Method of preparing loxapine film oral dosage form

Abstract

A loxapine film oral dosage form includes loxapine salt, free base, or prodrug in an amount effective to provide relief from acute agitation associated with schizophrenia or bipolar 1 disorder via oral transmucosal delivery, dispersed in a polymeric film forming system. Advantageously, the film oral dosage form further includes a sweetener, a refreshing agent, an antioxidant, a pH stabilizer, a penetration enhancer, a mucoadhesive agent and a plasticizer. The loxapine film oral dosage form provides rapid onset of relief from acute agitation associated with schizophrenia or bipolar 1 disorder without presenting pulmonary health risks, thereby reducing risks to patients and others.

1 . A process of preparing a loxapine film oral dosage form, comprising:
 dissolving/suspending loxapine salt, free base or prodrug and a polymeric film forming system in a solvent to produce a film formulation, the solvent comprising methyl alcohol, ethyl alcohol, or both methyl alcohol and ethyl alcohol;   dispersing the film formulation on a substrate;   removing solvent from the film formulation to produce a dry film; and   cutting the film into individual dosage forms.   
     
     
         2 . The process of  claim 1 , in which the solvent further comprises water. 
     
     
         3 . The process of  claim 1 , in which the polymeric film-forming system comprises polyvinylpyrrolidone in an amount of from 3% to 50% by weight of the film on a dry basis. 
     
     
         4 . The process of  claim 1 , further comprising adding polyethylene glycol to the film formulation in an amount effective to increase the flexibility of the film. 
     
     
         5 . The process of  claim 1 , further comprising adding one or multiple permeation enhancers to the film formulation selected from sodium hyaluronate, sodium taurodeoxychlate, sodium glycodeoxycholate, sulphoxides (dimethylsulphoxide, decylmethyl sulfoxide), azones (laurocapram), pyrrolidones (2-pyrrolidone), alcohols/alkanols (ethanol or decanol), glycols (propylene glycol), surfactants (anionic: sodium lauryl sulfate, sodium decyl sulfate), (nonionic: Tween), (cationic: chitosan, cetylpyridinium chloride), terpenes (1,8-cineole, menthol, and menthone, D-limonene), fatty acids (oleic acid, sodium caprate), and bile salts (sodium deoxycholate, sodium deoxyglycocholate) added to the film formulation in an amount effective to promote enhanced absorption of loxapine via mucosal tissue. 
     
     
         6 . The process of  claim 1 , further comprising adding a sulfite salts to the film formulation in an amount effective to promote stability of the film. 
     
     
         7 . The process of  claim 1 , further comprising adding an alkaline substance to the film formulation that increases the pH of the film dosage form to maintain a neutral pH from 6 to 8. 
     
     
         8 . The process of  claim 1 , wherein the polymeric film comprises from 39.4% to 51.2% of a combination of hydroxypropyl cellulose and polyethylene oxide by weight on a dry basis and from 18.2% to 29.1% of a combination of polyvinylpyrrolidone and hydroxypropyl methylcellulose on a dry basis. 
     
     
         9 . The process of  claim 1 , further comprising adding a mucoadhesive agent to the film formulation. 
     
     
         10 . The process of  claim 1 , further comprising adding a plasticizer to the film formulation. 
     
     
         11 . The process of  claim 1 , further comprising adding sodium hyaluronate or sodium taurodeoxycholate and/or sodium glycodeoxycholate to the film formulation in an amount effective to promote enhanced absorption of loxapine via mucosal tissue.