Non-steroidal anti-inflammatory drug formulations for topical applications to the skin

a non-steroidal anti-inflammatory and skin technology, applied in the direction of biocide, drug composition, aerosol delivery, etc., can solve the problems of loss of activities, undesirable effects, and often failing to meet the stated objectives of conventional administration routes, so as to improve performance, improve performance, and improve performan

US20070134308A1Inactive Publication Date: 2007-06-14MACROCHEM CORP
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Patent Information

Authority / Receiving Office
US · United States
Patent Type
Applications(United States)
Current Assignee / Owner
Publication Date
2007-06-14
Estimated Expiration
Not applicable · inactive patent

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Abstract

Topical alcoholic or aqueous alcoholic gels containing ibuprofen or other NSAIDs, such as, naproxen, in substantially neutral salt form, have enhanced penetration through skin and may provide rapid pain / inflammation relief by including in the formulation 2-n-nonyl-1,3-dioxolane or other hydrocarbyl derivative of 1,3-dioxolane or 1,3-dioxane or acetal, as skin penetration enhancing compound. The amount of propylene glycol may be varied to adjust the initial flux of the NSAID through the skin, especially for ibuprofen, naproxen, and ketorolac.
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Description

FIELD OF INVENTION

[0001] This invention relates to topical compositions for transdermal administration of a non-steroidal antiinflammatory drug (NSAID) through the skin of a patient and to the method for transdermally administering the non-steroidal antiinflammatory drug using the topical composition. DISCUSSION OF THE PRIOR ART

[0002] All drugs must be administered in such a manner that they reach the intended site in the body in an optimal concentration (amount of drug per unit volume of blood) to achieve the desired effect at the proper time, and for an appropriate length of time. Customarily, drugs are taken orally, injected, inhaled, or applied topically. These conventional routes of administration often fail to meet the stated objectives, however. For example, when drugs are absorbed into the blood stream by whatever route, peaks and valleys in the blood concentration of the drug occur and may cause undesirable effects (e.g., peak levels), or loss of activities (e.g., valleys...

Examples

example 1

[0091] This example compares the percutaneous absorption through porcine skin, of ibuprofen from aqueous alcoholic gels containing 5 wt. % ibuprofen and either 5%, 10% or 15% of 2-n-nonyl-1,3-dioxolane, using an ethanol / water carrier at a 70:30 mixing ratio. The formulations include NaOH to adjust the pH to 7.4, but do not include a glycol. Hydroxypropyl cellulose (2 wt. %) is used as the gelling agent. The test compositions are applied to provide about 30 milligrams (mg) of the composition per square centimeter (cm2) of porcine skin.

[0092] The tests are run in standard static cells with phosphate buffered saline (PBS) as the receptor fluid (surface area 0.635 cm2, temperature 32° C.). The following Table 1 shows the total amount of ibuprofen applied to the skin for each formulation. The differences result from the slightly different thicknesses at which the test formulations are applied.

[0093] Each test was run for 24 hours under non-occluded conditions with the finite dose of th...

example 2

[0096] This example shows the effect of incorporating propylene glycol in the aqueous alcoholic gel formulation containing 5% ibuprofen and 10% 2-n-nonyl-1,3-dioxolane using an ethanol:water vehicle at a 70:30 weight mixing ratio. The compositions used in these tests are shown in Table 3 (NaOH is added to adjust the pH to 7.4):

TABLE 3propyleneibuprofenenhancerglycolEthanolWaterTotal(%)(%)(%)(%)(%)(%)A510059.525.5100B51055624100C5101052.522.5100D510154921100E5102045.519.5100

[0097] The test was run using the same conditions as described in Example 1. The flux was measured at 2, 4 and 6 hours. The results are shown graphically in FIG. 3. From this figure it is seen that the flux at 2 hours decreases nearly linearly as the propylene glycol (PG) content increases from 0% to 5% to 10% to 15% to 20%. At four hours after the composition is applied to the test skin sample the fluxes for each concentration of PG has increased but more so for the compositions containing the higher amounts of...

example 3

[0099] This example is similar to Example 1 but compares a topical aqueous alcoholic gel formulation with ibuprofen according to the present invention with a similar gel but without the enhancer and with four other commercially available topical ibuprofen formulations. Also, human skin was used rather than porcine skin. The composition according to the present invention and the comparison were as follows:

InventionComparisonIngredientAmount (wt. %)Amount (wt. %)Ibuprofen552-n-nonyl-1,3-100dioxolaneEthanol5965Propylene glycol1719Water79Hydroxypropyl22celluloseSodium Hydroxideq.s. to pH 7q.s. to pH 7

[0100] The commercially available products were: Gelufene® (ibuprofen 5%, isopropyl alcohol, hydroxyethylcellulose, sodium hydroxide, benzyl alcohol and purified water), Dolgit® cream (ibuprofen 5%, medium chain triglycerides, mixture of glycerol monostearate and polyoxyethylene stearates, polyoxyethylene fatty acid esters, xanthan gum, lavender oil, neroli oil, water, propylene glycol, p...