FILM DELIVERY SYSTEM FOR ACTIVE INGREDIENTS
The present invention includes a pharmaceutical-based film system which includes various small-scale forms of pharmaceutically active agents, including testosterone esters, in a film base. Such forms include nanoparticles, microparticles, and combinations thereof. Methods of producing such film and providing a dosage of the pharmaceutical in a film are also provided.
1 . A method of forming a stabilized solid form of an active agent in a solid matrix wherein said solid form is present in the form of nanoparticles, microparticles, or combinations thereof, with said method, comprising the steps of:
a. combining an active agent and an excipient to form an active complex having a melting point less than or equal to about 100° C.;
b. adding at least a portion of said active complex to a solution of a solvent and at least one water soluble polymer, said solution being heated to a temperature above said melting point of said active complex whereby said active complex melts and forms a liquid dispersion of the active complex in the solution; and
c. rapidly evaporating the solvent to form a solid matrix containing a stabilized solid dispersion of said active complex in said solid matrix, wherein said active complex is present in the form of nanoparticles, microparticles, or combinations thereof.
2 . The method of claim 1 , wherein said active complex is not freely water soluble.
3 . (canceled)
4 . The method of claim 1 , wherein said excipient is selected from the group consisting of lipids, excipients with lipid surfactive properties, liquid oily excipients, liquid solvents, and combinations thereof.
5 . The method of claim 1 , wherein said stabilized, solid form of said active complex is in a form of a collection or agglomeration of nanoparticles.
6 . The method of claim 1 , wherein said stabilized, solid form of said pharmaceutically active agent is in a form of a collection of microparticles.
7 . The method of claim 1 , wherein said active agent is a testosterone ester.
8 . The method of claim 1 , wherein said active agent is testosterone enthanate or testosterone undecanoate.
9 . The method of claim 8 , wherein said excipient is selected from the group consisting of ethoxy (35) castor oil, diethylene glycol monoethyl ether, propylene glycol monocaprylate, stearoyl polyoxyl-32 glycerides, and combinations thereof.
10 . The method of claim 1 , wherein said polymer is selected from the group consisting of a surfactant polymer, a cellulose polymer, and combinations thereof.
11 . The method of claim 1 , wherein said solvent is heated to a temperature at least higher than the melting point of the pharmaceutically active complex.
12 . The method of claim 1 , wherein said active complex comprises about 0.001 to 60% by weight of the mixture.
13 . The method of claim 1 , further comprising the step of preparing a film with said stabilized solid form of said active complex.
14 . The method of claim 1 , wherein the solid matrix is a film.
15 . The method of claim 14 , wherein said active agent is a testosterone ester.
16 . The method of claim 15 wherein said active agent is testosterone enthanate or testosterone undecanoate.
17 . The method of claim 16 , wherein said excipient is selected from the group consisting of ethoxy (35) castor oil, diethylene glycol monoethyl ether, propylene glycol monocaprylate, stearoyl polyoxyl-32 glycerides, and combinations thereof.
18 . The method of claim 14 , wherein the film is a dosage unit, the active agent is present in an amount of about 10 mg or greater, and the weight ratio of excipient to active agent is about 4 to 1 or less.
19 . A method of forming a stabilized solid form of a pharmaceutically active agent in a solid matrix wherein said solid form is present in the form of nanoparticles, microparticles, or combinations thereof, with said method comprising the steps of:
a. combining an active agent and an excipient to form an active complex having a melting point less than or equal to about 100° C.;
b. adding at least a portion of said active complex to a solution of a solvent and at least one water soluble polymer, said solution being heated to a temperature above said melting point of said active complex whereby said active complex melts and forms a liquid dispersion of the active complex in the solution;
c. rapidly evaporating the solvent to form a solid matrix containing a stabilized solid dispersion of said active complex in said solid matrix, wherein said active complex is present in the form of nanoparticles, microparticles, or combinations thereof; and
d. gathering the resulting residue, wherein said resulting residue comprises said pharmaceutically active agent in the form of nanoparticles, microparticles, or combinations thereof.
20 . The method of claim 19 , wherein said active agent is a testosterone ester.
21 . The method of claim 19 , wherein said active agent is testosterone enthanate or testosterone undecanoate.
22 . The method of claim 21 , wherein said excipient is selected from the group consisting of ethoxy (35) castor oil, diethylene glycol monoethyl ether, propylene glycol monocaprylate, stearoyl polyoxyl-32 glycerides, and combinations thereof.
23 . The method of claim 19 , wherein said polymer is selected from the group consisting of a surfactant polymer, a cellulose polymer and combinations thereof.
24 . The method of claim 19 , wherein said solvent is heated to a temperature at least higher than the melting point of the pharmaceutically active agent.
25 . The method of claim 19 , wherein said pharmaceutically active complex comprises about 0.001 to 60% by weight of the mixture.
26 . The method of claim 19 , wherein said residue comprises said active complex in the form of a collection or agglomeration of nanoparticles.
27 . The method of claim 19 , wherein said residue comprises said active complex in the form of microparticles.
28 . The method of claim 19 , further comprising the step of preparing a film with said residue.