Non-steroidal antiinflammatory drug formulations for topical application to the skin

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.

Description

[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). To meet these prob...

AI Technical Summary

Benefits of technology

[0117] This example further illustrates the effects of the invention with diclofenac as the NSAID. The test procedure was substantially the same as previously described using either human (H) or porcine (P) skin and an ethanol:water (70:30) vehicle. 2-n-nonyl-1,3-dioxolane was used as the skin permeation enhancer compound according to the invention. The results are shown in Table 12 below. In Run Nos. 10-A through 10-G 1 wt. % of diclofenac (as free acid) was used. In Run Nos. 10-I and 10-J (commercial product) 0.93 wt. % of diclofenac (as free acid) was used.

[0118] From the above results reported in Table 12 the following observations and conclusions may be drawn. The first set of experiments, Run Nos. 10A-10C, show that PG exerts a positive effect as a co-enhancer for diclofenac. In a second set of experiments Run Nos. 10D-10F, it is seen that the combination of PG with the dioxolane enhancer provides better performance than might be expected from the results with dioxolane enhancer alone and with PG alone. From the third set of experiments, Run Nos. 10-G and 10-H, it is observed that DEA as the counterion (base) provides better performance than sodium (Na). Finally, from the fourth set of experiments, Run Nos. 10-I and 10-J it is seen that the formulation according to the present invention provides significantly improved performance in comparison to a commercial diclofenac topical formulation.

Problems solved by technology

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).

Although these formulations attempt to control the release of drugs from their carriers, the desired effects are often not reproducible, may be subject to patient-to-patient variations, and may not be suitable for prolonged periods of delivery, such as days or even months.

However, present transdermal delivery systems have major drawbacks.

High molecular weight drugs or drugs with too high or low hydrophilic balance often cannot be incorporated into current transdermal systems in concentrations high enough to overcome their impermeability through the stratum corneum.

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