# US 12,005,145 B2 · Metal oxide encapsulated drug compositions and methods of preparing the same

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- Number: US 12,005,145 B2
- Document ID: US12005145B2
- Status: Granted
- Kind: B2
- Application number: 17/695,687
- Filed: 2022-03-15
- Published: 2022-06-30
- Granted: 2024-06-11
- Earliest claimed: 2018-01-16
- Assignees: Applied Materials, Inc.
- Applicants: Applied Materials, Inc.
- Inventors: Colin C. Neikirk; Jonathan Frankel
- Web page: https://patentgrep.com/patent/US12005145B2

## CPC

- A61K 9/5089: {Processes}
- A61J 3/07: into the form of capsules or similar small containers for oral use
- A61K 9/501: {Inorganic compounds}
- A61K 31/405: Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
- A61K 31/424: condensed with heterocyclic ring systems, e.g. clavulanic acid
- A61K 31/43: Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula [IMAGE cpc-sch-A61K-0952.gif], e.g. penicillins, penems
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 47/58: obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- C07K 16/22: against growth factors {; against growth regulators}
- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- C07K 16/32: against translation products of oncogenes
- C23C 16/40: Oxides
- C23C 16/403: {of aluminium, magnesium or beryllium}
- C23C 16/405: {of refractory metals or yttrium}
- C23C 16/4417: {Methods specially adapted for coating powder}
- C23C 16/45525: {Atomic layer deposition [ALD]}
- C23C 16/45555: {applied in non-semiconductor technology}
- C23C 16/458: characterised by the method used for supporting substrates in the reaction chamber
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C23C: COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL (making metal-coated products by extrusion B21C23/22; covering with metal by connecting pre-existing layers to articles, see the relevant places, e.g. B21D39/00, B23K; metallising of glass C03C; metallising mortars, concrete, artificial stone, ceramics or natural stone C04B41/00; enamelling of, or applying a vitreous layer to, metals C23D; treating metal surfaces or coating of metals by electrolysis or electrophoresis C25D; single-crystal film growth C30B; by metallising textiles D06M11/83; decorating textiles by locally metallising D06Q1/04)

## Abstract

A method of preparing a pharmaceutical composition having a drug-containing core enclosed by one or more metal oxide materials is provided. The method includes the sequential steps of (a) loading the particles comprising the drug into a reactor, (b) applying a vaporous or gaseous metal precursor to the particles in the reactor, (c) performing one or more pump-purge cycles of the reactor using inert gas, (d) applying a vaporous or gaseous oxidant to the particles in the reactor, and (e) performing one or more pump-purge cycles of the reactor using inert gas. The temperature of the particles does not exceed 35° C. This produces a pharmaceutical composition comprising a drug containing core enclosed by one or more metal oxide materials.

## Claims

### Claim 1

A method of preparing a pharmaceutical composition comprising a drug- containing core enclosed by one or more metal oxide materials, the method comprising the sequential steps of:
(a) loading particles comprising the drug into a reactor, wherein the particles have a median particle size, on a volume average basis between 0.1 μm and 1000 μm;
(b) applying a vaporous or gaseous metal precursor to the particles in the reactor;
(c) performing one or more pump-purge cycles of the reactor using an inert gas;
(d) applying vaporous or gaseous water as an oxidant to the particles in the reactor;
(e) performing one or more pump-purge cycles of the reactor using the inert gas; and
(f) repeating steps (b)-(e) one or more times to increase the total thickness of the one or more metal oxide materials that enclose the core, wherein the particles remain in the reactor during the repeated steps, each pump-purge cycle comprises flowing the inert gas into the reactor chamber to a desired pressure and after a delay time pumping the inert gas out of the reactor until the pressure of the inert gas is below 1 torr and repeating the steps of flowing the inert gas into the reactor chamber to a desired pressure and after a delay time pumping the inert gas out of the reactor until the pressure of the inert gas is below 1 torr, the temperature of the particles does not exceed 35° C., thereby producing a pharmaceutical composition comprising a drug containing core enclosed by one or more metal oxide materials,
wherein the one or more metal oxide materials are selected from the group consisting of: aluminum oxide, titanium oxide, iron oxide, gallium oxide, magnesium oxide, zinc oxide, niobium oxide, hafnium oxide, tantalum oxide, lanthanum oxide, and zirconium dioxide.

### Claim 2 (depends on 1)

The method of claim 1, wherein the reactor pressure is allowed to stabilize following step (a), step (b), and/or step (d).

### Claim 3 (depends on 1)

The method of claim 1, wherein a subset of vapor or gaseous content is pumped out prior to step (c) and/or step (e).

### Claim 4 (depends on 1)

The method of claim 1, wherein the particles comprise a drug and one or more pharmaceutically acceptable excipients.

### Claim 5 (depends on 1)

The method of claim 1, wherein the particles have a median particle size, on a volume average basis between 0.1 μm and 1000 μm.

### Claim 6 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition is removed from the reactor and admixed with a pharmaceutically acceptable diluent or carrier.

### Claim 7 (depends on 1)

The method of claim 1, wherein the particles consist essentially of the drug.

### Claim 8 (depends on 1)

The method of claim 1, wherein the drug is a small molecule, virus particle, polypeptide, polynucleotide, a composition comprising polypeptide and lipid, or a composition comprising polynucleotide and lipid.

### Claim 9 (depends on 1)

The method of claim 1, wherein the one or more metal oxide materials are selected from the group consisting of: aluminum oxide and titanium oxide.

### Claim 10 (depends on 1)

The method of claim 1, wherein the reactor contents are agitated prior to and/or during step (b), step (c), and/or step (e).

### Claim 11 (depends on 1)

The method of claim 1, wherein the temperature of the particles remains between 22° C. and 35° C.

### Claim 12 (depends on 1)

The method of claim 1, wherein the inert gas is nitrogen gas or a noble gas.

### Claim 13 (depends on 12)

The method of claim 12, wherein the inert gas is nitrogen gas.

### Claim 14 (depends on 1)

The method of claim 1, wherein the drug is a small molecule drug that is selected from the group consisting of: acetaminophen, clarithromycin, azithromycin, ibuprofen, fluticasone propionate, salmeterol, pazopanib HC1, palbociclib, and amoxicillin potassium clavulanate.

### Claim 15 (depends on 1)

The method of claim 1, wherein the drug is a small molecule drug that is selected from the group consisting of: clarithromycin, clarithromycin carbomer complex, pazopanib HC1, palbociclib, and amoxicillin potassium clavulanate.

### Claim 16 (depends on 1)

The method of claim 1, wherein step (c) is repeated between 6 and 20 additional times.

### Claim 17 (depends on 1)

The method of claim 1, wherein step (e) is repeated between 1 and 10 additional times.

### Claim 18 (depends on 1)

The method of claim 1, wherein the one or more metal oxide materials are selected from the group consisting of aluminum oxide, titanium oxide, and zinc oxide.