Transmucosal drug delivery system
Disclosed are preparations and formulations of high thermodynamic activity lipophilic associations (LA), in which there is pairing between an ionizable pharmaceutical agent and a lipophilic species having ionic characteristics opposite to that of the pharmaceutical agent. Such lipophilic associations manifest high thermodynamic activity, as evidenced by their being predominantly in a liquid phase at room temperature or solvated in a lower-than-water dielectric solvent. Further the pharmaceutical agent being solubilized means that dissolution is not rate limiting to transmucosal absorption. This LA or LA-solvate is formulated into a low dielectric dosage form, from when, upon the dosage form's hydration, the pharmaceutical agent is driven through the mucosal tissue and into systemic circulation. The invention therefore provides an enhanced transmucosal drug delivery system for ionizable pharmaceutical agents at or near physiological pH.
1. A pharmaceutical composition comprising:
(a) nicotine forming a lipophilic association (LA), with oleic acid, which is in a liquid state;
(b) a carrier wherein the carrier is a silica or a silicified microcrystalline cellulose and wherein the carrier has an available surface area which permits adsorption of the LA, in its liquid state thereto; and
(c) a water-soluble excipient selected from one or more of the group consisting of a dextrate, dextrin, dextrose, fructose, lactitol, lactose, erythritol, maltose, maltitol, maltodextrin, polydextrose, trehalose, mannitol, polyethylene glycol, sorbitol, sucrose and xylitol;
wherein the pharmaceutical composition is formulated in a transmucosal dosage form, wherein said dosage form is a solid dosage form for buccal or sublingual administration, and wherein said dosage form has a dissolution profile which provides greater than 90% release of nicotine from the dosage form within 10 minutes.
2. The pharmaceutical composition of claim 1 , wherein the water-soluble excipient is mannitol.
3. The pharmaceutical composition of claim 1 , wherein the molar ratio of nicotine to oleic acid is at least about 1:1.