Rotary reactor for uniform particle coating with thin films

Abstract

To provide a reactor for coating particles and a coating method.SOLUTION: A reactor according to the present invention includes: one or more motors; a rotary vacuum chamber configured to hold particles to be coated and coupled to the motors which rotate the chamber in a first direction about an axial axis of a cylinder portion of the rotary vacuum chamber; a vacuum port to exhaust gas from the rotary vacuum chamber; a paddle assembly including a rotatable drive shaft extending through the rotary vacuum chamber and coupled to the one or more motors, and at least one paddle extending radially from the drive shaft, such that rotation of the drive shaft by the motors orbits the paddle about the drive shaft in a second direction; and a chemical material delivery system including a gas outlet on the paddle configured inject process gas into the particles.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority to U.S. Provisional Patent Application No. 62 / 683,763, filed Jun. 12, 2018, the disclosure of which is incorporated herein by reference.

[0002] This disclosure relates to coating particles, e.g., particles containing an active pharmaceutical ingredient, with thin organic and inorganic films.

Background Art

[0003] Developing improved formulations of active pharmaceutical ingredients (APIs) is of great interest to the pharmaceutical industry. Formulations can affect the stability and bioavailability of APIs, as well as other properties. Formulations can also affect various aspects of drug product (DP) manufacturing, such as the ease and safety of the manufacturing process.

[0004] Numerous techniques have been developed for encapsulating or coating APIs. Some existing techniques for API coating include spray coating, plasma polymerization, thermal chemical vapor deposition (CVD), and rotary reactors. Spray coating is an industrially scalable technique widely adopted in the pharmaceutical industry. However, the non-uniformity of the coating (both within particles and from particle to particle) hinders the use of these techniques to improve the supply profile or stability of the active pharmaceutical ingredient (API). Particle aggregation during spray coating also poses a significant challenge. On the other hand, techniques such as plasma polymerization are difficult to scale, applicable only to specific precursor chemicals, and may cause degradation of sensitive APIs. A thermal ray system that utilizes a cold substrate as a condensation medium for gases and radicals has been developed. Rotary reactors include atomic layer deposition (ALD) and initiated CVD (iCVD) reactors. However, ALD reactors are suitable for inorganic coatings but not for organic polymer coatings, and existing iCVD designs do not sufficiently prevent API degradation and are not scalable for mass production. Other techniques include polymer mesh coating, pan coating, aerosolized coating, and fluidized bed reactor coating. Summary of the Invention

[0005] Generally, one innovative aspect of the subject matter described herein is a rotary vacuum chamber configured to hold one or more motors and a plurality of particles to be coated, wherein the cylindrical portion of the rotary vacuum chamber has an inner diameter, the rotary vacuum chamber is connected to one or more motors, and the rotary vacuum chamber is rotated in a first direction about the axial axis of the cylindrical portion of the rotary vacuum chamber, a rotary vacuum chamber, a vacuum port for exhausting gas from the rotary vacuum chamber, a rotatable drive shaft extending through the rotary vacuum chamber along the axial axis of the rotary vacuum chamber, and a paddle assembly including at least one paddle extending radially from the drive shaft, wherein the rotatable drive shaft is connected to one or more motors such that rotation of the drive shaft by the one or more motors causes the at least one paddle to orbit in a second direction about the drive shaft, a paddle assembly, and a chemical substance supply system configured to inject a process gas into the particles, wherein the at least one paddle includes a gas outlet of the chemical substance supply system for injecting the process gas into the particles, and can be implemented in a reactor for coating the particles.

[0006] Embodiments may include one or more of the following features. In some embodiments, the rotation in the first direction is in the same rotational direction as the rotation in the second direction, e.g., clockwise or counterclockwise.

[0007] In some embodiments, the gas outlet of the chemical substance supply system is located on the trailing edge of the at least one paddle.

[0008] In some embodiments, the vacuum port is located in line with the axial axis of the rotary vacuum chamber.

[0009] In some embodiments, at least one paddle is one of a plurality of paddles configured to sweep along the axial axis of the rotary vacuum chamber and along the entire length of the rotary vacuum chamber. The at least one paddle may further include an anti-static brush located between the outer edges of the paddle and contacting the surface of the inner diameter of the rotary vacuum chamber.

[0010] In some embodiments, the reactor further includes a port for supplying particles to or receiving particles from the rotary vacuum chamber.

[0011] In some embodiments, the axial axis of the rotary vacuum chamber is oriented horizontally with respect to gravity.

[0012] Generally, another aspect of the subject matter described herein is a reactor for coating particles, comprising one or more motors, a rotary vacuum chamber configured to hold a plurality of particles to be coated, the cylindrical portion of the rotary vacuum chamber having an inner diameter, a rotary vacuum chamber coupled to the one or more motors, a controller configured to rotate the rotary vacuum chamber about the axial axis of the cylindrical portion of the rotary vacuum chamber in a first direction at a rotational speed sufficient to centrifuge the plurality of particles against the inner diameter of the rotary vacuum chamber by the one or more motors, a vacuum port for evacuating gas from the rotary vacuum chamber, a rotatable drive shaft extending through the rotary vacuum chamber along the axial axis of the rotary vacuum chamber, and a paddle assembly including at least one paddle extending radially from the drive shaft, wherein the rotatable drive shaft is coupled to the one or more motors such that rotation of the drive shaft by the one or more motors causes the at least one paddle to orbit in a second direction around the drive shaft, and a chemical supply system configured to inject a process gas into the particles, the chemical supply system including the at least one paddle including a gas outlet of the chemical supply system for injecting the process gas into the particles.

[0013] In some embodiments, the controller is configured to rotate the rotary vacuum chamber around an axial axis at a rotational speed greater than 15 RPM to one or more motors. The rotational speed of the drive shaft relative to the rotary vacuum chamber around the axial axis can be at least 4 rpm.

[0014] In some embodiments, the reactor further includes a base for supporting the reactor on a mounting surface, and the rotary vacuum chamber is fixed to the base such that the axial axis is perpendicular to the mounting surface.

[0015] In some embodiments, rotation in the first direction is in a rotational direction opposite to rotation in the second direction.

[0016] In some embodiments, at least one paddle includes a scoop-shaped feature including a plurality of teeth such that the teeth of the paddle contact the particles when the chemical substance supply system injects the process gas into the particles. The gas outlet of the chemical substance supply system can be located at the trailing edge of at least one of the plurality of teeth of the scoop-shaped feature of the paddle. The outer edge of the paddle can be separated from the surface of the inner diameter of the rotary vacuum chamber by a gap, such as a gap of 1-3 mm.

[0017] In some embodiments, at least one paddle includes a T-shaped feature including a segment parallel to the surface of the inner diameter of the rotary vacuum chamber.

[0018] Generally, another aspect of the subject matter described herein can be implemented by a method including the operations of distributing particles within a rotary vacuum chamber, rotating the rotary vacuum chamber in a first direction along an axial axis of the rotary vacuum chamber such that the particles form a toroid on the inner wall of the rotary vacuum chamber, evacuating the chamber through a vacuum port within the rotary vacuum chamber aligned on the axial axis of the rotary vacuum chamber, rotating a paddle assembly in a second direction such that a plurality of paddles orbit a drive shaft, and injecting a process gas into the particles through a plurality of gas outlets located on the plurality of paddles.

[0019] In some embodiments, the method includes coating the particles by atomic layer deposition or molecular layer deposition.

[0020] Generally, another aspect of the subject matter described herein is a rotary vacuum chamber configured to hold one or more motors and a plurality of particles to be coated, wherein the cylindrical portion of the rotary vacuum chamber has an inner diameter, and the rotary vacuum chamber is connected to one or more motors; a controller configured to rotate the rotary vacuum chamber in a first direction around the axial axis of the cylindrical portion of the rotary vacuum chamber at a rotational speed such that the particles are subjected to tumbling agitation; a vacuum port for exhausting gas from the rotary vacuum chamber; a paddle assembly including a rotatable drive shaft extending through the rotary vacuum chamber along the axial axis of the rotary vacuum chamber and at least one paddle extending radially from the drive shaft, wherein the rotatable drive shaft is connected to one or more motors such that at least one paddle orbits around the drive shaft in a second direction by rotation of the drive shaft by one or more motors; and a chemical supply system configured to inject a process gas into the particles, wherein at least one paddle includes a gas outlet of the chemical supply system for injecting the process gas into the particles. The reactor can be implemented in a reactor including the chemical supply system.

[0021] In some embodiments, the controller is configured to rotate the rotary vacuum chamber around the axial axis at a rotational speed of less than 6 rpm.

[0022] The rotational speed of the drive shaft relative to the rotary vacuum chamber around the axial axis can be selected such that the relative movement of the paddle 158 in the powder does not cause grinding and / or damage to the powder during the rotational movement of the rotary vacuum chamber and the paddle assembly.

[0023] In some embodiments, the reactor further includes a stationary vacuum chamber, where the rotating vacuum chamber is disposed within the stationary vacuum chamber.

[0024] In some embodiments, the reactor further includes a vacuum pump that is connected to the stationary vacuum chamber and to the vacuum port to exhaust gas from the rotating vacuum chamber. The chemical supply system and the one or more motors can be connected to the stationary vacuum chamber.

[0025] In some embodiments, the rotating vacuum chamber further includes the inner diameter surface of the rotating vacuum chamber having a horizontal baffle or an angled baffle.

[0026] Generally, another aspect of the subject matter described herein can be implemented by a method that includes the operations of distributing particles within a rotating vacuum chamber, rotating the rotating vacuum chamber in a first direction along the axial axis of the rotating vacuum chamber so that the particles fill the lower portion of the rotating vacuum chamber when the rotating vacuum chamber is rotating in the first direction, evacuating the chamber through a vacuum port within the rotating vacuum chamber that is aligned on the axial axis of the rotating vacuum chamber, rotating a paddle assembly in a second direction so that a plurality of paddles orbit a drive shaft, and injecting a process gas into the particles through a plurality of gas outlets located on the plurality of paddles.

[0027] In some embodiments, the method includes coating the particles by atomic layer deposition or molecular layer deposition.

[0028] In some embodiments, the particles include a core containing a drug.

[0029] In some embodiments, the rotating vacuum chamber is configured to perform initiated chemical vapor deposition.

[0030] In some embodiments, the method further includes depositing an organic or inorganic coating on the particles. The organic or inorganic coating can be an inorganic metal oxide. The organic or inorganic coating can be an organic polymer.

[0031] Embodiments can include one or more of the following possible advantages, but are not limited thereto. Particles (e.g., API particles) can be coated in a mass production process, thereby providing lower manufacturing costs and reduced pharmaceutical prices. The particles can be coated with a thin layer(s), thus providing a pharmaceutical having an advantageous volume fraction of the API. Further, this process results in a layer(s) encapsulating the API that is uniform within and between the particles, and can provide consistent properties to the drug formulation.

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials for use in the present invention are described herein, and other suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting.

[0033] Other features and advantages of the present invention will become apparent from the following detailed description, drawings, and claims.

Brief Description of the Drawings

[0034]

Figure 1

Figure 2

Figure 3A

Figure 3B

Figure 4

Figure 5

Figure 6A-C

Figure 6D-G

Figure 7

Figure 8

DETAILED DESCRIPTION OF THE INVENTION

[0035] The same reference numbers and symbols in the various drawings represent the same elements.

[0036] There are various methods for encapsulating API particles. In many cases, these methods result in relatively thick coatings. Such coatings can impart desirable properties, but due to the high ratio of coating to API, it can be difficult to produce pharmaceuticals with a desired high volume fraction of API. Further, the coatings encapsulating the API can be non-uniform, making it difficult to provide formulations with consistent properties. Additionally, coating techniques that could provide satisfactory consistency were not scalable for industrial manufacturing.

[0037] A method capable of addressing these problems is to use a rotating "drum" in which particles are centrifuged against the inner wall of the rotating drum through the rotational movement of the drum in a first direction, and paddles rotating in a second direction (e.g., the same or opposite direction as the first direction) agitate the particle bed. The process gas can be injected into the particle bed through a gas outlet located on the paddles. Thereby, the process gas can penetrate through the particle bed and improve the uniformity of the coating over the particles.

[0038] Another method capable of addressing these problems is to use a rotating vacuum chamber "drum" in which the particles are agitated by both the rotation of the rotating vacuum chamber and the paddles of a paddle assembly rotating with respect to the rotating vacuum chamber, and the process gas is injected into the particles through a gas outlet located on the paddles. Thereby, the process gas can penetrate through the particles and improve the uniformity of the coating over the particles.

[0039] Drug The term "drug" in its broadest sense includes all small molecule (e.g., non-biological) APIs. Drugs can be selected from the group consisting of analgesics, anesthetics, anti-inflammatory drugs, anthelmintics, antiarrhythmics, anti-asthma drugs, antibiotics, anti-cancer drugs, anticoagulants, antidepressants, diabetes drugs, anti-epileptic drugs, antihistamines, cough suppressants, antihypertensive drugs, antimuscarinics, antiseptics, antineoplastic drugs, antioxidants, antipyretics, immunosuppressive drugs, immunostimulants, anti-thyroid drugs, antiviral drugs, anxiolytics, hypnotics, nerve blockers, astringents, bacteriostatics, beta-adrenergic blockers, blood products, blood substitutes, bronchodilators, buffers, cardiotonics, chemotherapeutic drugs, contrast agents, corticosteroids, cough medicines, expectorants, mucolytics, diuretics, dopaminergics, anti-Parkinson's drugs, free radical scavengers, growth factors, hemostatics, immunizing agents, lipid regulators, muscle relaxants, parasympathomimetics, parathyroid calcitonin, bisphosphonates, prostaglandins, radiopharmaceuticals, hormones, sex hormones, anti-allergy drugs, appetite stimulants, anorectics, steroids, sympathomimetics, thyroid agents, vaccines, vasodilators, and xanthines.

[0040] Exemplary types of small molecule drugs include, but are not limited to, acetaminophen, clarithromycin, azithromycin, ibuprofen, fluticasone propionate, salmeterol, pazopanib HCl, palbociclib, and amoxicillin potassium clavulanate.

[0041] Pharmaceutically acceptable excipients, diluents, and carriers Pharmaceutically acceptable excipients include, but are not limited to, the following. (1) Surfactants and polymers including polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), sodium lauryl sulfate, polyvinyl alcohol, crospovidone, polyvinylpyrrolidone-polyvinyl acrylate copolymer, cellulose derivatives, hydroxypropyl methylcellulose, hydroxypropyl cellulose, carboxymethyl ethyl cellulose, hydroxypropyl methylcellulose phthalate, polyacrylate and polymethacrylate, urea, sugar, polyol, carbomer and their polymers, emulsifiers, gum, starch, organic acids and their salts, vinylpyrrolidone and vinyl acetate, (2) Binders such as cellulose, crosslinked polyvinylpyrrolidone, microcrystalline cellulose, (3) Fillers such as lactose monohydrate, lactose anhydrous, microcrystalline cellulose, and various starches, (4) Lubricants such as colloidal silicon dioxide, talc, stearic acid, magnesium stearate, calcium stearate, and agents acting on the fluidity of compressed powders including silica gel, (5) Sweeteners such as any natural or artificial sweeteners including sucrose, xylitol, sodium saccharin, cyclamate, aspartame, and acesulfame K, (6) Flavors, (7) Preservatives such as potassium sorbate, methyl paraben, propyl paraben, benzoic acid and its salts, other esters of p-hydroxybenzoic acid such as butyl paraben, alcohols such as ethyl or benzyl alcohol, phenolic chemicals such as phenol, or quaternary compounds such as benzalkonium chloride, (8) Buffers, (9) Diluents such as pharmaceutically acceptable inert fillers such as microcrystalline cellulose, lactose, calcium hydrogen phosphate, saccharides, and / or any mixture of the foregoing, (10) Wetting agents such as corn starch, potato starch, corn starch, and modified starch, and mixtures thereof, (11) Disintegrants such as croscarmellose sodium, crospovidone, sodium starch glycolate, (12) Foaming agents such as foaming couples such as organic acids (e.g., citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, and alginic acid and anhydrides and acid salts), or carbonates (e.g., sodium carbonate, potassium carbonate, magnesium carbonate, sodium glycine carbonate, L-lysine, and arginine carbonate) or bicarbonates (e.g., sodium bicarbonate or potassium bicarbonate).

[0042] Metal oxide materials The term "metal oxide materials" includes, in its broadest sense, all materials formed from the reaction of an element considered to be a metal with an oxygen-based oxidizing agent. Exemplary metal oxide materials include, but are not limited to, aluminum oxide, titanium dioxide, iron oxide, gallium oxide, magnesium oxide, zinc oxide, niobium oxide, hafnium oxide, tantalum oxide, lanthanum oxide, and zirconium dioxide. Exemplary oxidizing agents include, but are not limited to, water, ozone, and inorganic peroxides.

[0043] Atomic layer deposition (ALD) Atomic layer deposition is a thin film deposition technique that enables the deposition of a film with a thickness and uniformity controlled at the atomic or molecular monolayer level by the sequential addition of self-limiting monolayers of elements or compounds. Self-limiting means that only a single atomic layer is formed at a time, and subsequent process steps are required to regenerate the surface and enable further deposition.

[0044] Molecular layer deposition (MLD) Molecular layer deposition is similar to atomic layer deposition but uses organic precursors to form organic thin films. During a typical MLD process, two homo-bifunctional precursors are used. The first precursor is introduced into the chamber. The molecules of the first precursor react with the reactive groups on the substrate surface via the corresponding linking chemistry, adding a molecular layer of the first precursor on the substrate surface with new reactive sites. After purging, the second precursor is introduced, and the molecules of the second precursor react with the new reactive sites provided by the first precursor to produce a molecular layer of the first precursor linked to the second precursor. Subsequently, another purge cycle is performed.

[0045] Reactor system Figures 1-2 show a reactor system 100 for coating particles by thin film coating. The reactor system 100 can perform coating using ALD and / or MLD coating conditions. The reactor system 100 enables the deposition process (ALD or MLD) to be carried out at a higher (above 50 °C, for example 50-100 °C) or lower processing temperature, for example below 50 °C, for example 35 °C or below. For example, the reactor system 100 can form a thin film metal oxide on the particles mainly by ALD at a temperature of 22-35 °C, for example 25-35 °C, 25-30 °C, or 30-35 °C. Generally, the particles can stay or be maintained at such a temperature. Thereby, the reaction gas and / or the inner surface of the reactor chamber can stay or be maintained at such a temperature. For example, heating can be achieved by a heater cartridge embedded within the chamber body, a water channel within the chamber body using a heat exchanger, or a heater jacket on the chamber body.

[0046] The reactor system 100 includes a stationary vacuum chamber 110 surrounding a rotating vacuum chamber 112. The stationary vacuum chamber 110 is surrounded by an outer chamber wall 114. The rotating vacuum chamber 112 is surrounded by an inner chamber wall 116. The chamber walls 114 and 116 can be made of a material inert to the deposition process (e.g., stainless steel), and / or the inner surfaces of the chamber walls 114 and 116 can be coated with a material inert to the deposition process.

[0047] The cross-section of the rotating vacuum chamber 112 can be uniform along the length of the chamber 112 (e.g., when viewed along the central axis of the cylinder) (the length is along the central axis of the cylinder). This can help ensure a uniform gas flow along the length of the chamber.

[0048] The stationary vacuum chamber 110 may include one or more vacuum ports 118 for exhausting gas (e.g., process gas) from the stationary vacuum chamber 110 and the rotary vacuum chamber 112. The stationary vacuum chamber includes a gas inlet port 120 connected to a chemical supply system 122 located outside the stationary vacuum chamber 110. The gas inlet port 120 further connects the process gas from the gas inlet port 120 located in the stationary vacuum chamber, through a gas supply manifold 124, to a gas inlet port 126 located on the central axis 165 of the rotary vacuum chamber 112. Although the gas supply manifold 124 is schematically depicted in FIG. 1 as entering the chamber along the perimeter of the cylindrical chamber, in the embodiment described with reference to FIGS. 1 and 2, the gas supply manifold is collinear with the central axis of the chamber 112 through a passage (e.g., shown in FIG. 2) within the drive shaft 156.

[0049] System 100 includes one or more motors 130a, 130b external to the stationary vacuum chamber 110 configured to provide torque to convert the rotational movement of one or more components of the system 100. Motors 130a, 130b can be, for example, a drum motor 130a and a paddle motor 130b. Motors 130a and 130b can be, for example, brushless direct current (DC) motors. In some embodiments, motors 130a and 130b incorporate gear reduction, for example, at a ratio of 20:1.

[0050] The drum motor 130a is connected to the rotary vacuum chamber 112 and is configured to provide torque that is converted into the rotational movement of the rotary vacuum chamber 112 during operation of the system 100. The paddle motor 130b is connected to the paddle assembly 132 and is configured to provide torque that is converted into the rotational movement of the paddle assembly during operation of the system 100. Although described with reference to FIGS. 1 and 2 as the drum motor 130a and the paddle motor 130b, fewer or more motors can be configured to provide torque that is converted into the rotational movement of one or more components of the system 100.

[0051] System 100 includes a vacuum source 134 (e.g., one or more vacuum pumps) connected to a vacuum port 118 via a gas exhaust manifold 136. In some embodiments, a gas source 139 is connected to the gas exhaust manifold 136 (e.g., a purge gas for diluting process gas exhausted from System 100). The gas exhaust manifold 136 is configured to establish a vacuum within a stationary vacuum chamber 110 and a rotating vacuum chamber 112. The vacuum source 134 can be an industrial vacuum pump sufficient to establish a pressure of less than 1 Torr (e.g., 1 - 100 mTorr, e.g., 50 mTorr). The vacuum source 134 enables chambers 110, 112 to be maintained at a desired pressure and removes reaction by-products and unreacted process gas.

[0052] The chemical supply system 122 includes a plurality of fluid sources 138 connected by respective supply tubes 140, controllable valves 142, and fluid supply lines 144. The chemical supply system 122 supplies fluid to a gas supply manifold 124, which injects the fluid in vapor form into the rotating vacuum chamber 112 via a gas inlet port 126. The gas inlet port 126 is further connected to a paddle manifold 164 that is connected to one or more gas outlets 166 (shown in FIG. 2) located on at least one paddle 158 of the paddle assembly 132. The chemical supply system 122 can include a combination of restrictors, gas flow controllers, pressure transducers, and thermal mass flow controllers / meters to provide a controllable flow rate of various gases to the rotating vacuum chamber 112. The chemical supply system 122 can also include one or more temperature control components (e.g., heat exchangers, resistance heaters, etc.) to heat or cool the various gases before they enter the chamber 112.

[0053] The chemical substance supply system 122 may include five fluid sources 138a, 138b, 138c, 138d, 138e. Two of the fluid sources (e.g., fluid sources 138a, 138b) can provide two chemically different precursors or reactants for a deposition process to form a metal oxide layer on particles. For example, the first fluid source 138a can provide trimethylaluminum (TMA) or titanium tetrachloride (TiCl4), while the fluid gas source 138b can provide water. Another two fluid sources (e.g., fluid sources 138c, 138d) can provide two chemically different precursors or reactants for a deposition process to form a polymer material on the metal oxide layer. For example, the third fluid source 138c can provide adipoyl chloride, and the fourth gas source 138d can provide ethylenediamine. One of the fluid sources (e.g., the fifth fluid source 138e) can provide an inert gas (e.g., argon or N2) for purging during a cycle or half-cycle of the deposition process.

[0054] FIG. 1 shows five fluid sources, but the use of fewer gas sources can still be compatible with the deposition of metal oxide or polymer layers, and the use of more gas sources could enable the formation of a wider range of laminated structures.

[0055] For one or more of the fluid sources, the chemical substance supply system 122 supplies the precursor or reactant in liquid form to the gas supply manifold 124. The chemical substance supply system 122 may include a vaporizer 146 for converting the liquid to vapor immediately before the precursor or reactant enters the gas inlet 120. This reduces upstream pressure loss and more pressure loss may occur across the particles 148 in the chamber 112. The greater the pressure loss occurring across the particles 148, the lower the placement of the injection orifice can be, and the more likely it is that all of the precursor will react as the precursor crosses the particle bed at a given flow rate. The vaporizer 146 can be directly adjacent to, for example, the outer wall of the stationary vacuum chamber 110, which is fixed to or housed adjacent to the gas inlet port 120.

[0056] As shown in FIG. 1, the gas supply manifold 124 can be utilized to supply a plurality of precursor or reactant fluid sources 138. The manifold 151 is fluidly connected to the gas inlet port 120.

[0057] The rotary vacuum chamber 112 is encapsulated within and supported by the stationary vacuum chamber 110. The rotary vacuum chamber 112 includes an inner surface 150 along the inner diameter of the chamber wall 116. In some embodiments, as depicted in FIGS. 1 and 2, the rotary vacuum chamber includes a cylindrical portion and the axis of rotation is aligned on the central axis of the cylinder. The rotary vacuum chamber 112 is connected to a vacuum-tight rotary union and is connected to the stationary vacuum chamber 110 by threads inside the rotary vacuum chamber 112 via a rotary motion feedthrough 129, as depicted in FIG. 2.

[0058] Referring now to FIG. 2, the rotary vacuum chamber 112 is coupled to one or more motors (e.g., drum motor 130a), where the drum motor 130a is operable to generate torque that can be converted into a rotational movement of the rotary vacuum chamber in a first direction 152 (e.g., clockwise with respect to the axial axis Q-Q). The coupling between the rotary vacuum chamber 112 and the one or more motors can pass through a rotary motion vacuum feedthrough 128 as depicted in FIG. 2. To convert the torque output from the motor 130a into a rotational movement of the rotary vacuum chamber 112 in the first direction 152, one or more mechanical couplings 154 can be utilized between the drum motor 130a and the rotary vacuum chamber 112. In some embodiments, the mechanical coupling 154 can be a belt and pulley system, and the belt can have a compliance that allows for some misalignment and wobbling of the drum motor 130a and the rotary vacuum chamber 112. The movement of the rotary vacuum chamber 112 can be clockwise (CW), counterclockwise (CCW), or alternating between CW and CCW. In some embodiments, the port 113 of the rotary vacuum chamber is coupled to a rotary motion feedthrough 129 by a key block to transfer torque between the drum motor 130a and the rotary vacuum chamber 112.

[0059] The paddle assembly 132 includes a drive shaft 156 and one or more paddles 158 coupled to the drive shaft 156. The drive shaft 156 is oriented along the axial axis Q-Q of the rotary vacuum chamber 112. The paddles 158 are secured to the drive shaft 156 along the length of the drive shaft 156. The paddles are arranged such that the outer surface 115 of the paddles 158 is spaced from the inner surface 150 of the rotary vacuum chamber 112 by a threshold distance (e.g., gap 117). Details of the paddles 158 will be described later.

[0060] The paddle assembly 132 is coupled to one or more motors (e.g., paddle motor 130b) outside the vacuum chamber 110 via a rotary vacuum feedthrough 128 (e.g., including a vacuum-compatible bearing). The paddle motor 130b is configured to apply torque to the drive shaft 156 such that the drive shaft 156 rotates about an axis of the central axis 118 that is aligned with the axis Q-Q of the drive shaft 156 in a second direction 160. One or more mechanical couplings 162 can be utilized between the paddle motor 130b and the drive shaft 156 to convert the torque output from the motor 130b into rotational motion of the paddle assembly 132 in the second direction 160 (e.g., counterclockwise with respect to the axial axis Q-Q). In some embodiments, the mechanical coupling 162 can be a belt and pulley system, and the belt can have a compliance that allows for some misalignment and wobble of the paddle motor 130b and the drive shaft 156 of the paddle assembly 132. The motion of the drive shaft 156 can be clockwise (CW) or counterclockwise (CCW).

[0061] In some embodiments, the rotary motion vacuum feedthrough 128 is a bearing vacuum seal that can be used to seal the stationary vacuum chamber 110 from the external environment. The drive shaft 156 can then pass through a portion of the stationary vacuum chamber 110 and a port 113 of the rotary vacuum chamber 112 so as to rotate freely with respect to the rotary vacuum chamber 112. A lip seal can be positioned between the port 113 and the rotary motion feedthrough 129 to prevent powder within the rotary vacuum chamber 112 from traveling down the drive shaft 156 and onto the bearing of the rotary motion feedthrough 129.

[0062] In some embodiments, the first direction 152 and the second direction 160 are opposite directions, e.g., clockwise and counterclockwise. The first direction 152 and the second direction 160 can alternatively be the same direction, e.g., both clockwise or both counterclockwise.

[0063] The paddle assembly 132 further includes a paddle manifold 164 that is connected to the gas inlet port 126. The paddle manifold 164 connects the inlet port 126 to one or more gas outlets 166 located on at least one paddle 158 of the paddle assembly 132. Thereby, a process gas (e.g., a reactant or a precursor gas) can flow from the chemical substance distribution system 122 and be injected into the rotary vacuum chamber 112 through the outlets on the paddles 158. In some embodiments, the plurality of paddles 158a, 158b, 158c of the paddle assembly 132 each include a plurality of gas outlets 166 connected to the paddle manifold 164 such that the process gas is injected into the rotary vacuum chamber through the plurality of gas outlets 166.

[0064] The plurality of paddles 158 of the paddle assembly 132 can be distributed (e.g., arranged at uniform intervals) along the axial axis of the drive shaft 156, ensuring a uniform distribution of the process gas injected into the rotary vacuum chamber 112 through the gas outlets 166 located on each of the plurality of paddles 158.

[0065] As depicted in FIG. 2, the paddles 158 of the paddle assembly 132 are oriented on the drive shaft 156 such that, due to the alignment of the paddles, little or no lateral gap occurs between the paddles 158 and the particles 148. In some embodiments, as shown in FIG. 2, only a portion 159 of the paddles 158 of the paddle assembly 132 contacts the particles 148 during operation of the system 100.

[0066] In some embodiments, for rotation of the paddle assembly 132 in the second direction 160, process gas is injected into the rotary vacuum chamber 112 from gas outlets located on the paddle 158 in a direction 168 opposite to the instantaneous movement of the paddle 158. In other words, a plurality of gas outlets 166 are located on the trailing edge of the paddle 158 such that process gas is injected from the gas outlets 166 into the rotary vacuum chamber 112 in a direction opposite to the rotational movement of the paddle 158. In one example, the paddle assembly 132 is rotating in a clockwise direction and the process gas is injected counterclockwise into the rotary vacuum chamber 112. Further details of the configuration of the gas outlets are discussed below.

[0067] An inert carrier gas (e.g., N2) can flow from one of the fluid sources (e.g., fluid source 138e) into the paddle manifold 164. During operation, the carrier gas can continuously flow into the paddle manifold 164 (i.e., regardless of whether a precursor or reactor gas is flowing into the paddle manifold 164). When a precursor or reactor gas is not being injected through the manifold 164 into the chamber 112, the flow of the carrier gas can prevent backflow of another precursor or reactor gas being injected from another manifold into the gas outlet 166. The flow of the carrier gas can also prevent fouling of the gas outlet 166 by particles 148, e.g., blockage of the apertures. Further, the carrier gas can provide a purge gas for a purge operation when a precursor or reactor gas is not being injected into the chamber 112.

[0068] The flow of the carrier gas to the vaporizer 146 when a precursor gas is also flowing can also improve vaporization of the precursor or reactant liquid. Without being limited by any particular theory, the carrier gas flow can help shear the liquid during aerosolization, resulting in smaller droplet sizes that can vaporize more rapidly. The flow of the carrier gas to the paddle manifold 164 when a precursor gas is also flowing can help draw the precursor gas out of the vaporizer 146.

[0069] In some embodiments, one or more temperature control components are integrated into the inner chamber wall 116 to enable control of the temperature of the rotary vacuum chamber 112. For example, a resistive heater, a thermoelectric cooler, a heat exchanger, or a coolant flowing through cooling channels in the chamber wall, or other components within or on the side wall 116.

[0070] System 100 further includes a controller 170 operable to control at least the operation of the chemical substance distribution system 122 and one or more motors 130a, 130b. The controller 170 may be configured to operate the paddle motor 130b to generate a rotational movement of the paddle assembly 132 in a second direction 160 at a rotational speed up to 200 revolutions per minute (rpm). The controller 170 may be further configured to operate the drum motor 130a to generate a rotational movement of the rotary vacuum chamber 112 in a first direction 152 at a rotational speed up to 200 rpm (e.g., in the range of 1 - 60 (rpm)). In some embodiments, the controller 170 is configured to operate the drum motor 130a to generate a rotational speed of the rotary vacuum chamber 112 that exceeds a threshold rotational movement (e.g., exceeds 15 rpm). As depicted in FIGS. 1 and 2, the rotational speed is high enough such that the particles 148 are pressed against the inner surface 150 of the rotary vacuum chamber 112 by centrifugal force (which can be referred to as a "high-speed" rotational movement). Thereby, a toroidal bed of particles 148 can be formed on the inner surface 150. The amount of compression of the particle bed formed by the high-speed rotational movement of the rotary vacuum chamber 112 may depend, for example, on the rotational speed of the rotary vacuum chamber 112. The controller 170 may also be coupled to various sensors (e.g., pressure sensors, flow meters, etc.) to provide closed-loop control of the rotational speed of the chamber and the pressure of the gas within the chamber 110.

[0071] In some embodiments, the rotational speed of the drum motor 130a can be selected based on the desired force experienced by the particles 148 present within the rotary vacuum chamber 112 during operation of the reactor, as explained by Equation (1). TIFF2025098023000002.tif8170 Here, F is the force received by the particle 148 that is proportional to the acceleration of the rotary vacuum chamber 112 (e.g., the square of the number of revolutions per minute (rpm 2 )) multiplied by the radius r of the rotary vacuum chamber 112. When the threshold amount of the force received by the particle 148 is exceeded, the particle 148 will be pressed against the inner surface 150 of the rotary vacuum chamber 112 by centrifugal force. The amount of the force F depends partially on the radius of the rotary vacuum chamber 112 which can be in the range of, for example, 100 - 300 mm. In one example, the radius of the rotary vacuum chamber 112 is 215 mm.

[0072] Generally, the controller 170 is configured to operate the reactor system 100 according to a "policy". The policy specifies the operating values of each controllable element as a function of time. For example, the policy can specify the time when the vacuum source 132 operates, the time and flow rate of each gas source 138a - 138e, the rotational speeds of the rotary vacuum chamber 114 and the drive shaft 156 as set by the motors 130a, 130b, etc. The controller 170 can receive the policy as computer-readable data (e.g., stored in a non-transitory computer-readable medium).

[0073] The system 100 further includes a first loading port 172 located on the stationary vacuum chamber 110 and a second loading port 174 located on the rotary vacuum chamber 112, and can be aligned to enable access to the inside of the rotary vacuum chamber 112 for transporting the particles 148 to be processed. The first loading port 172 and the second loading port 174 can be sealed during the operation of the reactor system 100 so that the ports hold the vacuum established in their respective vacuum chambers. A method for the operation of the reactor system 100 is described in more detail below.

[0074] System 100 further includes a particle filter 176 that enables the evacuation of gas from the rotary vacuum chamber 112 through a vacuum port 118 located within the stationary vacuum chamber 110. In some embodiments, as depicted in FIG. 2, the vacuum port 118 for system 100 is collinear with the drive shaft 156 along the Q-Q axis. Additionally, system 100 may include a filter cleaner for removing particles from the filter 176. As one example, the filter cleaner can be a mechanical knocker for rapping the filter, which shakes off particles from the filter. As another example, the gas source 139 can periodically supply pulses of an inert gas (e.g., nitrogen) to the exhaust manifold 136 between the vacuum port 118 and the vacuum source 134. The gas pulses can return through the filter 176 towards the chamber 112 and blow off particles from the filter 176. The isolation valves 139a, 139b can be used to ensure that only one of the gas source 138 or the vacuum source 134 is fluidly connected to the exhaust manifold 136 at a time.

[0075] The reactor system 100 can include a base 173 for supporting the reactor 100 on the mounting surface 171. In some embodiments, the reactor system 100 is fixed to the base 173 such that the axial axis 165 is perpendicular to the mounting surface 171. As a result, assuming a horizontal mounting surface 171, the drive shaft and the axial axis 165 are parallel to gravity, i.e., vertically oriented. FIG. 3A is a schematic side view of another exemplary reactor for ALD and / or CVD coating of particles (e.g., drugs) that includes a vertically oriented rotary vacuum chamber 100'.

[0076] In some embodiments, as depicted in FIGS. 1 and 2, the reactor system 100 is fixed to the base 173 such that the axial axis 165 and the drive shaft 156 are perpendicular to the mounting surface 171. As a result, assuming a horizontal mounting surface, the axis of rotation of the rotary vacuum chamber 114 is perpendicular to gravity.

[0077] As depicted in FIG. 3A, the vertical drive shaft 157 is connected to the rotary vacuum chamber 135 that is vertically oriented at the bottom surface 174 of the rotary vacuum chamber 135. In some embodiments, the vertical drive shaft 157 may instead be connected to the rotary vacuum chamber 135 that is vertically oriented at the surface 175 of the rotary vacuum chamber 135.

[0078] During operation of the reactor system 100’ depicted in FIG. 3A, the controller 170 is configured to operate the drum motor 130a to generate a rotational speed of the vertically oriented rotary vacuum chamber 135 that is high enough for the particles 148 to be pressed against the inner surface 150 of the vertically oriented rotary vacuum chamber 135 by centrifugal force. Thereby, a toroidal bed of particles 148 may be formed on the inner surface 150.

[0079] In some embodiments, the vacuum port 119 for exhausting gas from the chamber 113 is located on the side surface of the stationary vacuum chamber 110. The vacuum port 119 may be oriented on the opposite side of the rotary motion vacuum feedthrough 128 that connects the drive shaft 157 into the chamber 113.

[0080] FIG. 3B is a schematic side view of another exemplary reactor for ALD and / or CVD coating of particles (e.g., drugs) including a vertically oriented rotary vacuum chamber 100’’. As depicted in FIG. 3B, the vertical drive shaft 157 is connected to the rotary vacuum chamber 135 that is vertically oriented at the bottom surface 174 of the rotary vacuum chamber 135. In some embodiments, the vertical drive shaft 157 may instead be connected to the rotary vacuum chamber 135 that is vertically oriented at the surface 175 of the rotary vacuum chamber 135.

[0081] In addition, reactor 100'' includes an inner wall 149 (e.g., defining an inner circumference) within a rotating vacuum chamber 135, and the inner wall 149 separates a first region 151 of the rotating vacuum chamber configured to receive particles 148 from a second region 153 not configured to receive particles 148. The paddle 158 of paddle assembly 133 is coupled to drive shaft 157 such that the paddle 158 and at least one gas outlet 166 located on the paddle 158 are partially located within the first region 151. During operation of reactor system 100' depicted in FIG. 3B, controller 170 operates drum motor 130a to produce a rotational speed of the vertically oriented rotating vacuum chamber 135 such that particles within chamber 135 do not form a torus relative to the inner surface 150 of the rotating vacuum chamber 135.

[0082] FIGS. 4-5 show another exemplary reactor system 100''' for coating particles with a thin film coating. Reactor system 100''' can perform coating using ALD and / or MLD coating conditions.

[0083] In some embodiments, the rotational speed of the rotating vacuum chamber 112 is less than a threshold rotational speed (e.g., less than 15 rpm), and particles 148 within the rotating vacuum chamber are subject to tumbling agitation while the rotating vacuum chamber 112 is in rotational motion. For example, chamber 112 can rotate at 6-15 rpm. At a sufficiently low rotational speed, particles within chamber 112 do not form a torus relative to the inner surface 150 of the rotating vacuum chamber 112. Controller 182 is configured to operate drum motor 130a to produce a rotational speed of the rotating vacuum chamber 112 in a first direction 152 that is less than the threshold rotational speed.

[0084] During operation of the reactor system 100''', the particles conveyed to the rotary vacuum chamber 112 form a particle bed 178 that is located below the lower portion 180 inside the rotary vacuum chamber 112 against gravity. When the rotary vacuum chamber 112 rotates around the axial axis defined by Q-Q, the particles in the particle bed 178 are subjected to tumbling agitation. Some of the particles may temporarily rise due to rotation but fall back into the powder bed due to gravity. Thus, most or all of the particles remain in the lower portion 180 of the rotary vacuum chamber 112.

[0085] In some embodiments, the rotary vacuum chamber 112 rotates at a rotational speed below a threshold rotational speed (e.g., a speed of 6 - 15 RPM). The controller 170 may be configured to operate the drum motor 130a to generate a rotational movement in alternating directions (e.g., an alternating rotational movement between clockwise and counterclockwise) within the rotary vacuum chamber 112. This can assist in agitating the particles to improve the coating uniformity. The speed in the alternating directions, e.g., the amount of time the chamber 112 rotates in a first direction versus a second direction, may be selected based on the particular recipe and / or particles 178 being coated by the reactor system 100'''.

[0086] In some embodiments, as depicted in FIGS. 4 and 5, one or more paddles 158 of the paddle assembly 132 do not contact the particle bed 178 at a given time during rotation of the paddle assembly around the axial axis defined by Q-Q. For example, paddle 158a contacts the particle bed 178, and paddles 158b and 158c do not contact the particle bed 178 at the instant of rotation of the paddle assembly 132.

[0087] In some embodiments, as depicted in FIG. 4, the rotary vacuum chamber 112 rotates in a first direction 152 and the paddle assembly 132 rotates in a second opposite direction 160. The respective centers of rotation of the rotary vacuum chamber 112 and the paddle assembly 132 are the same axial axis aligned with the center of the cylindrical portion of the rotary vacuum chamber 112.

[0088] In some embodiments, the rotary vacuum chamber 112 includes a baffle on the inner surface 150 of the chamber 112, and when the rotary vacuum chamber 112 rotates about an axial axis at a rotational speed in a first direction 152, the baffle is oriented to move particles from the particle bed 178 from a first side of the rotary vacuum chamber 112 to a second side of the rotary vacuum chamber 112.

[0089] As described above with reference to FIGS. 1 and 2, the paddles 158 of the paddle assembly 132 can have various configurations. Here, three variations regarding the paddle design of the paddle assembly will be described. However, alternative embodiments having similar functions can be envisioned. Generally, the shape and orientation of the paddles 158 of the paddle assembly 132 are selected such that the paddles 158 provide mechanical agitation of the particles 148 (and / or particle bed 178) present within the rotary vacuum chamber 112 during operation of the reactor system (e.g., reactor systems 100, 100', 100'''). The paddle 158 further includes one or more gas outlets 166 located on the paddle 158 for injecting process gas into the rotary vacuum chamber 112 from the chemical substance distribution system 122 during operation of the reactor systems 100, 100', 100'''. The paddle 158 is secured on a drive shaft (e.g., drive shaft 156), is oriented along the drive shaft 156, and provides a substantially uniform application range of mechanical agitation and process gas injection along the length of the cylindrical portion of the rotary vacuum chamber 112 during operation of the reactor systems 100, 100', 100''' (e.g., during the rotational movement of the paddle assembly 132 in a second direction 160).

[0090] As depicted in FIGS. 1-5, the paddle 158 of the paddle assembly 132 can be a scoop-shaped paddle. FIGS. 6A-6C are schematic views of various perspectives of a scoop-shaped paddle 600. As depicted in FIG. 6A, the scoop-shaped paddle 600 includes a base shaft 602 that is coupled to a drive shaft of the paddle assembly (e.g., drive shaft 156 of paddle assembly 132). The paddle further includes a crossbar 604 coupled to the base shaft 602 of the paddle 600 and a plurality of teeth 606 each coupled to the crossbar 604 and extending away from the base 608 of the paddle 600. The plurality of teeth 606 can have a length in the range of 50-100 mm (e.g., 78 mm). The profile of the teeth 606 can be selected such that as the paddle assembly rotates, the teeth 606 move smoothly through the powder. In one example, the teeth 606 are teardrop-shaped.

[0091] In some embodiments, when the paddle 600 is fixed to the drive shaft of the paddle assembly (e.g., drive shaft 156 of paddle assembly 132), the dimensions of the paddle 600 (e.g., the length of the base shaft 603 and the length 605 of the teeth 606) can be selected such that the distance (e.g., gap 117) between the outer surfaces 607 (e.g., outer surface 115) of the teeth 606 of the paddle 600 is less than a threshold distance (e.g., 1-3 mm) from the inner surface of the rotary vacuum chamber (e.g., rotary vacuum chamber 112).

[0092] Each of the base shaft 602, the crossbar 604, and the plurality of teeth 606 has an internal piping and / or passage 610 that is coupled to a paddle manifold (e.g., paddle manifold 164). Process gas can flow into the crossbar 604 through the base shaft 602 and further into the plurality of teeth 606 via the internal piping and / or passage 610. FIG. 6B shows a "top-down" view C illustrating an exemplary position of the internal piping and / or passage 610 within the teeth 606 of the paddle 600.

[0093] Next, as shown in FIG. 6C, the process gas is injected into the rotary vacuum chamber (e.g., rotary vacuum chamber 112) through a plurality of gas outlets 614 (e.g., gas outlet 166) located on the paddle 600, such as one or more gas outlets 614 located on each tooth 606. The gas outlet 614 has a diameter in the range of 0.5 - 3 mm (e.g., a diameter of 1 mm), and the spacing between adjacent gas outlets 614 can be in the range of 5 - 15 mm (e.g., a spacing of 8 mm). The number of gas outlets 614 per tooth 606 can be in the range of 5 - 20 gas outlets 614 (e.g., 7 gas outlets 614 per tooth 606). The gas outlet 614 can be arranged on the tooth 606 along a line bisecting the width of the tooth 606.

[0094] In some embodiments, the plurality of gas outlets 614 are located on the plurality of teeth 606 of the paddle 600. For example, each tooth 606 can have a single gas outlet 614. The plurality of gas outlets 614 are located on the surface indicated by B of each tooth 606 corresponding to the rear edge of the paddle 600 when the paddle 600 is rotating about a second direction (e.g., second direction 160) within the rotary vacuum chamber 112. FIG. 6C shows the plurality of gas outlets 614 aligned along axis D - D having evenly distributed spacings 616 between each gas outlet 614, but the plurality of gas outlets can be offset from each other and / or have variable spacings.

[0095] In some embodiments, the paddle of the paddle assembly (e.g., paddle assembly 132) is T - shaped. FIGS. 6D - 6G are schematic views of various diagrams of the T - shaped paddle 650 with and without the anti - static brush component 664. As depicted in FIG. 6D, the T - shaped paddle 650 includes a base shaft 652 and a crossbar 654. The base shaft 652 is connected to the drive shaft of the paddle assembly (e.g., drive shaft 156 of paddle assembly 132), and the crossbar 654 is located at the end 656 of the base shaft 652 opposite the surface where the base shaft 652 is connected to the drive shaft.

[0096] In some embodiments, when the paddle 650 is secured to the drive shaft of the paddle assembly (e.g., drive shaft 156 of paddle assembly 132), the distance (e.g., gap 117) between the surfaces 655 (e.g., surface 115) of the crossbar 654 is less than a threshold distance (e.g., 1-3 mm) from the inner surface of the rotating vacuum chamber (e.g., rotating vacuum chamber 112), the dimensions of the paddle 650 (e.g., the length 651 of the base shaft 652 and the width 653 of the crossbar 654) can be selected.

[0097] Each of the base shaft 652 and the crossbar 654 has internal piping and / or passages 610 that are connected to a paddle manifold (e.g., paddle manifold 164). Process gas can flow through the base shaft 652 and into the crossbar 654 via the internal piping and / or passages 610. FIG. 6E shows a "top-down" view C illustrating an exemplary location of the internal piping and / or passages 610 within the crossbar 654 of the paddle 650.

[0098] Next, as shown in FIG. 6F, process gas is injected into the rotating vacuum chamber (e.g., rotating vacuum chamber 112) via a plurality of gas outlets 658 (e.g., gas outlets 166) located on the paddle 650, such as one or more gas outlets 658 located on the crossbar 54. The gas outlets 658 have a diameter in the range of 0.5 mm - 3 mm (e.g., a diameter of 1 mm), and the spacing between the gas outlets 658 can be in the range of 5 - 15 mm (e.g., 10 mm between each gas outlet 658). The number of gas outlets 658 located on each paddle 650 can be in the range of 5 - 20 gas outlets 658 (e.g., 8 gas outlets). In some embodiments, the plurality of gas outlets 658 are located on the crossbar 654 of the paddle 650, and the plurality of gas outlets 658 are located on the surface indicated by E of the crossbar 654 corresponding to the trailing edge of the paddle 650 when the paddle 650 is rotating about a second direction (e.g., second direction 160) within the rotating vacuum chamber 112. Further details of the paddle assembly including the T-shaped paddle 650 are discussed below with reference to FIGS. 7A, 7B.

[0099] FIG. 6F shows a plurality of gas outlets 654 aligned along axis G-G having an evenly distributed spacing 660 between each gas outlet 658, although the plurality of gas outlets may be offset relative to each other and / or have a variable spacing. The plurality of gas outlets 658 may be distributed in a plurality of rows and / or a plurality of patterns on the surface of the rear edge of the crossbar shown at E on the rear edge of the paddle 650. Here, the configuration of the plurality of gas outlets 658 may be selected to optimize a substantially even distribution of the process gas injected into the rotating vacuum chamber (e.g., rotating vacuum chamber 112 by paddle assembly 132) by the paddle assembly.

[0100] In some embodiments, the T-shaped paddle 650 further includes an anti-static brush component 662 located on the outer surface 655 of the crossbar 654, as shown in FIG. 6G. The anti-static brush component 662 can be composed of a semi-flexible material (e.g., high-temperature inert rubber / plastic, thin aluminum fins, etc.). The material of the anti-static brush 662 can be selected to sweep particles (e.g., particles 148 and / or particle bed 178) from the inner surface of the rotating vacuum chamber during the rotational movement of the paddle assembly. The material of the anti-static brush component 662 can be further selected to avoid damage to the inner surface of the rotating vacuum chamber (e.g., avoid scratching or denting of the surface) due to contact between the anti-static brush component 662 and the inner surface of the rotating vacuum chamber 112.

[0101] When the paddle 650 is fixed and oriented on the drive shaft of the paddle assembly within the rotating vacuum chamber (e.g., drive shaft 156 of paddle assembly 132 within rotating vacuum chamber 112), the anti-static brush component 662 is located between the end faces 655 of the T-shaped paddle 650 and contacts the inner surface of the rotating vacuum chamber (e.g., inner surface 150 of rotating vacuum chamber 112).

[0102] In some embodiments, the anti-static brush component 662 includes a plurality of fins 664, and the density and / or spacing of the fins 664 of the anti-static brush component 662 can be selected to ensure complete coverage of the entire length of the inner surface of the rotary vacuum chamber through a full rotation (e.g., 360 degrees) of the paddle assembly with respect to the rotary vacuum chamber.

[0103] In some embodiments, the reactor systems 100, 100', and 100''' described with reference to FIGS. 1-5 can include a T-shaped paddle 650. FIGS. 7A and 7B are schematic side views of the reactor systems of FIGS. 1-5 having a T-shaped paddle (e.g., T-shaped paddle 650). The gap 117 between the surface 115 of the crossbar 654 of the T-shaped paddle 650 and the inner surface 150 of the rotary vacuum chamber 112 can be less than a threshold distance (e.g., less than 3 mm).

[0104] In some embodiments, during the rotational movement operation of the paddle assembly 132, the spacing 702 of the T-shaped paddles 650 of the paddle assembly 132 along the axial axis Q-Q can be selected such that there is substantially uniform mechanical agitation and process gas injection across the plurality of paddles 650 along the length of the cylindrical portion of the rotary vacuum chamber 112. In some embodiments, the spacing 702 can be zero or less than zero (e.g., the T-shaped paddles 650 can overlap).

[0105] In some embodiments, as described with reference to FIG. 7B, the T-shaped paddle 650 can include an anti-static brush component 662. FIG. 7B is a schematic side view of the reactor systems of FIGS. 1-5 having a T-shaped paddle including an anti-static brush component. The anti-static brush component 662 located on the T-shaped paddle 650 of the paddle assembly 132 is in contact with the inner surface 150 of the rotary vacuum chamber 112.

[0106] Operation of the Reactor System FIG. 8 is a flow diagram of an exemplary process that utilizes a reactor system to coat particles. In a first step, particles are dispensed into a rotating vacuum chamber (802). As described with reference to FIGS. 1-7, a reactor system (e.g., reactor systems 100, 100', and 100''') includes an external stationary vacuum chamber 110 and an internal rotating vacuum chamber 112, where loading ports (e.g., loading ports 172, 174) on each of the stationary vacuum chamber and the rotating vacuum chamber can be aligned to enable conveyance of particles to be coated into and out of the reactor system.

[0107] The particles (e.g., particle 148) can have a solid core that includes a drug (e.g., one of the drugs described above). The solid core can optionally also include an excipient. When any loading port (e.g., loading ports 172, 174) is sealed, a controller (e.g., controller 170) operates the reactor system (e.g., reactor systems 100, 100', 100''') according to a strategy to form a thin film metal oxide layer and / or a thin polymer layer on the particles.

[0108] The rotating vacuum chamber is rotated (804) along a first direction along the axial axis of the rotating vacuum chamber so that the particles form a torus on the inner wall of the rotating vacuum chamber. In some embodiments, a controller (e.g., controller 170) operates a drum motor (e.g., drum motor 130a) to generate a rotational movement within the rotating vacuum chamber (e.g., rotating vacuum chamber 112) at a rotational speed greater than a threshold rotational speed so that the particles form a torus on the inner wall 150 of the rotating vacuum chamber 112. The threshold rotational speed can be, for example, a rotational speed such as 10 RPM, 12 RPM, 15 RPM, etc.

[0109] In some embodiments, the controller is configured to operate the drum motor to generate a rotational movement of the rotary vacuum chamber at a rotational speed of the rotary vacuum chamber that is less than a threshold rotational speed. For a rotational speed less than the threshold rotational speed, the rotary vacuum chamber is rotated in a first direction along the axial axis of the rotary vacuum chamber such that particles fill the lower portion of the rotary vacuum chamber when the rotary vacuum chamber is rotating in the first direction (805). The rotational speed less than the threshold rotational speed can be, for example, in the range of 6 - 15 RPM. In one example, the lower portion 180 of the rotary vacuum chamber 112 is filled with the particle bed 178 such that the rotary vacuum chamber 112 rotates in the first direction 152 and the particles in the particle bed 178 are subjected to tumbling agitation.

[0110] The rotary vacuum chamber is evacuated through a vacuum port in the rotary vacuum chamber that is aligned on the axial axis of the rotary vacuum chamber (806). In some embodiments, the vacuum source 134 evacuates the rotary vacuum chamber 112 through the exhaust manifold 134 via the stationary vacuum chamber 110 (e.g., via the filter 176). A low-pressure environment can be established within the rotary vacuum chamber 112, for example, at a pressure of less than 1 Torr, for example, 1 - 500 mTorr, for example, up to 50 mTorr.

[0111] The paddle assembly is rotated in a second direction such that a plurality of paddles orbit a drive shaft (808). In some embodiments, the controller 170 is configured to operate the paddle motor 130b to generate a rotational movement of the paddle assembly 132 in the second direction 160 at a second rotational speed. The second rotational direction of the paddle assembly 132 can be the same as or opposite to the first rotational direction of the rotary vacuum chamber 112. The controller 170 can be configured to generate a rotational movement of the paddle assembly 132 at a rotational speed of up to 200 rpm for the paddle motor 130a.

[0112] The process gas is injected into the particles (810) through a plurality of gas outlets located on a plurality of paddles. In some embodiments, the reactor system performs an ALD and / or MLD thin film coating process by introducing a coating gas precursor into the rotary vacuum chamber 112. The gas precursor can instead be spiked into the rotary vacuum chamber 112. This can make the deposition process a solventless process. The half-reactions of the deposition process are self-regulated, and deposition control at the angstrom or nanometer level can be provided. Further, ALD and / or MLD can be performed under low temperature conditions (e.g., less than 50 °C, e.g., less than 35 °C). The flow rate of the process gas can be selected based on the type of process gas being injected. For example, the flow rate of the H2O process gas can be 1 - 2 standard liters per minute (slm) of vaporized precursor for 10 kg of powder. In another example, the flow rate of the H2O process gas can be in the range of 0.5 - 1 slm for powders with a small surface area. In another example, TMA or TiCl4 can have a volume flow rate of less than 1 slm, for example. In another example, the carrier gas flow rate can be in the range of 1 - 3 slm for 10 - 15 kg of powder, for example.

[0113] Reactants suitable for the ALD method include monomer vapors, metal organics, metal halides, oxidizing agents such as ozone or water vapor, and either polymeric or nanoparticle aerosols (dry or wet), or combinations thereof. For example, the first fluid source 142a can provide gaseous trimethylaluminum (TMA) or titanium tetrachloride (TiCl4), and the second gas source 138b can provide water. For the MLD method, as an example, the liquid source 142c can provide adipoyl chloride, and the fourth liquid 142d can supply evaporative or gaseous ethylenediamine.

[0114] In some embodiments, one of the process gases flows from the chemical supply system 122 to the particles 148 through a gas outlet 166 located on the paddle 158 of the paddle assembly 132 as the paddle assembly 132 rotates. The rotation of the paddle assembly 132 agitates the particles to keep them in a separated state, ensuring that the large surface area of the particles remains exposed. This enables a rapid and uniform interaction between the particle surface and the process gas.

[0115] For both the ALD process and the MLD process, two reactive gases are alternately supplied to the rotary vacuum chamber 112, and a purge cycle follows each step of supplying the reactive gas. In that purge cycle, an inert gas is supplied to the chamber 112 to push out the reactive gas and by-products used in the previous step.

[0116] In some embodiments, the reactor system is operated in a continuous flow mode, for example, for an ALD process. During the ALD process, the controller 170 can operate the reactor system (e.g., reactor systems 100, 100', 100''') as follows. In the first reactant half-cycle, the drum motor 130a rotates the rotary vacuum chamber 112, and the paddle motor 130b rotates the paddle assembly 132 to agitate the particles 148. i) The chemical distribution system 122 is operated to flow a first reactive gas (e.g., TMA) from the gas source 138a through the gas outlet 166 located on the paddle 158 into the rotary vacuum chamber 112 until the particles 148 (e.g., particle bed 178) are saturated with the first reactive gas. For example, the first reactive gas can flow at a specific flow rate and for a specific time, or until a sensor measures a specific first pressure or partial pressure of the first reactive gas in the chamber 112. In some embodiments, the first reactive gas is mixed with an inert gas as it flows into the chamber. The specific pressure or partial pressure can be from 0.1 Torr to half of the saturation pressure of the reactive gas. ii) The flow of the first reaction gas is stopped, and the vacuum source 134 evacuates the chamber 112 to a pressure of less than, for example, 1 Torr, for example, 1 - 100 mTorr, for example, 50 mTorr.

[0117] These steps (i)-(ii) can be repeated a number of times set by a strategy, for example, 2 - 10 times.

[0118] Next, in the first purge cycle, the drum motor 130a rotates the rotary vacuum chamber 112, and the paddle motor 130b rotates the paddle assembly 132 to stir the particles 148. iii) The chemical substance distribution system 122 is operated to flow only an inert gas (e.g., N2) from the gas source 138e into the chamber 112 through the gas outlet 166 located on the paddle 158 of the paddle assembly 132. The inert gas can flow at a specific flow rate and for a specific time, or until the sensor measures a specific second pressure of the inert gas in the chamber 112. The second specific pressure can be 1 - 100 Torr. iv) The vacuum source 134 evacuates the chamber 112 to a pressure of less than, for example, 1 Torr, for example, 1 - 500 mTorr, for example, 50 mTorr.

[0119] These steps (iii)-(iv) can be repeated a number of times set by a strategy, for example, 6 - 20 times.

[0120] In the second reactant half-cycle, the drum motor 130a rotates the rotary vacuum chamber 112, and the paddle motor 130b rotates the paddle assembly 132 to stir the particles 148. v) The chemical substance distribution system 122 is operated to flow a second reaction gas (e.g., H2O) from the gas source 138b through the gas outlet 166 located in the paddle 158 of the paddle assembly 132 into the chamber 112 until the particles 148 are saturated with the second reaction gas. Again, the second reaction gas can flow at a specific flow rate, over a specific time, or until the sensor measures a specific third pressure or partial pressure of the second reaction gas in the chamber 112. In some embodiments, the second reaction gas is mixed with an inert gas when flowing into the chamber. The third pressure can be from 0.1 Torr to half of the saturation pressure of the second reaction gas. vi) The vacuum source 134 evacuates the chamber 112 to a pressure of less than, for example, 1 Torr, for example, 1 - 500 mTorr, for example, 50 mTorr.

[0121] These steps (v) - (vi) can be repeated a number of times set by a strategy, for example, 2 - 10 times.

[0122] Next, a second purge cycle is executed. This second purge cycle with steps (vii) and (vii) may be the same as the first purge cycle, or may have different repetition numbers and / or different specific pressures of steps (iii) - (iv).

[0123] The cycles of the first reactant half - cycle, the first purge cycle, the second reactant half - cycle, and the second purge cycle can be repeated a number of times set by a strategy, for example, 1 - 10 times.

[0124] The operation has been described above using the ALD process, but the operation is the same for MLD. In particular, in steps (i) and (v), the reaction gas is replaced with an appropriate process gas and pressure for the deposition of the polymer layer. For example, in step (i), adipoyl chloride in vapor or gaseous form can be used, and in step (v), ethylene diamine in vapor form can be used.

[0125] Furthermore, the operation has been described above using an ALD or MLD process, but this system could be used for a chemical vapor deposition (CVD) process. In this case, both reactants are simultaneously flowed into chamber 110 so that they react within the chamber, for example, during step (i). The second reactant half-cycle can be omitted.

[0126] In some embodiments, the reactor system (e.g., reactor systems 100, 100’, 100’’’) operates in a pulsed flow operation mode, and one or more of the gases (e.g., reaction gas and / or inert gas) can be supplied in pulses, where the chamber 112 is filled with gas to a specific pressure, a delay time can elapse, and before the next pulse begins, the chamber is evacuated by the vacuum source 134.

[0127] In particular, for an ALD process, the controller 170 can operate the reactor system 100 as follows.

[0128] In the first reactant half-cycle, the drum motor 130a rotates the rotary vacuum chamber 112 and the paddle motor 130b rotates the paddle assembly 132 to stir the particles 148. i) The chemical distribution system 122 is operated to flow a first reaction gas (e.g., TMA) into the chamber 112 through a gas outlet 166 located on the paddle 158 of the paddle assembly 132 from the gas source 138a until a first specific pressure is achieved within the chamber 112. The specific pressure can be from 0.1 Torr to half of the saturation pressure of the reaction gas. ii) The flow of the first reaction gas is stopped and a specific delay time can elapse, as measured, for example, by a timer within the controller. This allows the first reactant to flow through the particles 148 within the rotary vacuum chamber 112 and react with the surface of the particles. iii) The vacuum source 134 evacuates the chamber 112 to a pressure of less than, for example, 1 Torr, for example, 1 - 100 mTorr, for example, 50 mTorr.

[0129] These steps (i)-(iii) can be repeated a number of times set by a strategy, for example, 2-10 times.

[0130] Next, in the first purge cycle, the drum motor 130a rotates the rotary vacuum chamber 112, and the paddle motor 130b rotates the paddle assembly 132 to agitate the particles 148. iv) The chemical substance distribution system 122 is operated to cause an inert gas (e.g., N2) to flow from the gas source 138e into the chamber 112 through the gas outlet 166 located on the paddle 158 of the paddle assembly 132 until a second specific pressure is achieved. The second specific pressure can be 1-100 Torr. v) The flow of the inert gas is stopped, and a specific delay time can elapse, as measured, for example, by a timer in the controller. This enables the inert gas to diffuse through the particles in the particle bed 10 and displace the reaction gas and any vaporous by-products. vi) The vacuum source 132 evacuates the chamber 112 to a pressure of less than, for example, 1 Torr, for example, 1-500 mTorr, for example, 50 mTorr.

[0131] These steps (iv)-(vi) can be repeated a number of times set by a strategy, for example, 6-20 times.

[0132] In the second reactant half-cycle, the drum motor 130a rotates the rotary vacuum chamber 112, and the paddle motor 130b rotates the paddle assembly 132 to agitate the particles 148. vii) The chemical substance distribution system 122 is operated to cause a second reaction gas (e.g., H2O) to flow from the gas source 138b into the chamber 112 through the gas outlet 166 located on the paddle 158 of the paddle assembly 132 until a third specific pressure is achieved. The third pressure can be from 0.1 Torr to half of the saturation pressure of the reaction gas. viii) The flow of the second reaction gas is stopped, and a specific delay time can elapse, as measured, for example, by a timer in the controller. This allows the second reaction gas to flow through the particles 148 and react with the surface of the particles within the rotary vacuum chamber 112. ix) The vacuum source 134 evacuates the chamber 112 to a pressure of less than, for example, 1 Torr, for example, 1 - 500 mTorr, for example, 50 mTorr.

[0133] These steps (vii) - (ix) can be repeated a number of times set by the strategy, for example, 2 - 10 times.

[0134] Next, a second purge cycle is executed. This second purge cycle may be the same as the first purge cycle, or may have different numbers of repetitions and / or different delay times and / or different pressures in steps (iv) - (vi).

[0135] The cycles of the first reactant half - cycle, the first purge cycle, the second reactant half - cycle, and the second purge cycle can be repeated a number of times set by the strategy, for example, 1 - 10 times.

[0136] Furthermore, one or more of the gases (e.g., reaction gas and / or inert gas) can be supplied in pulses, where the rotary vacuum chamber 112 is filled with gas to a specific pressure, a delay time can elapse, and the chamber is evacuated by the vacuum source 134 before the next pulse begins.

[0137] The operation has been described above using the ALD process, but the same applies to MLD. In particular, in steps (i) and (vii), the reaction gas is replaced with an appropriate process gas and pressure for the deposition of the polymer layer. For example, in step (i), adipoyl chloride in vapor or gas form can be used, and in step (vii), ethylenediamine in vapor form can be used.

[0138] Furthermore, the operation has been described above using an ALD or MLD process, but this system could be used for a chemical vapor deposition (CVD) process. In this case, both reactants are simultaneously flowed into chamber 110 so as to react within the chamber, for example, during step (i). The second reactant half-cycle can be omitted.

[0139] As described above, the coating process can be carried out at a low temperature, for example, below 50 °C, for example, 35 °C or lower. In particular, the particles 148 can remain or be maintained at such a temperature throughout all of the above steps (i)-(ix). Generally, the temperature inside the reactor chamber does not exceed 35 °C during steps (i)-(ix). This can be achieved by injecting the first reaction gas, the second reaction gas, and the inert gas into the chamber at such a temperature during their respective cycles. Additionally, the physical components of the chamber can remain or be maintained at such a temperature, for example, by using a cooling system (e.g., a thermoelectric cooler) as needed.

[0140] In some embodiments, the controller can deposit a metal oxide layer on the drug-containing particles and then deposit a polymer layer on the metal oxide layer on the particles, for example, using the processes described above. In some embodiments, the controller can cause the reactor system 100 to alternately deposit a metal oxide layer and deposit a polymer layer on the drug-containing particles so as to form a multilayer structure having layers of alternating composition.

[0141] The controller 170 of the system described in this specification and other computing device parts can be implemented in digital electronic circuits or in computer software, firmware, or hardware. For example, the controller can include a processor that executes a computer program stored in a computer program product (e.g., a non-transitory machine-readable storage medium). Such a computer program (also known as a program, software, software application, or code) can be written in any form of programming language, including compiled or translated languages, and can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. In some embodiments, the controller 105 is a general-purpose programmable computer. In some embodiments, the controller can be implemented using special-purpose logic circuits, such as FPGAs (field-programmable gate arrays) or ASICs (application-specific integrated circuits).

[0142] Saying that a system of one or more computers is configured to perform a particular operation or action means that software, firmware, hardware, or a combination thereof that causes the system to perform the operation or action during operation is installed in the system. Saying that one or more computer programs are configured to perform a particular operation or action means that the one or more programs include instructions that cause an operation or action to be performed on a data processing device when executed by the data processing device. The present disclosure provides an apparatus and method for preparing a pharmaceutical composition comprising API-containing particles encapsulated by one or more layers of metal oxide and / or one or more layers of polymer. The coating layer is conformal and has a controlled thickness of from a few nanometers to a few micrometers in total. The article to be coated can be composed of only the API or a combination of the API and one or more excipients. The coating process described herein can provide an API with an increased glass transition temperature of the API compared to the uncoated API, a decreased crystallization rate of the amorphous form of the API compared to the uncoated API, and a decreased surface mobility of the API molecules in the particles compared to the uncoated API. Importantly, the dissolution of the particles can be altered. Since the coating is relatively thin, pharmaceuticals with a high drug load can be realized. Finally, since multiple coatings can be applied within the same reactor, there are advantages in terms of cost and ease of manufacture.

[0143] The term relative positioning is used to refer to the relative positioning of components within a system or the orientation of components during operation, and it should be understood that the reactor system can be held in a vertical orientation or some other orientation during transportation, assembly, etc. Many embodiments of the present invention have been described. Nevertheless, it will be understood that various modifications can be made without departing from the essence and scope of the present invention.

Claims

1. 1. A reactor for coating particles, comprising: One or more motors; a rotary vacuum chamber configured to hold a plurality of particles to be coated, a cylindrical portion of the rotary vacuum chamber having an inner diameter, the rotary vacuum chamber coupled to the one or more motors to rotate the rotary vacuum chamber in a first direction about an axial axis of the cylindrical portion of the rotary vacuum chamber; a vacuum port for evacuating gas from the rotary vacuum chamber; a paddle assembly including a rotatable drive shaft extending through the rotary vacuum chamber along the axial axis of the rotary vacuum chamber and at least one paddle extending radially from the drive shaft, the rotatable drive shaft coupled to the one or more motors such that rotation of the drive shaft by the one or more motors causes the at least one paddle to orbit about the drive shaft in a second direction; a chemical supply system configured to inject a process gas at the plurality of particles, the at least one paddle including a gas outlet of the chemical supply system for injecting the process gas at the plurality of particles; A reactor comprising:

2. 10. The reactor of claim 1 wherein said rotation in said first direction is in the same rotational sense as said rotation in said second direction.

3. 10. The reactor of claim 1 , wherein said gas outlet of said chemical delivery system is located on a trailing edge of said at least one paddle.

4. 10. The reactor of claim 1 wherein a vacuum port is aligned with said axial axis of said rotating vacuum chamber.

5. 10. The reactor of claim 1 , wherein said at least one paddle is a plurality of paddles configured to sweep along an entire length of said rotating vacuum chamber along said axial axis of said rotating vacuum chamber.

6. 10. The reactor of claim 1 wherein said at least one paddle further comprises an anti-static brush located between outer edges of said paddle and in contact with a surface of said inner diameter of said rotating vacuum chamber.

7. 10. The reactor of claim 1 further comprising a port for supplying particles to or receiving particles from said rotating vacuum chamber.

8. 10. The reactor of claim 1 wherein said axial axis of said rotating vacuum chamber is oriented horizontally with respect to gravity.

9. 1. A reactor for coating particles, comprising: One or more motors; a rotary vacuum chamber configured to hold a plurality of particles to be coated, a cylindrical portion of the rotary vacuum chamber having an inner diameter, the rotary vacuum chamber coupled to the one or more motors; a controller configured to cause the one or more motors to rotate the rotary vacuum chamber in a first direction about an axial axis of the cylindrical portion of the rotary vacuum chamber at a rotational speed sufficient to centrifuge the plurality of particles against the inner diameter of the rotary vacuum chamber; a vacuum port for evacuating gas from the rotary vacuum chamber; a paddle assembly including a rotatable drive shaft extending through the rotary vacuum chamber along the axial axis of the rotary vacuum chamber and at least one paddle extending radially from the drive shaft, the rotatable drive shaft coupled to the one or more motors such that rotation of the drive shaft by the one or more motors causes the at least one paddle to orbit about the drive shaft in a second direction; a chemical supply system configured to inject a process gas at the plurality of particles, the at least one paddle including a gas outlet of the chemical supply system for injecting the process gas at the plurality of particles; A reactor comprising:

10. 10. The reactor of claim 9, wherein said controller is configured to cause said one or more motors to rotate said rotary vacuum chamber about said axial axis at a rotational speed greater than 15 RPM.

11. 11. The reactor of claim 10 wherein said rotational speed of said drive shaft relative to said rotating vacuum chamber about said axial axis is at least 4 rpm.

12. 10. The reactor of claim 9, further comprising a base for supporting said reactor on a mounting surface, said rotatable vacuum chamber being secured to said base such that said axial axis is perpendicular to said mounting surface.

13. 10. The reactor of claim 9 wherein said rotation in said first direction is an opposite rotational sense from said rotation in said second direction.

14. 10. The reactor of claim 9, wherein said at least one paddle comprises a rake-shaped feature including a plurality of tines such that the tines of said paddle contact said plurality of particles when said chemical delivery system is injecting reactant or precursor gases at said plurality of particles.

15. 15. The reactor of claim 14 wherein said gas outlet of said chemical delivery system is located on a trailing edge of at least one of said plurality of teeth of said rake-shaped feature of said paddle.

16. 15. The reactor of claim 14 wherein an outer edge of said paddle is separated from a surface of said inner diameter of said rotating vacuum chamber by a gap.

17. The reactor of claim 16, wherein the gap is 1-3 mm.

18. 10. The reactor of claim 9 wherein said at least one paddle comprises a T-shaped feature with a segment parallel to a surface of said inner diameter of said rotating vacuum chamber.

19. 1. A method for coating particles, comprising the steps of: Dispensing particles into a rotating vacuum chamber; rotating the rotary vacuum chamber in a first direction along an axial axis of the rotary vacuum chamber such that the particles form a toroid on an inner wall of the rotary vacuum chamber; evacuating the chamber through a vacuum port in the rotary vacuum chamber aligned on the axial axis of the rotary vacuum chamber; rotating the paddle assembly in a second direction such that the plurality of paddles orbit the drive shaft; injecting a process gas into the particles through a plurality of gas outlets located on the plurality of paddles; The method includes:

20. 20. The method of claim 19, comprising coating the particles by atomic layer deposition or molecular layer deposition.

21. 1. A reactor for coating particles, comprising: One or more motors; a rotary vacuum chamber configured to hold a plurality of particles to be coated, a cylindrical portion of the rotary vacuum chamber having an inner diameter, the rotary vacuum chamber coupled to the one or more motors; a controller configured to cause the one or more motors to rotate the rotary vacuum chamber in a first direction about an axial axis of the cylindrical portion of the rotary vacuum chamber at a rotational speed such that the particles undergo tumbling agitation; a vacuum port for evacuating gas from the rotary vacuum chamber; a paddle assembly including a rotatable drive shaft extending through the rotary vacuum chamber along the axial axis of the rotary vacuum chamber and at least one paddle extending radially from the drive shaft, the rotatable drive shaft coupled to the one or more motors such that rotation of the drive shaft by the one or more motors causes the at least one paddle to orbit about the drive shaft in a second direction; a chemical supply system configured to inject a process gas at the plurality of particles, the at least one paddle including a gas outlet of the chemical supply system for injecting the process gas at the plurality of particles; A reactor comprising:

22. 22. The reactor of claim 21 , wherein said controller is configured to cause said one or more motors to rotate said rotary vacuum chamber about said axial axis at said rotational speed of less than 6 RPM.

23. 22. The reactor of claim 21 wherein said rotational speed of said drive shaft relative to said rotating vacuum chamber is less than 4 rpm.

24. 22. The reactor of claim 21 further comprising a stationary vacuum chamber, said rotating vacuum chamber being disposed within said stationary vacuum chamber.

25. 25. The reactor of claim 24 further comprising a vacuum pump coupled to said stationary vacuum chamber and coupled to said vacuum port to evacuate gases from said rotating vacuum chamber.

26. 25. The reactor of claim 24 wherein said chemical delivery system and said one or more motors are coupled to said stationary vacuum chamber.

27. 25. The reactor of claim 24 wherein said rotating vacuum chamber further comprises a surface of said inner diameter of said rotating vacuum chamber having a horizontal or angled baffle.

28. 1. A method for coating particles, comprising the steps of: Dispensing particles into a rotating vacuum chamber; rotating the rotary vacuum chamber in a first direction along an axial axis of the rotary vacuum chamber such that the particles fill a lower portion of the rotary vacuum chamber as the rotary vacuum chamber rotates in the first direction; evacuating the chamber through a vacuum port in the rotary vacuum chamber aligned on the axial axis of the rotary vacuum chamber; rotating the paddle assembly in a second direction such that the plurality of paddles orbit the drive shaft; injecting a process gas into the particles through a plurality of gas outlets located on the plurality of paddles; The method includes:

29. 30. The method of claim 28, comprising coating the particles by atomic layer deposition or molecular layer deposition.

30. 30. The method of claim 28, wherein the particle comprises a core containing a drug.

31. 30. The method of claim 28, wherein the rotating vacuum chamber is configured to perform initiated chemical vapor deposition.

32. 30. The method of claim 28, further comprising depositing an organic or inorganic coating on the particles.

33. 33. The method of claim 32, wherein the organic or inorganic coating comprises an inorganic metal oxide.

34. The method of claim 32, wherein the organic or inorganic coating comprises an organic polymer.

35. 33. The method of claim 32, wherein the first direction is opposite to the second direction.

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