Title:  Buccal and sublingual administration of physostigmine

United States Patent:  6,264,974

Appl. No.:  111550

Physostigmine, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b] indol-5ol methylcarbamate, administered buccally or sublingually in non-sustained release dosage form provides extremely prolonged blood levels. This active agent is physically compounded with materials of some or all of classes of ingredients that function as pH controls, preservative agents, viscosity control agents, absorption enhancers, stabilizing agents, solvents, and carrier vehicles. This compounding will produce a pharmaceutical composition in the form of a liquid, tablet, gel, patch or lozenge for administration of the active agent, Physostigmine, by absorption through the buccal or sublingual mucosa of the patient. This method of delivery of Physostigmine and similar compounds is useful for treatment of cognitive deficiencies and/or neurological function deficits, mood and/or mental disturbances in mammals including human beings.

DETAILED DESCRIPTION OF THE INVENTION

Detailed descriptions of the preferred embodiment are provided herein; however, it is to be understood that the present invention may be embodied in various forms. Therefore, specific details disclosed herein are not to be interpreted as limiting, but rather as a basis for the claims and as a representative basis for teaching one skilled in the art to employ the present invention in virtually any appropriately detailed system, structure or manner.

Compounds of the present invention incorporating Physostigmine or structurally similar active ingredients can be administered buccally or sublingually to treat cognitive or neurological dysfunction including Alzheimer's Disease patients or as a treatment for nerve gas poisoning using any pharmaceutically suitable formulation that results in the active agent reaching the agent's sites of action in the body of mammals and particularly humans. The benefits of the Physostigmine have been previously established or evidenced by its approval by the United States Food and Drug Administration and its placement on the approved drug list for the treatment of Alzheimer's Disease patients.

This invention provides a delivery technique for administration of Physostigmine, a generic drug, to the patient through the mucous membranes of the mouth, buccally/sublingually, in a non-sustained release dosage form while obtaining and providing plasma concentrations of Physostigmine that are extremely sustained, simulating a slow intravenous infusion. The acetylcholinesterase inhibitors in general, and specifically Physostigmine, can be administered buccally or sublingually either as an individual agent or in combination with other therapeutic agents such as muscarinic agonists or neurotransmitter release enhancers. These drugs generally are administered with a pharmaceutical carrier selected on the basis of the chosen formulation and standard pharmaceutical practices. Whenever a dosage that is not in a solution form is used, the carrier dissolves in the saliva to release and expose the active drug Physostigmine to the mucosa of the mouth for absorption thereby.

The administered dose of the cholinesterase inhibitor will vary depending upon known factors such as: the pharmacodynamic characteristics of the particular agent; the age, health and weight of the recipient; the nature and extent of symptoms; the kind of concurrent treatment; frequency of treatment; and the effect desired. Usually a daily buccal or sublingual dosage of drug can be about 0.001 to 1.0 mg/kg of body weight while the preferred dosage range is about 0.001-0.01 mg/kg given either once a day or in divided doses 2 to 4 times a day, to provide a more consistent plasma level of the drug.

The active ingredients can be administered buccally or sublingually by preparing a suitable formulation of the active ingredient and utilizing procedures well known to those skilled in the art. Preferably, the formulations are prepared with suitable nontoxic pharmaceutically acceptable ingredients. These ingredients are known to those skilled in the preparation of buccalisublingual dosage forms; some of these ingredients can be found in Remington's Pharmaceutical Sciences, 17th edition, 1985, a standard reference in the field. The choice of suitable carriers is highly dependent upon the exact nature of the buccal/sublingual dosage form desired, e.g. solutions, sprays, drops, gels, tablets, pastes, patches, or lozenges.

The compounding of ingredients identified in Remington's Pharmaceutical Sciences may include minor amounts of other ingredients such as pH adjusters, emulsifiers or dispersing agents, preservatives, surfactants, gelling agents, as well as buffering and other stabilizing and solubilizing agents.

Claim 1 of 4 Claims

I claim:

1. A method of buccal or sublingual administration of Physostigmine for achieving prolonged plasma concentrations of said Physostigmine in a mammal comprising the steps of: preparing a solution of said Physostigmine or a salt thereof dissolved in an aqueous carrier solution; disposing the said solution, containing physostigmine or a salt thereof, within a sublingual or buccal cavity of said mammal in a quantity to deliver a dosage of 0.001 to 1.0 mg/kg of body weight of said mammal; and absorbing said Physostigmine or salt thereof into buccal or sublingual mucosa, thereby creating and maintaining prolonged plasma concentrations of said Physostigmine for at least 90 minutes.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.