Process for preparing coating powder compositions

Abstract

[0003] Embodiments of the present disclosure generally relate to a vapor coating process for preparing a coating powder composition. In one or more embodiments, a method for preparing a coating powder composition is provided, comprising: positioning a plurality of powder particles in a processing region, each of the powder particles comprising one or more organic materials, one or more inorganic materials, or a combination thereof; and coating the plurality of powder particles with a metal oxide coating during a cyclical vapor coating process to form a plurality of coated particles. The metal oxide coating comprises aluminum oxide, zinc oxide, or aluminum zinc oxide, and the cyclical vapor coating process comprises one or more deposition cycles.

Description

[Technical Field]

[0001] FIELD OF THE DISCLOSURE Embodiments of the present disclosure relate generally to coating processes, and more particularly to vapor coating processes for preparing coated particles. [Background technology]

[0002] Atomic layer epitaxy (ALE) and atomic layer deposition (ALD) are self-limiting processes that each utilize alternating pulses of reactants to saturate the substrate surface, leaving a monolayer of material per cycle. Each reactant pulse typically lasts from a few milliseconds to a few seconds. Deposition conditions and reactants are selected to ensure a self-saturating reaction, so that the layer adsorbed in one pulse leaves a surface termination that is unreactive with the vapor-phase reactant of the same pulse. Subsequent pulses of a different reactant react with the previous termination, allowing continued deposition. Thus, each cycle of alternating pulses typically leaves approximately one molecular layer of deposited material.

[0003] Materials produced by ALE or ALD processes are typically deposited on substrates, such as semiconductor or microelectronic substrates, that have relatively large, flat wafer surfaces, such as silicon wafers with diameters of 200 mm or 300 mm. These ALE and ALD processes are often carried out as thermal or plasma reactions at temperatures greater than 50°C, e.g., 100°C to 500°C, or even higher. Furthermore, particles of organic materials often decompose when heated to the temperatures typically used during ALE or ALD processes.

[0004] Therefore, there is a need for improved processes for preparing coated particles. Summary of the Invention

[0005] Embodiments of the present disclosure generally relate to a vapor coating process for preparing a coated powder composition. The coated powder composition is prepared from powder particles that can be or include one or more organic materials (e.g., active pharmaceutical ingredients (APIs), pharmaceutically acceptable excipients (PAEs), and / or other organic compounds), one or more inorganic materials (e.g., metal oxide particles), or a combination thereof. A plurality of powder particles are coated with a metal oxide, such as aluminum oxide, zinc oxide, or zinc aluminum oxide.

[0006] In one or more embodiments, a method for forming, producing, or otherwise preparing a coating powder composition is provided, comprising positioning a plurality of powder particles in a processing region of a processing chamber, each of the powder particles being or including an organic material, and coating the plurality of powder particles with a metal oxide coating during a cyclic vapor coating process to form a plurality of coated particles. The metal oxide coating comprises aluminum oxide, zinc oxide, or aluminum zinc oxide. The cyclic vapor coating process comprises one or more deposition cycles. Each of the deposition cycles includes introducing two or more pulses of a metal precursor into the processing region via a first mass flow control (MFC) valve, exposing the plurality of powder particles to the metal precursor, and infiltrating the plurality of powder particles with the metal precursor through spaces between the powder particles. Thereafter, each of the deposition cycles includes introducing two or more pulses of a purge gas into the processing region via a second MFC valve, and exposing the plurality of powder particles to the purge gas during a first purge process. Thereafter, each deposition cycle includes introducing two or more pulses of an oxidizer into the processing region through a third MFC valve, exposing the plurality of powder particles to the oxidizer, and infiltrating the plurality of powder particles with the oxidizer through spaces between the powder particles to produce a metal oxide coating disposed on an outer surface of each of the powder particles. Thereafter, each deposition cycle includes introducing two or more pulses of a purge gas through a second MFC valve, and exposing the plurality of powder particles to the purge gas during a second purge process.

[0007] In some embodiments, a method for forming, producing, or otherwise preparing a coating powder composition is provided, comprising positioning a plurality of powder particles in a processing region of a processing chamber, each of the powder particles being or including an inorganic material, and coating the plurality of powder particles with a metal oxide coating during a cyclic vapor coating process to form a plurality of coated particles. The metal oxide coating comprises aluminum oxide, zinc oxide, or aluminum zinc oxide. The cyclic vapor coating process comprises one or more deposition cycles, each of which includes introducing two or more pulses of a metal precursor into the processing region through a first MFC valve, exposing the plurality of powder particles to the metal precursor, and infiltrating the plurality of powder particles with the metal precursor through spaces between the powder particles. Thereafter, each of the deposition cycles includes introducing two or more pulses of a purge gas into the processing region through a second MFC valve, and exposing the plurality of powder particles to the purge gas during a first purge process. Thereafter, each deposition cycle includes introducing two or more pulses of an oxidizer into the processing region through a third MFC valve, exposing the plurality of powder particles to the oxidizer, and infiltrating the plurality of powder particles with the oxidizer through spaces between the powder particles to produce a metal oxide coating disposed on an outer surface of each of the powder particles. Thereafter, each deposition cycle includes introducing two or more pulses of a purge gas through a second MFC valve, and exposing the plurality of powder particles to the purge gas during a second purge process.

[0008] In another embodiment, a method for forming, producing, or otherwise preparing a coating powder composition is provided, comprising positioning a plurality of powder particles in a processing region of a processing chamber and coating the plurality of powder particles with a metal oxide coating during a cyclic vapor coating process to form a plurality of coated particles. The metal oxide coating comprises aluminum zinc oxide. The cyclic vapor coating process includes one or more deposition cycles, each of which includes introducing two or more pulses of a first metal precursor into the processing region through a first MFC valve, exposing the plurality of powder particles to the first metal precursor, and infiltrating the plurality of powder particles with the first metal precursor through spaces between the powder particles. Thereafter, each of the deposition cycles includes introducing two or more pulses of a purge gas into the processing region through a second MFC valve and exposing the plurality of powder particles to the purge gas during a first purge process. Each deposition cycle then includes introducing two or more pulses of an oxidizer into the processing region via a third MFC valve, exposing the plurality of powder particles to the oxidizer, and infiltrating the plurality of powder particles with the oxidizer through spaces between the powder particles to produce a first metal oxide layer disposed on the outer surfaces of each of the powder particles. Each deposition cycle then includes introducing two or more pulses of a purge gas through a second MFC valve and exposing the plurality of powder particles to the purge gas during a second purge process. Each deposition cycle then includes introducing two or more pulses of a second metal precursor into the processing region via a fourth MFC valve, exposing the plurality of powder particles to the second metal precursor, and infiltrating the plurality of powder particles with the second metal precursor through spaces between the powder particles. Each deposition cycle then includes introducing two or more pulses of a purge gas into the processing region via the second MFC valve and exposing the plurality of powder particles to the purge gas during a third purge process.Each deposition cycle then includes introducing two or more pulses of an oxidizer into the processing region through a third MFC valve, exposing the powder particles to the oxidizer, and allowing the oxidizer to penetrate the powder particles through spaces between the particles to produce a second metal oxide layer disposed on the first metal oxide layer disposed on the outer surface of each of the powder particles. Each deposition cycle then includes introducing two or more pulses of a purge gas through a second MFC valve and exposing the powder particles to the purge gas during a fourth purge process. The first and second metal precursors are different from each other. The metal oxide coating includes a first metal oxide layer and a second metal oxide layer. The first metal oxide layer includes aluminum oxide and the second metal oxide layer includes zinc oxide, or the first metal oxide layer includes zinc oxide and the second metal oxide layer includes aluminum oxide.

[0009] So that the above-mentioned features of the present disclosure may be understood in detail, a more particular description of the present disclosure briefly summarized above can be had by reference to embodiments, some of which are illustrated in the accompanying drawings. It should be noted, however, that the accompanying drawings illustrate only exemplary embodiments and are therefore not to be considered limiting of the scope thereof, as other equally effective embodiments may be recognized. [Brief explanation of the drawings]

[0010] [Figure 1A-1B] 1 is a flowchart illustrating one or more cyclic vapor coating processes as described and discussed in one or more embodiments herein. [Figure 2A-2B] 1 is a flowchart illustrating another cyclic vapor coating process as described and contemplated in one or more embodiments herein. [Figure 3A-3C]

[0023] Figure 3A illustrates a deposition system that can be used to perform the cyclic vapor coating process described and discussed in one or more embodiments herein. Figure 3A illustrates a schematic cross-sectional front view of the deposition system, Figure 3B illustrates a schematic side view of the deposition system shown in Figure 3A, and Figure 3C illustrates a schematic cross-sectional side view of the deposition system shown in Figure 3A. The view of Figure 3C may be taken along line 3C-3C of Figure 3A. DETAILED DESCRIPTION OF THE INVENTION

[0011] For ease of understanding, the same reference numerals have been used, where possible, to designate identical elements common to the figures. It is contemplated that elements and features of one or more embodiments may be beneficially incorporated in other embodiments.

[0012] Embodiments of the present disclosure generally relate to a vapor coating process for preparing a coated powder composition. The coated powder composition is prepared from powder particles that can be or include one or more organic materials (e.g., active pharmaceutical ingredients (APIs), pharmaceutically acceptable excipients (PAEs), and / or other organic compounds), one or more inorganic materials (e.g., metal oxide particles), or a combination thereof. A plurality of powder particles are coated with a metal oxide, such as aluminum oxide, zinc oxide, or zinc aluminum oxide.

[0013] In one or more embodiments, a method of forming, producing, or otherwise preparing a coating powder composition is provided, comprising positioning a plurality of powder particles in a processing region of a processing chamber or reactor and coating the plurality of powder particles with a metal oxide coating during a cyclic vapor coating process to form a plurality of coated particles. Each of the powder particles may be or include one or more organic materials, one or more inorganic materials, or any combination thereof. The metal oxide coating includes aluminum oxide, zinc oxide, or aluminum zinc oxide.

[0014] 1A-1B are flowcharts illustrating a cyclical vapor coating process 100 as described and discussed in one or more embodiments herein. In some embodiments, each deposition cycle of the cyclical vapor coating process 100 includes operations 110a-140a, as shown in FIG. 1A. In other embodiments, each deposition cycle of the cyclical vapor coating process 100 includes operations 110b-140b, as shown in FIG. 1B. The cyclical vapor coating process 100 may include one, two, three, or more deposition cycles. Each of the deposition cycles of the cyclical vapor coating process 100 may be repeated to form, produce, or otherwise prepare a metal oxide coating having a desired thickness. Metal oxide coatings including aluminum oxide or zinc oxide may be prepared by the cyclical vapor coating process 100.

[0015] In one or more embodiments, as shown in FIG. 1A , during cyclic vapor coating process 100, a plurality of powder particles are exposed to two or more pulses of a metal precursor (in operation 110a), then the plurality of powder particles are exposed to two or more pulses of a purge gas (in operation 120a), then the plurality of powder particles are exposed to two or more pulses of an oxidizer (in operation 130a), and then the plurality of powder particles are exposed to two or more pulses of a purge gas (in operation 140a).

[0016] In another embodiment, as shown in FIG. 1B, during a metal precursor exposure process, two or more pulses of metal precursor are introduced into a processing region of a processing chamber or reactor via a first mass flow control (MFC) valve in operation 110b. A plurality of powder particles are exposed to the metal precursor. The plurality of powder particles are infiltrated by the metal precursor through spaces disposed between the powder particles.

[0017] In operation 120b, during a first purge process, two or more pulses of purge gas are introduced into the processing region through the second MFC valve. The powder particles are exposed to the purge gas. The purge gas penetrates the powder particles through spaces between the powder particles, and gas residue is removed by the purge gas. The gas residue may include excess amounts of metal precursor, purge gas, and / or other gases in the processing region.

[0018] In operation 130b, during an oxidizer exposure process, two or more pulses of oxidizer are introduced into the treatment region through the third MFC valve. The plurality of powder particles are exposed to the oxidizer. The plurality of powder particles are infiltrated by the oxidizer through spaces between the powder particles to produce a metal oxide coating disposed on the outer surface of each of the powder particles.

[0019] In operation 140b, during a second purge process, two or more pulses of purge gas are introduced into the processing region through the second MFC valve. The powder particles are exposed to the purge gas. The purge gas penetrates the powder particles through spaces between the powder particles, and the gas residue is removed by the purge gas. The gas residue may include excess amounts of metal precursor, oxidizer, purge gas, one or more reaction byproducts, and / or other gases in the processing region.

[0020] In some examples, the metal precursor comprises an aluminum precursor and the metal oxide coating comprises aluminum oxide during the cyclic vapor coating process 100. In other examples, the metal precursor comprises a zinc precursor and the metal oxide coating comprises zinc oxide during the cyclic vapor coating process 100.

[0021] 2A-2B are flowcharts illustrating a cyclical vapor coating process 200 as described and discussed in one or more embodiments herein. In some embodiments, each deposition cycle of the cyclical vapor coating process 200 includes operations 210a-280a, as shown in FIG. 2A. In other embodiments, each deposition cycle of the cyclical vapor coating process 200 includes operations 210b-280b, as shown in FIG. 2B. The cyclical vapor coating process 200 may include one, two, three, or more deposition cycles. Each deposition cycle of the cyclical vapor coating process 200 may be repeated to form, produce, or otherwise prepare a metal oxide coating having a desired thickness. A metal oxide coating including aluminum zinc oxide may be prepared by the cyclical vapor coating process 200. The metal oxide coating includes at least one layer of aluminum oxide and at least one layer of zinc oxide to form aluminum zinc oxide. The metal oxide coating includes successive pairs of aluminum oxide and zinc oxide layers.

[0022] 2A , during cyclic vapor coating process 200, a plurality of powder particles are exposed to two or more pulses of a first metal precursor (in operation 210a), then the plurality of powder particles are exposed to two or more pulses of a purge gas (in operation 220a), then the plurality of powder particles are exposed to two or more pulses of an oxidizer (in operation 230a), and then the plurality of powder particles are exposed to two or more pulses of a purge gas (in operation 240a). Thereafter, during cyclic vapor coating process 200, a plurality of powder particles are exposed to two or more pulses of a second metal precursor (in operation 250a), then the plurality of powder particles are exposed to two or more pulses of a purge gas (in operation 260a), then the plurality of powder particles are exposed to two or more pulses of an oxidizer (in operation 270a), and then the plurality of powder particles are exposed to two or more pulses of a purge gas (in operation 280a).

[0023] In another embodiment, as shown in FIG. 2B , in operation 210b, during a first metal precursor exposure process, two or more pulses of a first metal precursor are introduced into a processing chamber or reactor processing region via a first MFC valve. A plurality of powder particles are exposed to the first metal precursor. The plurality of powder particles are infiltrated by the first metal precursor through spaces disposed between the powder particles. In some examples, if the first metal precursor in operation 210b is or includes an aluminum precursor, the second metal precursor in operation 250b is or includes a zinc precursor. In other examples, if the first metal precursor in operation 210b is or includes a zinc precursor, the second metal precursor in operation 250b is or includes an aluminum precursor.

[0024] In operation 220b, during a first purge process, two or more pulses of purge gas are introduced into the processing region through the second MFC valve. The powder particles are exposed to the purge gas. The purge gas penetrates the powder particles through spaces between the powder particles, and gas residue is removed by the purge gas. The gas residue may include excess amounts of the first metal precursor, the purge gas, and / or other gases in the processing region.

[0025] In operation 230b, during a first oxidizer exposure process, two or more pulses of oxidizer are introduced into the treatment region via the third MFC valve. The plurality of powder particles are exposed to the oxidizer. The plurality of powder particles are infiltrated by the oxidizer through spaces between the powder particles to produce a first metal oxide layer disposed on the outer surface of each of the powder particles. The first metal oxide layer is part of the metal oxide coating prepared by the cyclic vapor coating process 200.

[0026] In operation 240b, during a second purge process, two or more pulses of purge gas are introduced into the processing region through the second MFC valve. The powder particles are exposed to the purge gas. The purge gas penetrates the powder particles through spaces between the powder particles, and a gas residue is removed by the purge gas. The gas residue may include excess amounts of the first metal precursor, the oxidizer, the purge gas, one or more reaction byproducts, and / or other gases in the processing region.

[0027] In operation 250b, during a second metal precursor exposure process, two or more pulses of a second metal precursor are introduced into a processing region of a processing chamber or reactor via a fourth MFC valve. A plurality of powder particles are exposed to the second metal precursor. The plurality of powder particles are infiltrated by the second metal precursor through spaces disposed between the powder particles.

[0028] In operation 260b, during a third purge process, two or more pulses of purge gas are introduced into the processing region through the second MFC valve. The plurality of powder particles are exposed to the purge gas. The purge gas penetrates the plurality of powder particles through spaces between the powder particles, and gas residue is removed by the purge gas. The gas residue may include excess amounts of the first metal precursor, the second metal precursor, the oxidizer, the purge gas, one or more reaction byproducts, and / or other gases in the processing region.

[0029] In operation 270b, during a second oxidizer exposure process, two or more pulses of oxidizer are introduced into the treatment region via the third MFC valve. The plurality of powder particles are exposed to the oxidizer. The oxidizer penetrates the plurality of powder particles through spaces between the powder particles to produce a second metal oxide layer disposed on the first metal oxide layer disposed on the outer surface of each of the powder particles. The first and second metal oxide layers form the metal oxide coating prepared by the cyclic vapor coating process 200.

[0030] In operation 280b, during a fourth purge process, two or more pulses of purge gas are introduced into the processing region through the second MFC valve. The plurality of powder particles are exposed to the purge gas. The purge gas penetrates the plurality of powder particles through spaces between the powder particles, and gas residue is removed by the purge gas. The gas residue may include excess amounts of the first metal precursor, the second metal precursor, the oxidizer, the purge gas, one or more reaction byproducts, and / or other gases in the processing region.

[0031] To prepare a metal oxide coating comprising aluminum zinc oxide by cyclic vapor coating process 200, the first and second metal precursors are different from one another, such as an aluminum precursor and a zinc precursor. In some examples, during cyclic vapor coating process 200, the first metal precursor is or comprises an aluminum precursor and the first metal oxide layer comprises aluminum oxide, while the second metal precursor is or comprises a zinc precursor and the second metal oxide layer comprises zinc oxide. In other examples, during cyclic vapor coating process 200, the first metal precursor is or comprises a zinc precursor and the first metal oxide layer comprises zinc oxide, while the second metal precursor is or comprises an aluminum precursor and the second metal oxide layer comprises aluminum oxide.

[0032] powder particles The powder particles coated by the cyclic vapor coating process 100, 200 to produce coated particles may be or include one or more organic materials, one or more inorganic materials, or any combination thereof. In one or more embodiments, the powder particles include one or more organic materials. The organic materials included in the powder particles may be or include one or more drugs, one or more active pharmaceutical ingredients (APIs), one or more pharmaceutically acceptable excipients (PAEs), other types of organic compounds, or any combination thereof. In the broadest sense, "drug" includes all small molecule (e.g., non-biological) APIs. Exemplary drugs and / or APIs include analgesics, anesthetics, anti-inflammatory agents, anthelmintics, antiarrhythmic agents, antiasthmatic agents, antibiotics, anticancer agents, anticoagulants, antidepressants, antidiabetics, antiepileptics, antihistamines, antitussives, antihypertensives, antimuscarinics, antimycobacterial agents, antineoplastic agents, antioxidants, antipyretics, immunosuppressants, immunostimulants, antithyroid agents, antivirals, anxiolytics, sedatives, hypnotics, neuroleptics, astringents, bacteriostatics, beta-adrenergic receptor blocking agents, blood products, blood substitutes, bronchodilators, buffers, cardiac inotropes, chemotherapeutics, contrast media, corticosteroids, cough suppressants, The small molecule drug may be or may include an opiate, an expectorant, a mucolytic, a diuretic, a dopaminergic agent, an antiparkinsonian, a free radical scavenger, a growth factor, a hemostatic agent, an immunological agent, a lipid-regulating agent, a muscle relaxant, a parasympathomimetic, a parathyroid calcitonin, a biphosphonate, a prostaglandin, a radiopharmaceutical, a hormone, a sex hormone, an antiallergic agent, an appetite stimulant, an appetite suppressant, a steroid, a sympathomimetic, a thyroid agent, a vaccine, a vasodilator, a xanthine, a salt thereof, a complex thereof, or a combination thereof. Exemplary classes of small molecule drugs may be or may include acetaminophen, clarithromycin, azithromycin, ibuprofen, fluticasone propionate, salmeterol, pazopanib HCl, palbociclib, and amoxicillin clavulanate potassium, a salt thereof, a complex thereof, or a combination thereof.

[0033] Exemplary PAEs, diluents, and / or carriers may be or include surfactants, polymers, sugars, binders, fillers, lubricants, sweeteners, flavoring agents, preservatives, buffers, diluents, wetting agents, disintegrants, effervescent agents, salts thereof, hydrates thereof, or any combination thereof. Exemplary surfactants and polymers may be or include polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), sodium lauryl sulfate, polyvinyl alcohol, crospovidone, polyvinylpyrrolidone-polyvinyl acrylate copolymers, cellulose derivatives, hydroxypropyl methylcellulose, hydroxypropyl cellulose, carboxymethylethylcellulose, hydroxypropylmethylcellulose phthalate, polyacrylates and polymethacrylates, urea, sugars, polyols, carbomers and polymers thereof, emulsifiers, sugar gums, starches, organic acids and salts thereof, vinylpyrrolidone and vinyl acetate, salts thereof, esters thereof, or any combination thereof. Exemplary binders may be or include cellulose, cross-linked polyvinylpyrrolidone, microcrystalline cellulose, salts thereof, or any combination thereof. Exemplary fillers may be or include lactose monohydrate, anhydrous lactose, microcrystalline cellulose, starch, salts thereof, complexes thereof, or any combination thereof. Exemplary lubricants, such as agents that affect the flowability of the powder to be compressed, may be or include colloidal silicon dioxide, talc, stearic acid, magnesium stearate, calcium stearate, silica gel, or any combination thereof. Exemplary sweeteners may be or include sucrose, xylitol, saccharin sodium, cyclamate, aspartame, and acesulfame K, other natural sweeteners, other artificial sweeteners, salts thereof, or any combination thereof.Exemplary preservatives may include or include potassium sorbate, methylparaben, propylparaben, benzoic acid, benzoates, parahydroxybenzoic acid, esters of parahydroxybenzoic acid (e.g., butylparaben), alcohols (e.g., ethyl alcohol or benzyl alcohol), phenolic chemicals (e.g., phenol), quaternary compounds (e.g., benzalkonium chloride), salts thereof, esters thereof, or any combination thereof. Exemplary diluents and / or pharmaceutically acceptable inert fillers may include or include microcrystalline cellulose, lactose, dibasic calcium phosphate, sugars, salts thereof, or any combination thereof. Exemplary wetting agents may include or include corn starch, potato starch, maize starch, modified starch, salts thereof, or any combination thereof. Exemplary disintegrants may include or include croscarmellose sodium, crospovidone, sodium starch glycolate, salts thereof, or any combination thereof. Exemplary effervescent agents and / or effervescent couples may be or include organic acids (e.g., citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, and alginic acid, anhydrides, and / or acid salts), or carbonates (e.g., sodium carbonate, potassium carbonate, magnesium carbonate, sodium glycine carbonate, L-lysine carbonate, and arginine carbonate), or bicarbonates (e.g., sodium bicarbonate or potassium bicarbonate), salts thereof, esters thereof, or any combination thereof.

[0034] In some embodiments, the powder particles include one or more inorganic materials. The inorganic materials included in the powder particles may be or may include one or more metal oxides, one or more metal nitrides, silicon oxide, silicon nitride, or any combination thereof. For example, the inorganic materials included in the powder particles may be or may include aluminum oxide, titanium dioxide, iron oxide, gallium oxide, magnesium oxide, zinc oxide, niobium oxide, hafnium oxide, tantalum oxide, lanthanum oxide, zirconium dioxide, silicon oxide, silicates thereof, nitrides thereof, or any combination thereof.

[0035] In some examples, the plurality of powder particles, whether comprising one or more organic materials, one or more inorganic materials, or a combination thereof, are produced from a spray-drying or freeze-drying process. Other techniques can be used to fabricate, manufacture, or otherwise produce the plurality of powder particles.

[0036] The plurality of powder particles may have an average particle size in the range of about 0.1 μm, about 0.2 μm, about 0.3 μm, about 0.5 μm, about 0.8 μm, about 1 μm, about 2 μm, about 3 μm, about 5 μm, about 8 μm, about 10 μm, about 12 μm, about 15 μm, about 18 μm, about 20 μm, about 25 μm, about 30 μm, or about 35 μm to about 40 μm, about 50 μm, about 60 μm, about 70 μm, about 80 μm, about 90 μm, about 100 μm, about 120 μm, about 150 μm, about 200 μm, about 300 μm, about 400 μm, about 500 μm, about 600 μm, about 700 μm, about 800 μm, about 900 μm, or about 1,000 μm. For example, the plurality of powder particles may have a diameter of about 0.1 μm to about 1,000 μm, about 0.1 μm to about 500 μm, about 0.1 μm to about 200 μm, about 0.1 μm to about 150 μm, about 0.1 μm to about 100 μm, about 0.1 μm to about 80 μm, about 0.1 μm to about 50 μm, about 0.1 μm to about 30 μm, about 0.1 μm to about 20 μm, about 0.1 μm to about 10 μm, about 0.1 μm to about 8 μm, about 0.1 μm to about 5 μm, about 0.1 μm to about 2 μm, about 0.1 μm to about 1 μm, about 0.1 μm to about 0.5 μm, about 1 μm to about 1,000 μm, about 1 μm to about 500 μm, about 1 μm to about 200 μm, The average particle size may be about 1 μm to about 150 μm, about 1 μm to about 100 μm, about 1 μm to about 80 μm, about 1 μm to about 50 μm, about 1 μm to about 30 μm, about 1 μm to about 20 μm, about 1 μm to about 10 μm, about 1 μm to about 8 μm, about 1 μm to about 5 μm, about 1 μm to about 2 μm, about 10 μm to about 1,000 μm, about 10 μm to about 500 μm, about 10 μm to about 200 μm, about 10 μm to about 150 μm, about 10 μm to about 100 μm, about 10 μm to about 80 μm, about 10 μm to about 50 μm, about 10 μm to about 30 μm, about 10 μm to about 20 μm, or about 10 μm to about 15 μm.

[0037] In one or more examples, the plurality of powder particles may have an average particle size of about 0.1 μm to about 1,000 μm. In some examples, the plurality of powder particles may have an average particle size of about 1 μm to about 100 μm. In other examples, the plurality of powder particles may have an average particle size of about 1 μm to about 30 μm, or about 1 μm to about 10 μm.

[0038] Cyclic Vapor Coating Process In the embodiments described and discussed herein, a plurality of powder particles may be coated by a cyclic vapor coating process 100, 200 to form, produce, or otherwise prepare a coated powder composition. The cyclic vapor coating process 100, 200 is a stagnant-flow vapor deposition process that provides a consistent, uniform metal oxide coating on the powder particles. The method includes mass flow controllers (“MFCs”) calibrated to deliver precise chemical moles to a pressure isolation vessel. Any of the MFCs can have orifices sized (e.g., about 0.062 inches or larger) to deliver metal precursors (e.g., metal-organic vapors) at room temperature (e.g., about 25° C. or lower) and therefore low vapor pressures (e.g., about 20 Torr or lower). The orifices of the MFCs used for the oxidizer and purge gases may also be sized about 0.062 inches or larger.

[0039] Some active pharmaceutical ingredients ("APIs") are prone to thermal decomposition, and some high-surface-area substrates (e.g., powder particles) are prone to uneven coating during conventional deposition processes. However, the cyclic vapor coating processes 100, 200 having stagnant flow and utilizing MFCs as described and discussed herein overcome these drawbacks, including near-room temperature metal-organic vapor delivery by compensating for ampoule pressure drift and chamber pressure increases due to reaction by-product generation. Some embodiments enable dosing control and provide process validation for Good Manufacturing Practice ("GMP") compliance.

[0040] Several different types of chambers or reactors can be used to perform the cyclic vapor coating process 100, 200. The chamber and / or reactor includes a processing region for containing a plurality of powder particles to be coated by the cyclic vapor coating process to form, generate, or otherwise prepare a coating powder composition. In some embodiments, rotating reactors with drums, stationary reactors with paddles, and other types of chambers and reactors may be used to perform the cyclic vapor coating process 100, 200, as further disclosed in U.S. Pat. No. 11,674,223 B2 and U.S. Patent Application Publication No. 20230128094, which are incorporated by reference in their entireties. Other conventional chemical vapor deposition (CVD) chamber reactors or atomic layer deposition (ALD) chambers or reactors can be used as suitable processing chambers for performing the cyclic vapor coating or vapor deposition process 100, 200. An example of a tool or system that can benefit from the cyclic vapor coating process is the Centura® system or Endura® system equipped with the iSprint™ ALD / CVD SSW chamber available from Applied Materials.

[0041] In one or more embodiments, the plurality of powder particles may be heated, cooled, or otherwise maintained at a temperature ranging from about 0° C., about 10° C., about 12° C., about 15° C., about 18° C., or about 20° C. to about 22° C., about 23° C., about 25° C., about 28° C., or about 30° C. during the cyclical vapor coating process 100, 200. For example, the plurality of powder particles may be heated, cooled, or otherwise maintained at a temperature ranging from about 0° C. to about 30° C., about 0° C. to about 25° C., about 10° C. to about 25° C., about 15° C. to about 25° C., about 18° C. to about 25° C., about 20° C. to about 25° C., about 22° C. to about 25° C., about 0° C. to about 20° C., about 10° C. to about 20° C., about 15° C. to about 20° C., or about 18° C. to about 20° C.

[0042] The processing region within the chamber or reactor may be conditioned or otherwise maintained at a stagnant atmosphere at a pressure less than 760 Torr when each pulse of metal precursor (e.g., first metal precursor or second metal precursor), oxidizer, and / or purge gas is independently introduced into the processing region during the cyclic vapor coating process 100, 200. The stagnant atmosphere in the processing region may be at a pressure of about 10 Torr, about 50 Torr, or about 100 Torr to about 200 Torr, about 500 Torr, or about 750 Torr. In one or more examples, the stagnant atmosphere in the processing region may be at a pressure of about 10 Torr to about 750 Torr.

[0043] In some examples, the metal precursor (or first metal precursor or second metal precursor) may be or may include one or more aluminum precursors used during the cyclic vapor coating process 100, 200. Exemplary aluminum precursors may be or may include trimethylaluminum, dimethylaluminum hydride, triethylaluminum, diethylaluminum hydride, tripropylaluminum, dipropylaluminum hydride, tributylaluminum, dibutylaluminum hydride, their isomers, their salts, or any combination thereof. In some examples, each pulse of aluminum precursor is introduced into the processing region without a carrier gas. In other examples, a carrier gas may entrain the aluminum precursor into the processing region. The aluminum precursor (or first metal precursor or second metal precursor) may be introduced into the processing region at a flow rate ranging from about 10 sccm, about 20 sccm, about 25 sccm, or about 30 sccm to about 40 sccm, about 50 sccm, about 80 sccm, or about 100 sccm. In one or more examples, the aluminum precursor (or first metal precursor or second metal precursor) may be introduced into the processing region at a partial pressure of less than 2 Torr, such as in a range of about 0.001 Torr, about 0.01 Torr, about 0.1 Torr, or about 0.5 Torr to about 0.8 Torr, about 1 Torr, or about 1.8 Torr. In one or more examples, the aluminum precursor (or first metal precursor or second metal precursor) may be at a temperature of about −20° C. to about 25° C., about −20° C. to about 23° C., about −20° C. to about 20° C., about −20° C. to about 18° C., about 0° C. to about 25° C., about 0° C. to about 23° C., about 0° C. to about 20° C., about 0° C. to about 18° C., about 15° C. to about 25° C., about 15° C. to about 23° C., about 15° C. to about 20° C., or about 15° C. to about 18° C. and a pressure of about 0.01 Torr to about 20 Torr when introduced into the MFC valve.

[0044] In other examples, the metal precursor (including the first metal precursor or the second metal precursor) may be or may include one or more zinc precursors during the cyclic vapor coating process 100, 200. Exemplary zinc precursors may be or may include dimethyl zinc, diethyl zinc, dipropyl zinc, dibutyl zinc, their isomers, their salts, or any combination thereof. In some examples, each pulse of zinc precursor is introduced into the processing region without a carrier gas. In other examples, a carrier gas can accompany the zinc precursor into the processing region. The zinc precursor (or the first metal precursor or the second metal precursor) may be introduced into the processing region at a flow rate ranging from about 10 sccm, about 20 sccm, about 25 sccm, or about 30 sccm to about 40 sccm, about 50 sccm, about 80 sccm, or about 100 sccm. In one or more examples, the zinc precursor (or first metal precursor or second metal precursor) may be introduced into the processing region at a partial pressure of less than 2 Torr, such as in a range of about 0.001 Torr, about 0.01 Torr, about 0.1 Torr, or about 0.5 Torr to about 0.8 Torr, about 1 Torr, or about 1.8 Torr. In one or more examples, the zinc precursor (or first metal precursor or second metal precursor) may be at a temperature of about −20° C. to about 25° C., about −20° C. to about 23° C., about −20° C. to about 20° C., about −20° C. to about 18° C., about 0° C. to about 25° C., about 0° C. to about 23° C., about 0° C. to about 20° C., about 0° C. to about 18° C., about 15° C. to about 25° C., about 15° C. to about 23° C., about 15° C. to about 20° C., or about 15° C. to about 18° C. and a pressure of about 0.01 Torr to about 20 Torr when introduced into the MFC valve.

[0045] The oxidizing agent during the cyclic vapor coating process 100, 200 may be or may include water, oxygen (O), hydrogen peroxide, inorganic peroxide, ozone, atomic oxygen, oxygen plasma, or any combination thereof. In some examples, each pulse of oxidizing agent is introduced into the processing region without a carrier gas. In other examples, a carrier gas may entrain the oxidizing agent into the processing region. The oxidizing agent (e.g., water vapor) may be introduced into the processing region at a flow rate ranging from about 10 sccm, about 20 sccm, about 25 sccm, or about 50 sccm to about 80 sccm, about 100 sccm, about 150 sccm, or about 200 sccm. In one or more examples, the oxidizing agent may be introduced into the processing region at a partial pressure of less than 2 Torr, such as in a range of about 0.001 Torr, about 0.01 Torr, about 0.1 Torr, or about 0.5 Torr to about 0.8 Torr, about 1 Torr, or about 1.8 Torr.

[0046] The purge gas (including the first, second, third, and / or fourth purge gas) may be or may include argon, helium, nitrogen (N), or any combination thereof during the cyclic vapor coating process 100, 200. The purge gas may be introduced into the processing region at a flow rate ranging from about 10 sccm, about 20 sccm, about 50 sccm, or about 80 sccm to about 100 sccm, about 200 sccm, about 300 sccm, or about 500 sccm.

[0047] In one or more embodiments, each deposition cycle in the cyclic vapor coating process 100, 200 includes introducing multiple pulses of a metal precursor into the processing region during a metal precursor exposure process. The metal precursor may be a first metal precursor, a second metal precursor, an aluminum precursor, and / or a zinc precursor during the metal precursor exposure process. Thus, each deposition cycle includes introducing multiple pulses of a metal precursor into the processing region during the metal precursor exposure process, ranging from 2, 3, 4, 5, 6, 7, 8, 9, 10, about 12, about 15, about 18, about 20, about 25, about 30 pulses to about 32, about 35, about 38, about 40, about 45, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120 pulses, or more, of the metal precursor. For example, each of the deposition cycles may comprise 2 to about 100 pulses, 2 to about 80 pulses, 2 to about 50 pulses, 2 to about 35 pulses, 2 to about 30 pulses, 2 to about 25 pulses, 2 to about 20 pulses, 2 to about 15 pulses, 2 to about 10 pulses, 2 to about 8 pulses, 2 to about 5 pulses, 3 to about 100 pulses, 3 to about 80 pulses, 3 to about 50 pulses, 3 to about 35 pulses, 3 to about 30 pulses, 3 to about 25 pulses, 3 to about 20 pulses, 3 to about 15 pulses, 3 to about 10 pulses of each of the first metal precursor and / or the second metal precursor. pulses, 3 to about 8 pulses, 3 to about 5 pulses, 5 to about 100 pulses, 5 to about 80 pulses, 5 to about 50 pulses, 5 to about 35 pulses, 5 to about 30 pulses, 5 to about 25 pulses, 5 to about 20 pulses, 5 to about 15 pulses, 5 to about 10 pulses, 5 to about 8 pulses, 8 to about 100 pulses, 8 to about 80 pulses, 8 to about 50 pulses, 8 to about 35 pulses, 8 to about 30 pulses, 8 to about 25 pulses, 8 to about 20 pulses, 8 to about 15 pulses, or 8 to about 10 pulses to the treatment region during the metal precursor exposure process.

[0048] In one or more examples, each deposition cycle includes introducing between 3 pulses of the metal precursor and about 100 pulses of each of the first metal precursor and / or second metal precursor to the processing region during the metal precursor exposure process. In other examples, each deposition cycle includes introducing between 5 pulses of the metal precursor and about 50 pulses of each of the first metal precursor and / or second metal precursor to the processing region during the metal precursor exposure process. In some examples, each deposition cycle includes introducing between 8 pulses of the metal precursor and about 25 pulses of each of the first metal precursor and / or second metal precursor to the processing region during the metal precursor exposure process.

[0049] In some embodiments, each pulse of metal precursor is introduced into the treatment region for a period ranging from about 20 seconds, about 30 seconds, about 40 seconds, about 45 seconds, or about 50 seconds to about 60 seconds, about 70 seconds, about 75 seconds, about 80 seconds, about 90 seconds, about 100 seconds, about 120 seconds, or longer during the metal precursor exposure process. For example, each pulse of metal precursor is introduced into the treatment region for a period ranging from about 20 seconds to about 120 seconds, about 20 seconds to about 100 seconds, about 20 seconds to about 90 seconds, about 20 seconds to about 75 seconds, about 20 seconds to about 60 seconds, about 20 seconds to about 45 seconds, about 20 seconds to about 30 seconds, about 30 seconds to about 120 seconds, about 30 seconds to about 100 seconds, about 30 seconds to about 90 seconds, about 30 seconds to about 90 seconds, about 30 seconds to about 120 seconds, about 30 seconds to about 10 ... The treatment zone is introduced for 0 seconds to about 75 seconds, about 30 seconds to about 60 seconds, about 30 seconds to about 45 seconds, about 40 seconds to about 120 seconds, about 40 seconds to about 100 seconds, about 40 seconds to about 90 seconds, about 40 seconds to about 75 seconds, about 40 seconds to about 60 seconds, about 60 seconds to about 120 seconds, about 60 seconds to about 100 seconds, about 60 seconds to about 90 seconds, or about 60 seconds to about 75 seconds.

[0050] Between pulses of metal precursor introduced into the treatment region, there is a dwell period during which no metal precursor is introduced into the treatment region. During the dwell period, the metal precursor can penetrate multiple powder particles and be absorbed into or react with the particle surfaces. This dwell period can be about 20 seconds, about 30 seconds, about 40 seconds, about 45 seconds, or about 50 seconds to about 60 seconds, about 70 seconds, about 75 seconds, about 80 seconds, about 90 seconds, about 100 seconds, about 120 seconds, or longer between pulses of metal precursor during the metal precursor exposure process. For example, the stagnation period may last for about 20 seconds to about 120 seconds, about 20 seconds to about 100 seconds, about 20 seconds to about 90 seconds, about 20 seconds to about 75 seconds, about 20 seconds to about 60 seconds, about 20 seconds to about 45 seconds, about 20 seconds to about 30 seconds, about 30 seconds to about 120 seconds, about 30 seconds to about 100 seconds, about 30 seconds to about 90 seconds, about 30 seconds to about 75 seconds, about 30 seconds to about 60 seconds, about 30 seconds to about 45 seconds, about 40 seconds to about 120 seconds, about 40 seconds to about 100 seconds, about 40 seconds to about 90 seconds, about 40 seconds to about 75 seconds, about 40 seconds to about 60 seconds, about 60 seconds to about 120 seconds, about 60 seconds to about 100 seconds, about 60 seconds to about 90 seconds, or about 60 seconds to about 75 seconds.

[0051] In one or more embodiments, each deposition cycle includes introducing multiple pulses of oxidizer into the treatment region during an oxidizer exposure process. The oxidizer may be a first oxidizer and / or a second oxidizer during the oxidizer exposure process. Thus, each deposition cycle includes introducing multiple pulses of oxidizer into the treatment region during the oxidizer exposure process, ranging from 2, 3, 4, 5, 6, 7, 8, 9, 10, about 12, about 15, about 18, about 20, about 25, about 30 pulses to about 32, about 35, about 38, about 40, about 45, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120 pulses, or more, of oxidizer. For example, each of the deposition cycles may include 2 to about 100 pulses, 2 to about 80 pulses, 2 to about 50 pulses, 2 to about 35 pulses, 2 to about 30 pulses, 2 to about 25 pulses, 2 to about 20 pulses, 2 to about 15 pulses, 2 to about 10 pulses, 2 to about 8 pulses, 2 to about 5 pulses, 3 to about 100 pulses, 3 to about 80 pulses, 3 to about 50 pulses, 3 to about 35 pulses, 3 to about 30 pulses, 3 to about 25 pulses, 3 to about 20 pulses, 3 to about 15 pulses, or 3 to about 10 pulses of the first oxidizer and / or the second oxidizer. , 3 pulses to about 8 pulses, 3 pulses to about 5 pulses, 5 pulses to about 100 pulses, 5 pulses to about 80 pulses, 5 pulses to about 50 pulses, 5 pulses to about 35 pulses, 5 pulses to about 30 pulses, 5 pulses to about 25 pulses, 5 pulses to about 20 pulses, 5 pulses to about 15 pulses, 5 pulses to about 10 pulses, 5 pulses to about 8 pulses, 8 pulses to about 100 pulses, 8 pulses to about 80 pulses, 8 pulses to about 50 pulses, 8 pulses to about 35 pulses, 8 pulses to about 30 pulses, 8 pulses to about 25 pulses, 8 pulses to about 20 pulses, 8 pulses to about 15 pulses, or 8 pulses to about 10 pulses to the treatment area during the oxidant exposure process.

[0052] In one or more examples, each of the deposition cycles includes introducing between 3 pulses of oxidizer and about 100 pulses of each of the first oxidizer and / or second oxidizer to the treatment region during the oxidizer exposure process. In other examples, each of the deposition cycles includes introducing between 5 pulses of oxidizer and about 50 pulses of each of the first oxidizer and / or second oxidizer to the treatment region during the oxidizer exposure process. In some examples, each of the deposition cycles includes introducing between 8 pulses of oxidizer and about 25 pulses of each of the first oxidizer and / or second oxidizer to the treatment region during the oxidizer exposure process.

[0053] In some embodiments, each pulse of oxidizing agent is introduced into the treatment region for a period ranging from about 20 seconds, about 30 seconds, about 40 seconds, about 45 seconds, or about 50 seconds to about 60 seconds, about 70 seconds, about 75 seconds, about 80 seconds, about 90 seconds, about 100 seconds, about 120 seconds, or longer during the oxidizing agent exposure process. For example, each pulse of oxidizing agent may be introduced into the treatment region for a period ranging from about 20 seconds to about 120 seconds, about 20 seconds to about 100 seconds, about 20 seconds to about 90 seconds, about 20 seconds to about 75 seconds, about 20 seconds to about 60 seconds, about 20 seconds to about 45 seconds, about 20 seconds to about 30 seconds, about 30 seconds to about 120 seconds, about 30 seconds to about 100 seconds, about 30 seconds to about 90 seconds, about 30 seconds The treatment zone is introduced for about 75 seconds, about 30 seconds to about 60 seconds, about 30 seconds to about 45 seconds, about 40 seconds to about 120 seconds, about 40 seconds to about 100 seconds, about 40 seconds to about 90 seconds, about 40 seconds to about 75 seconds, about 40 seconds to about 60 seconds, about 60 seconds to about 120 seconds, about 60 seconds to about 100 seconds, about 60 seconds to about 90 seconds, or about 60 seconds to about 75 seconds.

[0054] Between pulses of oxidizer introduced into the treatment area, there is a stagnation period during which no oxidizer is introduced into the treatment area. During the stagnation period, the oxidizer can penetrate the powder particles and be absorbed or react with the particle surfaces. This stagnation period can range from about 20 seconds, about 30 seconds, about 40 seconds, about 45 seconds, or about 50 seconds to about 60 seconds, about 70 seconds, about 75 seconds, about 80 seconds, about 90 seconds, about 100 seconds, about 120 seconds, or longer during the oxidizer exposure process. For example, the stagnation period may last for about 20 seconds to about 120 seconds, about 20 seconds to about 100 seconds, about 20 seconds to about 90 seconds, about 20 seconds to about 75 seconds, about 20 seconds to about 60 seconds, about 20 seconds to about 45 seconds, about 20 seconds to about 30 seconds, about 30 seconds to about 120 seconds, about 30 seconds to about 100 seconds, about 30 seconds to about 90 seconds, about 30 seconds to about 75 seconds, about 30 seconds to about 60 seconds, about 30 seconds to about 45 seconds, about 40 seconds to about 120 seconds, about 40 seconds to about 100 seconds, about 40 seconds to about 90 seconds, about 40 seconds to about 75 seconds, about 40 seconds to about 60 seconds, about 60 seconds to about 120 seconds, about 60 seconds to about 100 seconds, about 60 seconds to about 90 seconds, or about 60 seconds to about 75 seconds.

[0055] In one or more embodiments, each deposition cycle includes introducing multiple pulses of purge gas into the processing region, which may independently be a first purge gas, a second purge gas, a third purge gas, and / or a fourth purge gas during the purge process. Thus, each deposition cycle includes introducing multiple pulses of purge gas into the processing region during the purge process, ranging from 2, 3, 4, 5, 6, 7, 8, 9, 10, about 12, about 15, about 18, about 20, about 25, about 30 pulses to about 32, about 35, about 38, about 40, about 45, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120 pulses, or more, of purge gas. For example, each of the deposition cycles may include 2 to about 100 pulses, 2 to about 80 pulses, 2 to about 50 pulses, 2 to about 35 pulses, 2 to about 30 pulses, 2 to about 25 pulses, 2 to about 20 pulses, 2 to about 15 pulses, 2 to about 10 pulses, 2 to about 8 pulses, 2 to about 5 pulses, 3 to about 100 pulses, 3 to about 80 pulses, 3 to about 50 pulses, 3 to about 35 pulses, 3 to about 30 pulses, 3 to about 25 pulses, 3 to about 20 pulses, 3 to about 15 pulses of the first purge gas, the second purge gas, the third purge gas, and / or the fourth purge gas, respectively. , 3 to about 10 pulses, 3 to about 8 pulses, 3 to about 5 pulses, 5 to about 100 pulses, 5 to about 80 pulses, 5 to about 50 pulses, 5 to about 35 pulses, 5 to about 30 pulses, 5 to about 25 pulses, 5 to about 20 pulses, 5 to about 15 pulses, 5 to about 10 pulses, 5 to about 8 pulses, 8 to about 100 pulses, 8 to about 80 pulses, 8 to about 50 pulses, 8 to about 35 pulses, 8 to about 30 pulses, 8 to about 25 pulses, 8 to about 20 pulses, 8 to about 15 pulses, or 8 to about 10 pulses into the treatment region during the purging process.

[0056] In one or more examples, each of the deposition cycles includes independently introducing three pulses of purge gas to about 100 pulses of each of the first purge gas, the second purge gas, the third purge gas, and / or the fourth purge gas into the processing region during the purge process. In other examples, each of the deposition cycles includes independently introducing five pulses of purge gas to about 50 pulses of each of the first purge gas, the second purge gas, the third purge gas, and / or the fourth purge gas into the processing region during the purge process. In some examples, each of the deposition cycles includes independently introducing eight pulses of purge gas to about 25 pulses of each of the first purge gas, the second purge gas, the third purge gas, and / or the fourth purge gas into the processing region during the purge process.

[0057] In some embodiments, each pulse of purge gas is introduced into the processing region for a period ranging from about 20 seconds, about 30 seconds, about 40 seconds, about 45 seconds, or about 50 seconds to about 60 seconds, about 70 seconds, about 75 seconds, about 80 seconds, about 90 seconds, about 100 seconds, about 120 seconds, or longer during the purge process. For example, each pulse of purge gas may be introduced into the processing region for a period ranging from about 20 seconds to about 120 seconds, about 20 seconds to about 100 seconds, about 20 seconds to about 90 seconds, about 20 seconds to about 75 seconds, about 20 seconds to about 60 seconds, about 20 seconds to about 45 seconds, about 20 seconds to about 30 seconds, about 30 seconds to about 120 seconds, about 30 seconds to about 100 seconds, about 30 seconds to about 90 seconds, about 30 seconds The treatment zone is introduced for about 75 seconds, about 30 seconds to about 60 seconds, about 30 seconds to about 45 seconds, about 40 seconds to about 120 seconds, about 40 seconds to about 100 seconds, about 40 seconds to about 90 seconds, about 40 seconds to about 75 seconds, about 40 seconds to about 60 seconds, about 60 seconds to about 120 seconds, about 60 seconds to about 100 seconds, about 60 seconds to about 90 seconds, or about 60 seconds to about 75 seconds.

[0058] Between pulses of purge gas introduced into the processing region, there is a stagnation period during which no purge gas is introduced into the processing region. During the stagnation period, the purge gas can penetrate the powder particles and flush or purge out any gas residue from the particles. This stagnation period can be about 20 seconds, about 30 seconds, about 40 seconds, about 45 seconds, or about 50 seconds to about 60 seconds, about 70 seconds, about 75 seconds, about 80 seconds, about 90 seconds, about 100 seconds, about 120 seconds, or longer during the purge process. For example, the stagnation period may last for about 20 seconds to about 120 seconds, about 20 seconds to about 100 seconds, about 20 seconds to about 90 seconds, about 20 seconds to about 75 seconds, about 20 seconds to about 60 seconds, about 20 seconds to about 45 seconds, about 20 seconds to about 30 seconds, about 30 seconds to about 120 seconds, about 30 seconds to about 100 seconds, about 30 seconds to about 90 seconds, about 30 seconds to about 75 seconds, about 30 seconds to about 60 seconds, about 30 seconds to about 45 seconds, about 40 seconds to about 120 seconds, about 40 seconds to about 100 seconds, about 40 seconds to about 90 seconds, about 40 seconds to about 75 seconds, about 40 seconds to about 60 seconds, about 60 seconds to about 120 seconds, about 60 seconds to about 100 seconds, about 60 seconds to about 90 seconds, or about 60 seconds to about 75 seconds.

[0059] The cyclic vapor coating process can include various numbers of deposition cycles. In some embodiments, the cyclic vapor coating process can include a plurality of deposition cycles ranging from 1, 2, 3, 4, 5, 6, 7, or 8-9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, about 22, or about 25 cycles, or more. For example, the cyclic vapor coating process can include from 1 to about 25, from 1 to about 20, from 1 to about 18, from 1 to about 15, from 1 to about 12, from 1 to about 10, from 1 to 9, from 1 to 8, from 1 to 7, from 1 to 6, from 1 to 5, from 1 to 4, from 1 to 3, from 1 to 2, from 2 to about 25, from 2 to about 20, from 2 to about 18, from 2 to about 15, from 2 to about 12, from 2 to about 10, from 2 to 9, from 2 to 8, from 2 to 7, from 2 to 6, from 2 to 5, or from 2 to 3. The deposition may include a plurality of deposition cycles of from 4, 2 to 3, 3 to about 25, 3 to about 20, 3 to about 18, 3 to about 15, 3 to about 12, 3 to about 10, 3 to 9, 3 to 8, 3 to 7, 3 to 6, 3 to 5, 3 to 4, 4 to about 25, 4 to about 20, 4 to about 18, 4 to about 15, 4 to about 12, 4 to about 10, 4 to 9, 4 to 8, 4 to 7, 4 to 6, or 4 to 5.

[0060] In one or more examples, the deposition cycle is repeated 2 to about 20 times. In some examples, the deposition cycle is repeated 3 to about 10 times. In other examples, the deposition cycle is repeated 4 to about 8 times, or 5 to about 7 times.

[0061] To avoid flow anomalies, conventional MFC operation is typically performed at high differential pressures (e.g., greater than 10 Torr) between the source ampoule and the chamber or reactor processing region. To avoid condensation, conventional ampoule vapor delivery via metering valves has precise multi-zone heating, pressure monitoring, and valve timing. Stagnant flow during the MFC and cyclic vapor coating processes described and discussed in embodiments herein prevents heating of the source above 25°C and enables pulsed-mode chemical delivery for application-specific particle and vapor coating reactions.

[0062] It was surprising and unexpected that the size or diameter of the orifice for each of the MFC valves can be independently selected for enhanced delivery of each gas, such as a precursor gas (e.g., a metal precursor and an oxidizer) or a purge gas, during the cyclic vapor coating process 100, 200. Each of the first MFC valve, second MFC valve, third MFC valve, fourth MFC valve, and any other MFC valve described and discussed herein has a separate orifice for delivering a respective gas, such as a precursor gas (e.g., a metal precursor and an oxidizer) or a purge gas. Each of the orifices has a predetermined size or diameter to help provide a desired flow rate of the respective gas. Each of the orifices of the first MFC valve, the second MFC valve, the third MFC valve, the fourth MFC valve, and other MFC valves described and contemplated herein may independently be about 0.045 inches, about 0.048 inches, about 0.050 inches, about 0.052 inches, about 0.055 inches, about 0.058 inches, about 0.060 inches, about 0.062 inches, greater than 0.062 inches, about 0.065 inches, about 0.068 inches, about 0.070 inches, about 0.075 inches, or between about 0.080 inches and about 0.085 inches, and having a diameter in the range of about 0.090 inch, about 0.093 inch, about 0.095 inch, about 0.100 inch, about 0.105 inch, about 0.110 inch, about 0.111 inch, about 0.112 inch, about 0.113 inch, about 0.114 inch, about 0.115 inch, about 0.118 inch, about 0.120 inch, about 0.125 inch, about 0.130 inch, about 0.135 inch, about 0.140 inch, about 0.145 inch, about 0.150 inch, about 0.155 inch, about 0.160 inch, about 0.170 inch, or greater. For example, each of the orifices of the first MFC valve, the second MFC valve, the third MFC valve, the fourth MFC valve, and other MFC valves described and contemplated herein may independently have an orifice size of about 0.050 inches to about 0.150 inches, about 0.050 inches to about 0.140 inches, about 0.050 inches to about 0.130 inches, about 0.050 inches to about 0.125 inches, about 0.050 inches to about 0.120 inches, ...0.050 inches to about 0.118 inches, about 0.050 inches to about 0.115 inches, about 0.050 inches to about 0.113 inches, about 0.050 inches to about 0.110 inches, about 0.050 inches to about 0.108 inches, about 0.050 inches to about 0.105 inches, about 0.050 inches to about 0.100 inches, about 0.050 inches to about 0.095 inches, about 0.050 inches to about 0.090 inches, about 0.050 inches to about 0.080 inches, about 0.050 inches to about 0.075 inches, about 0.050 inches to about 0.070 inches, about 0.050 inches to about 0.060 inches, greater than 0.062 inches, or about 0.062 inches to about 0.150 inches, greater than 0.062 inches, or about 0.062 inches to about 0.140 inches, greater than 0.062 inches, or about 0.062 inches to about 0.130 inches, greater than 0.062 inches, or about 0.062 inches to about 0.125 inches, greater than 0.062 inches, or about 0.062 inches to about 0.120 inches, greater than 0.062 inches, or about 0.062 inches to about 0.118 inches, greater than 0.062 inches or about 0.062 inches to about 0.115 inches, greater than 0.062 inches, or about 0.062 inches to about 0.113 inches, greater than 0.062 inches, or about 0.062 inches to about 0.110 inches, greater than 0.062 inches, or about 0.062 inches to about 0.108 inches, greater than 0.062 inches, or about 0.062 inches to about 0.105 inches, greater than 0.062 inches, or about 0.062 inches to about 0.100 inches, greater than 0.062 inches, or about 0.062 inches to about 0.0 95 inches, about 0.062 inches to about 0.093 inches, greater than 0.062 inches or about 0.062 inches to about 0.090 inches, greater than 0.062 inches or about 0.062 inches to about 0.080 inches, greater than 0.062 inches or about 0.062 inches to about 0.075 inches, greater than 0.062 inches or about 0.062 inches to about 0.070 inches, greater than 0.062 inches or about 0.062 inches to about 0.065 inches, about 0.075 inches to about 0.150 inches, about 0.075 inches to about 0.140 inches, about 0.075 inches to about 0.130 inches, about 0.075 inches to about 0.125 inches, about 0.075 inches to about 0.120 inches, about 0.075 inches to about 0.118 inches, about 0.075 inches to about 0.115 inches, about 0.075 inches to about 0.113 inches, about 0.075 inches to about 0.110 inches, about 0.075 inches to about 0.108 inches, about 0.075 inches to about 0.105 inches, about 0.075 inches to about 0.100 inches, about 0.075 inches to about 0.095 inches, about 0.075 inches to about 0.090 inches, about 0.075 inches to about 0.080 inches, or about 0.075 inches to about 0.078 inches.

[0063] In one or more examples, each of the orifices of the first MFC valve, the second MFC valve, the third MFC valve, and the fourth MFC valve independently has a diameter ranging from about 0.050 inches to about 0.150 inches. In some examples, each of the orifices of the first MFC valve, the second MFC valve, the third MFC valve, and the fourth MFC valve independently has a diameter ranging from about 0.062 inches to about 0.113 inches. In other examples, each of the orifices of the first MFC valve, the second MFC valve, the third MFC valve, and the fourth MFC valve independently has a diameter ranging from about 0.075 inches to about 0.105 inches.

[0064] 3A-3C illustrate a deposition system 300 for coating particles with a thin film coating, as described and discussed in one or more embodiments herein. The deposition system 300 can be used to perform the cyclic vapor coating processes 100, 200 and other cyclic vapor coating processes, such as a process for coating a plurality of powder particles with a metal oxide coating to form a plurality of coated particles.

[0065] Figure 3A shows a schematic cross-sectional front view of a deposition system 300 for performing a cyclic vapor coating process to coat particles. The deposition system 300 includes a rotating cylindrical reactor tube 410 (e.g., a rotating vacuum chamber). Figure 3B shows a schematic side view of the deposition system 300 shown in Figure 3A. Figure 3C shows a schematic cross-sectional side view of the deposition system 300 shown in Figure 3A. The view in Figure 3C may be taken along line 3C-3C in Figure 3A.

[0066] The deposition system 300 includes a reactor system 400 having a rotating cylindrical reactor tube 410 (also referred to as a "drum") that can be partially filled with a plurality of powder particles 308 to form a particle bed within a processing region 414 of the reactor drum 410. Briefly, as the reactor drum rotates, one or more process gases are injected into the drum through an inlet port and exhausted from the drum through an outlet port. Thus, the plurality of powder particles 308 within the drum undergo tumbling agitation so that the gas is uniformly applied to the particles and can deposit a metal oxide layer or coating on the powder particles to produce coated particles. In one or more examples, the powder particles and / or coated particles may have an average or median size (PSD D50) of about 0.5 μm to about 200 μm, about 2 μm to about 200 μm, or about 5 μm to about 100 μm.

[0067] The deposition system 300 also includes an isolator 310 that forms an isolated chamber 312. At least some components of the reactor system, including at least the reactor tube 410, are located within the chamber 312 of the isolator 310. The isolator 310 may be a glove box that includes one or more, e.g., four, gloves 314 (glove ports 315 are shown in FIG. 3B). The front panel 316 of the isolator 310 may be transparent, e.g., formed from monolithic tempered glass, to allow an operator to view the interior chamber of the isolator 310. Additionally, the gloves 314 are positioned to allow an operator to manipulate portions of the reactor system 400, e.g., remove a reactor tube 410 containing coated particles from other portions of the reactor system 400 after a deposition process and install a new reactor tube containing uncoated particles for a subsequent deposition process. The isolator 310 can provide ISO 10648-2 Class 2 containment against leaks and / or containment of API up to OEB5 toxicity levels.

[0068] The isolator 310 may include an air intake port 320 equipped with an H14 HEPA filter to filter air entering the internal chamber 312, and an exhaust pump 322 connected to an air outlet port 324 also equipped with an H14 HEPA filter. One or more outlet ports (not shown) return air to the environment surrounding the isolator 310, or the one or more outlet ports may be directly connected to a facility exhaust line for further processing. The exhaust pump operates to exhaust the internal chamber 312 to approximately -50 Pa to approximately -100 Pa relative to the ambient pressure of the environment surrounding the isolator 310. Additionally, the isolator may be configured for aseptic operation at pressures slightly above atmospheric pressure, for example, approximately 2% to 20% above atmospheric pressure. In some embodiments, a polished, sanitary stainless steel filter housing can be used with a USP Class VI 0.2 μm exhaust filter. Additionally or alternatively, an oxidizer ampoule heater can heat water to 135°C for sterilization. Sterilization may continue periodically, as needed, after ampoule refilling.

[0069] 3B and 3C, the isolator 310 also includes a rapid transfer port. In particular, the rapid transfer port includes a removable transfer container 330 having an interior space 332. The transfer container may be sealed by a valve 334, and similarly, an access port connecting the container 330 to the isolator 310 may be sealed by a valve 336. When both valves 334, 336 are open, an operator can access the interior space 332 of the container 330 using gloves 314. For example, a reactor drum 410 may be placed in the transfer container 330. As another example, coated particles may be transferred from the reactor drum 410 to a canister 311 within the isolator 310, and the canister may then be placed in the container 330 by an operator (using gloves 314). Once both valves 334, 336 are closed, the canister 130 may be manually removed from the isolator so that the contents may be transported to another location without risk of contaminating the coated particles or the interior of the isolator 310, for example to remove the coated particles from the drum or for further processing of the particles, such as mixing with excipients, extrusion into tablets, or encapsulation into shells.

[0070] The interior 312 of the isolator 310 may also include a pedestal or platform 340 for supporting various components, such as parts of the reactor system 400, or tools used in assembling or disassembling the reactor system 400 or transferring powder, within reach of an operator using gloves 314. For example, the canister 311 may be positioned on the platform 340.

[0071] 3A , some parts of the deposition system 300, such as the isolator 310 and the rotatable reactor drum 410, may be located in a clean room 302. In contrast, some other parts of the deposition system 300, such as the vacuum pump 250 and the electrical cabinet 510 of the reactor system 400, may be located in a technical area 304, which has a much lower level of cleanliness than the clean room 302. The clean room 302 may be separated from the technical area by a partition wall 306. A controller 500, such as a programmed general-purpose computer, may be located in the technical area 304 for an operator to control the operation of the reactor system 400. In some embodiments, the user interface (e.g., touchscreen display, keyboard) of the controller 500 is located in the clean room 302.

[0072] 3A, the deposition system 300 also includes a heater assembly 520 for controlling the temperature of at least the reactor drum 410. The heater assembly 520 may include two semi-cylindrical blocks, a lower semi-cylindrical block 522 and an upper semi-cylindrical block 324. Embedded in or disposed on the surface of each cylindrical block 522 are one or more heating elements (e.g., resistive heaters powered by the electrical cabinet 510). Each cylindrical block may be formed from a heat sink material, such as anodized aluminum.

[0073] 3A, the controller 500 is configured to operate the reactor system 400 according to a "recipe." The recipe specifies the operating values ​​of each controllable element as a function of time. For example, the recipe may specify the time for which the vacuum source 450 operates, the time and flow rate of each gas source, and the rotation speed of the rotating reaction drum 410 set by the motor 442. The controller 500 may receive the recipe as computer-readable data (e.g., stored on a non-transitory computer-readable medium).

[0074] 3C, the reactor system 400 is further described. The reactor system 400 includes a rotatable reactor drum 410, a rotatable inlet pipe 420, and a rotatable outlet pipe 430. The rotatable inlet pipe 420 and the rotatable outlet pipe 430 are collinear with the axis of rotation 412 of the rotatable reactor drum 410. The rotatable inlet pipe 420 is fluidly connected to a stationary inlet line 422 by an inlet rotary seal 424, and the rotatable outlet pipe 430 is fluidly connected to a stationary outlet line 432 by an outlet rotary seal 434. The rotary seals 424, 434 can reduce the risk of particles escaping from the reactor system 400.

[0075] For rotating seals 424, 434, one option is to use a labyrinth seal. Generally, the circular path of a labyrinth seal can provide many opportunities for particles to adhere to the seal surface. Labyrinth seals can help maintain a vacuum without the need for an external purge gas.

[0076] Another option for the rotating seals 424, 434 is a double-cartridge mechanical seal. Such a mechanical seal may include a pair of bearings. In each bearing, an inner ring is in physical contact with an outer ring. Because the rings are in physical contact, relative motion can cause wear. Therefore, the rings may be formed from a non-toxic material that does not interfere with the deposition process, such as graphite or a ceramic with a very low wear rate. To prevent atmospheric leakage into the reactor, a purge gas may be injected into the space between the pair of bearings. For example, the pressure of the purge gas can be controlled from less than 10 mTorr to approximately 30 psig to avoid N2 leakage into the reactor and prevent contamination from the air.

[0077] The rotatable outlet pipe 430 can also function as a drive shaft for the rotatable reactor drum 410. In particular, the rotary drive system 440 includes a drive motor 442 for rotating the rotatable components, e.g., the reactor drum 410, the rotatable inlet pipe 420, and the rotatable outlet pipe 430. A drive wheel 444 is fixed to the rotatable outlet pipe 430 at a spot between the reactor drum 410 and the outlet rotary seal 434. The drive wheel 444 is coupled to the motor 442 by a drive belt 446. In operation, the rotary drive motor system 440 can rotate the reactor drum 410 at a speed between about 1 rpm and about 50 rpm, e.g., between about 6 rpm and about 50 rpm. The motion of the reactor drum 410 can be clockwise (CW), counterclockwise (CCW), or alternating between CW and CCW.

[0078] Returning to FIG. 3A, the deposition system 300 includes a vacuum source 450 (e.g., one or more vacuum pumps) coupled to the outlet line 432. The vacuum source 450 may be an industrial vacuum pump sufficient to establish a pressure less than 1 Torr, e.g., between about 1 mTorr and about 100 mTorr, e.g., between about 20 mTorr and about 100 mTorr. In some embodiments, the vacuum pump is capable of establishing a pressure less than 760 Torr but greater than or equal to 1 Torr, e.g., between about 1 Torr and about 100 Torr. The vacuum source 450 allows the interior 414 of the reactor drum 410 to be maintained at a desired pressure, allowing for the removal of reaction by-products and unreacted process gases.

[0079] In some embodiments, a purge gas source 452 is connected to the exit line 432 to create backpressure, for example, to remove powder blockages in the reactor drum end caps, as discussed below. The purge gas may be, for example, argon or nitrogen. One or more valves 454 can be used to control whether the vacuum source 450 or the purge gas source 452 is connected to the exit line 432.

[0080] An ultra-low particulate air filter 458 may be placed in the outlet line 432 between the vacuum source 450 and the outlet rotary seal 434 to prevent powder contamination downstream of the filter housing. In some embodiments, the ultra-low particulate air filter 458 may be a hygienic Parker demi-stainless steel filter housing with a 0.2 μm TETPOR Air Filter Cartridge that meets USP Class VI standards. The housing may be further polished to a surface finish of 0.4 roughness (Ra) on the surface upstream of the filter, and O-rings, such as USP Class VI Viton O-rings, may be used to seal joints between components. Because the upstream surface of the ultra-low particulate air filter 458 may come into contact with APIs, having a sufficiently cleanable surface can prevent biological contamination.

[0081] Chemical delivery system 460 includes multiple fluid sources connected to inlet line 422 by respective delivery pipes and controllable valves. Chemical delivery system 460 injects fluids in vapor form into reactor drum 410. Chemical delivery system 460 includes a combination of restrictors, gas flow controllers, pressure transducers, and thermal mass flow controllers / meters to provide controllable flow rates of various gases into reactor drum 410. Chemical delivery system 460 may also include one or more temperature control components (e.g., heat exchangers, resistance heaters) to heat or cool the various gases before they enter reactor drum 410.

[0082] As shown in FIG. 3C , ampoule cabinet 350 may be located adjacent to isolator 310. Ampoule cabinet 350 comprises part of chemical delivery system 460 for reactor system 400. In particular, located in ampoule cabinet 350 are one or more ports 462 configured to receive one or more ampoules 333 or other precursor or gas sources containing precursor or purge gases (e.g., in gaseous or liquid form) for the cyclic vapor coating process described and discussed herein. Ports 4632 may be connected by a manifold 464, which may include various delivery tubes and controllable valves for controlling flow to inlet line 422. For example, ampoule cabinet 350 may include three or more ports 462 and three or more mass flow control (MFC) valves 455, such as two MFC valves 455 for two metal precursors (one precursor per valve) and one MFC valve 455 for an oxidizer. The reagents and / or process gases may be, for example, a first metal precursor, a second metal precursor, an oxidizer, and one or more purge gases. For example, one or more aluminum precursors, one or more zinc precursors, water vapor, and a purge gas including N2 and / or argon. Each of the MFC valves 455, 456 can independently include an orifice having a diameter ranging from about 0.050 inches to about 0.150 inches, from about 0.062 inches to about 0.113 inches, or from about 0.075 inches to about 0.105 inches.

[0083] In some embodiments, chemical delivery system 460 may include five fluid sources. Two of the fluid sources may provide two chemically distinct precursors or reactants for a deposition process to form a metal oxide coating or layer on the particles. In one or more examples, a first fluid source may provide a first metal source, such as an aluminum precursor (e.g., trimethylaluminum (TMA)), to first MFC valve 455, a second source may provide a purge gas (e.g., N2 and / or Ar) to second MFC valve 455, and a third source may provide an oxidant (e.g., water) to third MFC valve 455. In some examples, a first fluid source may provide a first metal source, such as a zinc precursor (e.g., diethylzinc (DEZ)), to the first MFC valve 455, a second source may provide a purge gas (e.g., N2 and / or Ar) to the second MFC valve 455, and a third source may provide an oxidant (e.g., water) to the third MFC valve 455. In another example, a first fluid source may provide a first metal precursor, an aluminum precursor (e.g., trimethylaluminum (TMA)), to a first MFC valve 455, a purge gas source 452 may provide a purge gas (e.g., N2 and / or Ar) to an MFC valve 456, a second source may provide an oxidant (e.g., water) to a second MFC valve 455, and a third source may provide a second metal precursor, for example, a zinc precursor (e.g., diethylzinc (DEZ)), to a third MFC valve 455.

[0084] 3A, the mass flow rate of chemicals into the reactor may be sensed, for example, by MFC valve 456 in inlet line 432. MFC valve 456 can send a signal indicative of the mass flow rate to controller 500, which can control the valve based on the received signal to establish the desired mass flow rate, thus providing a mass flow controller.

[0085] The MFC valve 456 may be a thermal MFC. Such a thermal MFC senses changes in temperature to determine mass flow rate. Different materials have different calibration constants, e.g., different partial pressures as a function of temperature. To properly convert temperature measurements to mass flow measurements, the calibration constant must be programmed into the thermal MFC. However, the calibration constant for TMA was determined through empirical measurements and found to be unexpectedly low. For example, its Antoine vapor pressure ranges from about 9 Torr at about 20°C to about 16 Torr at about 30°C, which is about half that of water or DEZZ. Because the calibration constant is unusually low, the mass flow controller itself may need to be customized, for example, for orifice size and flow rate range. This may allow for high flow rates using a low vapor pressure source.

[0086] The controller 500 and other computing device components of the systems described herein may be implemented in digital electronic circuitry, or in computer software, firmware, or hardware. For example, the controller may include a processor executing a computer program product, e.g., a computer program stored on a non-transitory machine-readable storage medium. Such computer programs (also known as programs, software, software applications, or code) may be written in any form of programming language, including compiled or interpreted languages, and may 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 500 is a general-purpose programmable computer. In some embodiments, the controller may be implemented using special-purpose logic circuitry, e.g., an FPGA (field-programmable gate array) or an ASIC (application-specific integrated circuit).

[0087] A system of one or more computers configured to perform a specific operation or action means that the system has installed thereon software, firmware, hardware, or a combination thereof that causes the system to perform the operation or action when operated. A system of one or more computer programs configured to perform a specific operation or action means that the one or more programs, when executed by a data processing device, contain instructions that cause the device to perform the operation or action. The present disclosure provides an apparatus and method for preparing pharmaceutical compositions 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 total thickness ranging from a few nanometers to a few micrometers. The coated article may consist 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 compared to the uncoated API, a reduced crystallization rate of the amorphous form of the API compared to the uncoated API, and reduced surface mobility of the API molecules within the particle compared to the uncoated API. Importantly, the dissolution of the particles may be altered. Because the coating is relatively thin, drug products with high drug loadings can be achieved. Finally, multiple coatings can be applied in the same reactor, providing advantages in terms of cost and ease of manufacturing.

[0088] In one or more embodiments, a method of forming, producing, or otherwise preparing a coating powder composition is provided, including positioning a plurality of powder particles, each of which can be or can include an organic material, in a processing region of a processing chamber, such as deposition system 300, and coating the plurality of powder particles with a metal oxide coating during a cyclic vapor coating process to form a plurality of coated particles. The metal oxide coating includes aluminum oxide, zinc oxide, or aluminum zinc oxide. The cyclic vapor coating process includes one, two, or more deposition cycles. A controller 500 may be configured and used to execute the following deposition cycles for the cyclic vapor coating process: Each deposition cycle includes introducing two or more pulses of a metal precursor (aluminum precursor or zinc precursor) into the processing region through a first MFC valve having an orifice with a diameter ranging from about 0.050 inches to about 0.150 inches, or from about 0.062 inches to about 0.113 inches, exposing a plurality of powder particles to the metal precursor, and allowing the metal precursor to penetrate the plurality of powder particles through spaces between the powder particles. Thereafter, each deposition cycle includes introducing two or more pulses of a purge gas (e.g., N or Ar) into the processing region through a second MFC valve having an orifice with a diameter ranging from about 0.050 inches to about 0.150 inches, or from about 0.062 inches to about 0.113 inches, and exposing the plurality of powder particles to the purge gas during a first purge process. Thereafter, each deposition cycle includes introducing two or more pulses of an oxidizer (e.g., water vapor) into the treatment region through a third MFC valve having an orifice with a diameter ranging from about 0.050 inches to about 0.150 inches, or from about 0.062 inches to about 0.113 inches, exposing the plurality of powder particles to the oxidizer, and permeating the plurality of powder particles through spaces between the powder particles to produce a metal oxide coating disposed on an outer surface of each of the powder particles.Thereafter, each deposition cycle includes introducing two or more pulses of purge gas through the second MFC valve and exposing a plurality of powder particles to the purge gas during the second purge process.

[0089] In some embodiments, a method for forming, producing, or otherwise preparing a coating powder composition is provided, including positioning a plurality of powder particles, each of which may be or may include an inorganic material, in a processing region of a processing chamber, such as deposition system 300, and coating the plurality of powder particles with a metal oxide coating during a cyclic vapor coating process to form a plurality of coated particles. The metal oxide coating includes aluminum oxide, zinc oxide, or aluminum zinc oxide. The cyclic vapor coating process includes one, two, or more deposition cycles. The controller 500 may be configured and used to execute the following deposition cycles for the cyclic vapor coating process: each of the deposition cycles includes introducing two or more pulses of a metal precursor into the processing region through a first MFC valve having an orifice with a diameter ranging from about 0.050 inches to about 0.150 inches, or from about 0.062 inches to about 0.113 inches; exposing the plurality of powder particles to the metal precursor; and infiltrating the plurality of powder particles with the metal precursor through spaces between the powder particles. Thereafter, each deposition cycle includes introducing two or more pulses of purge gas into the processing region through a second MFC valve having an orifice with a diameter ranging from about 0.050 inches to about 0.150 inches, or from about 0.062 inches to about 0.113 inches, and exposing a plurality of powder particles to the purge gas during a first purge process. Thereafter, each deposition cycle includes introducing two or more pulses of oxidizer into the processing region through a third MFC valve having an orifice with a diameter ranging from about 0.050 inches to about 0.150 inches, or from about 0.062 inches to about 0.113 inches, exposing a plurality of powder particles to the oxidizer, and infiltrating the plurality of powder particles through spaces between the powder particles to produce a metal oxide coating disposed on an outer surface of each of the powder particles. Thereafter, each deposition cycle includes introducing two or more pulses of purge gas through the second MFC valve and exposing a plurality of powder particles to the purge gas during a second purge process.

[0090] In another embodiment, a method for forming, producing, or otherwise preparing a coating powder composition is provided, comprising positioning a plurality of powder particles in a processing region of a processing chamber, such as deposition system 300, and coating the plurality of powder particles with a metal oxide coating during a cyclic vapor coating process to form a plurality of coated particles. The metal oxide coating comprises aluminum zinc oxide. The cyclic vapor coating process includes one, two, or more deposition cycles. Controller 500 may be configured and used to execute the following deposition cycles for the cyclic vapor coating process: each of the deposition cycles includes introducing two or more pulses of a first metal precursor (e.g., an aluminum precursor) into the processing region through a first MFC valve having an orifice with a diameter ranging from about 0.050 inches to about 0.150 inches, or from about 0.062 inches to about 0.113 inches; exposing the plurality of powder particles to the first metal precursor; and infiltrating the plurality of powder particles with the first metal precursor through spaces between the powder particles. Thereafter, each deposition cycle includes introducing two or more pulses of a purge gas (e.g., N or Ar) into the processing region through a second MFC valve having an orifice with a diameter ranging from about 0.050 inches to about 0.150 inches, or from about 0.062 inches to about 0.113 inches, and exposing the plurality of powder particles to the purge gas during a first purge process. Thereafter, each deposition cycle includes introducing two or more pulses of an oxidizer (e.g., water vapor) into the processing region through a third MFC valve having an orifice with a diameter ranging from about 0.050 inches to about 0.150 inches, or from about 0.062 inches to about 0.113 inches, exposing the plurality of powder particles to the oxidizer, and permeating the plurality of powder particles through spaces between the powder particles to produce a first metal oxide layer disposed on an outer surface of each of the powder particles. Thereafter, each deposition cycle includes introducing two or more pulses of purge gas through the second MFC valve and exposing a plurality of powder particles to the purge gas during the second purge process.Thereafter, each deposition cycle includes introducing two or more pulses of a second metal precursor (e.g., a zinc precursor) into the processing region through a fourth MFC valve having an orifice with a diameter ranging from about 0.050 inches to about 0.150 inches, or from about 0.062 inches to about 0.113 inches, exposing a plurality of powder particles to the second metal precursor, and allowing the second metal precursor to penetrate the plurality of powder particles through spaces between the powder particles. Thereafter, each deposition cycle includes introducing two or more pulses of a purge gas into the processing region through the second MFC valve, and exposing the plurality of powder particles to the purge gas during a third purge process. Thereafter, each deposition cycle includes introducing two or more pulses of an oxidizer into the processing region through a third MFC valve, exposing the plurality of powder particles to the oxidizer, and allowing the oxidizer to penetrate the plurality of powder particles through spaces between the powder particles to produce a second metal oxide layer disposed on the first metal oxide layer disposed on the outer surface of each of the powder particles. Each deposition cycle then includes introducing two or more pulses of purge gas through the second MFC valve and exposing the plurality of powder particles to the purge gas during a fourth purge process. The first and second metal precursors are different from each other. The metal oxide coating includes a first metal oxide layer and a second metal oxide layer. The first metal oxide layer includes aluminum oxide and the second metal oxide layer includes zinc oxide, or the first metal oxide layer includes zinc oxide and the second metal oxide layer includes aluminum oxide.

[0091] Coated particle product The coating powder composition is produced, manufactured, or otherwise prepared by the cyclic vapor coating process 100, 200. Each of the coated particles of the coating powder composition has a core comprising a powder particle and a metal oxide coating. The powder particles may be or may include one or more organic materials or compounds, one or more inorganic materials or compounds, or any combination thereof. In some examples, the powder particles include, consist of, or consist essentially of one or more organic materials or compounds, one or more inorganic materials or compounds, or any combination thereof. The metal oxide coating may be or may include one or more aluminum oxides, zinc oxides, or aluminum zinc oxides. In some examples, the metal oxide coating includes, consists of, or consists essentially of aluminum oxides, zinc oxides, or aluminum zinc oxides.

[0092] The plurality of coated particles may have an average particle size in the range of about 0.1 μm, about 0.2 μm, about 0.3 μm, about 0.5 μm, about 0.8 μm, about 1 μm, about 2 μm, about 3 μm, about 5 μm, about 8 μm, about 10 μm, about 12 μm, about 15 μm, about 18 μm, about 20 μm, about 25 μm, about 30 μm, or about 35 μm to about 40 μm, about 50 μm, about 60 μm, about 70 μm, about 80 μm, about 90 μm, about 100 μm, about 120 μm, about 150 μm, about 200 μm, about 300 μm, about 400 μm, about 500 μm, about 600 μm, about 700 μm, about 800 μm, about 900 μm, or about 1,000 μm. For example, the plurality of coated particles may have a diameter of about 0.1 μm to about 1,000 μm, about 0.1 μm to about 500 μm, about 0.1 μm to about 200 μm, about 0.1 μm to about 150 μm, about 0.1 μm to about 100 μm, about 0.1 μm to about 80 μm, about 0.1 μm to about 50 μm, about 0.1 μm to about 30 μm, about 0.1 μm to about 20 μm, about 0.1 μm to about 10 μm, about 0.1 μm to about 8 μm, about 0.1 μm to about 5 μm, about 0.1 μm to about 2 μm, about 0.1 μm to about 1 μm, about 0.1 μm to about 0.5 μm, about 1 μm to about 1,000 μm, about 1 μm to about 500 μm, about 1 μm to about 200 μm, The average particle size may be about 1 μm to about 150 μm, about 1 μm to about 100 μm, about 1 μm to about 80 μm, about 1 μm to about 50 μm, about 1 μm to about 30 μm, about 1 μm to about 20 μm, about 1 μm to about 10 μm, about 1 μm to about 8 μm, about 1 μm to about 5 μm, about 1 μm to about 2 μm, about 10 μm to about 1,000 μm, about 10 μm to about 500 μm, about 10 μm to about 200 μm, about 10 μm to about 150 μm, about 10 μm to about 100 μm, about 10 μm to about 80 μm, about 10 μm to about 50 μm, about 10 μm to about 30 μm, about 10 μm to about 20 μm, or about 10 μm to about 15 μm.

[0093] In one or more examples, the plurality of coated particles may have an average particle size of about 1 μm to about 1,000 μm. In some examples, the plurality of coated particles may have an average particle size of about 1 μm to about 100 μm. In other examples, the plurality of coated particles may have an average particle size of about 1 μm to about 30 μm, or about 1 μm to about 10 μm.

[0094] Each metal oxide coating of the coated particles may have a thickness of about 0.5 nm, about 1 nm, about 2 nm, about 3 nm, about 5 nm, about 8 nm, about 10 nm, about 12 nm, about 15 nm, about 18 nm, about 20 nm, about 25 nm, about 30 nm, or in the range of about 35 nm to about 40 nm, about 50 nm, about 60 nm, about 70 nm, about 80 nm, about 90 nm, about 100 nm, about 150 nm, about 200 nm, or greater. For example, the metal oxide coating may have a thickness of about 0.5 to about 200 nm, about 1 nm to about 100 nm, about 1 nm to about 95 nm, about 1 nm to about 90 nm, about 1 nm to about 80 nm, about 1 nm to about 70 nm, about 1 nm to about 50 nm, about 1 nm to about 40 nm, about 1 nm to about 30 nm, about 1 nm to about 25 nm, about 1 nm to about 20 nm, about 1 nm to about 15 nm, about 1 nm to about 10 nm, about 1 nm to about 5 nm, about 1 nm to about 3 nm, about 10 nm to about 100 nm, about 10 nm to about 95 nm, about 10 nm to about 90 nm, The thickness is about 10 nm to about 80 nm, about 10 nm to about 70 nm, about 10 nm to about 50 nm, about 10 nm to about 40 nm, about 10 nm to about 30 nm, about 10 nm to about 25 nm, about 10 nm to about 20 nm, about 10 nm to about 15 nm, about 20 nm to about 100 nm, about 20 nm to about 95 nm, about 20 nm to about 90 nm, about 20 nm to about 80 nm, about 20 nm to about 70 nm, about 20 nm to about 50 nm, about 20 nm to about 40 nm, about 20 nm to about 30 nm, or about 20 nm to about 25 nm.

[0095] In one or more examples, the metal oxide coating of each coated particle has a thickness of about 0.5 nm to about 200 nm. In some examples, the metal oxide coating has a thickness of about 1 nm to about 100 nm. In other examples, the metal oxide coating has a thickness of about 10 nm to about 50 nm.

[0096] In one or more embodiments, the cyclic vapor coating processes described and discussed herein provide low thermal budget and condensation-free metal-organic vapor flow, stable and repeatable mass flow rates as chamber backpressure increases, precise chemical consumption per pulse or process run, repeatable chemical concentration operation at low vapor pressure with other reactive chemical sources or oxidizers, and repeatable inter-process chemical concentration control and mass flow verification.

[0097] High surface area substrates, such as APIs and other powder particles, can be coated with metal oxide coatings to impart various bulk and particle-scale properties, including, but not limited to, improved flowability and dissolution rate. Vapor-phase metal oxide coating of high surface area substrates is challenging. Vapor diffusion inhibition due to chamber geometry, variations in the molecular sticking coefficient of vapor species, variations in the surface morphology and functional groups of the substrate, and variations in total chamber pressure during processing can increase or decrease vapor condensation and chemical bonding on high surface area substrates at low pressures (<20 Torr) and low temperatures (<25°C). The embodiments described and discussed herein provide a method for reproducibly delivering metal-organic vapors to a processing chamber.

[0098] Embodiments of the present disclosure further relate to any one or more of the following Examples 1-31:

[0099] 1. A method of forming a coated powder composition, comprising: positioning a plurality of powder particles in a processing region of a processing chamber, each of the powder particles comprising an organic material; and coating the plurality of powder particles with a metal oxide coating during a cyclic vapor coating process to form a plurality of coated particles, the metal oxide coating comprising aluminum oxide, zinc oxide, or aluminum zinc oxide, the cyclic vapor coating process comprising one or more deposition cycles, each of the deposition cycles comprising introducing two or more pulses of a metal precursor into the processing region via a first mass flow control valve; exposing the plurality of powder particles to the metal precursor; and infiltrating the plurality of powder particles with the metal precursor through spaces between the powder particles. a first mass flow control valve, then introducing two or more pulses of a purge gas into the processing region via a second mass flow control valve, exposing the plurality of powder particles to the purge gas during a first purge process, then introducing two or more pulses of an oxidizer into the processing region via a third mass flow control valve, exposing the plurality of powder particles to the oxidizer, permeating the plurality of powder particles with the oxidizer through spaces between the powder particles to produce a metal oxide coating disposed on an outer surface of each of the powder particles, then introducing two or more pulses of a purge gas into the processing region via a second mass flow control valve, and exposing the plurality of powder particles to the purge gas during a second purge process.

[0100] 2. A method of forming a coated powder composition, comprising: positioning a plurality of powder particles in a processing region of a processing chamber, each of the powder particles comprising an inorganic material; and coating the plurality of powder particles with a metal oxide coating during a cyclic vapor coating process to form a plurality of coated particles, the metal oxide coating comprising aluminum oxide, zinc oxide, or aluminum zinc oxide, the cyclic vapor coating process comprising one or more deposition cycles, each of the deposition cycles comprising introducing two or more pulses of a metal precursor into the processing region via a first mass flow control valve; exposing the plurality of powder particles to the metal precursor; and infiltrating the plurality of powder particles with the metal precursor through spaces between the powder particles. a first mass flow control valve, then introducing two or more pulses of a purge gas into the processing region via a second mass flow control valve, exposing the plurality of powder particles to the purge gas during a first purge process, then introducing two or more pulses of an oxidizer into the processing region via a third mass flow control valve, exposing the plurality of powder particles to the oxidizer, permeating the plurality of powder particles with the oxidizer through spaces between the powder particles to produce a metal oxide coating disposed on an outer surface of each of the powder particles, then introducing two or more pulses of a purge gas into the processing region via a second mass flow control valve, and exposing the plurality of powder particles to the purge gas during a second purge process.

[0101] 3. A method of forming a coated powder composition, comprising: positioning a plurality of powder particles in a processing region of a processing chamber; and coating the plurality of powder particles with a metal oxide coating during a cyclical vapor coating process to form a plurality of coated particles, wherein the metal oxide coating comprises aluminum zinc oxide; and the cyclical vapor coating process includes one or more deposition cycles, each of the deposition cycles including: introducing two or more pulses of a first metal precursor into the processing region via a first mass flow control valve; exposing the plurality of powder particles to the first metal precursor; infiltrating the plurality of powder particles with the first metal precursor through spaces between the powder particles; then introducing two or more pulses of a purge gas into the processing region via a second mass flow control valve; exposing the plurality of powder particles to the purge gas during the first purge process; then introducing two or more pulses of an oxidizer into the processing region via a third mass flow control valve; exposing the plurality of powder particles to the oxidizer; infiltrating the plurality of powder particles with the oxidizer through spaces between the powder particles to produce a first metal oxide layer disposed on an outer surface of each of the powder particles; then introducing two or more pulses of a purge gas into the processing region via a third mass flow control valve; introducing two or more pulses of a purge gas through the valve, exposing the plurality of powder particles to the purge gas during a second purge process; introducing two or more pulses of a second metal precursor into the processing region through a fourth mass flow control valve, exposing the plurality of powder particles to the second metal precursor; infiltrating the plurality of powder particles with the second metal precursor through spaces between the powder particles; thereafter introducing two or more pulses of a purge gas into the processing region through the second mass flow control valve, exposing the plurality of powder particles to the purge gas during a third purge process; then introducing two or more pulses of an oxidizer into the processing region via a third mass flow control valve; exposing the plurality of powder particles to the oxidizer; permeating the plurality of powder particles with the oxidizer through spaces between the powder particles to generate a second metal oxide layer disposed on the first metal oxide layer disposed on the outer surface of each of the powder particles; then introducing two or more pulses of a purge gas via a second mass flow control valve; exposing the plurality of powder particles to the purge gas during a fourth purge process, wherein the first and second metal precursors are different from each other and the metal oxide coating isA method comprising forming a first metal oxide layer and a second metal oxide layer, wherein the first metal oxide layer comprises aluminum oxide and the second metal oxide layer comprises zinc oxide, or the first metal oxide layer comprises zinc oxide and the second metal oxide layer comprises aluminum oxide.

[0102] 4. The method of example 3, wherein the first or second metal precursor comprises trimethylaluminum, dimethylaluminum hydride, triethylaluminum, diethylaluminum hydride, tripropylaluminum, dipropylaluminum hydride, tributylaluminum, dibutylaluminum hydride, an isomer thereof, a salt thereof, or any combination thereof.

[0103] 5. The method of example 3 or 4, wherein the first or second metal precursor comprises dimethylzinc, diethylzinc, dipropylzinc, dibutylzinc, an isomer thereof, a salt thereof, or any combination thereof.

[0104] 6. The method of any one of Examples 1-5, wherein each of the powder particles comprises an organic material.

[0105] 7. The method of any one of Examples 1-6, wherein each of the powder particles comprises an inorganic material.

[0106] 8. The method of any one of Examples 1-7, wherein each pulse of metal precursor is introduced into the treatment area for about 30 seconds to about 60 seconds, each pulse of oxidizer is introduced into the treatment area for about 30 seconds to about 60 seconds, and each pulse of purge gas is introduced into the treatment area for about 30 seconds to about 60 seconds.

[0107] 9. The method of any one of Examples 1-8, wherein each of the deposition cycles comprises introducing between 3 pulses of the metal precursor and about 100 pulses of the metal precursor to the treatment region, or each of the deposition cycles comprises introducing between 5 pulses of the metal precursor and about 50 pulses of the metal precursor, or each of the deposition cycles comprises introducing between 8 pulses of the metal precursor and about 35 pulses of the metal precursor.

[0108] 10. The method of any one of Examples 1-9, wherein each of the deposition cycles includes introducing between 3 pulses of oxidizer and about 100 pulses of oxidizer to the treatment region, or each of the deposition cycles includes introducing between 5 pulses of oxidizer and about 50 pulses of oxidizer, or each of the deposition cycles includes introducing between 8 pulses of oxidizer and about 35 pulses of oxidizer.

[0109] 11. The method of any one of Examples 1-10, wherein each of the deposition cycles includes introducing between 3 pulses of purge gas and about 100 pulses of purge gas into the processing region for each of the first and second purge processes, or each of the deposition cycles includes introducing between 5 pulses of purge gas and about 50 pulses of purge gas into the processing region for each of the first and second purge processes, or each of the deposition cycles includes introducing between 8 pulses of purge gas and about 35 pulses of purge gas into the processing region for each of the first and second purge processes.

[0110] 12. The method of any one of Examples 1-11, wherein the deposition cycle is repeated 2 to about 20 times, or the deposition cycle is repeated 3 to about 10 times, or the deposition cycle is repeated 4 to about 8 times, or the deposition cycle is repeated 5 to about 7 times.

[0111] 13. The method of any one of Examples 1-12, wherein each of the metal precursor and the oxidant is independently at a partial pressure of less than 2 Torr when introduced into the processing region.

[0112] 14. The method of any one of Examples 1-13, wherein each of the metal precursor and the oxidant is independently introduced into a processing region having a stagnant atmosphere at a pressure less than 760 Torr or at a pressure between about 10 Torr and about 750 Torr.

[0113] 15. The method of any one of Examples 1-14, wherein each of the orifices of the first, second, third, and fourth mass flow control valves independently has a diameter in the range of about 0.050 inches to about 0.150 inches, about 0.062 inches or greater than 0.062 inches to about 0.113 inches, or about 0.062 inches or greater than 0.062 inches to about 0.093 inches.

[0114] 16. The method of any one of Examples 1-15, wherein the plurality of powder particles is maintained at a temperature in the range of about 15°C to about 25°C during the cyclic vapor coating process.

[0115] 17. The method of any one of Examples 1-16, wherein the metal oxide coating consists essentially of aluminum oxide, zinc oxide, or aluminum zinc oxide.

[0116] 18. The method of any one of Examples 1-17, wherein the metal precursor comprises trimethylaluminum, dimethylaluminum hydride, triethylaluminum, diethylaluminum hydride, tripropylaluminum, dipropylaluminum hydride, tributylaluminum, dibutylaluminum hydride, an isomer thereof, a salt thereof, or any combination thereof.

[0117] 19. The method of any one of examples 1-18, wherein the metal precursor comprises dimethyl zinc, diethyl zinc, dipropyl zinc, dibutyl zinc, an isomer thereof, a salt thereof, or any combination thereof.

[0118] 20. The method of any one of Examples 1 to 19, wherein the metal precursor, when introduced into the first mass flow control valve, is at a temperature of about −20° C. to about 25° C., about −20° C. to about 23° C., about −20° C. to about 20° C., about −20° C. to about 18° C., about 0° C. to about 25° C., about 0° C. to about 23° C., about 0° C. to about 20° C., or about 0° C. to about 18° C., and a pressure of about 0.01 Torr to about 20 Torr.

[0119] 21. The method of any one of Examples 1-20, wherein the oxidizing agent comprises water, oxygen (O2), hydrogen peroxide, inorganic peroxide, ozone, atomic oxygen, oxygen plasma, or any combination thereof.

[0120] 22. The method of any one of examples 1-21, wherein the purge gas comprises argon, helium, nitrogen (N2), or any combination thereof.

[0121] 23. The method of any one of Examples 1-22, wherein the organic material comprised in the powder particles comprises one or more active pharmaceutical ingredients (APIs), one or more pharmaceutically acceptable excipients (PAEs), or any combination thereof.

[0122] 24. The method of any one of Examples 1-23, wherein the inorganic material comprised in the powder particles comprises aluminum oxide, titanium dioxide, iron oxide, gallium oxide, magnesium oxide, zinc oxide, niobium oxide, hafnium oxide, tantalum oxide, lanthanum oxide, zirconium dioxide, silicon oxide, silicates thereof, nitrides thereof, or any combination thereof.

[0123] 25. The method of any one of Examples 1-24, wherein the plurality of powder particles is produced from a spray-drying process or a freeze-drying process.

[0124] 26. The method of any one of Examples 1-25, wherein the plurality of powder particles have an average particle size of about 0.1 μm to about 1,000 μm, or about 1 μm to about 100 μm, or about 1 μm to about 30 μm, or about 1 μm to about 10 μm.

[0125] 27. The method of any one of Examples 1-26, wherein the metal oxide coating has a thickness of about 1 nm to about 100 nm.

[0126] 28. A method of forming a coated powder composition, comprising: positioning a plurality of powder particles in a processing region of a processing chamber, each of the powder particles comprising an active pharmaceutical ingredient (API); and coating the plurality of powder particles with a metal oxide coating during a cyclic vapor coating process to form a plurality of coated particles, the metal oxide coating comprising aluminum oxide or zinc oxide, the cyclic vapor coating process comprising one or more deposition cycles, each of the deposition cycles comprising: introducing a pulse of a metal precursor into the processing region via a first mass flow control valve having an orifice with a diameter of greater than 0.062 inches to about 0.113 inches; exposing the plurality of powder particles to the metal precursor; a first mass flow control valve configured to control the flow of a metal precursor into a processing region; a second mass flow control valve configured to control the flow of a purge gas into the processing region; a third mass flow control valve configured to control the flow of a metal precursor into the processing region; a third mass flow control valve configured to control the flow of a metal precursor into the processing region; a fourth mass flow control valve configured to control the flow of a metal precursor into the processing region; a fifth mass flow control valve configured to control the flow of a metal precursor into the processing region; a fifth mass flow control valve configured to control the flow of a metal precursor into the processing region; a sixth mass flow control valve configured to control the flow of a metal precursor into the processing region; a sixth mass flow control valve configured to control the flow of a metal precursor into the processing region; a sixth mass flow control valve configured to control the flow of a metal precursor into the processing region;

[0127] 29. A method of forming a coated powder composition, comprising: positioning a plurality of powder particles in a processing region of a processing chamber, each of the powder particles comprising an active pharmaceutical ingredient (API), wherein the plurality of powder particles is maintained at a temperature in a range of about 15°C to about 25°C during a cyclical vapor coating process; and coating the plurality of powder particles with a metal oxide coating during the cyclical vapor coating process to form a plurality of coated particles, wherein the metal oxide coating comprises aluminum oxide, and the cyclical vapor coating process comprises one or more deposition cycles, each of the deposition cycles comprising introducing pulses of a metal precursor into the processing region through a first mass flow control valve having an orifice with a diameter of greater than 0.062 inches to about 0.113 inches, wherein the metal precursor is maintained at a temperature of about -20°C to about 20°C when introduced into the first mass flow control valve. and a pressure of about 0.01 Torr to about 20 Torr, exposing the plurality of powder particles to a metal precursor, infiltrating the plurality of powder particles with the metal precursor through spaces between the powder particles, then introducing a pulse of purge gas into the processing region via a second mass flow control valve, exposing the plurality of powder particles to the purge gas during a first purge process, then introducing a pulse of oxidizer into the processing region via a third mass flow control valve, exposing the plurality of powder particles to the oxidizer, infiltrating the plurality of powder particles with the oxidizer through spaces between the powder particles to form a metal oxide coating disposed on each of the outer surfaces of the powder particles, then introducing a pulse of purge gas into the processing region via a third mass flow control valve, and exposing the plurality of powder particles to the purge gas during a second purge process.

[0128] 30. The method of example 28 or 29, further comprising any of the methods described in any one of examples 1-27.

[0129] 31. A coating powder composition made, produced, manufactured, prepared or formed by the method of any one of Examples 1-30.

[0130] While the foregoing is directed to embodiments of the present disclosure, other and further embodiments may be devised without departing from the basic scope thereof, the scope of which is determined by the claims that follow. All documents set forth herein, including priority documents and / or testing procedures, are incorporated herein by reference to the extent not inconsistent therewith. As is apparent from the general description and specific embodiments set forth above, while forms of the disclosure have been illustrated and described, various modifications can be made without departing from the spirit and scope of the disclosure. Accordingly, no limitation of the present disclosure is intended. Similarly, the term "comprising" is considered synonymous with the term "including" for purposes of U.S. law. Similarly, whenever a composition, element, or group of elements is preceded by the transitional phrase "comprising," it is understood that the transitional phrases "consisting essentially of," "consisting of," "selected from the group consisting of," or "is" contemplate the same composition or group of elements preceding the list of elements, and vice versa. As used herein, the term "about" refers to a + / - 10% variation from the nominal value. It is understood that such a variation can be included in any value provided herein.

[0131] Certain embodiments and features have been described using a set of upper numerical limits and a set of lower numerical limits. Unless otherwise indicated, it should be understood that ranges including any two combinations of values ​​are contemplated, for example, any lower limit with any upper limit, any two lower limits, and / or any two upper limits. Particular lower limits, upper limits, and ranges appear in one or more of the following claims.

Claims

1. 1. A method of forming a coating powder composition, comprising: positioning a plurality of powder particles within a processing region of a processing chamber, each of the powder particles comprising an active pharmaceutical ingredient (API); and coating the plurality of powder particles with a metal oxide coating during a cyclical vapor coating process to form a plurality of coated particles, the metal oxide coating comprising aluminum oxide or zinc oxide, the cyclical vapor coating process comprising one or more deposition cycles, each of the deposition cycles comprising: introducing a pulse of metal precursor into the processing region through a first mass flow control valve having an orifice with a diameter of greater than 0.062 inches to about 0.113 inches; exposing the plurality of powder particles to the metal precursor; infiltrating the metal precursor into the plurality of powder particles through spaces between the powder particles; and introducing a pulse of purge gas into the processing region via a second mass flow control valve; exposing the plurality of powder particles to the purge gas during a first purge process; and introducing a pulse of oxidizer into the processing region via a third mass flow control valve; exposing the plurality of powder particles to the oxidizing agent; infiltrating the plurality of powder particles with the oxidizing agent through spaces between the powder particles to form the metal oxide coating disposed on an outer surface of each of the powder particles; and introducing a pulse of the purge gas through the second mass flow control valve; and exposing the plurality of powder particles to the purge gas during a second purge process. Including, forming A method comprising:

2. The method of claim 1 , wherein each of the pulses of the metal precursor is introduced into the treatment region for about 30 seconds to about 60 seconds.

3. The method of claim 1 , wherein each of the pulses of the oxidizing agent is introduced into the treatment region for about 30 seconds to about 60 seconds.

4. The method of claim 1 , wherein each of the pulses of the purge gas is introduced into the processing region for about 30 seconds to about 60 seconds.

5. The method of claim 1 , wherein the deposition cycle is repeated from 2 to about 20 times.

6. 10. The method of claim 1, wherein each of the metal precursor and the oxidizer is independently introduced into the processing region having a stagnant atmosphere at a pressure less than 760 Torr.

7. 10. The method of claim 1, wherein the orifice of the first mass flow control valve has a diameter of greater than 0.062 inches to about 0.093 inches.

8. The method of claim 1 , wherein the plurality of powder particles is maintained at a temperature in the range of about 15° C. to about 25° C. during the cyclic vapor coating process.

9. The method of claim 1 , wherein the metal oxide coating consists essentially of aluminum oxide or zinc oxide.

10. 10. The method of claim 1, wherein the metal precursor comprises trimethylaluminum, dimethylaluminum hydride, triethylaluminum, diethylaluminum hydride, tripropylaluminum, dipropylaluminum hydride, tributylaluminum, dibutylaluminum hydride, an isomer thereof, a salt thereof, or any combination thereof.

11. 10. The method of claim 1, wherein the metal precursor comprises dimethyl zinc, diethyl zinc, dipropyl zinc, dibutyl zinc, an isomer thereof, a salt thereof, or any combination thereof.

12. 10. The method of claim 1, wherein the metal precursor is at a temperature of about −20° C. to about 20° C. and a pressure of about 0.01 Torr to about 20 Torr when introduced into the first mass flow control valve.

13. The oxidizing agent is water, oxygen (O 2 ), hydrogen peroxide, inorganic peroxide, ozone, atomic oxygen, oxygen plasma, or any combination thereof.

14. The purge gas may be argon, helium, nitrogen (N 2 ), or any combination thereof.

15. 10. The method of claim 1, wherein the plurality of powder particles has an average particle size of about 0.1 μm to about 1,000 μm, and the metal oxide coating has a thickness of about 1 nm to about 100 nm.

16. 1. A method of forming a coating powder composition, comprising: positioning a plurality of powder particles within a processing region of a processing chamber, each of the powder particles comprising an active pharmaceutical ingredient (API), wherein the plurality of powder particles is maintained at a temperature in the range of about 15°C to about 25°C during a cyclical vapor coating process; and coating the plurality of powder particles with a metal oxide coating during a cyclical vapor coating process to form a plurality of coated particles, the metal oxide coating comprising aluminum oxide, the cyclical vapor coating process comprising one or more deposition cycles, each of the deposition cycles comprising: introducing pulses of a metal precursor into the processing region through a first mass flow control valve having an orifice with a diameter of greater than 0.062 inches to about 0.113 inches, wherein the metal precursor is at a temperature of about −20° C. to about 20° C. and a pressure of about 0.01 Torr to about 20 Torr when introduced into the first mass flow control valve; exposing the plurality of powder particles to the metal precursor; infiltrating the metal precursor into the plurality of powder particles through spaces between the powder particles; and introducing a pulse of purge gas into the processing region via a second mass flow control valve; exposing the plurality of powder particles to the purge gas during a first purge process; and introducing a pulse of oxidizer into the processing region via a third mass flow control valve; exposing the plurality of powder particles to the oxidizing agent; infiltrating the plurality of powder particles with the oxidizing agent through spaces between the powder particles to form the metal oxide coating disposed on an outer surface of each of the powder particles; and introducing a pulse of the purge gas through the second mass flow control valve; and forming the powder particles, the powder particles being exposed to the purge gas during a second purge process. A method comprising:

17. The method of claim 16, wherein the deposition cycle is repeated from 2 to about 20 times.

18. 18. The method of claim 17, wherein the orifice of the first mass flow control valve has a diameter of greater than 0.062 inches to about 0.093 inches.

19. 20. The method of claim 18, wherein the plurality of powder particles has an average particle size of about 0.1 μm to about 1,000 μm and the metal oxide coating has a thickness of about 1 nm to about 100 nm.

20. 20. The method of claim 19, wherein the metal oxide coating consists essentially of aluminum oxide.

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