Apparatus and method for transdermal delivery of bupropion

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Reexamination Certificate

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C514S649000, C514S769000, C514S772000

Reexamination Certificate

active

06280763

ABSTRACT:

BACKGROUND OF THE INVENTION
Bupropion hydrochloride is a known antidepressant sold in instant release tablet form under the brand names Wellbutkin® and Zyban®. Bupropion hydrochloride is an antidepressant of the aminoketone class and is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitors or other known antidepressant agents. Bupropion (BUP) hydrochloride is highly metabolized in both rats and humans. The major metabolites are the erythroamino alcohol (EB), the threoamino alcohol (TB), and the hydroxy metabolite (HB). The metabolites exhibit pharmacological activity in an antitetrabenzene model. Bupropion hydrochloride is also useful in preventing functional impairment and drowsiness seen upon administration of benzodiazepine, in the treatment of minimal brain dysfunction, tardive dyskinesia, impaired mental alertness upon ingestion of ethanol and psychosexual dysfunction. While the instant release tablets currently sold are suitable for the indicated use, there is a disadvantage to bupropion hydrochloride in that there can be an accumulation of metabolites that can be detrimental to one's health.
In a study of pharmacokinetics of bupropion hydrochloride in the elderly, six elderly patients with diagnosed depression were examined in a single and multiple dose study. Half-lives (t1/2app) of the metabolites TB, EB, and HB were 38.8+/−7.6 hours, 61.4+/−21.6 hours, and 34.2+/−4.6 hours, respectively. After multiple dosing, the half-life for bupropion and its metabolites did not change significantly, although in some patients the half-life of metabolites was substantially prolonged. In addition, there was also evidence of inordinate accumulation of metabolites. The elderly are at risk for accumulation of bupropion and its metabolites. See
J Clin. Pharmacol
. 35:876-884 (1995).
Therefore, a need exists for a new form of bupropion for delivering to the body while minimizing the formation of metabolites.
SUMMARY OF THE INVENTION
The invention includes an apparatus and method for transdermal delivery of bupropion base.
In the method of this invention, a patient is administered transdermally a bupropion base in an amount effective to alleviate withdrawal symptoms and to enhance the ability of a patient to abstain from smoking. Alternatively, an effective amount of bupropion base is delivered to alleviate depression in a patient.
A transdermal delivery system includes a bupropion base. The bupropion base can be mixed with an acceptable pharmaceutical carrier.


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