Title of Invention

A METHOD AND APPARATUS FOR TRANSPORTING A FINE POWDER

Abstract The invention provides methods, systems and apparatus for the metered transport of fine powders into receptacles. According to one exemplary embodiment, an apparatus is provided which comprises a hopper having an opening. The hopper is adapted to receive a bed of fine powder. At least one chamber, which is moveable to allow the chamber to be placed in close proximity to the opening, is also provided. An element having a proximal end and a distal end is positioned within the hopper such that the distal end is near the opening. A vibrator motor is provided to vibrate the element when within the fine powder.
Full Text

POWDER FILLING APPARATUS AND METHODS
CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation-in-part application of and claims the benefit of U.S. Provisional
Patent Application Serial No. , which was
converted from U.S. Patent Application Serial No. 08/949,047, filed October 10, 1997, the complete disclosures of which are here.! n incorporated by reference .
BACKGROUND OF THE INVENTION
1 . Field of the Invention
The present invention relates generally to the field of fine powder processing, and particularly to the metered transport of fine powders. More particularly, the present invention relates to systems, apparatus and methods for fill i.ng receptacles wi th unit dosages of non- f lowable but di spersible fine powdered medi caments, particularly for siibsequent inhalation by a patient.
Effecti ve delivery to a patient is a critical aspect of any snccessful drug therapy. Various routes of del ivery exist, and each has its ov/n advantages and disadvantages. Oral drug delivery of tablets, capsules, elixirs, and the like, is perhaps the most convenient method, but many drugs have di sagreeable flavors, and the size of the tablets makes them d i F f icult to swallow . Moreover, such medicaments are ogten degraded in the di gest i ve tract before they can be alisorbed. Such degradat i on i s a particular problem with modern protein drugs which are rapidly degraded by proteolytic enzymes i n the digestive tract. Subcutaneous injection is frequently an effective route for systemic drug delivery, inc1udinq the delivery very of prnt e i ns , but has a low pat lent acceptance and produces sliaip waste items, e,.g. needles, which
are difficult to dispose Sine the need too inject drugs on a froquent schedule such as instil in one or more times a day, can

be a source of poor patient compliance, a variety of alternative routes of administration have been developed, including transdermal, intranasal, intrarectal, intravaginal, and pulmonary delivery.
Of particular interest to the present invention are pulmonary drug delivery procedures which rely on inhalation of a drug dispersion or aerosol by the patient so that the active drug within the dispersion can reach the distal (alveolar) regions of the lung. It has been found that certain drugs are readily absorbed through the alveolar region directly into blood circulation. Pulmonary delivery is particularly promisi ng for the delivery of proteins and polypeptides which are difficult to deliver by other routes of administration. Such pulmonary delivery can be effective both for systemic delivery and for localized delivery to treat diseases of the lungs.
Pulmonary drug delivery (including both systemic and local) can itself be achieved by different approaches, includinq liquid nebulizers, metered dose inhalers (MDI's) and dry powder dispersion devices. Dry powder dispersion devices are part icularly promisinq for delivering protein and polypeptide drugs which may be readily formulated as dry powders . Many otherwise 1 ahi 1 e proteins and polypeptides may be stably stored as lyophilized or spray-dried powders by themselves or in combi nat: i on with suitable powder carriers . A further advantage is that dry powders have a much higher concentration than medicaments in 1iquid form.
The abi1ity to deliver proteins and polypeptides as dry [)nwders, however, is problematic in certain respects. The donage of many protein and polypeptide drugs is often cri.tica] so it is necessary that any dry powder delivery system be able to arr:urately, precise! y and repeat ably deliver the intended amount of drug. Moreover, many proteins and polypeptides are quite expensice, typical1y being many t imes more costly than conventional drugs on a per dose basis. Thus, the ability to efficiently deliver the dry powders to the target region of the lung with a minimal loss of drug is critical .


Of particular interest to the present invention are the physical characteristics of poorly flowing powders. Poorly flowing powders are those powders having physical characteristics, such as flowability, which are dominated by cohesive forces between the individual units or particles (hereinafter "individual particles") which constitute the powder. In such cases, the powder does not flow well becavise the individual particles cannot easily move independently with respect to each other, hut instead move as clumps of many particles. When such powders are subjected to low forces, the powders will tend not to flow at all. However, as the forces actinq upon the powder are increased to exceed the forces of cohesion, the powder wi11 move i.n large agglomerated "chunks" of the individual particles When the powder comes to rest, the large agglomerateons remain, resulting in a non-uniform


For example, when metering the fine powders prior to placement in the unit dose receptacle, the powders often agglomerates inconsistently, creating voids and excessive density variation, thereby reducing the accuracy of the volumetric metering processes which are commonly used to meter in high throughput production. Such inconsistent agglomeration is further undesirable in that the powder agglomerates need to be broken down to the individual particles, i.e. made to be dispersible, for pulmonary delivery. Such de-agglomeration often occurs in dispersion devices by shear forces created by the air stream used to extract the medicament from the unit dose receptacle or other containment, or by other mechanical energy transfer mechanisms (e.g. , ultrasonic, fan/impeller, and the like) . Hov/ever, if the small powder agglomerates are too compacted, the shear forces provided by the air st:ream or other dispersing mechanisms will be insufficient to effectively disperse the medicament to the individual particles.
Some at tempt: s to prevent agglomeration of the individual particles are to create blends of multi-phase powders (typically a carrier or diluent) where larger particles (sometimes of multiple size ranges) , e.g. approxi mately 50 µm, are combi ned with smaller drug part icles, e. g. 1 /nn to 5 µm. In this case, the smaller particles attach to the larger particles so that under processing and filling the powder wil] have the characteristics of a 50 /im powder.

Such a powder is able to more easily flow and meter. One disadvantage of svich a powder, however, is that removal of the smaller particles from the larger particles is difficult, and the resulting powder formulation is made up largely of the bulky flowing agent component which can end up in the device, or the patient's throat.
Current methods for filling unit dose receptacles with powdered medicaments include a direct pouring method where a granular powder is directly poured via gravity (sometimes in combination with stirring or "bulk" agitation) i nto a metering chamber. When the chamber is filled to the desired level, the medicament is then expelled from the chamber and into the receptacle. In such a direct pouring process, variations in density can occur in the metering chamber, thereby reducing the effectiveness of the metering chamber in accurately measuring a unit dose amount of the medicament. Moreover, the powder is in a granular state which can be undesirable for many applications.
Some attempts have been made to minimize density variations by compacting the powder within, or prior to depositing it in the metering chamber. However, such compaction is undesirable, especially for powders made up of only fine particles, in that it decreases the dispersibility of the powder, i.e. reduces the chance for the compacted powder to be broken down to the i ndividual particles during pulmonary delivery with a dispersion device.
It would therefore be desirable to provide systems and methods for the processing of fine powders whi ch would overcome or greatly reduce these and other problems. Such systems and methods should allow for accurate and precise metering of the fine powder when divided into unit doses for p]acement in unit dose receptacles, particularly for low mass fills. The systems and methods should further ensure that the fine powder remains suf ficiently dispersible during processing so that the fine powder may be used with existing inhalation devices which requi re the powder to be broken down to the indiVidual part i cles before pulmonary delivery. Further, the systems and methods should provide for the rapid processing of

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the fine powders so that large numbers of unit dose receptacles can rapidly be filled with unit dosages of fine powder medicaments in order to reduce cost,
2. Description of the Background Art
U.S. Patent No. 5,765,607 describes a machine to meter products into containers and includes a metering unit to supply the product into containers.
U.S. Patent No. 4,640,322 describes a machine which applies sub-atmospheric pressure through a filter to pull material directly from a hopper and laterally into a non-rotatable chamber.
U.S. Patent 4,509,560 describes a granular material processing apparatus employing a rotating paddle to stir the granular material.
U.S. Patent No. 2,540,059 describes a powder filling apparatus having a rotating wire loop stirrer for stirring powder in a hopper before directly pouring the powder into a metering chamber by gravity.
German patent DE 3607187 describes a mechanism for the metered transport of fine particles.
Product brochure, "E-13 00 Powder Filler" describes a powder filler available from Perry Industries, Corona, CA.
U.S. Patent No. 3,874,431 describes a machine for filling capsules with powder. The machine employs coring tubes that are held on a rotatable turret.
British Patent No. 1,420,364 describes a membrane assembly for use in a metering cavity employed to measure quant ities of dry powders.
British Patent No. 1,309,424 describes a powder filling apparatus having a measuring chamber with a piston head used to create a negative pressure in the chamber.
Canadian Patent No. 94 9,786 describes a powder filling machine having measuring chambers that are dipped into t-he powder. A vacuum is then employed to fill the chamber with power.

SUMMARY OF TFIE INVENTION The invention provides systems, apparatus and methods for the metered transport of fine powders into unit dose receptacles. In one exemplary method, such fine powders are transported by first agitating the fine powders with a vibrating element, and then capturing at least a portion of the fine powder. The captured fine powder is then transferred to a receptacle, with the transferred powder being sufficiently uncompacted so that it can be substantially dispersed upon removal from the receptacle. Usually, the fine powder v;ill comprise a medicament with the individual particles having a mean size that is less than about 100 /im, usually less than about 10 µm, and more usually in the range from about 1 µm to 5 µm.
The fine powder will preferably be placed into a hopper having an opening at a bottom end. The element is vibrated to agitate the fine powder. Vibration of the powder in the vicinity of the opening assists in the transfer of a portion of the fine powder through the opening where it may be captured into a chamber. Vibration of the element also assists in de-agglomerating powder within the metering chamber so that the metering chamber may more uniformly be filled.
The vibratable element is preferably vibrated in an up and down, i.e. vertical, motion relative to the powder in the hopper. In one aspect, an ultrasonic horn is employed to vertically vibrate the element. Alternatively, the element may comprise a rod that is vibrated back and forth, i.e. laterally, within the powder. In another alternative, the vibratable element is vibrated in an orbital manner. In one aspect, the rod is operably attached to a piezoelectric motor whi ch vi brates the rod. Preferably, the element is vertically vibrated at a frequency in the range from about 1, 000 Hz to about 180,000 Hz, and more preferably from about 10,000 Hz to about 40,000 Hz, and most preferably from about 15,000 Hz to about 25,000 Hz. The rod i s preferably vibrated laterally at a frequency in the range from about 50 Hz to about 50,000 Hz, and more preferably in the range from about 5 0 Hz to about

V
5,000 Hz, and most preferably in the range from about BO Hz to about 1. , 000 Hz .
In another aspect, the element has a distal end which is placed near the opening. Further, the distal end has an end member which is vi brated over the chamber to assist in transfer of the fine powder from the hopper to the chamber. The end member preferably projects laterally outward from the element. In one aspect, the end member comprises a cylinder when the element is vibrated vertically. In another aspect, the end member comprises a cross-member when the rod is 1ateral]y vibrated. Preferably, the end-member is vertically spaced apart from the chamber by a distance in the range from about 0.01 mm to about 10 mm, and more preferably from about 0.5 mm to about 3.0 mm. Such a distance assists in keeping the powder uncompacted when transferred to the chamber.
In sti]1 another aspect, the element is preferably moved across the opening while being vibrated. For instance, the element may be translated along the opening at a rate that is preferably less than about 100 cm/s. However, the part icular rate of translation will typically depend on the vibrational frequency of the element. In this way, the element is swept across the chamber while being vibrated.
Movement of the element along the opening is particularly preferable when multiple chambers are aligned with the opening. In this way, the element may be employed to assist in the transfer of fine powder from the hopper into each of the chambers. Optionally, a plurality of elements or rods may be vibrated within the hopper in the vicinity of the openings. Preferably, the rods will be aligned with each other and will be translated along the opening while being vibrated, although in some cases the rods or elements may remain stationary over each chamber.
To assist in the capture of the fine powder in the chamber, air is preferably drawn through the chamber bottom to draw the fine powder into the chamber. Following capture of the fi ne powder, the powder is preferably transferred to a receptacle. Transferring of the fine powder is preferably

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g
In still another aspect, the powder captured by the chamber is adjusted to be a unit dose amount. This may be accomplished by placing a thin plate (or doctor sheet) between the hopper and the chamber. The plate has an aperture to a]low for the transfer of the powder from the hopper and into the chamber. The chamber is then moved relative to the plate, with the plate scraping any excess powder from the chamber. Alternatively, a doctor blade may be employed to scrape any excess powder from the chamber as the chamber is rotated.
In one particvilar aspect, the powder is transferred to the hopper from a secondary hopper. Preferably, the secondary hopper is vibrated to transfer the powder onto a chute where it passes into the primary hopper. In still yet another aspect, the chamber is periodically removed and replaced with a chamber of a different size to adjust the volume of the chamber. In this way, different unit dosages may be produced by the invention.
The invention further provides an exemplary apparat us for transporting a fi ne powder. The apparatus comprines a hopper for ho]ding the fine powder. The apparatus further includes at least one chamber which is moveable to allow the chamber to be placed in close proximity to an openinq in the hopper. A vibratable element is also provided having a proximal end and a distal end, with the element being placed within the hopper such that the distal end is near the openinq. A vibrator is provided to vibrate the element when within the fine powder. In this way, the element may be

Vibrated to agitate the fine powder to assist in its transfer from the hopper to the chamber. Preferably, the vibrator comprises an ultrasonic horn which vibrates the element in an np and down or vertical motion. Alternatively, a piezoelectric motor may be employed to laterally vibrate the element.
In one exemplary aspect, the apparatus further includes a mechanism for translat ing the vibratable element or rod over the chamber as the element is vibrated. Such a mechanism is particularly advantageous when a plurality of chambers are provided in a rotatable member which is rotated to align the chambers with the opening. The translating mechanism may then be employed to translate the element over the rotatable member so that the vibrating element passes over each chamber to assist in the filling of each with powder. The translating mechanism preferably comprises a linear drive mechanism which translates the rod along the opening at a rate that is less than about 100 cm/s.
In another aspect, the vibrator is configured to vibrate the element in an up and down motion at a frequency in the range from about 1,000 Hz to about 180,000 Hz, and more preferably in the range from about 10,000 Hz to about 40,000 Hz, and most preferably in the range from about 15,000 Hz to about 2S,000 Hz. When vibrated up and down, the vibratable element: preferably comprises a cylindrical shaft having a diameter in the range from about 1.0 mm to about 10 mm. When vibrated laterally, the element preferably comprises a rod or wi re having a diameter in the range from about 0.01 inch to about 0.04 inch.
An end-member is preferably operably attached to the distal 1 end of the vi bra table element to assist in agitation of the f i ne powder. The end-member is preferably vertically spaced apart from the chamber by a distance in the range from about: 0.01 mm to about 10 mm, and more preferably from about 0.5 nun to about 3.0 mm. In one alternative, the apparatus is Provided wi th a pi ural ity of vi.bratable elements so that multiple elements may be vibrated within the fine powder.

I
Tn still another aspect, the chamber is disposed w i tin n a rotatable member which is placed in a first position havinq the chamber aligned with the opening in the hopper, and a second position having the chamber aligned with a receptacle. In this way, the chamber may be filled with powder when in the first position. The rotatable member is then rotated to the second position to allow the powder to be expelled from the chamber and into the receptacle. The chamber preferably includes a port which is in communication with a vacuum source to assist in drawing the fine powder from the hopper and into the chamber. A filter is preferably disposed across the port to assist in capturing the powder. A source of compressed gas is preferably also in communication with the port to eject the captured powder from the chamber and' into the receptacle. A controller may be provided for controlling actuation of the gas source, the vacuum source and operation of the vibrator.
The apparatus may also include a mechanism for adjusting the amount of captured powder in the chamber due to the chamber volume. In this way, the captured amount will be a unit dose amount. Such an adjustment mechanism may comprise an edge for removing fine powder extending above the chamber. In one embodiment, the adjustment mechanism comprises a thin plate having an aperture which may be aligned with the chamber during filling. As the rotatable member is rotated, the edge of the aperture scrapes the excess powder from the chamber.
In one part icular aspect, the vibratable element i ncludes a proj ecting member which is spaced above the distal end. The projecting member serves as a leveller to level powder within the hopper as the vibratable element is trans1ated a 1ong t he hoppe r .
In another aspect, a secondary hopper is provided to store the powder until de]ivered to the primary hopper. A shaki nq mechanism is provided to vibrate the secondary hopper when powder is to be transferred to the primary hopper. Preferably, the powder passes down a chute so that the powder may be transferred without interfering with the translation of the vi bratable member along the primary hopper,

In still another aspect, the chamber is formed in a change tool. In this way, the size of the chamber may be varied simply by attaching a change tool with a different sized chamber to the rotatable member.
The invention further provides an exemplary system for transporting fine powders. The system comprises a plvrrality of rotatable members which each include a row of chambers. A hopper is disposed above each rotatable member and has an opening to allow powder to be transferred to the chambers. A vibratable element is disposed in each hopper, and vibrators are provided to vibrate the elements in an up and down motion. A translation mechanism is further provided to translate the vibratable members along the hoppers to assist in transferring the powder from the hoppers and into the chambers. Conveniently, a controller may be provided to control operation of the rotatable members, the vibrators, and the translation mechanism.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a cross-sectional side view of an exemplary apparatus for transporting fine powders according to the invention.
Fig. 2 is an end view of the apparatus of Fig. 1.
Fig. 3 is a more detailed view of a chamber of the apparatus of Fig. 1 showing a vibrating rod being translated over the chamber according to the invention.
Fig. 4 is a left front perspective view of an exemple ary system for transporting powder according to the i nvent i on.
Fig. 5 is a right front perspective view of the system of Fig. 4.
Fig. 6 is a cross-sect ional view of the system of Fiq. 4.
Fig. 7 is a schematic view of an alternative apparatus for transport i ng f i ne powders according to the i nvent i on.

Fig. 8 is a srhematic view of still another
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a 1 tor nat i ve apparatus for transporting fine powders according to t:he i nvent ion .
Fig. 9 is a schematic view of still another a]tornat ive apparatus for t ransporting fine powders according to the i nvention.
Fig. 10 i s a perspect ive view of a further embodiment of an apparatus for transporting fine powders accord ing to the invention.
Fig. 11 is a cross - sect ional view of the apparatus ;, of Fic|. 10 taken along lines 11-11.
Fig. 12 is a cross - sectional view of the apparatus of Fig. 10 taken along lines 12 12.
Fig. 13 is an exploded view of a rotatable member of the apparatus of Fig. 10.
Fig. 14A is a schematic view of a scraping mechanism for scrraping excess powder from a chamber of a rotatable member.
Fig. 14B is an end view of the scraping mechanism of Fi g. 14A as mounted above the rotatable member.
Fig. 14C is a perspective view of an alternative mechanism for scraping excess powder from a chamber of a rotatable member according to the invention.
Fig. 15 is a perspective view of a particularly preferable system for transporting powders according to the invention.
DETAILED DESCRIPTION OF THE SPECIFIC EMBODIMENTS The invention provides methods, systems, and apparatus for the metered transport of fine powders into receptacles. The f i ne powders are very fine, usually having a mean s i ze in the range that is less than about 2 0 µm, usually less than about 10 µm, and more usually from about 1 µm to 5 µm, although the invention may in some cases be useful with 1arger part icles, e.g up to about 5 0 µm or more . The fine powrler may be composed of a variety of const i tuents and wi11 preferably y comprise a medicament such as proteins , nucleic aoids, carbohydrates , buffer salts , peptides , other small


amount do]ivered to the receptacle is sufficiently dispersible to bo useful when used with existing inhalation devices. The fine powders prepared by the invention will be especially useful with, although not 1imited to, "low energy" inhalation devices which rely on manual operation or solely upon inhalation to disperse the powder. With such inhalation devices, the powder will preferably be at least 20% (by weight) dispersible or extractable into a flowing air stream, more preferably be at least 60% dispersible, and most preferably at least 90% dispersible as defined in U.S. Patent Mo. 5,785,049, previously incorporated by reference. Since



Agitat: i on of the fine powders is preferably accomplished by vibrating a vibratable member within the fine powder in the vicinity just above the capture chamber. Preferably, the element is vibrated in an up and down, i.e., vertical, motion. Alternatively, the element may be laterally vibrated. A variety of mechanisms may be employed to vibrate the elements including an ultrasonic horn, a piezoelectric bending motor, a motor rotating a cam or a crank shaft, an


hoped12 is a rotatable member 22 havi nq a plurality of chambers 2 4 about i ts periphery . Rotable member 2 2 may be lotated to align chambers 24 with opening 18 to allow pov;der 20 to be transferreed from hopper 12 and into chambers 24 .
Positioned above hopper 12 is pi ezoelectric bending


I
assists in transferring the powder f rom bed 2 0 and i n t o
4
chamber 24 . While vibratinq, rod 28 is translated over
chamber 24 as indicated by arrow 34 . In this way, agi tat ion
of the powder bed 20 will occur over substantially the entire


field is applied across the two outer electrodes to cause one layer to expand while the other contracts.
Rod 6 0 will preferably comprise a stainless steel wire rod having a diameter in the range from about 0.005 inch to about 0.10 inch, and more preferably from about 0.02 inch to about 0.04 inch. However, it will be appreciated that other materials and geometries may be used when constructing rod 60. For example, a variety of rigid materials may be employed, including other metals and alloys, a steel music



when in the downward position, a compressed gas is forced through each of chambers 52 to eject the fine powder into receptacles (not shown). In this way, a convenient method is provided for transferring fine powder from a hopper intro receptacles in a metered amount.
Referring now to Fig. 7, an alternative embodiment of an apparatus 74 for transferring metered doses of fine powder will be described. Apparatus 74 comprises a housing 76 and a piezo substrate 78 operably attached to housing 7 6. piezo substrate 78 includes a plurality of holes 80 (or a screen). Positioned above substrate 78 is a hopper 82 having



transferring metered doses of fine powder is illustrated in Fig. 9. Apparatus 120 comprises a motor 122 which rotates a wire loop 124. As shown, wire loop 124 is disposed within a bed of fine powder 12 6 just above a chamber 128 . In this way, when wire loop 124 is rotated, t:he powder will be f].uidized and drav;n into chamber 128 in a manner similar to previous embodiments. Further, loop 124 may be translated over chamber 128 during its rotation in a manner similar to that previously



to be laterally offset from vibrator 208 so that it will not i nterfere with the mot j on of: vibrator 208 . One particular advant age of inclnding block 238 within opening 236 is that any puriculate qenerated as block 238 is vibrated will he

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down otoin, i.e., radial to rota table member 204 , ar. it passes over each of meteri nq chambers 242. Preferabl y, yivrator 208 is laterally translated along hopper 206 at a


so that they will drag over the top of the powder to assist in leveling the powder as vibrator 2 08 is translated along the hopper. As another alternative, an elongate vibratory element, such as a screen, may be disposed within the powder bed to assist in levelling the powder.
As shown in Figs. 11 and 12, rotatable member 204 is in a filling position where metering chambers 242 are aligned with hopper 206. As with the other embodiments described herein, once metering chambers 242 are filled, rotatable member 204 is rotated 180° where the powder is ejected from



inlet 260 until passing through chambers 242b. In this manner, two separate air circuits are provided. Alternatively, it will be appreciated that one of the air inlets could be eliminated so that a vacuum or pressurized gas may be simultaneously provided to all of metering chambers 242 .
Also disposed above manifold 262 is a change tool 274 . Motering chambers 242 are formed in change tool 274, and fi1ters 276 are disposed between change tool 274 and air bracket 272 to form a bottom end of metering chambers 242. Air may be drav/n into chambers 242 by attaching a vacuum to


It is possible \.n si ide chanqe tool 274 from aperture 27R , Tn this way, change tool 2 74 may easily be replaced with another change tool having different sized metering chambers. In this; manner, apparatus 200 may be provided with a wide assortment of changetools which allows a nser to easily change the si7,e of the metering chambers simply by inserting a new change tool 2 7 4.



THEBOTTOM of hopper 206 to agitate the powder. As end member 240 passes over each metering chamber 242, an aerosol cloud is produced that is draen int"o the metering chamber 242 by vacuum and by gravity. As end member 242 passes over metering chambers 242, ultrafionic energy radiates down into metering chambers 242 to agitate the powder already inside the metering
i


Referring now to Fig. 15, an exemplary embodiment of a system 300 for metering and transporting a fine powder will be described. System 300 operates in a manner similar to apparatus 200 bnt includes milltiple vibrators and multiple hoppers for simultaneounly fi11ing a plurality of receptacles with uni t dosages of fine powder. System 300 comprises a frame302 to v/hich are rotatably coupled a plurality of rotatable members 304 . Rotatable members 304 may be


Frame 302 in roupled to a base 324 which includes a plurality of elonqate grooves 326. Grooves 326 are adapted to receive torn ends of a plurality of receptacles 328 which are formed in a sheet 330. Sheet 330 is preferably supplied froma hister maker, such as a commercially available Uhlmann packaging Machine , Model Mo . 104 0 . Rotatabl e members 304 preferably include a numbrer of metering chambers that correspond to the number of receptacles in each row of sheets 330. In this way, four rows of receptacles may be filled duging each cycle of operation. Once four of the rows are


Although shown with vibrators which comprise ultrasonic horns, it will be appreciated that other types of vibrators and vibratable elements may be employed, including those previously described herein. Further, it will be apprerciated that the number of vibrators and size of the troughs may be varied according to the particular need.
Although the foregoing invent ion has been described in some detail by way of illustration and example, for purponpR of clarity of understanding, it will be obvious that certain changes and modifications may be practiced within the seope of the appended c1aims .




We Claim:
1. A method for transporting a fine powder (20) comprising: placing the fine powder (20) into a hopper (12) having an opening (18) therein; vibrating a vibratable element (28) within the fine powder (20) in the vicinity of the opening (18);
moving the element (28) across the opening (18) while vibrating the element (28); and
capturing at least a portion of the fine powder (20) exiting the opening (18) within a chamber (24), wherein the captured powder (20) is sufficiently uncompacted so that it may be dispersed upon removal from the chamber (24).
2. A method as in claim 1, wherein the vibratable element (28) is vibrated in an up and down motion relative to the powder (20) in the hopper (12).
3. A method as in claim 2, wherein the vibratable element (28, 210) is coupled to an ultrasonic hom, and wherein the vibrating step comprises actuating the ultrasonic hom,
4. A method as in claim 1, wherein the vibratable element (28, 210) is vibrated at a frequency in the range from about 1,000 Hz to about 180,000 Hz.
5. A method as in claim 1, wherein the vibratable element (28) has a distal end (29) which is placed near the opening (18), and wherein the distal end (29) has an end-member (240) attached thereto which is vibrated over the chamber (24).
6. A method as in claim 1, wherein the end-member (240) is vertically spaced

apart from the chamber (24) by a distance in the range from about 0.01 mm to about 10 mm.
7. A method as in claim 6, comprising translating the element (28, 210) along the opening (18) at a rate that is less than about 100 cm/s.
8. A method as in claim 1, comprising periodically leveling the powder (20) within the hopper (12).
9. A method as in claim 8, wherein the leveling step comprises placing a projecting member (30, 244) on the vibratable element (28, 210) at a location spaced apart from a distal end (29) of the vibratable element (28, 210).
10. A method as in claim 1, wherein multiple chambers (24, 52) are aligned with
the opening (18, 56), and comprising moving the vibratable element (28, 60) along
the opening (18, 56) to pass over each chamber (24, 52).
11. A method as in claim 1, wherein the fine powder (20) comprises a medicament composed of individual particles having a means size in the range from about 1 |im to 100 µm,
12. A method as in claim 1, wherein the capturing step comprises drawing air through the chamber (24, 52) which is positioned below the opening (18, 56), wherein the drawn air assists in drawing the fine powder (20) into the chamber
(24,52).
13. A method as in claim 1, comprising transferring the captured powder (20)
from the chamber (24, 52) to a receptacle.

14. A method as in claim 13, wherein the transferring step comprises introducing a compressed gas into the chamber (24, 52) to expel the captured powder (20) into the receptacle.
15. A method as in claim 1, comprising adjusting the amount of captured powder (20) to be a unit dosage amount.
16. A method as in claim 15, wherein the adjusting step comprises providing a thin plate (284) below the hopper (12), with the plate (284) having an aperture (286) that is aligned with the chamber (24, 242), and comprising moving the chamber (24, 242) relative to the plate (284) to scrape the excess powder (20) from the chamber (24, 242).
17. A method as in claim 1, wherein the hopper (12) is a primary hopper (206, 306), and wherein the placing step comprises transferring the powder (20) from a secondary hopper (218) to the primary hopper (206, 306).
18. A method as in claim 17, comprising vibrating the secondary hopper (218) to transfer the powder (20) to the primary hopper (206, 306).
19. A method as in claim 1, comprising dispensing the powder (20) from the chamber (242) and changing the size of the chamber (242).
20. Apparatus (200) for transporting a fme powder (20), comprising:
a hopper (12) having an opening (18) therein, the hopper (12) being adapted to receive the fme powder (20);
at least one chamber (242) which is movable to allow the chamber (242) to be placed in close proximity to the opening (18);

a vibratable member (210) having a proximal end and a distal end (29), the vibratable member (210) being positionable within the hopper (12) such that the distal end (29) is near the opening (18);
a vibrator motor (208) to vibrate the vibratable member (210) when within the fine powder (20); and
a mechanism (216, 217) for translating the vibratable member (210) over the chamber (242).
21. An apparatus (200) as in claim 20, comprising a rotatable member (204) having a plurality of chambers (242) about its periphery which are alignable with the opening (18, 56), and wherein the translating mechanism (216, 217), is configured to translate the vibratable member (210) along the opening (18, 56) so that the vibratable member (210) passes over each chamber (242).
22. An apparatus (200) as in claim 20, wherein the translating mechanism (216, 217) comprises a linear drive mechanism which translates the vibratable member (210) along the opening at a rate that is less than about lOOcm/s.

23. An apparatus (200) as in claim 20, wherein the vibrator motor (208) vibrates the vibratable member (210) at a firequency in the range fi"om about 1,000 Hz to about 180,000 Hz.
24. An apparatus (200) as in claim 20, wherein the vibrator comprises an ultrasonic horn that vibrates the element in said up and down motion relative to the powder (20).
25. An apparatus (200) as in claim 24, wherein the vibratable element is cylindrical in geometry and has a diameter in the range from about 1.0 mm to about 10 mm.

26. An apparatus (200) as in claim 25, comprising an end member (240) at the distal end (29) of the vibratable member (210).
27. An apparatus (200) as in claim 26, wherein the end member (240) radially extends from the vibratable element.
28. An apparatus (200) as in claim 26, comprising a powder leveling member (244) spaced about the end member (240).
29. An apparatus (200) as in claim 20, wherein the chamber (242) is disposed within a rotatable member (304) which is placed in a first position having the chamber (242) aligned with the opening, and a second position having the chamber (242) aligned with a receptacle (328).
30. An apparatus (200) as in claim 20, comprising a port in the bottom of the chamber (242), and a vacuum source in communication with the port to assist in drawing the fine powder (20) from the hopper (306) and into the chamber (242).
31. An apparatus (200) as in claim 30, comprising a filter (276) disposed across the port.
32. An apparatus (200) as in claim 30, comprising a source of compressed gas in communication with the port to eject the captured powder (20) from the chamber (242) and into the receptacle (328).
33. An apparatus (200) as in claim 32, comprising a controller for controlling actuation of the gas source and the vacuum source.

34. An apparatus (200) as in claim 29, comprising a plurality of hoppers disposed above a plurality of rotatable members which each include a plurality of chambers (242), and comprising a plurality of elements and a plurality of vibrators to vibrate the elements.
35. An apparatus (200) as in claim 20, comprising a plate disposed below the hopper, with the plate having an aperture that is aligned with the chamber (242), and wherein the chamber (242) is movable relative to the plate to allow excess powder (20) to be scraped from the chamber (242).
36. An apparatus (200) as in claim 20, wherein the hopper is a primary hopper (206) and comprising a secondary hopper (218) disposed above the primary hopper (206) to transfer powder (20) to the primary hopper (206).
37. An apparatus (200) as in claim 36, comprising a shaking mechanism to vibrate the secondary hopper (218).
38. An apparatus (200) as in claim 29, wherein the chamber is formed in a change tool (274), and wherein the change tool (274) is removably coupled to the rotatable member (304).
39. A system (300) for transporting a fine powder (20), comprising:
a plurality of rotatable members each having a row of chambers (242) about their periphery;
a hopper (306) disposed above each rotatable member (304), wherein each hopper (306) includes an opening;
a vibratable element (310) that is positionable within each of the hoppers, wherein each vibratable element has a distal end (29) near the opening;

a vibrator (308) coupled to each vibratable element to vibrate the elements in an up and down motion; and
a mechanism (322) to translate each vibratable element along each of the hoppers while the elements are vibrating.
40. A system (300) as in claim 39 comprising a controller to control rotation of the vibratable members (310), the vibrators (308), and the translation mechanism (322).


Documents:

2176-mas-1998-abstract.pdf

2176-mas-1998-claims filed.pdf

2176-mas-1998-claims granted.pdf

2176-mas-1998-correspondnece-others.pdf

2176-mas-1998-correspondnece-po.pdf

2176-mas-1998-description(complete)filed.pdf

2176-mas-1998-description(complete)granted.pdf

2176-mas-1998-drawings.pdf

2176-mas-1998-form 1.pdf

2176-mas-1998-form 13.pdf

2176-mas-1998-form 19.pdf

2176-mas-1998-form 26.pdf

2176-mas-1998-form 3.pdf

2176-mas-1998-form 4.pdf

2176-mas-1998-form 6.pdf

2176-mas-1998-other documents.pdf


Patent Number 211924
Indian Patent Application Number 2176/MAS/1998
PG Journal Number 02/2008
Publication Date 11-Jan-2008
Grant Date 13-Nov-2007
Date of Filing 28-Sep-1998
Name of Patentee M/S. NEKTAR THERAPEUTICS
Applicant Address 150 INDUSTRIAL ROAD, SAN CARLOS, CALIFORNIA 94071,
Inventors:
# Inventor's Name Inventor's Address
1 GORDON STOUT 401 EVELYN #27 ALBANY, CA 94706,
2 MICHAEL J ROCCHIO 2542 JACOB ST., HAYWARD, CA 94541,
3 DERRICK J PARKS 1535 WHITE OAK WAY, SAN CARLOS, CA 94070,
4 PATRICK REICH 1555 W HILSDALE BLVD., 110 SAN MATEO CA 94402,
5 XUYEN PHAM 114 LURENE DRIVE, FREMONT, CA 94541,
6 KYLE A NAYDO 902 ROCKERFELLER DR., 3A SUNNYVALE, CA 94087,
PCT International Classification Number B65B 1/36
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 08/949, 047 1997-10-10 U.S.A.