Novel compositions
Compositions and method are provided, for the treatment of pain, e.g. acute breakthrough pain, by means of a systemic, non-invasive mode of administration. Specifically, the invention relates to a sublingual presentation of an opioid analgesic, such as fentanyl, or its salts, in amounts that are sufficient to treat the pain.
1 . A pharmaceutical formulation having a pH of between about 7.4 and about 8.5, and comprising:
(a) fentanyl;
(b) water as carrier;
(c) a polar organic solvent in sufficient amount to enhance the solubility of the fentanyl in the water; and
(d) a buffer.
2 . The formulation according to claim 1 , wherein the fentanyl is present at a concentration of 0.1-10 mg/ml.
3 . The formulation according to claim 1 , wherein the polar organic solvent is selected from ethanol, propylene glycol, glycerol, polyethylene glycol and mixtures thereof.
4 . The formulation according to claim 1 , wherein the polar organic solvent is ethanol.
5 . The formulation according to claim 1 , wherein the polar organic solvent is present in an amount of 6-50% w/w.
6 . The formulation according to claim 1 , wherein the buffer is citrate buffer.
7 . The formulation according to claim 1 , which has pH around 8.2.
8 . The formulation according to claim 1 , which contains a sweetener.
9 . The formulation according to claim 8 , wherein the sweetener is saccharin.
10 . The formulation according to claim 1 , which contains menthol.
11 . The formulation according to claim 1 , wherein the fentanyl is introduced as the free base.
12 . A metered dose dispensing system comprising a sealed container fitted with a metering pump, an actuator and a channelling device, wherein the container contains a pharmaceutical formulation having a pH of between about 7.4 and about 8.5, and comprising:
(a) fentanyl;
(b) water as carrier;
(c) a polar organic solvent in sufficient amount to enhance the solubility of the fentanyl in the water; and
(d) a buffer;
and wherein the system is adapted for sublingual administration of the formulation as a spray.
13 . A pharmaceutical liquid composition comprising an opioid analgesic, the composition providing a plasma concentration of at least 250 pg/ml of opioid analgesic within a period of no more than 2 hours, following sublingual administration using a pump spray dispensing device.
14 . The composition according to claim 13 , wherein a plasma concentration of at least 250 pg/ml of opioid analgesic is achieved within a period of no more than 30 minutes.
15 . The composition according to claim 13 , wherein a plasma concentration of at least 250 pg/ml of opioid analgesic is achieved within a period of no more than 15 minutes.
16 . The composition according to claim 13 , wherein the opioid analgesic is fentanyl.
17 . The composition according to claim 13 , which is substantially free of any absorption enhancer.
18 . The composition according to claim 13 , which is substantially free of propellant.
19 . The composition according to claim 16 , wherein the fentanyl is present as the free base.
20 . The composition according to claim 13 , wherein the opioid analgesic is present at a concentration of 5 μg/ml to 50 mg/ml.
21 . A method for providing analgesia or for the treatment of pain, which comprises administering sublingually, as a spray, a pharmaceutical liquid composition comprising an opioid analgesic, the composition providing a plasma concentration of at least 250 pg/ml of opioid analgesic within a period of no more than 2 hours, following sublingual administration using a pump spray dispensing device.
22 . The method according to claim 21 , wherein a volume of at least 60 μl and no more than 150 μl of the composition is administered to the sublingual area.
23 . The method according to claim 21 , wherein the composition has a bioavailability of more than 60% when delivered by a non-propellant pump spray device to the sublingual area.
24 . The method according to claim 23 , wherein the bioavailability is more than 70%.