Transdermal Method and Patch for Nausea

Abstract

Provided, among other things, is a method of treating acute, delayed or anticipatory emesis for a sustained period in an individual, which involves applying to a portion of intact skin on the individual a composition of i. an antiemetically effective amount of a 5-HT3 receptor antagonist; ii. a permeation enhancing amount of permeation enhancer comprising 0.5% to 15% by weight of the skin-contacting layer; and iii. an adhesive, wherein a plasma concentration of the 5-HT3 receptor antagonist in a therapeutically effective range is provided for period of time from an onset time to 12 hours or more after the composition is removed.

Description

[0001] This application claims the priority of U.S. Application 60 / 682,251, filed May 18, 2005, U.S. Application 60 / 702,744, filed Jul. 27, 2005, and U.S. Application 60 / 759,381, filed Jan. 17, 2006.[0002] The present invention relates to a transdermal device and method for the treatment of nausea and vomiting, and more particularly to a transdermal method, composition, and device containing a 5-HT3 receptor antagonist for the treatment of nausea and vomiting for a sustained period of time. [0003] Most patients undergoing anticancer treatment either by chemotherapy or radiation suffer from side effects of the treatment such as nausea and vomiting, a common complaint by patients. To prevent or minimize these side effects of anticancer treatments, antagonists of 5-hydroxytryptamine subtype 3 (hereinafter referred to as ‘serotonin’) such as ondansetron, granisetron, tropisetron, dolasetron, hydrodolasetron, azasetron, ramosetron, lerisetron, indisetron, itasetron, palonosetron, lamoset...

AI Technical Summary

Benefits of technology

[0007] Attempts to develop a transdermally administered antiemetic agent have raised other problems. For example, some penetration enhancers used in transdermal compositions, (e.g., terpenes), induce skin irritation. Alcohols, which are often needed to solubilize the antiemetic agent for transdermal applications, are also irritating to the skin. Also, because of rapid depletion of the alcohol, sustained delivery over a period greater than a few hours is difficult to achieve. When a transdermal composition consisting of a solution with a low viscosity is used, the blood level of the drug may easily drop below the effective level thus lessening the desired pharmacological effect.

[0009] Thus, it is desirable to provide a transdermal composition of an antiemetic agent which is simple to use, nonirritating to the skin and which may be left in place on the skin for 24 hours, two days, three days or more for continuously and effectively preventing, ameliorating or treating nausea and vomiting. Moreover, with modest but functionally significant concentrations of active and permeation enhancer, it is nonetheless possible using the current teachings to formulate a patch that delivers antiemetic agent over a very substantial time period, and even maintain delivery as measured at the blood level well after removal of the composition.

Problems solved by technology

Most patients undergoing anticancer treatment either by chemotherapy or radiation suffer from side effects of the treatment such as nausea and vomiting, a common complaint by patients.

In any situation where a patient is suffering from nausea and vomiting, oral administration of an antiemetic agent is challenging and creates more discomfort for the patient.

Intravenous (IV) or intramuscular (IM) administration is generally impractical for home use.

Additionally, since nausea and vomiting are challenging to reverse, antiemetic agents are most effective if given prophylactically.

Attempts to develop a transdermally administered antiemetic agent have raised other problems.

For example, some penetration enhancers used in transdermal compositions, (e.g., terpenes), induce skin irritation.

Alcohols, which are often needed to solubilize the antiemetic agent for transdermal applications, are also irritating to the skin.

Also, because of rapid depletion of the alcohol, sustained delivery over a period greater than a few hours is difficult to achieve.

When a transdermal composition consisting of a solution with a low viscosity is used, the blood level of the drug may easily drop below the effective level thus lessening the desired pharmacological effect.

Other efforts to administer antiemetic agents transdermally have included complicated application devices or techniques such as supplemental energy to enhance the transdermal penetration of the drug.

However, salt forms of antiemetic agents have relatively low transdermal permeabilities, and it is difficult to achieve therapeutic plasma levels over a sustained period.

Use of the free base form is typically not considered since it could be irritating or considered to be unstable in the dosage form.

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