METHODS OF STABILIZING DRONABINOL
The present invention is directed to methods of stabilizing an oral pharmaceutical composition comprising dronabinol containing the steps filling a container, capping the container and placing the capped container in a secondary packaging system.
1 . A method of stabilizing an oral pharmaceutical composition comprising from about 0.1% to about 5% w/w dronabinol comprising the steps of:
a. filling a container with the oral pharmaceutical composition under a vacuum or a gas overlay;
b. capping the container to create a gaseous headspace in the container;
c. placing the container in a secondary packaging system under one or more conditions selected from the group consisting of under a gas overlay, with an oxygen absorbing means, and with an oxygen indicator,
d. sealing the secondary packaging system,
wherein the gaseous headspace contains less than 20% oxygen and wherein the secondary packaging system is selected from the group consisting of a pouch and a blister package.
2 . The method of claim 1 , wherein the gaseous headspace contains less than 10% oxygen.
3 . The method of claim 1 , wherein the gaseous headspace contains less than 1% oxygen.
4 . The method of claim 1 , wherein the gas is selected from the group consisting of helium, neon, argon, krypton, xenon, radon and nitrogen.
5 . The method of claim 1 , wherein the composition further comprises from about 20% to about 40% w/w water, from about 15% to about 65% w/w of ethanol, about 2% to about 10% w/w propylene glycol, about 8% to about 20% w/w polyethylene glycol, and an excipient selected from the group consisting of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), disodium ethylenediaminetetraacetic acid (EDTA), a paraben and a combination thereof.
6 . The method of claim 1 , wherein container is a glass bottle.
7 . The method of claim 6 , wherein the glass bottle is amber colored.
8 . The method of claim 6 , wherein the container is capped with a screw cap or a crimp cap.
9 . The method of claim 1 , wherein the secondary packaging system contains an oxygen absorbing means.
10 . The method of claim 9 , wherein the oxygen absorbing means is provided by one or more walls of the secondary packaging system.
11 . The method of claim 9 , wherein the oxygen absorbing means is provided by an auxiliary oxygen absorber displaced between two or more walls of the secondary packaging system.
12 . The method of claim 11 , wherein the auxiliary oxygen absorber is in the form of a pellet, strip, sheet, packet or in any other form.
13 . The method of claim 11 , wherein the auxiliary oxygen absorber is iron based or polymer based.
14 . The method of claim 13 , wherein the auxiliary oxygen absorber is iron based.
15 . The method of claim 13 , wherein the iron based auxiliary oxygen absorber provides absorption of from about 1 to about 3,000 cubic centimeters of oxygen.
16 . The method of claim 13 , wherein the iron based auxiliary oxygen absorber provides absorption of from about 10 to about 1,000 cubic centimeters of oxygen.
17 . The method of claim 13 , wherein the iron based auxiliary oxygen absorber provides absorption of from about 50 to about 500 cubic centimeters of oxygen.
18 . The method of claim 13 , wherein the iron based auxiliary oxygen absorber provides absorption of about 100 cubic centimeters of oxygen.
19 . The method of claim 1 , wherein the secondary packaging system contains an oxygen indicator.
20 . A container comprising an oral pharmaceutical composition comprising from about 0.1% to about 5% w/w dronabinol, wherein the container further comprises a gaseous headspace containing less than 20% oxygen.
21 . The container of claim 20 , wherein the container is a glass bottle.
22 . The container of claim 20 , wherein the container is an amber colored glass bottle.
23 . The container of claim 20 , wherein the gaseous headspace contains less than 10% oxygen.
24 . The container of claim 20 , wherein the gaseous headspace contains less than 1% oxygen.
25 . The container of claim 20 , further comprising from about 20% to about 40% w/w water, from about 15% to about 65% w/w of ethanol, from about 2% to about 10% w/w propylene glycol and from about 8% to about 20% w/w polyethylene glycol.
26 . The container of claim 25 , further comprising an excipient selected from the group consisting of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), disodium ethylenediaminetetraacetic acid (EDTA), a paraben and a combination thereof,
27 . The container of claim 20 , wherein the container comprises a cap.
28 . The container of claim 27 , wherein the cap is a screw cap or a crimp cap.