# US 2020/0390701 A1 · Transdermal non-aqueous nanoemulgels for systemic delivery of aromatase inhibitor

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2020/0390701 A1
- Document ID: US20200390701A1
- Status: Published application
- Kind: A1
- Application number: 16/957,017
- Filed: 2018-12-19
- Published: 2020-12-17
- Earliest claimed: 2017-12-22
- Assignees: Qatar University
- Applicants: Qatar University
- Inventors: Assayed AlArabi Nauman SALLAM; Husam M. YOUNES
- Web page: https://patentgrep.com/patent/US20200390701A1

## CPC

- A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 31/4196: 1,2,4-Triazoles
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- 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)
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

Transdermal nanoemugels for systemic delivery of potent drugs like aromatase inhibitors letrozole and anastrozole are disclosed. The disclosed compositions may include gelling agent, surfactants, cosolvents, and oily components. The process of preparing the nanoemulgels is simple and the formation of nanoemulgels is spontaneous. Penetration enhancers are included in the compositions of the transdermal nanoemugels. The compositions have penetration power with emollient effects to the skin. The transdermal drug delivery system may be applied to skin in a single dose that produces pharmacologically effective blood concentration of the potent drug for one week or up to one month depending on the amount and thickness of the applied nanoemugels in the transdermal matrix patches. The nanoemulgels can be used for topical delivery of NSAID.

## Claims

### Claim 1

A non-aqueous nanoemulgel comprising:
a therapeutic agent,
a hydrophilic continuous phase formed of cosolvents,
an oily dispersed phase formed of an oil component, wherein the oily component comprises glyceryl monooleate (GMO) and isohexadecane, and
an emulsifying gelling agent,
wherein
the type or grade of GMO is that containing more than 40% glycerl monooleate,
the cosolvents comprise propylene glycol and diethylene glycol ethyl ether,
the cosolvents form nanoglobules of the oily dispersed phase,
the size of the nanoglobules is less than 500 nm in diameter, and
the nanoemulgel is a clear gel.

### Claim 2 (depends on 1)

The nanoemulgel of claim 1, further comprising a penetration enhancer.

### Claim 3 (depends on 1, 2)

The nanoemulgel of claim 1 or 2, wherein the therapeutic agent is a potent drug.

### Claim 4 (depends on 1, 2, 3)

The nanoemulgel of any of claims 1 to 3, wherein the therapeutic agent is an aromatase inhibitor.

### Claim 5 (depends on 4)

The nanoemulgel of claim 4, wherein the aromatase inhibitor is letrozole or anastrozole.

### Claim 6 (depends on 1, 2)

The nanoemulgel of claim 1 or 2, wherein the therapeutic agent is a NSAID.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The nanoemulgel of any of claims 1-6, wherein the cosolvents consist of propylene glycol and diethylene glycol ethyl ether.

### Claim 8 (depends on 1, 2, 3, 4, 5, 6, 7)

The nanoemulgel of any of claims 1-7, wherein the oil component consists of GMO and isohexadecane.

### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

The nano-emulgel of any of claims 1-8, wherein the emulsifying gelling agent is a mixture of acrylamide/sodium acryloyldimethyl taurate copolymer, isohexadecane, and polyoxyethylene (20) sorbitan monooleate.

### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

The nanoemulgel of any of claims 1-8, wherein the grade of GMO is that containing about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95% of glyceryl monooleate.

### Claim 11 (depends on 2, 3, 4, 5, 6, 7, 8, 9, 10)

The nanoemulgel of any of claims 2-10, wherein the penetration modifier is selected from the group consisting of propylene glycol laurate, propylene glycol monocaprylate, and caprylic/capric acid ester of a saturated C12-C18 fatty alcohol.

### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

A method of making the non-aqueous nanoemulgel of any one of claims 1-11, the method comprising:
mixing an oil component and an emulsifying gelling agent to form a first mixture; wherein the oil component comprises glycerylmonooleate (GMO) and isohexadecane; the grade of GMO is that having more than 40% glyceryl monooleate content; and preferably the emulsifying gelling agent is SEPINEO P 600;
dissolving a therapeutic agent in a first cosolvent to form a second mixture;
adding the second mixture to the first mixture to form a third mixture; and
adding a second cosolvent to the third mixture thereby forming a non-aqueous nanoemulgel;
wherein
each mixture is mixed well; and
the first cosolvent comprises diethylene glycol ethyl ether and the second cosolvent comprises propylene glycol.

### Claim 13 (depends on 12)

The method of claim 12, further comprising:
adding a penetration enhancer to the first mixture, the second mixture, the third mixture, or the final mixture.

### Claim 14 (depends on 12, 13)

The method of claim 12 or 13, wherein the therapeutic agent is a potent drug or an aromatase inhibitor.

### Claim 15 (depends on 14)

The method of claim 14, wherein the aromatase inhibitor is letrozole or anastrozole.

### Claim 16 (depends on 12)

The method of claim 12, wherein the therapeutic agent is a NSAID.

### Claim 17 (depends on 12, 13, 14, 15, 16)

The method of any of claims 12-16, wherein the oil component consists of GMO and isohexadecane.

### Claim 18 (depends on 12, 13, 14, 15, 16, 17)

The method of any of claims 12-17, wherein the first solvent consists of diethylene glycol ethyl ether and the second solvent consists of propylene glycol.

### Claim 19 (depends on 12, 13, 14, 15, 16, 17, 18)

The method of any of claims 12-18, wherein the emulsifying gelling agent is a mixture of acrylamide/sodium acryloyldimethyl taurate copolymer, isohexadecane, and polyoxyethylene (20) sorbitan monooleate.

### Claim 20 (depends on 12, 13, 14, 15, 16, 17, 18, 19)

The method of any of claims 12-19, wherein the grade of GMO is that containing about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95% of glyceryl monooleate.

### Claim 21 (depends on 13, 14, 15, 16, 17, 18, 19, 20)

The method of any of claims 13-20, wherein the penetration enhancer is selected from the group consisting of propylene glycol laurate, propylene glycol monocaprylate, and caprylic/capric acid ester of saturated C12-C18 fatty alcohol.

### Claim 22

A method of making a non-aqueous nanoemulgel, the method comprising:
mixing an oil component and an emulsifying gelling agent to form a first mixture; wherein the oil component comprises glycerylmonooleate (GMO) and isohexadecane; the grade of GMO is that having more than 40% glyceryl monooleate content; and preferably the emulsifying gelling agent is SEPINEO P 600;
dissolving a therapeutic agent in a first cosolvent to form a second mixture;
adding the second mixture to the first mixture to form a third mixture; and
adding a second cosolvent to the third mixture thereby forming a non-aqueous nanoemulgel;
wherein
each mixture is mixed well;
the first cosolvent comprises diethylene glycol ethyl ether and the second cosolvent comprises propylene glycol; and
the nanoemulgel is a clear gel.

### Claim 23 (depends on 22)

The method of claim 22, further comprising
adding a penetration enhancer to the first mixture, the second mixture, the third mixture, or the final mixture.

### Claim 24 (depends on 22, 23)

The method of claim 22 or 23, wherein the therapeutic agent is a potent drug or an aromatase inhibitor.

### Claim 25 (depends on 24)

The method of claim 24, wherein the aromatase inhibitor is letrozole or anastrozole.

### Claim 26 (depends on 22, 23)

The method of claim 22 or 23, wherein the therapeutic agent is a NSAID.

### Claim 27 (depends on 22, 23, 24, 25, 26)

The method of any claims 22-26, wherein the oil component consists of GMO and isohexadecane.

### Claim 28 (depends on 22, 23, 24, 25, 26, 27)

The method of any of claims 22-27, wherein the first cosolvent consists of diethylene glycol ethyl ether and the second cosolvent consists of propylene glycol.

### Claim 29 (depends on 22, 23, 24, 25, 26, 27, 28)

The method of any of claims 22-28, wherein the emulsifying gelling agent is a mixture of acrylamide/sodium acryloyldimethyl taurate copolymer, isohexadecane, and polyoxyethylene (20) sorbitan monooleate.

### Claim 30 (depends on 22, 23, 24, 25, 26, 27, 28, 29)

The method of any of claims 22-29, wherein the grade of GMO is that containing about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95% of glyceryl monooleate.

### Claim 31 (depends on 23, 24, 25, 26, 27, 28, 29, 30)

The method of any of claims 23-30, wherein the penetration modifier is selected from the group consisting of propylene glycol laurate, propylene glycol monocaprylate, and caprylic/capric acid ester of saturated C12-C18 fatty alcohol.

### Claim 32 (depends on 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)

A non-aqueous nanoemulgel, made by the method of any of claims 22-31.