Civitas Therapeutics, Inc.

Advanced Inhalation Research, Inc.

Alkermes, Inc.

The Penn State Research Foundation

Merz Pharmaceuticals Gmbh

Richard P Batycky

Michael M Lipp

Giovanni Caponetti

Lloyd Johnston

David A Edwards

Ernest D Penachio

Abhijit Kamerkar

Ralph W Niven

Kevin D Kee

Jeffrey S Hrkach

Elliot Ehrich

Jeffrey Mintzes

Karen Fu

Jason Summa

Mei-Ling Pan

Mariko Childs

Wen-I Li

Donghao Chen

Michael W Lipp

Martin Freed

Charles D Blizzard

Jean C Sung

Ernest E Penachio

Blair C Jackson

Jeffrey D Mintzes

Marie Elizabeth Chung

Eliot Ehrich

Wen-I Ki

Lloyd P Johnston

The present invention provides methods of providing rapid relief of motor fluctuations in a Parkinson's disease patient. The methods of the invention comprise pulmonary administration of levodopa by inhalation at therapeutically effective concentrations such that the patient's plasma levodopa concentration increases by at least about 200 ng/ml within 10 minutes or less post inhalation as compared to the concentration of levodopa in the patient's plasma prior to inhalation of the levodopa and wherein the patient's plasma concentration remains increased by at least about 200 ng/ml for a time period of at least 15 minutes after inhalation. The methods of the invention are particularly useful for treatment of motor fluctuations which arise as a result of poorly controlled levodopa plasma levels in a patient.

Methods for providing rapid relief of motor fluctuations in a Parkinson's disease patient

The invention provides pharmaceutical compositions for pulmonary delivery comprising particles containing a pharmaceutical agent and having a geometric size of greater than about 5 &#x3bc;m and a tap density of less than about 0.075 g/cm. The invention also provides methods for delivering the pharmaceutical compositions of the invention to the respiratory tract of a patient.

Ultra low density pulmonary powders

The present invention provides a capsule containing an inhalable powder composition wherein the composition comprises about 75% by weight or more levodopa, dipalmitoylphosphatidylcholine (DPPC) and a salt characterized by a working density of less than about 100 g/L. The invention further provides a capsule containing an inhalable powder composition wherein the composition comprises about 75% by weight or more levodopa, dipalmitoylphosphatidylcholine (DPPC) and a salt characterized by a working density of less than about 100 g/L wherein the capsule material comprises hydroxypropylmethylcellulose (HPMC) and titanium dioxide.

Capsules containing high doses of levodopa for pulmonary use

Particles having a tap density of less than 0.4 g/cminclude a hydrophobic amino acid or salt thereof and a therapeutic, prophylactic or diagnostic agent or any combination thereof. Preferred particles include a phospholipid, have a median geometric diameter between about 5 and about 30 microns and an aerodynamic diameter between about 1 and about 5 microns. The particles can be formed by spray-drying and are useful for delivery to the pulmonary system.

Use of simple amino acids to form porous particles

The present invention provides methods of reducing the inter-patient variability of levodopa plasma concentrations in a population of Parkinson's disease patients. The methods of the invention comprise pulmonary administration of levodopa at therapeutically effective concentrations such that the inter-patient variability of levodopa plasma concentrations at time periods ranging from about 10 minutes post inhalation to about 60 minutes or more post inhalation have less than a 50% coefficient variation. The methods of the invention are particularly useful for treatment of motor fluctuations which arise as a side effect of L-Dopa therapy.

Methods for reducing inter-patient variability of levodopa plasma concentrations

The present invention is directed toward particles for delivery of epinephrine to the respiratory system and methods for treating a patient in need of epinephrine. The particles and respirable compositions comprising the particles of the present invention described herein comprise the bioactive agent epinephrine, or a salt thereof, as a therapeutic agent. The particles are preferably formed by spray drying. Preferably, the particles and the respirable compositions are substantially dry and are substantially free of propellents. In a preferred embodiment, the particles have aerodynamic characteristics that permit targeted delivery of epinephrine to the site(s) of action.

Inhalable epinephrine

A method for delivering an agent to the pulmonary system, in a single, breath-activated step or a single breath, comprises administering from a receptacle enclosing a mass of particles, to a subject's respiratory tract, particles which have a tap density of less than 0.4 g/cmand deliver at least about 50% of the mass of particles. The particles are capable of carrying agents. The agent is (1) part of the spray-drying pre-mixture and thereby incorporated into the particles, (2) added to separately-prepared particles so that the agent is in chemical association with the particles or (3) blended so that the agent is mixed with, and co-delivered with the particles. Respirable compositions comprising carrier particles having a tap density of less than 0.4 g/cmand a composition comprising an agent are also disclosed. Methods of delivering these respirable compositions are also included.

Highly efficient delivery of a large therapeutic mass aerosol

Particles having a tap density less than about 0.4 g/cm3 are formed by spray drying from a colloidal solution including a carboxylic acid or salt thereof, a phospholipid, a divalent salt and a solvent such as an aqueous-organic solvent. The colloidal solution can also include a therapeutic, prophylactic or diagnostic agent. Preferred carboxylic acids include at least two carboxyl groups. Preferred phospholipids include phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, phophstidylserines, phosphatidylinositols and combinations thereof. The particles are suitable for pulmonary delivery.

Formulations for spray-drying large porous particles

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Newton, MA, United States of America

Richard P Batycky