# US 10,500,201 B2 · Porous particles

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- Number: US 10,500,201 B2
- Document ID: US10500201B2
- Status: Granted
- Kind: B2
- Application number: 15/538,822
- Filed: 2015-12-21
- Published: 2017-12-07
- Granted: 2019-12-10
- Earliest claimed: 2014-12-23
- Assignees: Lucideon Limited
- Applicants: Lucideon Limited
- Inventors: Philip Robert Jackson; Mark Cresswell; Ian F. Campbell
- Web page: https://patentgrep.com/patent/US10500201B2

## CPC

- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 9/143: {with inorganic compounds}
- A61K 9/1611: {Inorganic compounds}
- A61K 9/2009: {Inorganic compounds}
- C01B 33/154: by acidic treatment of aqueous silicate solutions
- 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)
- C01B: NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; {METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C}

## Abstract

Processes for preparing porous particles are disclosed, in which the resulting particles release an encapsulated active ingredient more readily in aqueous media than they do in alcoholic media. Also described are the particles themselves, as well as tamperproof, abuse-deterrent, dosage forms comprising the porous particles. The release characteristics of the porous particles make them useful for overcoming drug-abuse techniques, such as dose-dumping in alcoholic media.

## Claims

### Claim 1

A sol-gel process for the preparation of a plurality of porous particles comprising at least one active ingredient present within the pores, wherein the at least one active ingredient is an opioid or opioid derivative and wherein the percentage release of the active ingredient from the pores of the particles into simulated intestinal fluid is greater than or equal to the percentage release of the active ingredient from the pores of the particles into 40% vol/vol ethanol in 0.1 M HCl,
the process comprising the steps of:
a) providing a mixture comprising water and HCl, said mixture having a pH of less than or equal to 2.5,
b) adding to the mixture of step a) an inorganic porous particle monomer such that the molar ratio of water to the inorganic porous particle monomer is less than or equal to 12.5,
c) adding to the mixture of step b) at least one active ingredient, wherein the at least one active ingredient comprises an opioid or opioid derivative,
d) drying the mixture resulting from step c) at a temperature of greater than or equal to 60°C.,
e) milling the material resulting from step d) to a particle size of 25-500 μm, and
f) drying the resulting porous particles at a temperature of greater than or equal to 60°C.;
wherein on addition of the at least one active ingredient to the mixture of step b), the mixture of step b) is a colloidal solution with a maximum viscosity at room temperature of 2.0 Pa·s; and drying steps d) and (f) are performed at a temperature of 60-90 °C.

### Claim 2 (depends on 1)

The process of claim 1, wherein the at least one active ingredient comprises an opioid or opioid derivative selected from oxycodone, codeine, hydrocodone, dihydrocodeine, morphine, oxymorphone, hydromorphone, naloxone or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The process of claim 1, wherein the at least one active ingredient comprises an opioid or opioid derivative selected from oxycodone, oxymorphone, hydrocodone, morphine or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The process of claim 1, wherein the at least one active ingredient comprises oxycodone or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The process of claim 1, wherein the percentage release of the active ingredient from the pores of the particles when 200 mg of the particles are placed in 900 mL of simulated intestinal fluid for 2 hours under stirring at 100 rpm is greater than or equal to the percentage release of the active ingredient from the pores of the particles when 200 mg of the particles are placed in 900 mL of 40% vol/vol ethanol in 0.1 M HCl for 2hours under stirring at 100 rpm.

### Claim 6 (depends on 5)

The process of claim 5, wherein the simulated intestinal fluid is pH 6.8 aqueous phosphate buffer at 37°C. ±0.5 °C., and the 40% vol/vol ethanol in 0.1 M HCl is at 37°C. ±0.5 °C.

### Claim 7 (depends on 5)

The process of claim 5, wherein the percentage release of the active ingredient from the pores of the particles when 200 mg of the particles are placed in 900 mL of simulated intestinal fluid for 2 hours under stirring at 100 rpm is greater than the percentage release of the active ingredient from the pores of the particles when 200 mg of the particles are placed in 900 mL of 40% vol/vol ethanol in 0.1 M HCl for 2 hours under stirring at 100 rpm.

### Claim 8 (depends on 5)

The process of claim 5, wherein the percentage release of the active ingredient into 40% vol/vol ethanol in 0.1 M HCl after 2 hours is less than or equal to 75%.

### Claim 9 (depends on 5)

The process of claim 5, wherein the percentage release of the active ingredient into the simulated intestinal fluid after 2 hours is less than or equal to 70%.

### Claim 10 (depends on 1)

The process of claim 1, wherein the quantity of the at least one active ingredient added in step c) is 0-12.3 wt % based on the weight of the inorganic porous particle monomer.

### Claim 11 (depends on 1)

The process of claim 1, wherein step a) comprises providing a mixture comprising water and HCl, said mixture having a pH in the range of 0.25-2.25.

### Claim 12 (depends on 1)

The process of claim 1, wherein step b) comprises adding to the mixture of step a) an inorganic porous particle monomer such that the molar ratio of water to the inorganic porous particle monomer ranges from 4.0-12.5.

### Claim 13 (depends on 1)

The process of claim 1, wherein the inorganic porous particle monomer is a silane, capable of forming a silicate.

### Claim 14 (depends on 1)

The process of claim 1, wherein step e) comprises milling the material resulting from step d) to a particle size of 50-400 μm.

### Claim 15 (depends on 1)

The process of claim 1, wherein the viscosity of the mixture resulting from either or both of steps b) and c) increases prior to performing the next step.

### Claim 16 (depends on 1)

A plurality of porous particles obtainable by the process according to claim 1.

### Claim 17 (depends on 16)

The plurality of porous particles of claim 16, wherein the moisture content of the particles is less than or equal to 6% by weight.

### Claim 18 (depends on 16)

A tamper-proof dosage form comprising the plurality of particles of claim 16.

### Claim 19 (depends on 17)

A solid dosage form comprising the plurality of particles of claim 17.

### Claim 20

A particle comprising a porous substrate and at least one active ingredient present within the pores, wherein the at least one active ingredient is an opioid or opioid derivative and the particle has a particle size of 25-500 μm and a moisture content of less than or equal to 6% by weight, and wherein
i. the percentage release of the at least one active ingredient from the particle in an aqueous solution of pH 6.8 at 37°C. is 30-50 after 1 hour, 45-65 after 2 hours, 60-80 after 4hours and 85 or more after 10 hours, and
ii. the percentage release of the at least one active ingredient from the particle in a solution of 40% vol/vol ethanol in 0.1 M HCl at 37°C. is 40 or less after 30 minutes, 50 or less after 1 hour and 65 or less after 2 hours.