Dry powder inhalation system

Abstract

Dry powder inhaler systems for pulmonary delivery of pharmaceuticals are disclosed. The dry powder inhalation systems comprise a dry powder inhalation device or inhaler and a cartridge containing a pharmaceutical formulation comprising an active ingredient for delivery to the pulmonary circulation. The present devices provide rugged devices which are reusable, use pre-metered unit dose cartridges which deliver a medicament in a liner manner, and can be disassembled for cleaning. The devices also provide a high resistance inhalation system which enables deagglomeration of dry powder particles, have a consistent airflow, are easy to manufacture and are simple and relatively easy to use.

1 . A dry powder inhaler comprising:
 a housing, and   a mouthpiece,   wherein said housing comprises a mouthpiece engaging section structurally configured to engage with said mouthpiece, and   said mouthpiece being separable from said housing and having a conduit permitting airflow between an air inlet and an air exit port, and comprising a chamber and an oral placement section; said mouthpiece further being structurally configured to be moveable within said housing in an engaged position and releasable from said housing at a predetermined position.   
   
   
       2 . The dry powder inhaler of  claim 1 , wherein said mouthpiece is structurally configured to receive, hold and/or release a medicament containing cartridge in said chamber. 
   
   
       3 . The dry powder inhaler of  claim 2 , wherein the medicament containing cartridge contains a pharmaceutical composition comprising a diketopiperazine and an active ingredient. 
   
   
       4 . The dry powder inhaler of  claim 3 , wherein the diketopiperazine is fumaryl diketopiperazine. 
   
   
       5 . The dry powder inhaler of  claim 3 , wherein the active ingredient is one or more than one active agents selected from the group consisting of a peptide, a protein, and a hormone of naturally-occurring or synthetic origin, or analogs thereof. 
   
   
       6 . The dry powder inhaler of  claim 3 , wherein the active ingredient is insulin, parathyroid hormone 1-34, GLP-1, oxyntomodulin, peptide YY, interleukin 2-inducible tyrosine kinase, Bruton's tyrosine kinase (BTK), inositol-requiring kinase 1 (IRE1), heparin, or analogs thereof. 
   
   
       7 . The dry powder inhaler of  claim 3 , wherein the pharmaceutical composition comprises fumaryl diketopiperazine and insulin. 
   
   
       8 . The dry powder inhaler of  claim 2 , wherein the medicament containing cartridge comprises a structure with a defined shape having a wall with one or more apertures having a closed configuration or open configuration, an outer surface and an inner surface defining an internal volume; and said closed configuration restricts communication to said internal volume and said open configuration forms an air passage through said internal volume. 
   
   
       9 . The dry powder inhaler of  claim 1 , wherein said housing comprises an air intake section having an air conduit with one or more first openings to allow ambient air intake and a second opening in communication with the mouthpiece engaging section with allows airflow therethrough, wherein the air conduit of the air intake section of the housing is in communication with the air exit port of the mouthpiece when the cartridge is in the open configuration; said airflow enters the one or more first openings in the housing, passes through the airflow conduit in the housing and exits the second opening in the housing at the mouthpiece engaging section and into the mouthpiece chamber wherein a percentage of intake air volume goes through the cartridge and a percentage of intake air volume goes around the cartridge during an inhalation maneuver. 
   
   
       10 . The dry powder inhaler of  claim 1 , wherein the chamber of the mouthpiece chamber comprises a flange structurally configured to engage with said housing. 
   
   
       11 . The dry powder inhaler of  claim 1 , wherein the mouthpiece chamber comprises a cartridge securing mechanism. 
   
   
       12 . The dry powder inhaler of  claim 1 , wherein the dry powder inhaler is structurally configured to have a tunable airflow resistance. 
   
   
       13 . An inhalation system for pulmonary drug delivery, comprising:
 a dry powder inhaler comprising a housing and a mouthpiece, said housing including an inlet and an outlet port;   a cartridge adapted to said dry powder inhaler and containing a dry powder medicament for inhalation;   said dry powder inhaler system comprising air conduits configured to have a predetermined airflow distribution around and through said cartridge operably configured to mix the medicament with air forming a powder plume for delivery to a patient's pulmonary system;   wherein said predetermined airflow distribution through said cartridge ranges from about 10 to 30% of total airflow volume entering said dry powder inhaler during inhalation.   
   
   
       14 . The inhalation system of  claim 13 , wherein the predetermined airflow distribution around said cartridge ranges from about 70 to 90% of total airflow volume. 
   
   
       15 . The inhalation system of  claim 13 , wherein the dry powder medicament comprises a diketopiperazine and a pharmaceutically active ingredient. 
   
   
       16 . The inhalation system of  claim 13 , wherein the pharmaceutically active ingredient is a peptide, a protein, a hormone, analogs thereof or combinations thereof. 
   
   
       17 . The inhalation system of  claim 13 , wherein the inhaler and cartridge are configured to provide an airflow resistance ranging from 0.08 and 0.15 √kPa/liters per minute. 
   
   
       18 . A dry powder inhaler comprising:
 a housing, and   a mouthpiece assembly,   said housing having a top wall, a bottom wall, a first side wall and a second side wall; a mouthpiece engaging section, a mouthpiece storage section, and an air intake section having a conduit with a first opening to allow ambient air intake and a second opening in communication with the mouthpiece engaging section which allows air flow therethrough;   said mouthpiece assembly being separable from said housing and comprising a chamber structurally configured to house a cartridge and to engage with said mouthpiece engaging section of said housing; an oral placement section extending from said chamber and having an air inlet which communicates with said chamber and an air outlet in communication with ambient air.   
   
   
       19 . The dry powder inhaler of  claim 18 , wherein said mouthpiece engaging section of said housing has an outer wall, an inner wall and a bottom wall contiguous with the said first side wall, said second side wall and bottom walls respective of said housing, and configured to adapt to said mouthpiece chamber of said mouthpiece assembly. 
   
   
       20 . The dry powder inhaler of  claim 18 , wherein said mouthpiece engaging section further comprises a protrusion from said bottom wall configured to receive and hold a medicament containing cartridge. 
   
   
       21 . The dry powder inhaler of  claim 18 , wherein the mouthpiece engaging section further comprises a securing mechanism from said inner wall structurally configured to engage said mouthpiece chamber of said mouthpiece assembly. 
   
   
       22 . The dry powder inhaler of  claim 18 , wherein the mouthpiece chamber further comprises a flange having gaps which mate said protrusions or projections from the inner wall of the mouthpiece engaging section. 
   
   
       23 . The dry powder inhaler of  claim 18 , wherein said mouthpiece assembly is moveable from a storage position to a cartridge loading position and to an inhalation position, and comprises a mixing chamber configured to hold a medicament containing cartridge and to have an opening which aligns with the second opening of the intake section in said inhalation position. 
   
   
       24 . The dry powder inhaler of  claim 18 , wherein the mouthpiece chamber comprises an air inlet and is configured to secure a medicament containing cartridge, and has an indicator to allow proper cartridge placement in the inhaler. 
   
   
       25 . The dry powder inhaler of  claim 18 , wherein the mouthpiece assembly comprises a cap over the chamber, movable from a closed to an open position, having an anvil which engages with the cartridge in a closed position. 
   
   
       26 . The dry powder inhaler of  claim 18 , wherein the housing further comprises an air flow control mechanism comprising a check valve. 
   
   
       27 . An inhalation system for pulmonary drug delivery, comprising:
 a) a dry powder inhaler comprising a housing, and
 a mouthpiece assembly, 
 said housing having a top wall, a bottom wall, side walls; a mouthpiece engaging section, a mouthpiece storage section, and an air intake section having a conduit with a first opening to allow ambient air intake and a second opening in communication with the mouthpiece engaging section which allows air flow therethrough; 
 said mouthpiece assembly being separable from said housing and comprising a chamber structurally configured to house a cartridge and to engage with said mouthpiece engaging section of said housing; an oral placement section extending from said chamber and having an air inlet which communicates with said chamber and an air outlet in communication with ambient air; and 
   b) a cartridge adapted to said dry powder inhaler and containing a dry powder medicament for inhalation;   said dry powder inhaler system in use has a predetermined air flow distribution around and through said cartridge of air flow volume entering said chamber.   
   
   
       28 . The inhalation system of  claim 27 , wherein the predetermined air flow distribution through said cartridge ranges from about 10% to about 30% of the air flow volume entering the mixing section. 
   
   
       29 . The inhalation system of  claim 27 , wherein the predetermined air flow distribution around said cartridge ranges from about 70% to about 90% of the air flow volume entering the mouthpiece chamber. 
   
   
       30 . A method of delivering an active ingredient comprising: a) providing the dry powder inhaler of  claim 1  containing a cartridge with a dry powder formulation comprising a diketopiperazine and the active agent; and b) delivering the active ingredient to an individual in need of treatment; wherein the air conduit of the inhaler and cartridge provide a combined resistance of between 0.08 and 0.15 √kPa/liters per minute. 
   
   
       31 . The method of  claim 30 , wherein the dry powder formulation comprises a diketopiperazine and the active ingredient is a peptide, a protein, a hormone, analogs or fragments thereof. 
   
   
       32 . The method of  claim 31 , wherein the diketopiperazine is fumaryl diketopiperazine and the active ingredient is insulin.