Delivery of oral drugs

Abstract

Disclosed is a system for delivery of a drug comprising a multiple unit dosing device comprising a housing and an actuator, said device containing multiple doses of multiparticulates comprising drug particles, said device upon actuation delivering a unit dose of said multiparticulates, said drug particles having a mean diameter of greater than 10 μm to about 1 mm such that an effective dose of said drug cannot be delivered into the lower lung of a human patient. Also disclosed are novel methods, devices and dosage forms for delivering a drug.

1 . A drug delivery system for gastrointestinal deposition, comprising a multiple unit dosing device comprising a housing and an actuator, said device containing multiple doses of multiparticulates comprising drug particles, said device upon actuation delivering a unit dose of said multiparticulates, said drug particles having a mean diameter of greater than about 50 μm to about 1 mm such that an effective dose of said drug cannot be delivered into the lower lung of a human patient.  
     
     
         2 . The system of  claim 1  wherein said delivery is by administering in vivo said unit dose into the oral cavity of said patient.  
     
     
         3 . The system of  claim 1  wherein said delivery is by dispensing ex vivo said unit dose into an intermediate receptacle.  
     
     
         4 . The system of  claim 1  wherein said unit dose is in the form of a discrete unit.  
     
     
         5 . The system of  claim 1 , wherein said device administers said unit dose onto the tongue of said patient.  
     
     
         6 . (canceled)  
     
     
         7 . The system of  claim 1  wherein said multiparticulates further comprise a pharmaceutically acceptable excipient.  
     
     
         8 . The system of  claim 7  wherein said excipient is coated with said drug.  
     
     
         9 . The system of  claim 7  wherein said drug is coated with said excipient.  
     
     
         10 . The system of  claim 7  wherein said excipient comprises a taste masking agent.  
     
     
         11 . The system of  claim 7  wherein said excipient comprises a sweetening agent, flavoring agent or combination thereof.  
     
     
         12 . The system of  claim 7  wherein said excipient comprises a salivary stimulant, an effervescent agent or a combination thereof.  
     
     
         13 . The system of  claim 7  wherein said excipient comprises a controlled release material.  
     
     
         14 . The system of  claim 13  wherein said excipient is less than about 20% by weight of said multiparticulates.  
     
     
         15 . The system of  claim 1  wherein said multiple doses are contained in a reservoir.  
     
     
         16 . The system of  claim 15  further comprising a metering component to meter a unit dose of said drug from said reservoir upon actuation of said system.  
     
     
         17 - 23 . (canceled)  
     
     
         24 . The system of  claim 1  wherein said device comprises a mouthpiece.  
     
     
         25 . The system of  claim 24  wherein said mouthpiece is of sufficient length to minimize moisture exposure of the multiparticulates from outside the device.  
     
     
         26 . The system of  claim 24  wherein said device further comprises a mouthpiece cap to minimize moisture exposure of the multiparticulates from outside the device.  
     
     
         27 . The system of  claim 1  further comprising a desiccant to minimize moisture exposure of the multiparticulates from outside the device.  
     
     
         28 . The system of  claim 1  wherein said doses are individually metered prior to said actuation.  
     
     
         29 . The system of  claim 28  further comprising blisters on a substrate base, each blister containing said individually metered unit dose, said blisters covered by a seal.  
     
     
         30 . The system of  claim 29  wherein said blisters are aligned linearly in the form of a strip.  
     
     
         31 . The system of  claim 30  wherein said strip is in the form of a roll.  
     
     
         32 . A device for delivery of a drug, for gastrointestinal deposition, comprising a housing and an actuator, said device capable of containing multiple doses of multiparticulates comprising drug particles, said device upon actuation capable of delivering a unit dose of said multiparticulates wherein said drug particles have a mean diameter of greater than about 50 μm to about 1 mm such that an effective dose of said drug cannot be delivered into the lower lung of a human patient.  
     
     
         33 . The device of  claim 32  wherein said delivery is by administering in vivo said unit dose into the oral cavity of said patient.  
     
     
         34 . The device of  claim 32  wherein said delivery is by dispensing ex vivo said unit dose into an intermediate receptacle.  
     
     
         35 . The device of  claim 32  wherein said unit dose is in the form of a discrete unit.  
     
     
         36 . The device of  claim 32  wherein said device administers said unit dose onto the tongue of said patient.  
     
     
         37 - 48 . (canceled)  
     
     
         49 . A method for delivery of a drug for gastrointestinal deposition, comprising delivering multiparticulates comprising drug particles via the use of a multiple unit dosing device comprising a housing and an actuator, said device upon actuation delivering a unit dose of said multiparticulates, and thereafter re-using said device to deliver additional unit doses of said drug at appropriate dosing intervals, said drug particles having a mean particle size of greater than about 50 μm to about 1 mm such that an effective dose of said drug cannot be delivered into the lower lung of a human patient.  
     
     
         50 . The method of  claim 49  wherein said delivery is by administering in vivo said unit dose into the oral cavity of a patient.  
     
     
         51 . (canceled)  
     
     
         52 . The method of  claim 49  wherein said unit dose is in the form of a discrete unit.  
     
     
         53 . The method of  claim 49  wherein said device administers said unit dose onto the tongue of said patient.  
     
     
         54 . (canceled)  
     
     
         55 . A drug delivery device for administering a drug in multiparticulate form into the oral cavity of a patient for gastrointestinal deposition, said device including a mouthpiece having an outlet for delivering said multiparticulates and an inlet for receiving said multiparticulates, wherein the mouthpiece protrudes downward from the drug delivery device at an angle greater than about 15 degrees measured from a horizontal baseline when the drug device is in an upright position, in order to direct the multiparticulates onto the tongue of said patient, said drug particles having a mean diameter of greater than 10 μm to about 1 mm.  
     
     
         56 . The mouthpiece of  claim 55  wherein the outlet of the mouthpiece faces downward to administer said multiparticulates onto the tongue of said patient.  
     
     
         57 . The mouthpiece of  claim 55  wherein the mouthpiece is conical in shape and has an outlet having a larger diameter than an inlet wherein the multiparticulates enter said mouthpiece.  
     
     
         58 . The mouthpiece of  claim 57  wherein the diameter of the outlet is 25% greater than the diameter of the inlet.  
     
     
         59 . The mouthpiece of  claim 57  wherein the diameter of the outlet is 50% greater than the diameter of the inlet.  
     
     
         60 . The mouthpiece of  claim 57  wherein the diameter of the outlet is 100% greater than diameter of the inlet.  
     
     
         61 . The mouthpiece of  claim 55  wherein the mouthpiece is rectangular in shape, having side walls which extend outward from an inlet at opposite angles, to provide an outlet having a larger area than the inlet area where the multiparticulates enter said mouthpiece.  
     
     
         62 . The mouthpiece of  claim 61  wherein the outlet area is 25% greater than the inlet area.  
     
     
         63 . The mouthpiece of  claim 61  wherein the outlet area is 50% greater than the inlet area.  
     
     
         64 . The mouthpiece of  claim 61  wherein the outlet area is 100% greater than the inlet area.  
     
     
         65 . The mouthpiece of  claim 61  having top and bottom walls which are convex on their outer edges.  
     
     
         66 - 68 . (canceled)  
     
     
         69 . A device for delivering multiple unit doses of a drug in multiparticulate form, for gastrointestinal deposition, comprising 
 a housing for containing multiple unit doses of multiparticulates comprising drug particles, said housing having an opening for delivering a unit dose of said multiparticulates; said drug particles having a mean diameter of greater than 10 μm to about 1 mm;    a metering component operable between a first position in which it receives a unit dose from said housing and a second position in which it delivers said unit dose to said opening in said housing; said unit dose being delivered from said metering component to the exterior of the device through said opening of said housing with an air flow of less than about 20 litres/min.    
     
     
         70 . The device of  claim 69  wherein said device does not include a propellant to facilitate the delivery of the unit dose.  
     
     
         71 . The device of  claim 69  wherein said unit dose is delivered through said opening substantially by gravitational force.  
     
     
         72 - 84 . (canceled)  
     
     
         85 . A device for delivering multiple unit doses of a drug in multiparticulate form for gastrointestinal deposition, comprising 
 a housing to contain multiple unit doses of a drug in multiparticulate form comprising drug particles; said drug particles having a mean diameter of greater than about 50 μm to about 1 mm, said housing having a mouthpiece for delivering a unit dose of said multiparticulates into the oral cavity of a patient;    means for removing a unit dose of said multiparticulates from said housing and transporting said unit dose to said mouthpiece, said mouthpiece having a drug receiving end connected to said means and a drug delivery end through which said unit dose is delivered outside the device, said mouthpiece being positioned on said device such that drug expelled through said mouthpiece can be deposited in the oral cavity of a patient substantially without deposition of said particulates into the lungs of said patient.    
     
     
         86 . A device for delivering multiple unit doses of a drug in multiparticulate form for gastrointestinal deposition, comprising 
 a housing to contain multiple unit doses of a drug in multiparticulate form comprising drug particles; said housing having a mouthpiece for delivering a unit dose of said multiparticulates into the oral cavity of a patient;    a meterer for removing a unit dose of said multiparticulates from said housing and transporting said unit dose to said mouthpiece, said mouthpiece having a drug receiving end connected to said metering device and a drug delivery end through which said unit dose is delivered outside the device, said drug particles having a mean diameter of greater than about 50 μm to about 1 mm, said mouthpiece being positioned on said device such that drug expelled through said mouthpiece can be deposited in the oral cavity of a patient substantially without deposition of said particulates into the lungs of said patient.    
     
     
         87 - 91 . (canceled)  
     
     
         92 . The system of  claim 1 , wherein said device comprises two reservoirs, wherein one reservoir contains said medicament and the other reservoir contains a liquid.  
     
     
         93 . The system of  claim 92 , wherein said device comprises two reservoirs, wherein one reservoir contains said medicament and the other reservoir contains a liquid.  
     
     
         94 . The system of  claim 92  wherein each reservoir has a dispensing hole and a retaining strip, the retaining strip covering the dispensing hole and sealing said the reservoir when the retaining strip is in a first position, the dispensing hole being uncovered when the retaining strip is in a second position.  
     
     
         95 . The system of  claim 92  wherein the reservoir is disposable.  
     
     
         96 . The system of  claim 92  wherein the reservoirs are permanently affixed to one another.  
     
     
         97 . The system of  claim 1 , wherein said device comprises two reservoirs, each reservoir containing said medicament.  
     
     
         98 . The system of  claim 1 , wherein said device comprises two reservoirs, wherein one reservoir contains said medicament and the other reservoir contains a different medicament.  
     
     
         99 . The system of  claim 97  wherein each reservoir has a dispensing hole and a retaining strip, the retaining strip covering the dispensing hole and sealing said the reservoir when the retaining strip is in a first position, the dispensing hole being uncovered when the retaining strip is in a second position.  
     
     
         100 . The system of  claim 97  wherein each reservoir is disposable.  
     
     
         101 . The system of  claim 97  wherein the reservoirs are permanently affixed to one another.  
     
     
         102 . The system of  claim 1 , wherein said device further comprises: a disk, the disk having a plurality of cavities arranged about on the periphery of the disk; the disk rotating about a central axis to position the cavities in alignment with a piercing member; and the piercing member for penetrating each of the cavities to expel a unit dose of said multiparticulates from the cavity.  
     
     
         103 . The system of  claim 102  wherein the multiparticulates from the cavity are dispensed into a delivery conduit affixed to the piercing member.  
     
     
         104 . The system of  claim 102  wherein the delivery conduit is coupled to a mouthpiece, the mouthpiece for dispensing the unit dose into the oral cavity of the patient.  
     
     
         105 . The system of  claim 103 , wherein the delivery conduit comprises a hollow tube.  
     
     
         106 . The system of  claim 104 , wherein the delivery conduit comprises a hollow tube.  
     
     
         107 . The system of  claim 102  wherein the device is disposable.  
     
     
         108 . The system of  claim 102  wherein the disk is replaceable.  
     
     
         109 . The system of  claim 1 , wherein said device further comprises: a disk, the disk having a plurality of blisters arranged about on the periphery of the disk, each blister comprising a premetered dose of the medicament; the disk rotating about a central axis to position each blister in alignment with a piercing member; and the piercing member for penetrating each aligned blister to expel the premetered dose from the aligned blister.  
     
     
         110 . The system of  claim 109  wherein the premetered dose from the blister is dispensed into a delivery conduit affixed to the piercing member.  
     
     
         111 . The system of  claim 110  wherein the delivery conduit is coupled to a mouthpiece, the mouthpiece for dispensing the unit dose into the oral cavity of the patient.  
     
     
         112 . The system of  claim 110 , wherein the delivery conduit comprises a hollow tube.  
     
     
         113 . The system of  claim 111 , wherein the delivery conduit comprises a hollow tube.  
     
     
         114 . The system of  claim 1 , wherein the medicament is stored in a plurality of containers, each container sealed via a removable seal.  
     
     
         115 . The system of  claim 92  wherein the medicament and the liquid are alternatively mixed within the device prior to administration.  
     
     
         116 . The system of  claim 92  wherein said device comprises two reservoirs, wherein one reservoir contains said medicament and the other reservoir contains a liquid, and wherein the medicament and the liquid are mixed in an intermediate receptacle.  
     
     
         117 . The system of  claim 97 , wherein said device comprises two reservoirs, each of the reservoirs containing a different dose of said medicaments.