Patent Application
20060041248
This invention relates generally to the administration of compositions (such as pharmaceutical compositions or bioactive materials) for cutaneous administration, including transdermal and transmucuosal administration. In addition, this invention relates to the creation of orally administered patches, and wafers for the delivery of such compositions. In particular, this invention combines the technologies of pharmaceutical administration and solvent-less delivery systems.
Pharmaceutical compositions provide effective treatments for a variety of illnesses. Unfortunately, there are many obstacles to the administration of therapeutically effective doses of many medications. For example, some drugs (particularly peptide based drugs such as insulin) are partially or totally inactivated following oral ingestion, by the highly acidic environment of the stomach. Another problem is the “first pass” effect, which refers to the partial inactivation of orally ingested drugs in the liver, after they have been absorbed from the gastrointestinal system, but before they have exerted their full therapeutic effect. Even when these problems are overcome, patients often fail to take their medications at the proper prescribed intervals, or for the necessary period of time, to achieve an optimal therapeutic response.
Inhalation and intranasal administration has been used as alternative routes of drug delivery. Inhaled drugs can be absorbed directly through the mucous membranes and epithelium of the respiratory tract, thereby minimizing initial inactivation of bioactive substances by the liver. Inhalational delivery can also provide drugs directly to therapeutic sites of action (such as the lungs or the sinuses). This mode of administration has been particularly effective for the delivery of pulmonary drugs (such as asthma medications) and peptide based drugs (usually via intranasal administration), using metered dose inhalers (MDls). However, MDIs often require coordinating inspiration with actuation of the MDI, and some patients are not able to master this technique. Moreover, patients still often forget to take the medication at prescribed times, or for the necessary period of time to achieve clinical goals. Other patients inadvertently or inappropriately use medications, leading to hospitalizations, morbidity, and even death.
In an effort to overcome such problems, some drugs are administered by passive cutaneous routes, such as transdermal delivery of drugs from a patch applied to the skin. Examples of drugs that are routinely administered by this route are nitroglycerin, steroid hormones, and some analgesics (such as fentanyl). Transdermal administration avoids initial inactivation of drugs in the gastrointestinal tract, and provides continuous dosages usually over a relatively short period of time (such as a day), without requiring active participation by the patient. Continuous sustained administration provides better bioavailability of the drug, without peaks and troughs, and eliminates the problem of the patient forgetting to take multiple doses of the drug throughout the day. However, the patch must be changed regularly, usually each day, to provide a necessary drug concentration in the patch to establish the correct concentration gradient for delivery of the appropriate dose of the drug across the skin.
In addition to transdermal systemic delivery of drugs, topical delivery of drugs to the surface of the skin is also used for treating many skin conditions. For example, antibiotics are topically administered to the skin to treat infection, anesthetics to treat pain, retinoids to treat acne, and minoxidil to treat hair loss. These drugs must be repeatedly applied to the skin to achieve their effect, and much of the dosage may be lost by drainage of liquid from the application site, or being inadvertently wiped away. Moreover, excess drug is usually applied to the skin, which can lead to undesired toxic effects particularly if the drug is absorbed through the skin.
Pharmaceutical compositions can also include various agents that enhance or improve disease diagnosis. For example, in U.S. Pat. No. 6,592,847(B1), by Weissleder et al., an optical imaging probe and method is disclosed. This invention features an in-vivo optical imaging method comprising: (a) administering to a living animal or human an intramolecularly-quenched fluorescence probe comprising a fluorochrome attachment moiety and a plurality of near infrared fluorochromes covalently linked to the fluorochrome attachment moiety at fluorescence-quenching interaction-permissive positions. These positions are separable by enzymatic cleavage at fluorescence activation sites, which enzymatic cleavage occurs preferentially in a target tissue; (b) allowing time for enzymes in the target tissue to activate the probe by enzymatic cleavage at fluorescence activation sites, if the target tissue is present; (c) illuminating the target tissue with near infrared light of a wavelength absorbable by the fluorochromes; and (d) detecting fluorescence emitted by the fluorochromes. The delivery of such optical imaging probes can radically improve disease diagnosis.
Devices and methods are disclosed herein for improving the cutaneous delivery of pharmaceutical compositions, by using solvent-less applicators for transdermal and other cutaneous delivery of such compositions, as well as orally administered delivery. Systems for administrating bioactive materials in this fashion are also described. “Receiver” for the purposes of this description can comprise all of the above mentioned delivery methods direct to skin, patches etc.
Technologies that deposit a marking material such as a toner particle onto a receiver using gaseous propellants are known. For example, Peeters et al., in U.S. Pat. No. 6,116,718, disclose a print head for use in a marking apparatus in which a propellant gas is passed through a channel, the functional material is introduced controllably into the propellant stream to form a ballistic aerosol for propelling non-colloidal, solid or semi-solid particulate or a liquid, toward a receiver with sufficient kinetic energy to fuse the marking material to the receiver. There is a problem with this technology in that the functional material and propellant stream are two different entities and the propellant is used to impart kinetic energy to the functional material. This can cause functional material agglomeration leading to nozzle obstruction and poor control over functional material deposition. Another problem with this technology is that when the functional material is added into the propellant stream in the channel it forms a non-colloidal ballistic aerosol prior to exiting the print head. This non-colloidal ballistic aerosol, which is a combination of the functional material and the propellant, is not thermodynamically stable. As such, the functional material is prone to settling in the propellant stream that, in turn, can cause functional material agglomeration leading to nozzle obstruction and poor control over functional material deposition.
Additionally, there is a need for a technology capable of controlled functional material deposition within a receiver or within a predetermined layer of a receiver. There is also a need for a technology that permits functional material deposition of ultra-small (nano-scale) particles.
Jagannathan et al. in U.S. Pat. No. 6,471,327(B2), incorporated by reference, disclose a method and apparatus for delivery of a focused beam of a thermodynamically stable/metastable mixture of functional material and a dense gas. The apparatus disclosed in Jagannathan et al. can be directly implemented in delivery of bioactive materials to a receiver.
U.S. 2003/0107614 A1, U.S. 2003/0227502 A1, U.S. 2003/0132993 A1, and U.S. 2003/0227499 A1, incorporated by reference, define various additions and further concepts for providing an apparatus and method for printing with a thermodynamically stable mixture of a fluid and marking material. The teachings of the above applications on print head design, the use of multiple marking materials, cleaning and calibration, can be applied to the delivery of bioactive materials.
An object of the present invention is to provide a technology that permits high speed, accurate, and precise deposition of a solvent free bioactive material on a receiver.
Another object of the present invention is to provide a technology capable of controlled bioactive material deposition within a receiver or within a predetermined layer of a receiver.
According to a feature of the present invention, a method of delivering a bioactive material to a receiver includes in order, providing a mixture of a fluid having a solvent and a bioactive material; causing the bioactive material to become free of the solvent; causing the bioactive material to contact a receiver, and penetrate said receiver to a predetermined layer.
According to another feature of the present invention, an apparatus for delivering a bioactive material to a receiver includes a pressurized source of solvent in a thermodynamically stable mixture with a bioactive material, the solvent being in a liquid state within the pressurized source. A discharge device having an inlet and an outlet, the discharge device being connected to the pressurized source at the inlet, the thermodynamically stable mixture being ejected from the outlet, the solvent being in a gaseous state at a location beyond the outlet of the discharge device.
According to another feature of the present invention, a method of delivering a bioactive material to a receiver includes providing a source of a thermodynamically stable mixture of a solvent in a liquid state and a bioactive material; providing a discharge device having a nozzle in fluid communication with the source of the thermodynamically stable mixture; positioning a receiver at a predetermined distance from the nozzle; ejecting the thermodynamically stable mixture from the nozzle, the solvent changing from the liquid state to a gaseous state; and depositing the solvent free bioactive material on the receiver.
The present invention is directed to overcoming one or more of the problems set forth above. Briefly summarized, according to one aspect of the present invention, there is provided a system for solvent-less delivery of a bioactive material to a receiver, comprising: a discharge device, a reservoir which holds a bioactive material, and a solvent at a supercritical fluid state for delivering the bioactive material through the discharge device to the receiver.
According to another aspect of the present invention there is provided a system for solvent-less delivery of a bioactive material to a receiver, comprising: a discharge device, a spacer positioned between the discharge device and the receiver, a reservoir which holds a bioactive material, and a solvent at a supercritical fluid state for delivering the bioactive material through the discharge device to the receiver.
According to yet another aspect of the present invention there is provided a kit for solvent-less delivery of a bioactive material to a receiver, the kit comprising:
In accordance with still another aspect of the present invention there is provided a method for solvent-less delivery of a bioactive material to a receiver, comprising:
In accordance with another aspect of the present invention there is provided a receiver for applying a bioactive material to a subject, the receiver having a plurality of different bio-active material to be applied to a subject, each located at a different location on the receiver.
In accordance with yet still another aspect of the present invention there is provided a receiver for applying a bioactive material to a subject, the receiver having a plurality of different bio-active material to be applied to a subject, each located at a different depth on the receiver.
These and other aspects, objects, features and advantages of the present invention will be more clearly understood and appreciated from a review of the following detailed description of the preferred embodiments and appended claims and by reference to the accompanying drawings.
The above and other objects, features, and advantages of the present invention will become more apparent when taken in conjunction with the following description and drawings wherein identical reference numerals have been used, where possible, to designate identical features that are common to the figures, and wherein:
To facilitate understanding, identical reference numerals have been used, where possible, to designate identical elements that are common to the figures.
Unless otherwise noted, technical terms are used according to conventional usage. Definitions of common terms in pharmacology may be found in Remington: The Science and Practice of Pharmacy, 19th Edition, published by Mack Publishing Company, 1995 (ISBN 0-912734-04-3). Transdermal delivery is discussed in particular at page 743 and pages 1577-1584.
The singular forms “a,” “an,” and “the” refer to one or more than one, unless the context clearly dictates otherwise. The term “comprising” means “including.”
An “array” refers to a predetermined pattern, which can be either regular or irregular. Examples of arrays are linear distributions or two-dimensional matrices.
A “bioactive” material, composition, substance or agent is a composition which affects a biological function of a subject to which it is administered. An example of a bioactive material used to create a composition is a pharmaceutical substance, such as a drug, which is given to a subject to alter a physiological condition of the subject, such as a disease. Bioactive materials, compositions and agents also include other biomolecules, such as proteins and nucleic acids, or liposomes and other carrier vehicles that contains bioactive materials. A “bioactive” composition can also include various agents that enhance or improve disease diagnosis. For example, in U.S. Pat. No. 6,592,847(B1), by Weissleder et al., an optical imaging probe and method is disclosed. This invention features an in-vivo optical imaging method comprising: (a) administering to a living animal or human an intramolecularly-quenched fluorescence probe comprising a fluorochrome attachment moiety and a plurality of near infrared fluorochromes covalently linked to the fluorochrome attachment moiety at fluorescence-quenching interaction-permissive positions. These positions are separable by enzymatic cleavage at fluorescence activation sites, which enzymatic cleavage occurs preferentially in a target tissue; (b) allowing time for enzymes in the target tissue to activate the probe by enzymatic cleavage at fluorescence activation sites, if the target tissue is present; (c) illuminating the target tissue with near infrared light of a wavelength absorbable by the fluorochromes; and (d) detecting fluorescence emitted by the fluorochromes. The delivery of such optical imaging probes can radically improve disease diagnosis.
“Cutaneous” refers to the skin, and “cutaneous delivery” means application to the skin. This form of delivery can include either delivery to the surface of the skin to provide a local or topical effect, or transdermal delivery. The following terms are intended to be defined as indicated below. The term “transdermal”, delivery captures both transdermal (or “percutaneous”) and transmucosal administration, i.e., delivery by passage of a bioactive material through the skin or mucosal tissue. See, e.g., Transdermal Drug Delivery: Developmental Issues and Research Initiatives, Hadgraft and Guy (eds.), Marcel Dekker, Inc., (1989); Controlled Drug Delivery: Fundamentals and Applications, Robinson and Lee (eds.), Marcel Dekker Inc., (1987); and Transdermal Delivery of Drugs, Vols. 1-3, Kydonieus and Berner (eds.), CRC Press, (1987). Aspects of the invention which are described herein in the context of “transdermal” delivery, unless otherwise specified, are meant to apply to both transdermal and transmucosal delivery. That is, the compositions, systems, and methods of the invention, unless explicitly stated otherwise, should be presumed to be equally applicable to transdermal and transmucosal modes of delivery.
The present disclosure is directed to solvent-less delivery systems that are based on the use of supercritical fluids. Supercritical fluids have unique properties, since they combine liquid-like solvent power with gas-like transport properties. They have a large compressibility compared to ideal gases. Therefore, a small change in temperature or pressure near the critical values will result in large changes in the fluid's density and hence its solvent power. These characteristics can be utilized to provide highly controllable solvent properties. Carbon dioxide is the most widely used supercritical fluid, due to the favorable critical parameters (Tc=31.1° C., Pc=73.8 bar), cost and non-toxicity.
This invention is directed more specifically at a compressed fluid based device such as is disclosed in U.S. Ser. No. 10/814,354 filed Mar. 31, 2004 entitled PROCESS FOR THE FORMATION OF PARTICULATE MATERIAL by Rajesh Vinodrai Mehta et al., and U.S. Pat. No. 6,752,484, both of which are incorporated by reference herein in their entirety and are explained in detail below. A significant feature of this invention is that precipitated particles of sizes less than 100 nanometers can be produced free of high levels of non-uniform large particles. The delivery system includes a container for holding the bioactive material and delivering it to a dispenser nozzle, or an array of dispenser nozzles. The spray from the delivery system is self-energized obviating the need for additional energy sources to propel the bioactive material from the delivery system toward a cutaneous target.
The medication dispensers disclosed herein may be similar to liquid dispensers known as solvent-less print heads used in solvent-less printing mechanisms, such as printers, plotters, facsimile machines and the like, some of which are described for example in Durbeck and Sherr, Output Hardcopy Devices, Academic Press Inc., 1987 (ISBN 0-12-225040-0), particularly in chapter 13, pages 311-370. These technologies have in common the extraction of small quantities of a fluid from a reservoir, which are converted into fine droplets, and transported through the air to a target medium by appropriate application of physical forces. This technology has been implemented in a variety of ways, but one of the common approaches has been thermal solvent-less technology, in which liquids are heated using resistors to form drops and propel them from a chamber through an orifice toward a target. Another approach is piezoelectric solvent-less technology, in which movement of a piezoelectric transducer changes a chamber volume to generate the drop. An additional approach is known as silicon electrostatic actuator (“SEA”) solvent-less technology, such as that disclosed in U.S. Pat. No. 5,739,831 to Nakamura (assigned to Seiko Epson Corporation).
In striving to duplicate the quality of photographic film images, the solvent-less printing industry has focused on decreasing the size of ink droplets ejected from the nozzles, as well as accurately placing these droplets on the print media. For instance, some of the more recent solvent-less print cartridges are able to deliver droplets of a size on the order of 0.5-6 Pico liters, although larger droplets can also be generated, for example droplets of 10, 50, 100 or more Pico liters. The resolution within which currently commercially available solvent-less printing mechanisms may place ink droplets on a page is on the order of 1200-4800 dots per inch (known in the industry as a “dpi” rating). Thus, while striving to achieve photographic print quality, solvent-less printing technology has become very adept at accurately metering and dispensing fluids. The ability to dispense very small and accurate amounts of fluids (including liquids and powders) is taken advantage of in constructing the transdermal cutaneous application systems illustrated herein.
While these solvent-less print heads may be used in the cutaneous application systems illustrated here, rather than using a printing analogy, the print head will instead be referred to in a more general nature as a “discharge device”, “delivery system” or “applicator.”
The bioactive material may be any flowable fluid (for example a liquid, gel or powder), although liquids are particularly useful in the delivery system. In some embodiments, at least one of the container modules may contain a bioactive material in powder or other dry form. The powder or other material is dispensed from the container, and may be combined with a liquid (such as a penetration enhancer) en route to the cutaneous delivery site.
In certain embodiments, the delivery system includes the bioactive material in the container. Examples of bioactive materials that can be included in the container include pharmaceutical compositions that are capable of transdermal delivery. As used herein, the terms “bio active material” and/or “particles of a bioactive material” intend any compound or composition of matter which, when administered to an organism (human or nonhuman animal) induces a desired pharmacologic, immunogenic, and/or physiologic effect by local and/or systemic action. The term therefore encompasses those compounds or chemicals traditionally regarded as drugs, vaccines, and biopharmaceuticals including molecules such as proteins, peptides, hormones, nucleic acids, gene constructs and the like. More particularly, the term “bioactive material” includes compounds or compositions for use in all of the major therapeutic areas including, but not limited to, anti-infectives such as antibiotics and antiviral agents; analgesics and analgesic combinations; local and general anesthetics; anorexics; anti-arthritics; anti-asthmatic agents; anticonvulsants; antidepressants; antihistamines; anti-inflammatory agents; antinauseates; anti-migraine agents; antineoplastics; antipruritics; antipsychotics; antipyretics; antispasmodics; cardiovascular preparations (including calcium channel blockers, beta-blockers, beta-agonists and antiarrythmics); anti-hypertensives; diuretics; vasodilators; central nervous system stimulants; cough and cold preparations; decongestants; diagnostics; hormones; bone growth stimulants and bone resorption inhibitors; immunosuppressives; muscle relaxants; psycho stimulants; sedatives; tranquilizers; proteins, peptides, and fragments thereof (whether naturally occurring, chemically synthesized or recombinantly produced); and nucleic acid molecules (polymeric forms of two or more nucleotides, either ribonucleotides (RNA) or deoxyribonucleotides (DNA) including double- and single-stranded molecules and supercoiled or condensed molecules, gene constructs, expression vectors, plasmids, antisense molecules and the like). Particles of a bioactive material, alone or in combination with other drugs or agents, are typically prepared as pharmaceutical compositions which can contain one or more added materials such as carriers, vehicles, and/or excipients. “Carriers,” “vehicles” and “excipients” generally refer to substantially inert materials which are nontoxic and do not interact with other components of the composition in a deleterious manner. These materials can be used to increase the amount of solids in particulate pharmaceutical compositions. Examples of suitable carriers include silicone, gelatin, waxes, and like materials. Examples of normally employed “excipients,” include pharmaceutical grades of dextrose, sucrose, lactose, trehalose, mannitol, sorbitol, inositol, dextran, starch, cellulose, sodium or calcium phosphates, calcium sulfate, citric acid, tartaric acid, glycine, high molecular weight polyethylene glycols (PEG), erodible polymers (such as polylactic acid, polyglycolic acid, and copolymers thereof), and combinations thereof. In addition, it may be desirable to include a charged lipid and/or detergent in the pharmaceutical compositions. Such materials can be used as stabilizers, anti-oxidants, or used to reduce the possibility of local irritation at the site of administration. Suitable charged lipids include, without limitation, phosphatidylcholines (lecithin), and the like. Detergents will typically be a nonionic, anionic, cationic or amphoteric surfactant. Examples of suitable surfactants include, for example, Tergitol® and Triton® surfactants (Union Carbide Chemicals and Plastics, Danbury, Conn.), polyoxyethylenesorbitans, e.g., TWEEN® surfactants (Atlas Chemical Industries, Wilmington, Del.), polyoxyethylene ethers, e.g., Brij, pharmaceutically acceptable fatty acid esters, e.g., lauryl sulfate and salts thereof (SDS), and like materials.
A delivery system made in accordance with the present invention may also include a controller for manually or automatically dispensing the bioactive material from the delivery system at selected times. The controller may take the form of an actuator that is manually depressed to activate the delivery system and dispense the agent. Alternatively, the controller may be a microprocessor, which is programmed to dispense the bioactive material at predetermined intervals, for example several times a day, as needed, directly on to the skin or on to a patch to be applied to a subject.
Referring to
In this context, the chosen materials taken to a compressed liquid and/or supercritical fluid state are gases at ambient pressure and temperature. Ambient conditions are preferably defined as temperature in the range from −100 to +100° C., and pressure in the range from 1×10−8-00 atm for this application.
In
A compressed liquid/supercritical fluid carrier, contained in the compressed liquid/supercritical fluid source 11, is any material that dissolves/solubilizes/disperses a bioactive material. The compressed liquid/supercritical fluid source 11 delivers the compressed liquid/supercritical fluid carrier at predetermined conditions of pressure, temperature, and flow rate as a supercritical fluid, or a compressed liquid. Materials that are above their critical point, defined by a critical temperature and a critical pressure, are known as supercritical fluids. The critical temperature and critical pressure typically define a thermodynamic state in which a fluid or a material becomes supercritical and exhibits gas-like and liquid-like properties. Materials that are at sufficiently high temperatures and pressures below their critical point are known as compressed liquids. Materials in their supercritical fluid and/or compressed liquid state that exist as gases at ambient conditions find application here because of their unique ability to solubilize and/or disperse bioactive materials of interest in the compressed liquid or supercritical state.
Fluid carriers include, but are not limited to, carbon dioxide, nitrous oxide, ammonia, xenon, ethane, ethylene, propane, propylene, butane, isobutane, chlorotrifluoromethane, monofluoromethane, sulphur hexafluoride and mixtures thereof. Due to its characteristics, e.g. low cost, wide availability, etc., carbon dioxide is generally preferred in many applications.
The formulation reservoir 12 is utilized to dissolve and/or disperse bioactive materials in compressed liquids or supercritical fluids with or without dispersants and/or surfactants, at desired formulation conditions of temperature, pressure, volume, and concentration. The combination of bioactive material and compressed liquid/supercritical fluid is typically referred to as a mixture, formulation, etc.
The formulation reservoir 12 can be made out of any suitable materials that can safely operate at the formulation conditions. An operating range from 0.001 atmosphere (1.013×102 Pa) to 1000 atmospheres (1.013×108 Pa) in pressure and from −25 degrees Centigrade to 1000 degrees Centigrade is generally preferred. Typically, the preferred materials include various grades of high pressure stainless steel. However, it is possible to use other materials if the specific deposition or etching application dictates less extreme conditions of temperature and/or pressure.
The formulation reservoir 12 should be precisely controlled with respect to the operating conditions (pressure, temperature, and volume). The solubility/dispersibility of bioactive materials depends upon the conditions within the formulation reservoir 12. As such, small changes in the operating conditions within the formulation reservoir 12 can have undesired effects on bioactive material solubility/dispensability.
Additionally, any suitable surfactant and/or dispersant material that is capable of solubilizing/dispersing the bioactive materials in the compressed liquid/supercritical fluid for a specific application can be incorporated into the mixture of bioactive material and compressed liquid/supercritical fluid. Such materials include, but are not limited to, fluorinated polymers such as perfluoropolyether, siloxane compounds, etc.
Referring to
Referring to
A temperature control mechanism 20 is positioned along delivery path 16 in order to create and maintain a desired temperature for a particular application. The temperature control mechanism 20 is preferably positioned at the formulation reservoir 12. The temperature control mechanism 20 can include a heater, a heater including electrical wires, a water jacket, a refrigeration coil, a combination of temperature controlling devices, etc. The temperature control mechanism 20 can also include any number of monitoring devices, gauges, etc., for monitoring the temperature of the delivery system 10.
The discharge device 13 includes a nozzle 23 positioned to provide direct delivery of the formulation towards the receiver 14. The discharge device 13 can also include a shutter 22 to regulate the flow of the supercritical fluid/compressed liquid and bioactive material mixture or formulation. The shutter 22 regulates flow of the formulation in a predetermined manner (i.e. on/off or partial opening operation at desired frequency, etc.). The shutter 22 can be manually, mechanically, pneumatically, electrically or electronically actuated. Alternatively, the discharge device 13 does not have to include the shutter 22 (shown in
The receiver 14 can be positioned on a media conveyance mechanism 50 that is used to control the movement of the receiver during the operation of the delivery system 10. The media conveyance mechanism 50 can be a drum, an x, y, z translator, any other known media conveyance mechanism, etc.
Referring to
When automated delivery of the bioactive material is desired, a pump 60 is positioned along a bioactive material delivery path 62 between a source of bioactive material 64 and the formulation reservoir 12. The pump 60 pumps a desired amount of bioactive material through inlet port 52 into the formulation reservoir 12. The formulation reservoir 12 can also include additional inlet/outlet ports 59 for inserting or removing small quantities of bioactive material or bioactive material and compressed liquid/supercritical fluid mixtures.
Referring to
Referring to
Referring to
The formulation reservoir 12 is made of appropriate materials of construction in order to withstand high pressures of the order of 10,000 psi or greater. Typically, stainless steel is the preferred material of construction although other high pressure metals, metal alloys, and/or metal composites can be used.
Referring to
Referring to
Referring to
Alternatively, the shutter device 22 can be positioned after the nozzle heating module 26 and the nozzle shield gas module 27 or between the nozzle heating module 26 and the nozzle shield gas module 27. Additionally, the nozzle shield gas module 27 may not be required for certain applications, as is the case with the stream deflector and catcher module 24 and/or the addition of a spacer-shield 25 (see
The nozzle 23 can be capable of translation in x, y, and z directions to permit suitable discontinuous and/or continuous bioactive material deposition and/or etching on the receiver 14. Translation of the nozzle 23 can be achieved through manual, mechanical, pneumatic, electrical, electronic or computerized control mechanisms. Receiver 14 and/or media conveyance mechanism 50 can also be capable of translation in x, y, and z directions to permit suitable bioactive material deposition and/or etching on the receiver 14. Alternatively, both the receiver 14 and the nozzle 23 can be translatabled in x, y, and z directions depending on the particular application.
Referring to
The discharge device 13 serves to direct the bioactive material onto the receiver 14. The discharge device 13 or a portion of the discharge device 13 can be stationary or can swivel or raster, as needed, to provide high resolution and high precision deposition of the bioactive material onto the receiver 14 or etching of the receiver 14 by the bioactive material. Alternatively, receiver 14 can move in a predetermined way while discharge device 13 remains stationary. The shutter device 22 can also be positioned after the nozzle 23. As such, the shutter device 22 and the nozzle 23 can be separate devices so as to position the shutter 22 before or after the nozzle 23 with independent controls for maximum deposition and/or etching flexibility. Alternatively, the shutter device 22 can be integrally formed within the nozzle 23.
Operation of the delivery system 10 will now be described.
The supercritical fluid and/or compressed liquid 41, forms a continuous phase and bioactive material 40 forms a dispersed and/or dissolved single phase. The formulation 42 (the bioactive material 40 and the supercritical fluid and/or compressed liquid 41) is maintained at a suitable temperature and a suitable pressure for the bioactive material 40 and the supercritical fluid and/or compressed liquid 41 used in a particular application. The shutter 22 is actuated to enable the ejection of a controlled quantity of the formulation 42. The nozzle 23 collimates and/or focuses the formulation 42 into a beam 43 as shown in
The bioactive material 40 is controllably introduced into the formulation reservoir 12. The compressed liquid/supercritical fluid 41 is also controllably introduced into the formulation reservoir 12. The contents of the formulation reservoir 12 are suitably mixed using mixing device 70 to ensure intimate contact between the bioactive material 40 and compressed liquid/supercritical fluid 41. As the mixing process proceeds, bioactive material 40 is dissolved or dispersed within the compressed liquid/supercritical fluid 41. The process of dissolution/dispersion, including the amount of bioactive material 40 and the rate at which the mixing proceeds, depends upon the bioactive material 40 itself, the particle size and particle size distribution of the bioactive material 40 (if the bioactive material 40 is a solid), the compressed liquid/supercritical fluid 41 used, the temperature, and the pressure within the formulation reservoir 12. When the mixing process is complete, the mixture or formulation 42 of bioactive material and compressed liquid/supercritical fluid is thermodynamically stable/metastable in that the bioactive material is dissolved or dispersed within the compressed liquid/supercritical fluid in such a fashion as to be indefinitely contained in the same state as long as the temperature and pressure within the formulation chamber are maintained constant. This state is distinguished from other physical mixtures in that there is no settling, precipitation, and/or agglomeration of bioactive material particles within the formulation chamber unless the thermodynamic conditions of temperature and pressure within the reservoir are changed. As such, the bioactive material 40 and compressed liquid/supercritical fluid 41 mixtures or formulations 42 of the present invention are said to be thermodynamically stable/metastable.
The bioactive material 40 can be a solid or a liquid. Additionally, the bioactive material 40 can be an organic molecule, a polymer molecule, a metallo-organic molecule, an inorganic molecule, an organic nanoparticle, a polymer nanoparticle, a metallo-organic nanoparticle, an inorganic nanoparticle, an organic microparticle, a polymer micro-particle, a metallo-organic microparticle, an inorganic microparticle, and/or composites of these materials, etc. After suitable mixing with the compressed liquid/supercritical fluid 41 within the formulation reservoir 12, the bioactive material 40 is uniformly distributed within a thermodynamically stable/metastable mixture, that can be a solution or a dispersion, with the compressed liquid/supercritical fluid 41. This thermodynamically stable/metastable mixture or formulation 42 is controllably released from the formulation reservoir 12 through the discharge device 13 as shown in
During the discharge process, still referring to
The delivery system 10 is also designed to appropriately change the temperature and pressure of the formulation 42 to permit a controlled precipitation and/or aggregation of the bioactive material 40. As the pressure is typically stepped down in stages, the formulation 42 fluid flow is self-energized. Subsequent changes to the formulation 42 conditions (a change in pressure, a change in temperature, etc.) result in the precipitation and/or aggregation of the bioactive material 40 coupled with an evaporation (shown generally at 45) of the supercritical fluid and/or compressed liquid 41. The resulting precipitated and/or aggregated bioactive material 44 deposits on the receiver 14 in a precise and accurate fashion. Evaporation 45 of the supercritical fluid and/or compressed liquid 41 can occur in a region located outside of the discharge device 13. Alternatively, evaporation 45 of the supercritical fluid and/or compressed liquid 41 can begin within the discharge device 13 and continue in the region located outside the discharge device 13. Alternatively, evaporation 45 can occur within the discharge device 13.
A beam 43 (stream, etc.) of the bioactive material 40 and the supercritical fluid and/or compressed liquid 41 is formed as the formulation 42 moves through the discharge device 13. When the size of the precipitated and/or aggregated bioactive material 44 is substantially equal to an exit diameter of the nozzle 23 of the discharge device 13, the precipitated and/or aggregated bioactive material 44 has been collimated by the nozzle 23. When the size of the precipitated and/or aggregated bioactive material 44 is less than the exit diameter of the nozzle 23 of the discharge device 13, the precipitated and/or aggregated bioactive material 44 has been focused by the nozzle 23.
Referring now to
The distance of the receiver 14 from the discharge nozzle 23 is chosen such that the supercritical fluid and/or compressed liquid 41 evaporates from the liquid/carrier and/or supercritical phase to the gas phase (shown generally at 45) prior to reaching the receiver 14. Hence, there is no need for subsequent receiver-drying processes. Further, subsequent to the ejection of the formulation 42 from the nozzle 23 and the precipitation of the bioactive material, additional focusing and/or collimation may be achieved using external devices such as electromagnetic fields, mechanical shields, magnetic lenses, electrostatic lenses etc. Alternatively, the receiver 14 can be electrically or electro statically charged such that the positional placement of the bioactive material 40 on the receiver can be controlled.
It is also desirable to control the velocity and thereby the momentum, with which individual particles 46 of the bioactive material 40 are ejected from the nozzle 23. As there is a sizable pressure drop from within the delivery system 10 to the operating environment, the pressure differential converts the potential energy of the delivery system 10 into kinetic energy that propels the bioactive material particles 46 onto the receiver 14. The velocity of these particles 46 can be controlled by suitable nozzle design and control over the rate of change of operating pressure and temperature within the system. Further, subsequent to the ejection of the formulation 42 from the nozzle 23 and the precipitation of the bioactive material 40, additional velocity regulation of the bioactive material 40 may be achieved using external devices such as electromagnetic fields, mechanical shields, magnetic lenses, electrostatic lenses etc. Nozzle design and location relative to the receiver 14 also determine the pattern of bioactive material 40 deposition. The actual nozzle design will depend upon the particular application addressed.
The nozzle 23 temperature can also be controlled via the nozzle heating module 26 shown in
The deposition characteristics of the bioactive material 40 are a function of several factors including the bulk modulus of the receiver 14, the bulk modulus of the bioactive material 40, density of the receiver 14, the density of the bioactive material 40, the pressure-difference between the formulation reservoir and ambient conditions, the temperature difference between the formulation reservoir and ambient conditions, the deposition time, the discharge nozzle geometry, the distance between the discharge nozzle and the receiver, bioactive material size and momentum, etc. These factors can be modified or held constant depending on the application. For example, in a printing application wherein the bioactive material 40 is to be deposited on the receiver surface, the nozzle geometry, formulation conditions, ambient conditions, and bioactive material can be fixed. The deposition of the bioactive material 40 can then be controlled by altering the receiver design (e.g. the bulk modulus of the receiver, the distance between the discharge nozzle and the receiver, the deposition time, etc.). Alternatively, for the same application, it is possible to alter formulation conditions (e.g. bioactive material concentration, etc.). Alternatively, for a printing application wherein the bioactive material 40 is to be deposited within the receiver, the deposition can be controlled by altering the receiver design (e.g. the bulk modulus of the receiver, formulation conditions, etc.), while keeping the other parameters fixed.
For a given constant nozzle geometry, constant conditions within the formulation reservoir, unchanging ambient conditions, constant deposition time, and a constant distance between the tip of the discharge nozzle and the receiver, the main receiver property that governs the accuracy of deposition of the bioactive material 40 is the receiver bulk modulus relative to the bioactive material bulk modulus. The bulk modulus of a material, typically expressed in Pascals, is a measure of its compressibility or its ability to absorb the momentum of a particle. Specifically, it is a measure of the change in volume of the material as the pressure is changed. It may be expressed isothermally or adiabatically. The isothermal bulk modulus is specified in this application.
The receiver can be a single layer as described in
Pascals can be converted to psi by multiplying by 1.45×10-4. One could also change the modulus by changing the gel layer structures as later described in
Referring to
When the beam control device 24 is an integral part of the discharge device 13, the functional material 40 is formed as the formulation moves through the beam control device 24. In this respect, the beam control device 24 can function as a focusing nozzle. As such, the nozzle 23 of the discharge device 13 can be replaced by the beam control device 24, as shown in
When additional focusing of the functional material is desired, the beam control device 24 can be positioned at the outlet 48 of the nozzle 23, as shown in
Alternatively, the beam control device 24 can be spaced apart from the nozzle 23 positioned in the material delivery path 16, as shown in
In one embodiment, a spacer-shield shown in
Again referring to
Alternatively, the aerodynamic lens 51 can include a first capillary tube of a given diameter in fluid communication with a second capillary tube of smaller diameter. These capillary tubes can also include one or more orifice plates 57, 61, 63 with smaller diameters.
The interface provided by a spacer-shield 25 between the orifice plate 57, 61, 63 and the target allows chemical reactions to occur, as well as phase changes to stabilize (such as a change from a solid to a liquid state). This interface may also provide flexibility in the distribution of the bioactive material 40, pharmaceutical composition, or drug across a larger target area, as compared to application of the bioactive material 40 from an orifice that abuts the target. Using existing solvent-less technology, distribution of the bioactive material 40 to the target may be carefully controlled, and exact dosing of the bioactive material 40 may be achieved. Controllers may be used to dispense simple or complex drug regimens, which is of particular advantage in patients 61 who require numerous daily medications. Computerized control of medication dosing, which may be programmed by medical personnel for subsequent automated delivery, can help avoid toxic drug interactions, overdosages, and deaths. Computerized control can mitigate against the forgetfulness of patients 61.
Referring to
The spacer-shield 25 may be carried by the delivery system 10 and positioned to be disposed against the cutaneous target (skin) while the delivery system 10 ejects the bioactive material 40 such as the pharmaceutical composition from the delivery system 10. A programmable microprocessor 77 in the transdermal applicator 63 may control ejection of the pharmaceutical composition from the delivery system 10 at pre-selected time intervals, such as every three or four hours, or even every few minutes or seconds, or ejection can be triggered by a sensor or other feedback mechanism.
Particles larger than about 250 μm can also be delivered from the devices, with the upper limitation being the point at which the size of the particles would cause untoward damage to the skin cells. The actual distance which the delivered particles will penetrate a target surface depends upon particle size (e.g., the nominal particle diameter assuming a roughly spherical particle geometry), particle density, the initial velocity at which the particle impacts the surface, and the density and kinematics viscosity of the targeted skin or mucosal tissue. In this regard, optimal particle densities for use in needleless injection generally range between about 0.1 and 25 g/cm3, preferably between about 0.9 and 1.5 g/cm3, and injection velocities can range from about 200 to about 3,000 m/sec.
The above mentioned conditions describe the physical properties necessary to allow bioactive materials to overcome the barrier properties, or the modulus of elasticity, of the stratum corneum layer of human skin. There is a great deal of variability in the modulus of elasticity of human skin. Factors influencing this would include age, sex, and location on the body. McElhaney et al. in the book “Handbook of Human Tolerance”, lists the effects of age on the modulus of elasticity
* Note -
the above information (modulus of elasticity data) has not been verified through the original text, library search is in progress.
As shown by
The delivery system 10 and applicator 63 may include the programming module 77, such as a keypad 81 for entering dosage information, a display screen 83 for showing what information has been entered on a display 100, and indicators 85 (such as one or more lights or a display screen on the exterior of the device) that provide information about how much drug remains in the device. Display screens 100 may also provide information about medications in the device, and provide an interface through which other information about the medications or their administration can be entered and/or obtained. The display may also provide information obtained by various sensors and/or monitors that may be provided in system 10. The sensors and/or monitors are used to monitor the subject to which the bio-active material is being applied. For example, but not limited to, the sensors may comprise a pulse oximetry sensor 91 for monitor pulse rate of the subject and oxygen levels in the blood of the subject. It is of course understood that various other sensors/monitors may be used to monitor other subject parameters. The information obtained by the sensors may be used as feed back for microprocessor 90 for controlling dispensing of the bioactive material by applicator 63. This may be in the form of a signal that generates a response in the delivery of the bio-active material. The sensors 91 may be optical sensors and may communicate the obtained information to the processor 90 by direct connection or by wireless infrared or radio communication. The system 10 may also be provided with audio and/or visual alarms to advising the status of the subject or of the operational conditions of the system 10.
The delivery system 10 may also include memory associated in the processor of a separate memory device 87. The memory may of course be used for storage of information or control data entered by the user or for storing of computer applications for controlling delivery system and its associated components. In addition, a removable memory 89, such as a memory card, may be received by the appropriate slot, which the computer/microprocessor can access for obtaining stored information for computer programs thereon. In this way the delivery system 10 may obtain new information for operating a new bioactive material and/or provide updated information for operating the delivery system 10 with respect to current or new bioactive materials.
The device 63 may be provided as part of a kit to be used by a subject. In addition to the device 63, instructions as to use may also be provided. Also transdermal patches may also be provided on which various bioactive material may be applied by device 63. The transdermal patch would then be applied to the subject. The kit may also include various other sensors and monitors to assist the user of the kit.
While the bioactive material 40 may be applied directly to skin surface 75 as shown in
Any of the many types of transdermal patches may be used, or modified for use with the delivery system. For example the Testoderm® transdermal system (Alza Pharmaceuticals) uses a flexible backing of transparent polyester, and a testosterone containing film of ethylene-vinyl acetate copolymer membrane that contacts the skin surface and controls the rate of release of active agent from the system. The surface of the drug containing film is partially covered by thin adhesive stripes of polyisobutylene and colloidal silicon dioxide, to retain the drug film in prolonged contact with the skin. In the present system, adhesive can be provided on both surfaces of the drug containing film, for example on both upper face 94 and under face 96 of patch 92, so that the flexible polyester backing 98 may be selectively removed to provide access to the drug-containing layer without removing the patch.
An adhesive release layer with openings in it can be provided between the patch 92 and backing 98, to help protect upper face 94 of patch 92 during repeated removals of backing 98. Alternatively, the patch 92 may be removed, recharged with the drug, and then reapplied, in which event the impermeable backing 98 may be permanently applied to patch 92. In this case, an adhesive layer 99 need only be present under surface 96 of patch 92. In yet other embodiments, there may be no impermeable backing, such as layer 98, over patch 92, so, for instance the selected drug may be continually administered, or the absorbency of the patch is sufficient to retain the drug in the patch without an impermeable backing. Further examples of transdermal patches that may be used or modified for use in the present system and method include the Nicoderm®, Latitude™ and Duragesic® patch.
Similarly, in the case of an orally taken time release medicine, semipermeable layers can also be used to control the release of bioactive particles into the stomach and intestines, however the diffusivity can be controlled via the RH at which time the release layer was formed as described above. Suppose the diffusivity at a given RH of each of the drugs composed the bioactive particles in both of the layers was the same. The patient would start seeing bioactive particle “A” 140 first and then bioactive particle “B” 141 once the diffusion was triggered by RH or contact.
Alternatively, the controller 200 can be used to adjust dosages of drug administered, for example for a particular time of day, an event (such as an activity that will require a dosage modification), or detection of a physiological condition (such as an adverse drug reaction that requires reduction or cessation of drug administration). When the delivery system 10 is used with a patch 100, the delivery system may be used to recharge the patch and avoid the necessity of changing the patch as often. Either with or without a patch, complex administration protocols may be followed, for example applying different drugs at different times throughout the day or longer period, for example as long as a week, a month, or even longer.
A number of use modes can be envisioned, for example, a patient can download information stored in the device about self-regulated dosage administrations or symptoms experienced (as indicated for example by which buttons have been depressed on the device, and/or the pattern and frequency of the buttons that are pushed). This information can be transmitted over a modem to a physician's or other health care provider's office, where it can be displayed (in electronic or other form) to a health care professional, and appropriate action can be taken. For example, if symptoms are noted to be increasing in spite of administration of a therapeutic amount of a particular drug, consideration can be given to providing a new drug or reconsidering the diagnosis for which the drug has been administered.
As illustrated in
Alternatively, power may be supplied from an external source, such as a standard electrical outlet not shown. Of course, rechargeable or replaceable batteries may be preferred in some embodiments for ease of portability and use. Controller 200 operates to apply firing signals to the delivery systems 151, 152, and 153, which respond by delivering bioactive materials.
In a more sophisticated embodiment shown in
Alternatively, keypad 215 may be eliminated and the controller 200 programmed to display various selections on screen 220. Use of a pair of scrolling buttons 230 and 235 may allow different instructions or selections to be scrolled across, or up and down along, screen 220, including such information such as desired dosages, frequency, and potential side effects.
Display screen 220 may also indicate various selections along an upper portion of the screen allowing a user to then select a particular drug, dosage or delivery method. Alternatively, selecting a particular drug or dosage could indicate the occurrence of a particular event, such as an adverse medication response that would alter (for example decrease) a subsequent dosage administration, or an event (such as physical exertion) that can signal a need to alter a medication dosage. The controller can also be programmed to prevent unauthorized alteration of dosages, for example an increase in a dosage of a controlled substance above that authorized by the prescribing physician. Alternatively, the controller can permit certain ranges of dosages to be administered, for example various doses of an opioid pain reliever in response to fluctuating pain.
In certain examples as illustrated in
While each of the container modules 305, 306, and 307 may carry different bioactive materials, it may also be convenient to have each container module 305, 306, and 307 carry the same materials, with controller 200, shown in
In another embodiment of the present invention, which relates generally to the controlled formation of nanometer-sized particles and/or molecular clusters of substances of interest by a Supercritical Anti-Solvent (SAS) type process as is disclosed in U.S. Ser. No. 10/814,354 filed Mar. 31, 2004 entitled PROCESS FOR THE FORMATION OF PARTICULATE MATERIAL by Rajesh Vinodrai Mehta, et al., U.S. Ser. No. 10/815,026 filed Mar. 31, 2004 entitled PROCESS FOR THE DEPOSITION OF UNIFORM LAYER OF PARTICULATE MATERIAL by Rajesh Vinodrai Mehta, and U.S. Ser. No. 10/815,010 filed Mar. 31, 2004 entitled PROCESS FOR THE SELECTIVE DEPOSITION OF PARTICULATE MATERIAL by Rajesh Vinodrai Mehta, all of which are incorporated by reference herein in their entirety and are explained in detail below.
Now referring to
Using the SAS process described above, it has been found that nanometer sized particles of a desired substance can be prepared by precipitation of the desired substance from a solution upon contact with a supercritical fluid anti-solvent under conditions as described herein. In practicing this invention, feed materials, i.e., the supercritical fluid anti-solvent and the solvent/solute solution are intimately mixed in a particle formation vessel in a zone of highly agitated turbulent flow to precipitate particles of the solute. The particles are then expelled from the highly agitated zone by action of bulk mixing in the particle formation vessel. In practicing the invention, it is generally desirable to introduce the feed streams into the highly agitated mixing zone in opposing directions although they can be introduced in the same direction, if desired. A significant feature of this invention is that precipitated particles of sizes less than 100 nanometers can be produced free of high levels of non-uniform large particles.
In this embodiment of the invention, the process may be performed in an essentially continuous manner by exhausting supercritical fluid, solvent and the desired substance from the particle formation vessel at a rate substantially equal to the rate of addition of such components to the vessel in step, while maintaining temperature and pressure in the vessel at a desired constant level, such that formation of particulate material occurs under essentially steady-state continuous conditions. Such continuous operation is believed to be facilitated by the very fine nature of the precipitated particles, which allows the supercritical fluid, solvent and desired substance to be simply exhausted from the particle formation vessel by passage to an expansion chamber. In such embodiment, passage to the expansion chamber may be through, e.g., a backpressure regulator, a capillary, or a flow distributor. Once passed to the expansion chamber, the particles of the desired substance may be collected without interruption of the precipitation in the agitated particle formation vessel. If desired, supercritical fluid, solvent and desired substance may be exhausted from the particle formation vessel directly into a solution to form a dispersion of the formed particles of the desired substance.
Since the process of the present invention produces fine powder that is comparable to those produced by RESS techniques, RESS-based thin film deposition techniques (including method and apparatus, with minor changes to account for low level of organic solvent present in the supercritical mixture) may also be employed for the particles produced by the present invention.
Very fine particles obtained in accordance with the invention may also be printed, coated, or otherwise deposited upon expansion of the supercritical fluid mixture, similarly as described in the deposition or printing processes of WO 02/45868 A2, U.S. Pat. No. 6,471,327, U.S. Pat. No. 6,692,906, U.S. 2002/0118246 A1, U.S. 2002/0118245 A1, and U.S. 2003/0107614, or as described in pending applications U.S. Ser. No. 10/815,010 and U.S. Ser. No. 10/815,026, the disclosures of which are incorporated by reference herein. Very fine particles obtained in accordance with the invention may further also be printed, coated, or otherwise deposited upon expansion of the supercritical fluid mixture in process similarly as described in copending, commonly assigned U.S. Ser. No. 10/313,549 filed Dec. 6, 2002 entitled SYSTEM FOR PRODUCING PATTERNED DEPOSITION FROM COMPRESSED FLUIDS by Suresh Sunderrajan et al.; U.S. Ser. No. 10/313,587 filed Dec. 6, 2002 entitled METHOD FOR PRODUCING PATTERNED DEPOSITION FROM COMPRESSED FLUID by Ramesh Jagannathan et al.; U.S. Ser. No. 10/460,814 filed Jun. 12, 2003 entitled A METHOD OF MANUFACTURING A COLOR FILTER by Sridhar Sadasivan et al.; U.S. Ser. No. 10/314,379 filed Dec. 6, 2002 entitled SYSTEM FOR PRODUCING PATTERNED DEPOSITION FROM COMPRESSED FLUID IN A DUAL CONTROLLED DEPOSITION CHAMBER by David J. Nelson, et al.; U.S. Ser. No. 10/313,427 filed Dec. 6, 2002 entitled SYSTEM FOR PRODUCING PATTERNED DEPOSITION FROM COMPRESSED FLUID IN A PARTIALLY OPENED DEPOSITION CHAMBER by David J. Nelson et al.; U.S. Ser. No. 10/313,591 filed Dec. 6, 2002 entitled APPARATUS AND METHOD FOR MAKING A LIGHT-EMITTING DISPLAY by Sridhar Sadasivan et al. (supercritical CO2 based marking system to make organic small molecule and polymeric light emitting diode devices); U.S. Ser. No. 10/224,783 filed Aug. 21, 2002 entitled SOLID STATE LIGHTING USING COMPRESSED FLUID COATING by Ramesh Jagannathan et al.; U.S. Ser. No. 10/300,099 filed Nov. 20, 2002 entitled SOLID STATE LIGHTING USING COMPRESSED FLUID COATINGS by Ramesh Jagannathan et al.; U.S. Ser. No. 0/602,429 filed Jun. 24, 2003 entitled AN APPARATUS AND M ETHOD OF COLOR TUNING A LIGHT-EMITTING DISPLAY by Sridhar Sadasivan et al., U.S. Ser. No. 10/602,134 filed Jun. 24, 2003 entitled A LIGHT EMITTING DISPLAY by Sridhar Sadasivan et al.; U.S. Ser. No. 10/602,430 filed Jun. 24, 2003 entitled AN ARTICLE HAVING MULTIPLE SPECTRAL DEPOSITS by David J. Nelson et al.; U.S. Ser. No. 10/602,840 filed Jun. 24, 2003 entitled AN APPARATUS AND METHOD OF PRODUCING MULTIPLE SPECTRAL DEPOSITS FROM A MIXTURE OF A COMPRESSED FLUID AND A MARKING MATERIAL by David J. Nelson et al.; and U.S. Ser. No. 10/625,426 filed Jul. 23, 2003 entitled AUTHENTICATION METHOD AND APPARATUS FOR USE WITH COMPRESSED FLUID PRINTED SWATCHES by Seshadri Jagannathan et al., the disclosures of which are incorporated by reference herein.
In accordance with various embodiments, the present invention provides technologies that permit functional material deposition of ultra-small particles; that permit high speed, accurate, and precise deposition of a functional material on a receiver; that permits high speed, accurate, and precise patterning of ultra-small features on the receiver; that provide a self-energized, self-cleaning technology capable of controlled functional material deposition in a format that is free from receiver size restrictions; that permits high speed, accurate, and precise patterning of a receiver that can be used to create high resolution patterns on the receiver; that permits high speed, accurate, and precise patterning of a receiver having reduced functional material agglomeration characteristics; that permits high speed, accurate, and precise patterning of a receiver using a mixture of nanometer sized functional material dispersed in dense fluid; that permits high speed, accurate, and precise patterning of a receiver using a mixture of one or more nanometer sized functional materials dispersed in dense fluid and where the nanometer sized functional materials are created by precipitation under steady state conditions; that permits high speed, accurate, and precise patterning of a receiver using a mixture of nanometer sized one or more functional material dispersed in dense fluid and where the nanometer sized functional materials are created as a dispersion in a dense fluid under steady state conditions in a vessel containing a mixing device or devices; that permits high speed, accurate, and precise patterning of a receiver that has improved material deposition capabilities; that provide a more efficient printing method without the previous limitations on the amount of functional material that could be used due to solubility in the compressed fluid; and that permit the use of very small orifice size print head nozzles without the need for filtration by ensuring that the functional material particles are all of a size range not to exceed 2 microns.
The invention has been described with reference to a preferred embodiment, however, it will be appreciated that variations and modifications can be effected by a person of ordinary skill in the art without departing from the scope of the invention.
Reference is made to commonly assigned U.S. patent application Ser. No. 10/814,354, filed Mar. 31, 2004, entitled, “PROCESS FOR THE FORMATION OF PARTICULATE MATERIAL” by Rajesh Vinodria Mehta et al.
