | Medical devices for dispensing powders |
WO2015112603A1 (en) | 2014-01-21 | 2015-07-30 | Proteus Digital Health, Inc. | Masticable ingestible product and communication system therefor |
US9756874B2 (en) | 2011-07-11 | 2017-09-12 | Proteus Digital Health, Inc. | Masticable ingestible product and communication system therefor |
BR112014001397A2 (en) | 2011-07-21 | 2017-02-21 | Proteus Biomedical Inc | device, system and method of mobile communication |
EP2748685A4 (en) | 2011-08-27 | 2015-05-20 | Daniel L Kraft | Portable drug dispenser |
EP2770986B1 (en) | 2011-10-28 | 2018-04-04 | Hewlett-Packard Development Company, L.P. | Apparatus and method for producing controlled dosage of bioactive agent |
US9235683B2 (en) | 2011-11-09 | 2016-01-12 | Proteus Digital Health, Inc. | Apparatus, system, and method for managing adherence to a regimen |
WO2014018454A1 (en) | 2012-07-23 | 2014-01-30 | Proteus Digital Health, Inc. | Techniques for manufacturing ingestible event markers comprising an ingestible component |
JP5869736B2 (en) | 2012-10-18 | 2016-02-24 | プロテウス デジタル ヘルス, インコーポレイテッド | Apparatus, system, and method for adaptively optimizing power dissipation and broadcast power in a power supply for a communication device |
TWI659994B (en) | 2013-01-29 | 2019-05-21 | 美商普羅托斯數位健康公司 | Highly-swellable polymeric films and compositions comprising the same |
WO2014151929A1 (en) | 2013-03-15 | 2014-09-25 | Proteus Digital Health, Inc. | Personal authentication apparatus system and method |
JP5941240B2 (en) | 2013-03-15 | 2016-06-29 | プロテウス デジタル ヘルス, インコーポレイテッド | Metal detector device, system and method |
JP6511439B2 (en) | 2013-06-04 | 2019-05-15 | プロテウス デジタル ヘルス, インコーポレイテッド | Systems, devices, and methods for data collection and outcome assessment |
US9796576B2 (en) | 2013-08-30 | 2017-10-24 | Proteus Digital Health, Inc. | Container with electronically controlled interlock |
AU2014321320B2 (en) | 2013-09-20 | 2019-03-14 | Otsuka Pharmaceutical Co., Ltd. | Methods, devices and systems for receiving and decoding a signal in the presence of noise using slices and warping |
WO2015044722A1 (en) | 2013-09-24 | 2015-04-02 | Proteus Digital Health, Inc. | Method and apparatus for use with received electromagnetic signal at a frequency not known exactly in advance |
US10084880B2 (en) | 2013-11-04 | 2018-09-25 | Proteus Digital Health, Inc. | Social media networking based on physiologic information |
US10653622B1 (en) * | 2015-04-13 | 2020-05-19 | Pharmacoustics Technologies LLC | Individualized solid dosage products and a system and method for the globally integrated pharmaceutical manufacturing and its monitoring thereof |
US20170042806A1 (en) | 2015-04-29 | 2017-02-16 | Dexcel Pharma Technologies Ltd. | Orally disintegrating compositions |
US11051543B2 (en) | 2015-07-21 | 2021-07-06 | Otsuka Pharmaceutical Co. Ltd. | Alginate on adhesive bilayer laminate film |
WO2017075576A1 (en) | 2015-10-30 | 2017-05-04 | Cancer Prevention Pharmaceuticals, Inc. | Eflornithine and sulindac, fixed dose combination formulation |
US10076494B2 (en) | 2016-06-16 | 2018-09-18 | Dexcel Pharma Technologies Ltd. | Stable orally disintegrating pharmaceutical compositions |
KR20210018961A (en) | 2016-07-22 | 2021-02-18 | 프로테우스 디지털 헬스, 인코포레이티드 | Electromagnetic sensing and detection of ingestible event markers |
IL265827B2 (en) | 2016-10-26 | 2023-03-01 | Proteus Digital Health Inc | Methods for manufacturing capsules with ingestible event markers |
EP3968971A1 (en) | 2019-05-17 | 2022-03-23 | Cancer Prevention Pharmaceuticals, Inc. | Methods for treating familial adenomatous polyposis |
Family Cites Families (79)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3241625A (en) | 1963-07-24 | 1966-03-22 | Howe Richardson Scale Co | Material feeding |
GB1054160A (en) | 1964-12-21 | |||
US3977323A (en) | 1971-12-17 | 1976-08-31 | Electroprint, Inc. | Electrostatic printing system and method using ions and liquid aerosol toners |
US3889636A (en) | 1972-08-02 | 1975-06-17 | Willoughby Arthur Smith | Coating of substrates with particle materials |
FR2258632B2 (en) | 1974-01-21 | 1976-10-08 | Rhone Poulenc Ind | |
US4021587A (en) | 1974-07-23 | 1977-05-03 | Pram, Inc. | Magnetic and electrostatic transfer of particulate developer |
US3999119A (en) | 1975-03-26 | 1976-12-21 | Xerox Corporation | Measuring toner concentration |
US4349531A (en) * | 1975-12-15 | 1982-09-14 | Hoffmann-La Roche Inc. | Novel dosage form |
US4029757A (en) * | 1975-12-15 | 1977-06-14 | Hoffmann-La Roche Inc. | Manufacture of pharmaceutical unit dosage forms |
US4197289A (en) * | 1975-12-15 | 1980-04-08 | Hoffmann-La Roche Inc. | Novel dosage forms |
JPS533348A (en) | 1976-06-30 | 1978-01-13 | Konishiroku Photo Ind Co Ltd | Process and device for controlling toner density of developer liquid |
US4071169A (en) | 1976-07-09 | 1978-01-31 | Dunn John P | Electrostatic metering device |
US4170287A (en) | 1977-04-18 | 1979-10-09 | E. I. Du Pont De Nemours And Company | Magnetic auger |
US4182447A (en) * | 1977-07-27 | 1980-01-08 | Ira Kay | Device for storing, transporting and mixing reactive ingredients |
US4255777A (en) | 1977-11-21 | 1981-03-10 | Exxon Research & Engineering Co. | Electrostatic atomizing device |
JPS5497040A (en) | 1978-01-17 | 1979-07-31 | Canon Inc | Developing agent conveyor |
JPS5619723U (en) | 1979-07-23 | 1981-02-21 | ||
US4339428A (en) * | 1980-08-18 | 1982-07-13 | Bristol-Myers Company | Capsule product containing high dosage of aspirin in powder or granulated form and alkaline tablet or pellet comprising magnesium carbonate, calcium carbonate and a magnesium dry component |
US4379969A (en) | 1981-02-24 | 1983-04-12 | Dennison Manufacturing Company | Corona charging apparatus |
US4455143A (en) * | 1982-03-22 | 1984-06-19 | Alza Corporation | Osmotic device for dispensing two different medications |
DK152744C (en) * | 1982-08-13 | 1988-10-31 | Benzon As Alfred | PROCEDURE FOR THE PREPARATION OF A PHARMACEUTICAL PERORAL POLYDEPOT PREPARATION |
CA1190593A (en) | 1983-02-01 | 1985-07-16 | Paul E. Plasschaert | Corona device |
US4555174A (en) | 1983-12-19 | 1985-11-26 | Minnesota Mining And Manufacturing Company | Magnetically attractable developer material transport apparatus |
US4626876A (en) | 1984-01-25 | 1986-12-02 | Ricoh Company, Ltd. | Solid state corona discharger |
US4594901A (en) | 1984-11-09 | 1986-06-17 | Kimberly-Clark Corporation | Electrostatic flow meter |
CA1224240A (en) | 1984-12-24 | 1987-07-14 | Andrzej Maczuszenko | Ion generator structure |
US4772470A (en) * | 1985-04-27 | 1988-09-20 | Nitto Electric Industrial Co., Ltd. | Oral bandage and oral preparations |
US4848267A (en) | 1985-10-25 | 1989-07-18 | Colorocs Corporation | Apparatus for removal and addition of developer to a toner module |
US5074426A (en) * | 1986-11-13 | 1991-12-24 | Warner-Lambert Company | Dividable capsule |
US4795644A (en) * | 1987-08-03 | 1989-01-03 | Merck & Co., Inc. | Device for pH independent release of drugs through the Donnan-like influence of charged insoluble resins |
GB8724763D0 (en) * | 1987-10-22 | 1987-11-25 | Aps Research Ltd | Sustained-release formulations |
JPH01141061A (en) | 1987-11-27 | 1989-06-02 | Fuji Xerox Co Ltd | Electrical discharge head |
US5009894A (en) * | 1988-03-07 | 1991-04-23 | Baker Cummins Pharmaceuticals, Inc. | Arrangement for and method of administering a pharmaceutical preparation |
JPH0217137U (en) * | 1988-07-21 | 1990-02-05 | ||
US4878454A (en) | 1988-09-16 | 1989-11-07 | Behr Industrial Equipment Inc. | Electrostatic painting apparatus having optically sensed flow meter |
US5207705A (en) * | 1988-12-08 | 1993-05-04 | Brigham And Women's Hospital | Prosthesis of foam polyurethane and collagen and uses thereof |
DE3907387A1 (en) | 1989-03-08 | 1990-09-13 | Singer Hermann | METHOD FOR MEASURING PARTICLES IN POLYDISPERSE SYSTEMS AND OF PARTICLE CONCENTRATIONS OF MONODISPERS AEROSOLS AND MEASURING DEVICE FOR IMPLEMENTING THE METHOD |
JPH066149B2 (en) * | 1989-03-16 | 1994-01-26 | 株式会社菊水製作所 | Nucleated molded product |
ES2087911T3 (en) | 1989-04-28 | 1996-08-01 | Riker Laboratories Inc | DRY DUST INHALATION DEVICE. |
US5005516A (en) | 1989-12-01 | 1991-04-09 | Eastman Kodak Company | Device for aiding in measuring pigmented marking particle level in a magnetic brush development apparatus |
US5204055A (en) | 1989-12-08 | 1993-04-20 | Massachusetts Institute Of Technology | Three-dimensional printing techniques |
DE4009366A1 (en) * | 1990-03-23 | 1991-09-26 | Heraeus Gmbh W C | METHOD FOR PRODUCING A METAL COMPOSITE WIRE |
US5075114A (en) * | 1990-05-23 | 1991-12-24 | Mcneil-Ppc, Inc. | Taste masking and sustained release coatings for pharmaceuticals |
US5102045A (en) | 1991-02-26 | 1992-04-07 | Binks Manufacturing Company | Apparatus for and method of metering coating material in an electrostatic spraying system |
JPH04277126A (en) | 1991-02-28 | 1992-10-02 | Yamaishi:Kk | Conveyer for magnetic powder |
US5404871A (en) | 1991-03-05 | 1995-04-11 | Aradigm | Delivery of aerosol medications for inspiration |
US5260068A (en) * | 1992-05-04 | 1993-11-09 | Anda Sr Pharmaceuticals Inc. | Multiparticulate pulsatile drug delivery system |
US5421816A (en) | 1992-10-14 | 1995-06-06 | Endodermic Medical Technologies Company | Ultrasonic transdermal drug delivery system |
GB9223144D0 (en) * | 1992-11-05 | 1992-12-16 | Scherer Corp R P | Controlled release device |
AU676315B2 (en) * | 1993-06-30 | 1997-03-06 | Takeda Chemical Industries Ltd. | Stabilized solid pharmaceutical preparation and method of producing the same |
IT1264696B1 (en) * | 1993-07-09 | 1996-10-04 | Applied Pharma Res | PHARMACEUTICAL FORMS INTENDED FOR ORAL ADMINISTRATION ABLE TO RELEASE ACTIVE SUBSTANCES AT A CONTROLLED AND DIFFERENTIATED SPEED |
WO1996010996A1 (en) * | 1993-07-21 | 1996-04-18 | The University Of Kentucky Research Foundation | A multicompartment hard capsule with control release properties |
ES2149874T3 (en) | 1993-07-22 | 2000-11-16 | Pfizer | OSMOTIC DEVICES WITH STEAM PERMEABLE COATINGS. |
JP2728847B2 (en) | 1993-07-23 | 1998-03-18 | 日本パーカライジング株式会社 | Powder flow rate measuring method and apparatus |
US5490962A (en) | 1993-10-18 | 1996-02-13 | Massachusetts Institute Of Technology | Preparation of medical devices by solid free-form fabrication methods |
JP3278273B2 (en) * | 1993-12-17 | 2002-04-30 | キヤノン株式会社 | Drug sustained release capsule |
JP3670016B2 (en) * | 1994-12-16 | 2005-07-13 | ワーナー−ランバート・カンパニー | Method for encapsulating a caplet in a capsule and solid dosage form obtainable by such method |
DE4446470A1 (en) * | 1994-12-23 | 1996-06-27 | Basf Ag | Process for the production of dividable tablets |
US5669973A (en) | 1995-06-06 | 1997-09-23 | David Sarnoff Research Center, Inc. | Apparatus for electrostatically depositing and retaining materials upon a substrate |
US5714007A (en) * | 1995-06-06 | 1998-02-03 | David Sarnoff Research Center, Inc. | Apparatus for electrostatically depositing a medicament powder upon predefined regions of a substrate |
SE9600072D0 (en) * | 1996-01-08 | 1996-01-08 | Astra Ab | New oral formulation of two active ingredients II |
US5858099A (en) | 1996-04-09 | 1999-01-12 | Sarnoff Corporation | Electrostatic chucks and a particle deposition apparatus therefor |
US5699649A (en) | 1996-07-02 | 1997-12-23 | Abrams; Andrew L. | Metering and packaging device for dry powders |
IT1289160B1 (en) * | 1997-01-08 | 1998-09-29 | Jagotec Ag | FULLY COATED PHARMACEUTICAL TABLET FOR THE CONTROLLED RELEASE OF ACTIVE INGREDIENTS WHICH PRESENT PROBLEMS OF |
SE9700642D0 (en) * | 1997-02-24 | 1997-02-24 | Kronvall Stefan Med Ab | Means and ways of preventing and treating the metabolic syndrome |
US5948483A (en) | 1997-03-25 | 1999-09-07 | The Board Of Trustees Of The University Of Illinois | Method and apparatus for producing thin film and nanoparticle deposits |
US6004625A (en) | 1997-06-16 | 1999-12-21 | Ibick Corporation | Method for adhering particles to an object by supplying air ions |
DE19730231A1 (en) | 1997-07-15 | 1999-01-21 | Abb Research Ltd | Process for electrostatic coating |
US6197331B1 (en) * | 1997-07-24 | 2001-03-06 | Perio Products Ltd. | Pharmaceutical oral patch for controlled release of pharmaceutical agents in the oral cavity |
US6013280A (en) * | 1997-10-07 | 2000-01-11 | Fuisz Technologies Ltd. | Immediate release dosage forms containing microspheres |
IT1296980B1 (en) | 1997-12-17 | 1999-08-03 | Istituto Pirri S R L | DOUBLE CAPSULE AS A PHARMACEUTICAL FORM FOR THE ADMINISTRATION OF ACTIVE INGREDIENTS IN MULTIPLE THERAPIES |
US5960609A (en) * | 1998-06-12 | 1999-10-05 | Microdose Technologies, Inc. | Metering and packaging method and device for pharmaceuticals and drugs |
US6428809B1 (en) * | 1999-08-18 | 2002-08-06 | Microdose Technologies, Inc. | Metering and packaging of controlled release medication |
AU3289301A (en) | 2000-01-20 | 2001-07-31 | Delsys Pharmaceutical Corporation | Multi-step drug dosage forms |
BRPI0209720A2 (en) | 2001-05-31 | 2017-06-13 | Microdose Tech Inc | dosage and packaging of controlled release medication |
CA2510465A1 (en) * | 2002-12-18 | 2004-07-08 | Pain Therapeutics | Oral dosage forms with therapeutically active agents in controlled release cores and immediate release gelatin capsule coats |
ATE366105T1 (en) * | 2003-03-03 | 2007-07-15 | Sprl Franpharma | STABILIZED PHARMACEUTICAL COMPOSITION CONTAINING AN NSAID AND A PROSTAGLANDIN |
US20050053649A1 (en) * | 2003-09-08 | 2005-03-10 | Anne-Marie Chalmers | Medication delivery device |
KR101259414B1 (en) | 2012-03-20 | 2013-05-10 | 한국과학기술정보연구원 | System and method for constructing a database for product demand/supply network |
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1999
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2000
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- 2000-08-16 JP JP2001516450A patent/JP2003517351A/en active Pending
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- 2000-08-16 EP EP00957487A patent/EP1207809B1/en not_active Expired - Lifetime
- 2000-08-16 ES ES00957487T patent/ES2323846T3/en not_active Expired - Lifetime
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DK1207809T3 (en) | 2009-07-20 |
US20020142035A1 (en) | 2002-10-03 |
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JP2003517351A (en) | 2003-05-27 |
WO2001012103A1 (en) | 2001-02-22 |
DE60042076D1 (en) | 2009-06-04 |
ES2323846T3 (en) | 2009-07-27 |
US7404968B2 (en) | 2008-07-29 |
EP2052697A1 (en) | 2009-04-29 |
US6702683B2 (en) | 2004-03-09 |
PT1207809E (en) | 2009-05-08 |
US6428809B1 (en) | 2002-08-06 |
EP1207809B1 (en) | 2009-04-22 |
EP1207809A1 (en) | 2002-05-29 |
US20040142036A1 (en) | 2004-07-22 |
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