Transmucosal drug delivery system

Abstract

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 whence, 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 rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising methylphenidate and a fatty acid. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the adsorbent is silica. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the fatty acid is selected from the group consisting of caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, myristoleic acid, palmitoleic acid, oleic acid, gadoleic acid, erucic acid, ricinoleic acid, linoleic acid, linolenic acid, licanic acid, arachidonic acid and clupanadonic acid. 
     
     
         4 . The pharmaceutical composition of  claim 1 , further including a co-solvent. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the co-solvent comprises polyethylene glycol (PEG), ethanol, ethyl acetate, isopropyl alcohol, triacetin, triethyl citrate, tributyl citrate, substituted polyethylene glycols, bisabolol, glycerin, mineral oil, ethyl oleate, oleic acid, fatty acid esters, squalane, animal oils, vegetable oils, propylene glycol, hydrogenated vegetable oils, isopropyl myristate, isopropyl palmitate, glycofurol, terpenes, essential oils, alcohols, polyols, silicone fluids, or mixtures thereof. 
     
     
         6 . The pharmaceutical composition of  claim 1 , further comprising a solid, water-soluble excipient, a disintegrant, a lubricant, or mixtures thereof. 
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein the solid water-soluble excipient is selected from the group consisting of a sugar, a polyol, a saccharide, a polysaccharide, a dextrate, a dextrin, dextrose, fructose, lactitol, lactose, erythritol, maltose, maltitol, a maltodextrin, a polydextrose, trehalose, mannitol, a polyethylene glycol, sorbitol, sucrose, xylitol and mixtures thereof. 
     
     
         8 . The pharmaceutical composition of  claim 6 , wherein the disintegrant is selected from the group consisting of sodium starch glycolate, crospovidone, croscarmellose sodium, low-substituted hydroxypropyl cellulose, starch, microcrystalline cellulose and mixtures thereof. 
     
     
         9 . The pharmaceutical composition of  claim 6 , wherein the lubricant is selected from the group consisting of sodium stearyl fumarate, magnesium stearate, stearic acid, sodium lauryl sulfate, talc, polyethylene glycol, calcium stearate and mixtures thereof. 
     
     
         10 . A pharmaceutical composition, comprising: a rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising fentanyl and a fatty acid. 
     
     
         11 . A pharmaceutical composition, comprising: a rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising sufentanil and a fatty acid. 
     
     
         12 . A pharmaceutical composition, comprising: a rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising alfentanil and a fatty acid. 
     
     
         13 . A pharmaceutical composition, comprising: a rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising lofentanil and a fatty acid. 
     
     
         14 . A pharmaceutical composition, comprising: a rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising carfentanil and a fatty acid. 
     
     
         15 . A pharmaceutical composition, comprising: a rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising an amphetamine and a fatty acid. 
     
     
         16 . A pharmaceutical composition, comprising: a rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising epinephrine and a fatty acid. 
     
     
         17 . A pharmaceutical composition, comprising: a rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising labetalol and a fatty acid. 
     
     
         18 . A pharmaceutical composition, comprising: a rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising isoproterenol and a fatty acid. 
     
     
         19 . A pharmaceutical composition, comprising: a rapid-release solid tablet further comprising: an adsorbent, and a liquid solution comprising terbutaline and a fatty acid.