Liquid topical pharmaceutical nano-emulsion formulations

Abstract

Aspects of the present invention are directed to compositions that are useful for delivery of an active ingredient to a subject. Some embodiments are formulated with an active ingredient, including, for example, a non-steroidal anti-inflammatory drug (NSAID), such as aspirin, ibuprofen, ketoprofen, or naproxen, acetaminophen, or a polypeptide or protein, such as insulin, wherein the active ingredient is stabilized and greater than 90% of the particles of the active ingredient have a particle size that is less than or equal to or any number in between 100, 90, 80, 70, 60, 50, 40, 30, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, or 4 nanometers, or smaller, as determined by Dynamic Light Scattering (DLS), using a volume-weighted particle size distribution calculation method.

Description

RELATED APPLICATIONS[0001]The present application claims priority to U.S. provisional application Ser. No. 61 / 748,036, filed Dec. 31, 2012, which is hereby expressly incorporated by reference in its entirety, and the present application also claims priority to U.S. provisional application Ser. No. 61 / 758,726, filed Jan. 30, 2013, which is hereby expressly incorporated by reference in its entirety.FIELD OF THE INVENTION[0002]Aspects of the present invention are directed to preparations that are useful for delivery of an active ingredient. Some embodiments of these preparations include transdermal and / or dermal compositions, which are formulated with an active ingredient, including, for example, a non-steroidal anti-inflammatory drug (NSAID), such as aspirin, ibuprofen, ketoprofen, or naproxen, acetaminophen, or a polypeptide or protein, such as insulin, wherein the active ingredient is stabilized and greater than 90% of the particles of the active ingredient have a particle size that...

AI Technical Summary

Benefits of technology

The present invention relates to the discovery of methods for reducing the particle size of active ingredients in transdermal and dermal formulations, which improves their stability and shelf-life. By reducing the particle size, the active ingredients can be better stabilized and remain in a liquid form for extended periods of time. The reduced particle size is achieved by adding ethoxylated oil and water to the formulation, with the water added after the active ingredient has mixed with the alcohol and oil. The resulting nanoemulsion delivery system technology allows for easy spreading and penetration across the skin, improving the delivery of the active ingredients. Overall, the invention provides a way to improve the stability and effectiveness of transdermal and dermal formulations.

Problems solved by technology

NSAIDs taken orally may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal.

This risk may increase with duration of systemic use.

Taking oral NSAIDs, including aspirin, can also increase the risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal.

Elderly patients are at greater risk for serious gastrointestinal events.

However, there are many obstacles to achieving a useful topical formulation containing an NSAID and / or acetaminophen, including safety, stability of the active ingredient over time, and efficacy.

Topical pain reliever formulations in the form of a liquid have been introduced in the past, but such topical pain relievers have traditionally lacked the ability to maintain the active ingredient in a suspension within the liquid of the topical pain reliever formulation.

Further, topical pain reliever formulations may have significant lag time between application to the skin and reducing pain / inflammation.

For example, the topical pain reliever formulations may not quickly or effectively permeate the skin.

As a consequence, it may take longer, if at all, for a user to experience any pain relief due to slow penetration of active ingredient of penetration of only an insignificant dose of active ingredient.

Additionally, current NSAID and / or acetaminophen-containing topical pain reliever formulations have not adequately stabilized the active ingredient in liquid.

That is, current NSAID and / or acetaminophen-containing topical pain formulations generally have a short shelf life since the active ingredient degrades, for example, by hydrolysis, glycolysis and / or transesterification.

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