Among the varied forms of pharmaceutical delivery, the inhalation of dry powder is preferable for some forms of pharmaceuticals. Inhalation does not require passing the pharmaceutical through the digestive system (as required by ingestion), and avoids the sometimes difficult and distasteful alternative of patients injecting themselves. For example, inhalation is often preferred for pharmaceuticals used to treat respiratory diseases.
During inhalation, a user receives a dose of a pharmaceutical in an inhaled airstream. The pharmaceutical optimally travels into the lungs where it is absorbed. Efficient delivery of powdered pharmaceuticals is dependent on the dispensing technique and particle size of the powder. Optimally, the particles should be 5 microns or less in size.
The use of a dry powder pharmaceutical for inhalation offers numerous advantages over aqueous or aerosol pharmaceuticals. Nebulizers, used for delivery of aqueous pharmaceuticals, are generally large and cumbersome devices that are complex to operate. The dosage precision provided by a nebulizer may vary depending on a variety of factors, e.g., atmospheric temperature and humidity, and the volume and strength of the patient's breathing. Furthermore, aqueous solutions do not generally provide an inert vehicle for the pharmaceutical, and thus drug stability is also an issue.
Metered Dose Inhalers (MDIs), used for delivering aerosolized pharmaceuticals, frequently work with chlorofluorocarbon propellants, which are in disfavor due to environmental concerns. Other media have not yet proven commercially viable. Furthermore, MDIs are sensitive to particle size, and frequently require additional dispersing agents to achieve proper drug dispersal. MDIs generally spray the particles into the mouth, and thus the administered dose frequently suffers from the particles, particularly larger ones, striking the back of the throat and not reaching the lungs. This problem is accentuated by the need for the patient to coordinate actuation and breathing.
While it offers advantages over other types of pharmaceutical delivery, the technology for inhaling dry powder presently suffers an array of difficulties limiting its usefulness to patients. Prior to delivery, powdered pharmaceuticals may deteriorate or form excessively dense agglomerations due to exposure to moisture. Some measures to protect the pharmaceutical, such as storage in capsules that must be broken to release the powder, require cumbersome procedures in preparing the inhaler for use. Even when kept dry, the powdered pharmaceuticals may tend to form an agglomerate that must be broken into finer particles for delivery.
There are also numerous problems related to the actual delivery of dry powder pharmaceuticals. Many devices rely on inhalation by the patient to provide the power to break up the dry material into free-flowing powder. These devices prove ineffective for those lacking the capacity to strongly inhale, such as young patients, old patients, or patients with asthma. Other devices spray the pharmaceutical into the mouth, requiring breathing to be coordinated with the spray. During delivery, large quantities of particles may become deposited on the delivery mechanism, reducing the "uptake efficiency" of the device. On passage into the mouth, the walls of the mouth and/or throat may absorb particles, causing a further loss in uptake efficiency. This problem is particularly dramatic when the pharmaceutical is sprayed into the mouth, rather than being gently inhaled. Numerous dry powder inhalers use gravity-sensitive reservoirs of dry powder, requiring the inhaler to be held at a proper angle relative to gravity for the powder to be effectively delivered. Additionally, many delivery mechanisms are large and/or expensive, problems which may be magnified when a patient requires several types of medication, each requiring the cost and inconvenience of a separate inhaler.
One apparatus for producing an aerosolized dose of a pharmaceutical for subsequent inhalation by a patient is disclosed in PCT International Publication No. WO93/00951 (published Jan. 21, 1993), by Inhale, Inc., incorporated herein by reference. The disclosed apparatus includes a trigger, controlling the release of gas from a gas cylinder, where the gas passes through a venturi that draws the dry powder from a reservoir. The gas passes to a chamber with a mouthpiece, from where a patient may breathe in the pharmaceutical. The chamber may be cylindrical, and include a one-way air inlet. The apparatus may be small enough to be hand-held.
The apparatus shown in the Inhale, Inc. application provides for storage and provision of a pharmaceutical from a reservoir, drawing the pharmaceutical out of the reservoir into a flowing air stream. As in any filled reservoir system, the powder may be exposed to contaminants or humidity prior to delivery. Thus, there is a risk of decomposition and excessive agglomeration. Even when dry, the powder might agglomerate, stick to the delivery mechanism or chamber, or not be fully delivered because the gravity-sensitive reservoir is not in a fully upright orientation. In use, the inhaler requires pumping a lever several times to bring the unit up to pressure. This can prove difficult when a patient is suffering from the onset of breathing difficulties. Furthermore, the inhaler cannot be interchangeably used with more than one type of pharmaceutical, and thus the inconvenience and cost are magnified if a patient requires multiple types of pharmaceuticals.
PCT International Publication No. WO94/08552 (published Apr. 28, 1994), by Dura Pharmaceuticals, Inc., shows an inhaler with a pharmaceutical stored in a multi-dosage medicine containing cartridge held between two plates. A plunger is used to thrust powder out of the cartridge and into a stream of air agitated by a motorized impeller. As with the Inhale, Inc. application described above, this device is plagued with the orientation limitations of a gravity-sensitive reservoir-based inhaler. Exposure to contaminants and moisture may cause decomposition of the pharmaceutical. The use of the plunger may compress the pharmaceutical into a more tightly packed agglomerate. Pulverization of this agglomerate is still limited by the patient's ability to inhale. Furthermore, the inhaler may not be used with multiple medications without risk of further exposing the pharmaceutical to decomposition. Finally, the pharmaceutical might deposit on the complex plunging and agitating mechanisms, limiting the uptake efficiency of the device.
U.S. Pat. No. 5,349,947 to Newhouse et al., discloses an inhaler with individual doses of a pharmaceutical stored in blisters. A blister is crushed between a piston and a cylinder, explosively releasing the air and pharmaceutical contained therein. The air and pharmaceutical are propelled into a chamber from which they may be inhaled. The device taught by Newhouse can leave substantial deposits of powder in the blister and/or chamber, reducing the uptake efficiency of the device.
U.S. Pat. No. 5,388,572 to Mulhouser et al., discloses a dry powder inhaler having a pharmaceutical impregnated in a mesh disk. Inhalation triggers the delivery of pharmaceutical, the suction activating a burst of manually pumped up air through the mesh disk. This inhaler potentially allows contamination of the pharmaceutical (from exposure to moisture and contaminants), lowers the uptake efficiency (by shooting powder into the mouth at high speed), and does not provide easy switching of pharmaceutical containers for multiple types of pharmaceuticals.
Accordingly, there exists a definite need for a dry powder pharmaceutical delivery device that can interchangeably provide different powdered pharmaceuticals, which have been safely stored to maintain stability until dispensing, without excessive loss of uptake efficiency due to deposition within the mechanism or to excessive absorption within the mouth or throat. There is a further need for such a device to be conveniently portable without being overly expensive. The present invention satisfies these and other needs, and provides further related advantages.
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USPTO Backgrounds