Compositions and devices to administer pharmaceutical compositions nasally

Abstract

Devices and methods for nasal administration of a pharmaceutical composition. In certain embodiments, the devices comprises a reservoir, a conduit in fluid communication with the reservoir, and an anatomic positioning device configured to position the conduit in a nasal cavity of a user. Particular embodiments include an actuator configured to transfer the pharmaceutical composition from the reservoir to the conduit and emit the pharmaceutical composition from the conduit.

1 . An apparatus for nasal administration of a pharmaceutical composition, the apparatus comprising:
 a reservoir;   a conduit in fluid communication with the reservoir;   an actuator configured to transfer a pharmaceutical composition from the reservoir to the conduit and emit the pharmaceutical composition from the conduit; and   an anatomic positioning device configured to position the conduit in a nasal cavity of a user.   
     
     
         2 . The apparatus of  claim 1  wherein the anatomic positioning device is modeled after anatomic features of an individual user. 
     
     
         3 . The apparatus of  claim 1  wherein the anatomic positioning device is modeled after a computerized tomography (CT) scan of an individual user. 
     
     
         4 . The apparatus of  claim 1  wherein the anatomic positioning device is modeled after a magnetic resonance imaging (MRI) scan of a nasal cavity of an individual user. 
     
     
         5 . The apparatus of  claim 1  wherein the anatomic positioning device comprises:
 an adjustable member coupled to the conduit, wherein:
 the adjustable member can be adjusted to control a depth at which the conduit is inserted into the nasal cavity; and 
 the adjustable member can be adjusted to control an angle at which the conduit is inserted into the nasal cavity. 
 
 
     
     
         6 . The apparatus of  claim 5  wherein the conduit is threaded and the adjustable member is threadably coupled to the conduit. 
     
     
         7 . The apparatus of  claim 5  wherein the anatomic positioning device further comprises:
 a dial mechanism for controlling the depth and the angle at which the conduit is inserted into the nasal cavity. 
 
     
     
         8 . The apparatus of  claim 1  wherein further comprising a sensor configured to detect an angle at which the conduit is positioned. 
     
     
         9 . The apparatus of  claim 8  wherein the sensor is a mechanical sensor. 
     
     
         10 . The apparatus of  claim 8  wherein the sensor is an electronic sensor. 
     
     
         11 . The apparatus of  claim 1  wherein the anatomic positioning device comprises an anatomical nostril insert. 
     
     
         12 . The apparatus of  claim 1  wherein the anatomic positioning device comprises an external frame structure. 
     
     
         13 . The apparatus of  claim 12  wherein the external frame structure is configured to be placed outside a nose and configured to guide the conduit into the nasal cavity. 
     
     
         14 . The apparatus of  claim 1  wherein the actuator is configured to increase pressure in the reservoir. 
     
     
         15 . The apparatus of  claim 1  wherein the actuator is configured to compress the reservoir. 
     
     
         16 . The apparatus of  claim 1  wherein the pharmaceutical composition comprises:
 (A) a therapeutic agent; and 
 (B) a pharmaceutical excipient, wherein:
 the pharmaceutical composition is formulated for administration intranasally for delivery to the brain; and 
 the pharmaceutical composition is formulated as a solid dispersion. 
 
 
     
     
         17 . The apparatus of  claim 16 , wherein the solid dispersion is amorphous. 
     
     
         18 . The apparatus of  claim 16 , wherein the solid dispersion is in a nanocrystalline state. 
     
     
         19 . The apparatus according to any one of  claims 16 - 18 , wherein the therapeutic agent is a chemotherapeutic compound. 
     
     
         20 . The apparatus of  claim 19 , wherein the therapeutic agent is mebendazole. 
     
     
         21 . The apparatus according to any one of  claims 16 - 20 , wherein the pharmaceutical excipient is a polymer. 
     
     
         22 . The apparatus of  claim 21 , wherein the pharmaceutical excipient is a polyvinylpyrrolidone copolymer. 
     
     
         23 . The apparatus of  claim 22 , wherein the pharmaceutical excipient is a polyvinylpyrrolidone and vinyl acetate copolymer. 
     
     
         24 . The apparatus of  claim 23 , wherein the pharmaceutical excipient is Kollidon® VA64. 
     
     
         25 . The apparatus of  claim 1  wherein the pharmaceutical composition comprises:
 (A) a therapeutic agent; and 
 (B) a pharmaceutical excipient, wherein:
 the pharmaceutical composition is formulated for administration intranasally for delivery to the brain; and 
 the pharmaceutical composition is formulated as a foam. 
 
 
     
     
         26 . The apparatus of  claim 25 , wherein the pharmaceutical excipient is a composition comprising a first polymer and a second polymer. 
     
     
         27 . The apparatus of  claim 26 , wherein the first polymer is a polyether. 
     
     
         28 . The apparatus of  claim 27 , wherein the first polymer is a triblock polyether. 
     
     
         29 . The apparatus of  claim 28 , wherein the first polymer is a polyethylene-polypropylene-polyethylene polymer. 
     
     
         30 . The apparatus of  claim 29 , wherein the first polymer is Poloxamer® 407. 
     
     
         31 . The apparatus according to any one of  claims 25 - 30 , wherein the therapeutic agent is a contrast agent. 
     
     
         32 . The apparatus of  claim 31 , wherein the therapeutic agent is perfluorooctylbromide. 
     
     
         33 . The apparatus according to any one of  claims 25 - 32 , wherein the pharmaceutical composition comprises an imaging agent. 
     
     
         34 . The apparatus of  claim 33 , wherein the imaging agent is fluorescein. 
     
     
         35 . The apparatus according to any one of  claims 25 - 34 , wherein the pharmaceutical composition further comprises a basic solution. 
     
     
         36 . The apparatus of  claim 35 , wherein the basic solution is a hydroxide solution. 
     
     
         37 . The apparatus of  claim 36 , wherein the basic solution is a sodium hydroxide solution. 
     
     
         38 . The apparatus according to any one of  claims 25 - 37  wherein the pharmaceutical composition comprises a propellant. 
     
     
         39 . The apparatus of  claim 38 , wherein the propellant is a haloalkane (C≤12) . 
     
     
         40 . The apparatus of  claim 39 , wherein the propellant is a haloalkane (C≤6) . 
     
     
         41 . The apparatus of  claim 40 , wherein the propellant is 1,1,1,2,3,3,3-heptafluoropropane. 
     
     
         42 . A method of developing individualized administration of a pharmaceutical composition to a person, the method comprising:
 obtaining one or more images of a nasal cavity of the person;   creating a three-dimensional model of the nasal cavity; and   determining person-specific parameters for a device configured to administer the pharmaceutical composition to the person, wherein the person-specific parameters are based on the three-dimensional model of the nasal cavity.   
     
     
         43 . The method of  claim 42  wherein the one or more images comprise computed tomography (CT) scans of the nasal cavity of the person. 
     
     
         44 . The method of  claim 42  wherein the three-dimensional model of the nasal cavity is created by image processing software utilizing the one or more images obtained of the nasal cavity of the person. 
     
     
         45 . The method of  claim 44  wherein the image processing software is segmentation software. 
     
     
         46 . The method of  claim 42  wherein the person-specific parameters include an administration angle of the device. 
     
     
         47 . The method of  claim 42  wherein the person-specific parameters include an insertion depth of the device. 
     
     
         48 . The method of  claim 42  wherein the person-specific parameters include a head tilt angle. 
     
     
         49 . The method of  claim 42  wherein the person-specific parameters include an actuation force of the device. 
     
     
         50 . The method of  claim 42  further comprising creating a three-dimensional casting of the nasal cavity from the three-dimensional model of the nasal cavity. 
     
     
         51 . The method of  claim 50  wherein creating a three-dimensional casting of the nasal cavity comprises:
 obtaining computed tomography (CT) scans of the nasal cavity; 
 using image processing software to generate cross-section views of the CT scans in the coronal, sagittal and axial positions; 
 creating a three-dimensional model of the nasal cavity with the image processing software; and 
 printing the three-dimensional casting from the three-dimensional model via stereolithography. 
 
     
     
         52 . The method of  claim 51  wherein the three-dimensional casting is printed in multiple anatomical segments. 
     
     
         53 . The method of  claim 52  wherein the multiple anatomical segments include an anterior segment, an upper segment, a middle segment, a lower segment and a naso-pharynx segment. 
     
     
         54 . The method of  claim 53  wherein the three-dimensional model comprises a superior turbinate, a middle turbinate, and an inferior turbinate. 
     
     
         55 . The method of  claim 54  wherein the anterior segment comprises a boundary at a coronal slice made directly anterior to the superior turbinate, the middle turbinate, and the inferior turbinate. 
     
     
         56 . The method of  claim 54  wherein the upper segment comprises a lower boundary between the superior turbinate and the middle turbinate. 
     
     
         57 . The method of  claim 54  wherein the middle segment comprises a first boundary between the middle turbinate and the superior turbinate and a second boundary between the middle turbinate and the inferior turbinate. 
     
     
         58 . The method of  claim 54  wherein the lower segment comprises an upper boundary between the inferior turbinate and the middle turbinate. 
     
     
         59 . The method of  claim 54  wherein a boundary of the naso-pharynx segment is a coronal slice made directly posterior to the superior turbinate, the middle turbinate, and the inferior turbinate. 
     
     
         60 . The method of  claim 52  further comprising:
 (1) providing an initial administration of a test compound into the anterior segment of the three-dimensional casting; and 
 (2) observing an initial amount of the test compound deposited in the upper segment of the three-dimensional casting after the initial administration of the test compound into the anterior segment. 
 
     
     
         61 . The method of  claim 60  further comprising:
 (3) altering one or more parameters of the initial administration of the test compound into the anterior segment; 
 (4) providing a subsequent administration of the test compound into the anterior segment of the three-dimensional casting; 
 (5) observing a subsequent amount of the test compound deposited in the upper segment of the three-dimensional casting after the subsequent administration of the test compound into the anterior segment; and 
 (6) comparing the subsequent amount of the test compound deposited to the initial amount of the test compound deposited; 
 (7) repeating steps (3)-(6) to maximize the subsequent amount of the test compound deposited in the upper segment of the three-dimensional casting. 
 
     
     
         62 . The method of  claim 61  wherein providing an initial administration of the test compound into the anterior segment comprises:
 inserting a device with a conduit into the anterior segment of the three-dimensional model; and 
 directing the test compound from the conduit into the anterior segment. 
 
     
     
         63 . The method of  claim 62  wherein altering the one or more parameters comprises altering an insertion depth of the device into the anterior segment of the three-dimensional model. 
     
     
         64 . The method of  claim 62  wherein altering the one or more parameters comprises altering an insertion angle of the device into the anterior segment of the three-dimensional model. 
     
     
         65 . The method of  claim 63  wherein the insertion angle is measured from a vertical reference line extending from a nostril of the anterior segment when viewed from the front. 
     
     
         66 . The method of  claim 63  wherein the insertion angle is measured from a vertical reference line extending from a nostril of the anterior segment when viewed from the side. 
     
     
         67 . The method of  claim 60  wherein the test compound comprises a fluorescent agent. 
     
     
         68 . The method of  claim 42  wherein computer software is utilized to determine the person-specific parameters based on the three-dimensional model of the nasal cavity. 
     
     
         69 . A pharmaceutical composition comprising:
 (A) a therapeutic agent; and   (B) a pharmaceutical excipient, wherein:
 the pharmaceutical composition is formulated for administration intranasally for delivery to the brain; and 
 the pharmaceutical composition is formulated as a solid dispersion. 
   
     
     
         70 . The pharmaceutical composition of  claim 69 , wherein the solid dispersion is amorphous. 
     
     
         71 . The pharmaceutical composition of  claim 69 , wherein the solid dispersion is in a nanocrystalline state. 
     
     
         72 . The pharmaceutical composition according to any one of  claims 69 - 71 , wherein the therapeutic agent is a chemotherapeutic compound. 
     
     
         73 . The pharmaceutical composition of  claim 72 , wherein the therapeutic agent is mebendazole. 
     
     
         74 . The pharmaceutical composition according to any one of  claims 69 - 73 , wherein the pharmaceutical excipient is a polymer. 
     
     
         75 . The pharmaceutical composition of  claim 74 , wherein the pharmaceutical excipient is a polyvinylpyrrolidone copolymer. 
     
     
         76 . The pharmaceutical composition of  claim 75 , wherein the pharmaceutical excipient is a polyvinylpyrrolidone and vinyl acetate copolymer. 
     
     
         77 . The pharmaceutical composition of  claim 76 , wherein the pharmaceutical excipient is Kollidon® VA64. 
     
     
         78 . A pharmaceutical composition comprising:
 (A) a therapeutic agent; and   (B) a pharmaceutical excipient, wherein:
 the pharmaceutical composition is formulated for administration intranasally for delivery to the brain; and 
 the pharmaceutical composition is formulated as a foam. 
   
     
     
         79 . The pharmaceutical composition of  claim 78 , wherein the pharmaceutical excipient is a composition comprising a first polymer and a second polymer 
     
     
         80 . The pharmaceutical composition of  claim 79 , wherein the first polymer is a polyether. 
     
     
         81 . The pharmaceutical composition of  claim 80 , wherein the first polymer is a triblock polyether. 
     
     
         82 . The pharmaceutical composition of  claim 81 , wherein the first polymer is a polyethylene-polypropylene-polyethylene polymer. 
     
     
         83 . The pharmaceutical composition of  claim 82 , wherein the first polymer is Poloxamer® 407. 
     
     
         84 . The pharmaceutical composition according to any one of  claims 78 - 83 , wherein the therapeutic agent is a contrast agent. 
     
     
         85 . The pharmaceutical composition of  claim 84 , wherein the therapeutic agent is perfluorooctylbromide. 
     
     
         86 . The pharmaceutical composition according to any one of  claims 78 - 85 , wherein the pharmaceutical composition comprises an imaging agent. 
     
     
         87 . The pharmaceutical composition of  claim 86 , wherein the imaging agent is fluorescein. 
     
     
         88 . The pharmaceutical composition according to any one of  claims 78 - 87 , wherein the pharmaceutical composition further comprises a basic solution. 
     
     
         89 . The pharmaceutical composition of  claim 88 , wherein the basic solution is a hydroxide solution. 
     
     
         90 . The pharmaceutical composition of  claim 89 , wherein the basic solution is a sodium hydroxide solution. 
     
     
         91 . The pharmaceutical composition according to any one of  claims 78 - 90  further comprising a propellant. 
     
     
         92 . The pharmaceutical composition of  claim 91 , wherein the propellant is a haloalkane (C≤12) . 
     
     
         93 . The pharmaceutical composition of  claim 92 , wherein the propellant is a haloalkane (C≤6) . 
     
     
         94 . The pharmaceutical composition of  claim 93 , wherein the propellant is 1,1,1,2,3,3,3-heptafluoropropane. 
     
     
         95 . A method of delivering a pharmaceutical composition to a subject, the method comprising:
 inserting an apparatus into a nasal cavity of the subject, wherein the apparatus is anatomically modeled after the nasal cavity of the subject; and   emitting the pharmaceutical composition from the apparatus into the nasal cavity of the subject.   
     
     
         96 . A method of delivering a pharmaceutical composition to a subject, the method comprising:
 inserting an apparatus according to any of  claims 1 - 41  into a nasal cavity of the subject; and   emitting the pharmaceutical composition from the apparatus into the nasal cavity of the subject.