Title:  Nasal drug delivery composition containing nicotine

United States Patent:  5,935,604

Inventors:  Illum; Lisbeth (The Park, GB)

Appl. No.:  553401

The present invention provides a nasal drug delivery composition comprising nicotine or a pharmacologically-acceptable salt or derivative thereof wherein the composition is adapted to delivery a pulse of nicotine for rapid absorption and a controlled release of nicotine for subsequent sustained absorption. The controlled release phase can be achieved by providing an ion-exchange material which will form a complex with the nicotine. The ion-exchange material may be a polymeric material such as a polysaccharide, or may be in the form of bioadhesive ion-exchange microspheres. The pulse release can be achieved by overloading the ion-exchange material with nicotine so that the composition contains some excess nicotine for immediate release and absorption. Alternatively, some nicotine may be associated with a non ion-exchange material which will release the nicotine immediately on contact with the nasal mucosa, for example non-ion-exchange bioadhesive microspheres.

Abstract of the Description of the Invention

"The controlled release effect can be achieved by providing an ion-exchange material in the composition. By-ion-exchange material is meant a natural or synthetic material comprising ionisable groups and which have the ability to exchange ions attracted to their ionised groups with ions of the same charge present in solution. Nicotine is a basic drug and when ionised it carries a positive charge. The ion-exchange material must therefore be one which when ionised releases a positive ion leaving a negative charge to which the ionised nicotine is attracted. The ion-exchange material forms a complex with the ionised nicotine and releases the nicotine slowly when in contact with the nasal mucosa.

The ion-exchange capacity of the ion-exchange material used should preferably be in the range 0.01-50 milli equivalents/g, more preferably 0.1-20 meq/g and most preferably 0.2-10 meq/g.

The ion-exchange material is preferably. bioadhesive to aid its retention in the nasal cavity. By bioadhesive is meant a material which will adhere to the surface of the nasal cavity. The ion-exchange material gradually releases nicotine, providing a controlled release and uptake of nicotine across the nasal mucosa.

Natural or synthetic nicotine may be used or a pharmacologically-acceptable salt or derivative of nicotine."

"The pulse release of nicotine may be achieved by providing a material which is not an ion-exchange material. The nicotine associated with this material will then be released immediately on contact with the nasal mucosa for rapid absorption. Alternatively, excess nicotine is provided in the composition so that the ion-exchange material is overloaded with nicotine. The excess nicotine not bound by-the ion-exchange material is available for immediate uptake on contact with the nasal mucosa. This excess nicotine is also referred to throughout as "free nicotine".

"Monovalent cations can also be included in the composition to compete with the nicotine for binding with the ion-exchange material, thus ensuring that some of the nicotine is left as free nicotine. Such cations should be non-toxic and pharmacologically acceptable, for example sodium, calcium and ammonium.

The ion-exchange material may be in the form of bioadhesive microspheres, or may be an aqueous solution, suspension or freeze-dried preparation of a polymeric material."

"The ion-exchange microspheres can be used with free nicotine to provide both the fast pulse release of nicotine and the controlled release, or can be mixed with non-ion-exchange microsphere. Nicotine is adsorbed to the surface of the non-ion-exchange microsphere and will be released quickly on contact with the nasal mucosa to provide the pulsed effect. Suitable materials for use as non-ion-exchange microspheres include starch, gelatin, collagen and albumin. When a mixture of ion exchange and non-ion-exchange microspheres are used, the composition should contain between 50:1 and 1:1 of ion-exchange-to non-ion-exchange microspheres, preferably 25:1 to 5:1, and more preferably 10:1."

Claim 1 of 18 Claims

1. A drug delivery composition for nasal administration comprising nicotine or a pharmacologically-acceptable compound releasing nicotine, in a formulation delivering to the nasal mucosa;

(a) an initial pulse of nicotine for rapid absorption, and

(b) a controlled release of nicotine for up to twelve hours for subsequent sustained absorption, wherein the formulation comprises an ion-exchange material which forms a complex with the nicotine to provide controlled release of nicotine.

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