Respiratory tract delivery of levodopa and DOPA decarboxylase inhibitor for treatment of Parkinson's Disease
A dry pharmaceutical composition is provided that is suitable for respiratory tract delivery of levodopa and DDI for treatment of Parkinson's disease or Parkinson syndrome. The dry pharmaceutical composition comprises levodopa, a dopa decarboxylase inhibitor (DDI) and at least one excipient. A unit dosage form of the dry pharmaceutical composition and a method of treating a patient with Parkinson's disease or Parkinson syndrome by administering the dry pharmaceutical composition are also provided.
1. An intranasal delivery device comprising:
a container containing a dry pharmaceutical composition comprising:
L-DOPA (levodopa), and
a dopa decarboxylase inhibitor (DDI); and
a propellant canister containing a compressed gas or a liquefied propellant, and
an inlet interface designed to deliver the dry pharmaceutical composition into a nasal surface area.
2. The intranasal delivery device of claim 1 , wherein the dry pharmaceutical composition comprises (i) a plurality of separate levodopa and DDI particles, or (ii) a plurality of particles that comprise both levodopa and DDI.
3. The intranasal delivery device of claim 2 , wherein a median diameter of the plurality of particles (D50) is 1 μm-500 μm.
4. The intranasal delivery device of claim 2 , wherein the plurality of particles are in a crystalline or amorphous form or in a partially crystalline and partially amorphous form.
5. The intranasal delivery device of claim 2 , wherein the plurality of particles are obtained by spray-drying.
6. The intranasal delivery device of claim 1 , wherein the dry pharmaceutical composition comprises no more than 95 wt % levodopa.
7. The intranasal delivery device of claim 1 , wherein the DDI is carbidopa or benserazide.
8. The intranasal delivery device of claim 7 , wherein the weight ratio between levodopa and DDI is between 1:1 and 12:1.
9. The intranasal delivery device of claim 1 , wherein the dry pharmaceutical composition comprises no more than 30 wt % DDI.
10. The intranasal delivery device of claim 1 , wherein the dry pharmaceutical composition consists of (i) 68 wt % levodopa, 2 wt % NaCl, 6.8 wt % carbidopa, 22.2 wt % HPMC, and 1% n-dodecyl β-D-maltoside, or (ii) 63.35 wt % levodopa, 2.36 wt % NaCl, 6.34 wt % carbidopa, 27.02 wt % HPMC, and 0.93% n-dodecyl β-D-maltoside.
11. The intranasal delivery device of claim 1 , wherein the dry pharmaceutical composition is in a unit dosage form.
12. The intranasal delivery device of claim 11 , wherein the unit dosage form contains 25-150 mg of levodopa.
13. The intranasal delivery device of claim 1 , wherein the intranasal delivery device is a handheld, manually actuated, propellant-drive, metered-dose administration device.
14. The intranasal delivery device of claim 1 , wherein the intranasal delivery device is a manually actuated, propellant-driven, metered-dose administration device.
15. The intranasal delivery device of claim 1 , wherein the dry pharmaceutical composition further comprises
hydroxypropyl methyl cellulose (HPMC),
0.9-1 wt % of n-dodecyl β-D-maltoside, and
1-3 wt % of NaCl.