SODIUM BICARBONATE IN SITU CONVERSION DRIVEN TRANSDERMAL DELIVERY OF AMINE DRUG
Compositions, devices, and methods for transdermal administration of active agents provided in their salt form instead of neutral form are provided.
1 . A composition for transdermal delivery, comprising:
a drug reservoir comprising an amine salt form of an active agent and an amphoteric inorganic base compound, wherein the pKa of the amphoteric inorganic base compound is lower than that of the amine salt form of the active agent.
2 . The composition of claim 1 , wherein the amphoteric inorganic base compound is sodium bicarbonate.
3 . The composition of claim 1 , wherein the active agent is selected from the group consisting of donepezil, memantine, fentanyl, oxybutynin, rotigotine, ropinirole, rivastigmine, tamsulosin, methylphenidate, fingolimod, and buprenorphine.
4 . The composition of claim 1 , wherein the drug reservoir comprises between about 5-35% w/w of the active agent.
5 . The composition of claim 1 , wherein the drug reservoir comprises between about 0.5-35% w/w of the sodium bicarbonate.
6 . The composition of claim 1 , further comprising a salt form solubilizer selected from the group consisting of water, alcohols, glycerol, propylene glycol, ethylene glycol, dimethyl sulfoxide, and N-methylpyrrolidone.
7 . The composition of claim 6 , wherein the drug reservoir comprises up to 15% w/w of the salt form solubilizer.
8 . The composition of claim 1 , further comprising a neutral form solubilizer selected from the group consisting of a fatty acid ester, a dicarboxylic acid ester, a glycerol ester, a lactate, a fatty alcohol, sorbitan monolaurate, sorbitan monooleate, lauryl lactate, propylene glycol monolaurate, dimethyl succinate, lauryl alcohol, and oleyl alcohol.
9 . The composition of claim 8 , wherein the drug reservoir comprises up to 20% w/w of the neutral form solubilizer.
10 . The composition of claim 1 , further comprising a plasticizer selected from the group consisting of a dicarboxylic acid ester, an adipate, a sebacate, a maleate, a tricarboxylic ester, triethyl citrate, tributyl citrate, a glycerol ester, and triacetin.
11 . The composition of claim 10 , wherein the drug reservoir comprises up to 20% w/w of the plasticizer.
12 . The composition of claim 1 , further comprising an additive selected from the group consisting of crospovidone and colloidal silicone dioxide.
13 . The composition of claim 12 , wherein the composition comprises up to 25% w/w of the additive.
14 . The composition of claim 1 , wherein the drug reservoir further comprises an adhesive agent selected from the group consisting of an acrylate, polyisobutylene, silicone adhesive, and styrene block copolymer based adhesive.
15 . The composition of claim 14 , wherein the adhesive agent comprises up to 65% w/w of the composition.
16 . A transdermal patch comprising the composition of claim 1 as a first drug reservoir and a backing layer.
17 . The transdermal patch of claim 16 , wherein the backing layer is an occlusive polymer film.
18 . The transdermal patch of claim 16 , further comprising a contact adhesive layer comprised of an adhesive selected from the group consisting of an acrylate, polyisobutylene, silicone adhesive, and styrene block copolymer based adhesive.
19 . The transdermal patch of claim 16 , further comprising a nonwoven tie layer between the drug reservoir and the contact adhesive layer.
20 . The transdermal patch of claim 16 , further comprising a rate-controlling membrane between the drug reservoir and the contact adhesive layer.
21 . The transdermal patch of claim 16 , wherein the patch comprises a second drug reservoir comprising an adhesive matrix comprising an amine salt form of an active agent and an amphoteric inorganic base compound, wherein the pKa of the amphoteric inorganic base compound is lower than that of the amine salt form of the active agent.
22 . The transdermal patch of claim 21 , wherein the first drug reservoir and second drug reservoir are separated by a nonwoven tie layer.
23 . The transdermal patch of claim 22 , wherein the first drug reservoir and second drug reservoir are separated by a rate-controlling membrane.
24 . A method of transdermally administering an active agent to a patient in need thereof, comprising: providing a composition according to claim 1 to a patient in need thereof.
25 . A method for treating Alzheimer's disease, Parkinson's disease, restless leg syndrome, attention deficit hyperactivity disorder, narcolepsy, depression, anxiety disorder, obsessive compulsive disorder, benign prostatic hyperplasia, acute urinary retention, opioid dependence, moderate acute pain in non-opioid-tolerant individuals, or moderate chronic pain, comprising: providing a composition according to claim 1 to a patient in need thereof.
26 . The method of claim 25 , further comprising administering or instructing to administer to the skin of the patient the composition.
27 . The method of claim 26 , wherein said administering achieves a therapeutically effective blood concentration of the active agent.
28 . A method of transdermally administering an active agent to a patient in need thereof, comprising: providing a transdermal patch according to claim 16 to a patient in need thereof.
29 . A method for treating Alzheimer's disease, Parkinson's disease, restless leg syndrome, attention deficit hyperactivity disorder, narcolepsy, depression, anxiety disorder, obsessive compulsive disorder, benign prostatic hyperplasia, acute urinary retention, opioid dependence, moderate acute pain in non-opioid-tolerant individuals, or moderate chronic pain, comprising: providing a transdermal patch according to claim 16 to a patient in need thereof.
30 . The method of claim 28 , further comprising administering or instructing to administer to the skin of the patient the transdermal patch.
31 . The method of claim 28 , wherein said administering achieves a therapeutically effective blood concentration of the active agent.