Transdermal norelgestromin delivery system

Abstract

A system for transdermal delivery of norelgestromin (NGMN) to an individual. The system has a high NGMN loading with suitable permeation enhancers to effect therapeutic flux rate. Polyacrylate drug reservoir with the NGMN and high loading of one or more of permeation enhancers and NGMN dissolved therein provides desirable adhesive characteristics and effective transdermal therapeutic properties. Estrogen can be delivered with the NGMN.

Description

CROSS REFERENCE TO RELATED U.S. APPLICATION DATA [0001] The present application is derived from and claims priority to provisional application U.S. Ser. No. 60 / 720,200, filed Sep. 23, 2005, which is herein incorporated by reference in its entirety.TECHNICAL FIELD [0002] This invention relates to a medical patch for transdermal administration of norelgestromin (NGMN) and to a method of treating a subject by administering norelgestromin (NGMN) thereto with the medical patch. In particular, the invention relates to transdermal systems for administration of NGMN preferably in combination with an estrogen with adhesive system having high enhancer tolerance when used in transdermal drug delivery. BACKGROUND [0003] Transdermnal devices for the delivery of biologically active agents have been used for maintaining health and therapeutically treating a wide variety of ailments. For example, analgesics, steroids, etc., have been delivered with such devices. Such transdermal devices include pat...

AI Technical Summary

Benefits of technology

[0009] The present invention provides a method and a device for transdermal delivery of an effective amount of NGMN, an estrogen, or NGMN in combination with an estrogen (for contraceptive effect or for providing hormone replacement) to an individual in need thereof. In one aspect, a patch with polyacrylate reservoir suitable for multiple day delivery of NGMN is provided. In another aspect, a high loading of permeation enhancer enables high flux rate with a relatively small area, suitable for a transdermal patch that can be maintained adhesively on the body surface for an extensive period of time, such as 3, 7 days, and even longer, with acceptable rheological and adhesive properties and better appearance.

[0010] The preparation of formulations with polyacrylate for adhesion rather than PIB results in improved cold-flow resistance. This feature in turn results in an improvement in both patch aesthetics, ease of removal and improved patient compliance. The use of polyacrylate also results in formulations that are and remain translucent (versus opaque in appearance due to undissolved PVP particles and moisture uptake during 7 day wear) which, when combined with a transparent or translucent backing, have an improved translucent appearance after application and during wear. Although PVP, either dissolved, dispersed (e.g., in micronized form), or combination thereof, can be used, it is not required for the formulation of the present invention to adhere to the body surface. Further, the increased drug flux per unit area also results in a smaller patch size, again improving aesthetics and patient acceptability, and reducing the likelihood of unintentional detachment.

[0011] In the currently commercially available 7-day wear patches, the amount of NGMN and EE loaded into the adhesive drug layer resulting in adhesive layer about 0.006 inch (0.15 mm) to 0.008 inch (0.20 mm) thick. The thicker adhesive layer requires the addition of a non-woven backing for structural support during manufacturing, patch application and patch removal. The thicker adhesive layer also results in severe cold flow during storage in the pouch, and higher affinity for lint and dirt to adhere to the edge of the patch during wear. The currently available ORTHO EVRA® patches utilizes less than 20% of the NGMN and EE loaded into the patch during 7 days of wear. The effective dose of NGMN and EE in an ORTHO EVRA® contraceptive patch is 150 μg / day of NGMN and 20 μg / day of EE having a basal surface area (i.e. the area in diffusional contact with the skin) of 20 cm2. ORTHO EVRA® patches deliver the NGMN at a flux of 0.3 μg / cm2-h, and EE at a flux of 0.04 μg / cm2-h.

[0012] The use of polyacrylates results in a simpler, less complex manufacturing process as the drug / adhesive layer is thinner removing the need for a non-woven. Thus, a transdermal NGMN or NGMN and EE delivery patch can be made to have NGMN or NGMN / EE loading of higher than 5 wt %, preferably from 5 to 20 wt %, more preferably from 5 to 10 wt % of NGMN in the reservoir to deliver NGMN about 125 to about 350 μg / day, preferably from about 150 to about 300 μg / day, and more preferably from about 150 to about 250 μg / day for 7 days. With the appropriate size, patches can be made with NGMN / EE in the reservoir to deliver NGMN about 50 to about 250 μg / day and EE about 5 to 35 μg / day, preferably from about 75 to about 225 μg / day NGMN and 10 to 30 μg / day of EE, and more preferably from about 125 to about 175 μg / day of NGMN and 15 to 25 μg / day of EE for 7 days with acceptable rheology such as cold flow property.

[0013] In one aspect of the invention, a novel technique is provided for increasing adhesive enhancer tolerance. It has been discovered that by increasing the glass transition temperature of the acrylate polymer using the ratio of soft monomer and hard monomer, it is possible to load enhancer concentrations into the polymer at a high weight percent to obtain a formulation and still achieve desirable adhesive characteristics. The loading of drug and / or enhancer into the polymer composition can be, e.g., greater than 20 dry weight %, greater than 30 dry weight % (or solids wt %), even up to 40-50 wt %, and still provide adequate adhesion and rheological characteristics for pressure sensitive adhesive (PSA) application. With sufficient loadings of permeation enhancers in such formulations, sustained high rates of drug delivery can be achieved. With adequate adhesive properties, the resulting reservoir with sufficient drug loading and permeation enhancers can be used to achieve effective therapeutic results.

[0014] In one aspect of the invention, a clear multiple day patch with 3 to 7-day dermal adhesion is provided. It has been discovered that the use of a polyacrylate adhesive or proadhesive, having been plasticized with permeation enhancers to have an elastic modulus (storage modulus) of 1×105 to 2×105 dyn / cm2, i.e., 10,000 to 20,000 Pa (measured at 1 rad / s, 25° C.), or more preferably 10,000 to 15,000 Pa (i.e., 1.0×105 to 1.5×105 dyn / cm2), either with or without PVP (e.g., up to about 6% PVP), when used with an occlusive nonporous backing, such as 0.5 mil PET / 1.5 mil EVA results in superior skin adhesion for 7 days. The resultant polyacrylate formulations further result in a reduction in measured residue upon patch removal relative to existing commercial PIB-based products while providing comparable wearing performance. With the use of transparent backing such as the PET / EVA laminate, a clear patch that would not turn cloudy after multiple day use (e.g., 3 days, 7 days) can be achieved.

Problems solved by technology

The thicker adhesive layer also results in severe cold flow during storage in the pouch, and higher affinity for lint and dirt to adhere to the edge of the patch during wear.

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