(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date PCT 30 April 2009 (30.04.2009) WO 2009/055030 A2 (51) International Patent Classification: J. [US/US]; 2622 Lincoln Avenue, Belmont, California A61M 15/00 (2006.01) B65B 1/30 (2006.01) 94002 (US). STOUT, Gordon [US/US]; 7825 Burns Court, El Cerrito, California 94530 (US). (21) International Application Number: PCT/US2008/0121 17 (74) Agents: WILSON, Mark A. et al; Nektar Therapeutics, 201 Industrial Road, San Carlos, California 94070 (US). (22) International Filing Date: 23 October 2008 (23.10.2008) (81) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of national protection available): AE, AG, AL, AM, AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, (26) Publication Language: English CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, (30) Priority Data: IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, 61/000,627 25 October 2007 (25.10.2007) US LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, (71) Applicant (for all designated States except US): NEK- RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TAR THERAPEUTICS [US/US]; 201 Industrial Road, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, San Carlos, California 94070 (US). ZW (72) Inventors; and (84) Designated States (unless otherwise indicated, for every (75) Inventors/Applicants (for US only): SESHADRI, kind of regional protection available): ARIPO (BW, GH, Sangita [US/US]; 14690 Horseshoe Drive, Saratoga, Cal GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ifornia 95070 (US). FONG, Barry [US/US]; 17351 Via ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), La Jolla, San Lorenzo, California 94580 (US). PALAKO- European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, DATY, Srinivas [IN/US]; 115 Goldhunter Court, Foster FR, GB, GR, HR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, City, California 94404 (US). ANACLETO II, Concor- NO, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, dio Candug [US/US]; 206 Palisades Drive, Daly City, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). California 94015 (US). REICH, Patrick [US/US]; 1669 Peachwood Drive, San lose, California 95132 (US). Published: BOECKL, Andrew John [US/US]; 123 Read Street, — without international search report and to be republished Tarpon Springs, Florida 34689 (US). PARKS, Derrick upon receipt of that report (54) Title: POWDER CONDITIONING (57) Abstract: The invention provides techniques for treating or conditioning powders subsequent to their packaging to facilitate extraction of the powders from their packaging. POWDER CONDITIONING CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of priority under 35 U. S. C. §119(e) to Provisional Application Serial No. 61/000,627, filed 25 October 2007, which is incorporated herein by reference in its entirety. FIELD OF THE INVENTION [0002] This invention provides (among other things) means for conditioning powder compositions in blisters or other configurations to improve dispersibility of the powder. The invention also provides various apparatuses to achieve the same. BACKGROUND OF THE INVENTION [0003] The need for effective therapeutic treatment of patients has resulted in the development of a variety of techniques for delivering a pharmaceutical formulation to a patient. One traditional technique involves the oral delivery of a pharmaceutical formulation in the form of a pill, capsule, or the like. Inhaleable drug delivery, where an aerosolized pharmaceutical formulation is orally or nasally inhaled by a patient to deliver the formulation to the patient's respiratory tract, has also proven to be an effective manner of delivery. In one inhalation technique, a pharmaceutical formulation is delivered deep within a patient's lungs where it may be absorbed into the blood stream. In another inhalation technique, a pharmaceutical formulation is delivered to a targeted region in the respiratory tract to provide local treatment to the region. Many types of inhalation devices exist including devices that aerosolize a dry powder pharmaceutical formulation. [0004] The pharmaceutical formulation is often packaged so that it may be made easily available to a user. For example, a dose or a portion of a dose may be stored between layers of a multi-layered package, conventionally referred to as a blister or blister pack. Typically, a cavity is formed in a lower layer, the pharmaceutical formulation is deposited within the cavity, and an upper layer is sealed onto the lower layer, such as by heating and/or compressing the layers, to secure the pharmaceutical formulation within the cavity. Alternatively, the dose may be stored in a capsule that is to be swallowed or from which the pharmaceutical formulation may be aerosolized. Other packages, such as bottles, vials, and the like, may also be used to store the pharmaceutical formulation. PCT application WOO1/43802 discloses systems and methods for treating packaged powders at the time of inhalation. [0005] It is often difficult to effectively fill packages with the pharmaceutical formulation. For example, during some powder filling process, it is difficult to sufficiently fluidize the powder and/or to maintain consistent flow properties of the powder. On the other hand, sometimes the powder may be compacted into 'pucks' for filling into formed blisters. Depending on the bulk powder characteristics, the vacuum and the ultrasonic probe amplitude on the filler are adjusted to form the puck to give the desired control over the fill mass. The puck may break down into powder during subsequent operations on the filler/packager or during transport. However, on occasions when the puck is relatively 'hard', it may not completely disperse into a uniform powder for its intended delivery. Mechanical vibrations during subsequent shipping of the final product could have effect on the powder in the blister pack. This may result in variable doses to the patient as the emitted dose results vary from the end of manufacturing release test to the time of dosing. It is, therefore, useful to 'condition' or break the powder puck after filling and sealing the blister to ensure a consistent product performance from the time of manufacture to the time of dosing. Therefore, there is a need in the filed, to develop novel mechanisms to condition the powders. SUMMARY OF THE INVENTION [0006] The invention provides techniques for treating or conditioning powders subsequent to their packaging to facilitate extraction of the powders from their packaging. These and other objects, aspects, embodiments and features of the invention will become more fully apparent when read in conjunction with the following detailed description. BRIEF DESCRIPTION OF THE FIGURES [0007] Figure 1 shows a web whacker. [0008] Figure 2.shows an acoustic speaker on a filler/packager. [0009] Figures 3A and 3B show ultrasonic conditioning of blisters. [0010] Figure 4 shows an ultrasonic bath with blisters. [0011] Figure 5 shows the effect of various conditioning methods on emitted dose and blister retention. [0012] Figure 6 shows the effect of ultrasonic energy on conditioning. [0013] Figure 7 shows the effect of ultrasonic conditioning on shipped and unshipped blisters at various energy levels. [0014] Figure 8 shows the effect of ultrasonic conditioning on bulk shipped and unshipped blisters. DETAILED DESCRIPTION OF THE INVENTION [0015] It must be noted that, as used in this specification, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. [0016] In describing and claiming the present invention, the following terminology will be used in accordance with the definitions described below. Definitions [0017] The terms used in this disclosure are defined as follows unless otherwise indicated. Standard terms are to be given their ordinary and customary meaning as understood by those of ordinary skill in the art, unless expressly defined herein. [0018] Term "conditioning" is used to describe processes to facilitate a more uniformly dispersible powder that exhibits less agglomeration compared to powders that are not conditioned. "Deagglomeration" is used interchangeably to mean conditioning. [0019] A composition that is "suitable for pulmonary delivery" refers to a composition that is capable of being aerosolized and inhaled by a subject so that a portion of the aerosolized particles reaches the lungs, e.g., to permit entry into the alveoli and into the blood. Such a composition may be considered "respirable" or "inhaleable." [0020] An "aerosolized" composition contains solid particles that are suspended in a gas (typically air), typically as a result of actuation (or firing) of an inhalation device. A passive dry powder inhaler would be actuated by a user's breath. [0021] A "dry powder inhaler" is a device that is loaded with a unit dose reservoir (e.g., a blister), of the drug in powder form. Depending on the treatment regimen, more than one unit dose may need to be delivered to a subject in need thereof. Generally, the inhaler is activated by taking a breath. For example, a capsule or blister is punctured and the powder is dispersed so that it can be inhaled, e.g., in a "Spinhaler" or "Rotahaler." "Turbohalers" are fitted with canisters that deliver measured doses of the drug in powder form. [0022] As used herein, the term "emitted dose" or "ED" refers to an indication of the delivery of dry powder from an inhaler device after an actuation or dispersion event from a powder unit or reservoir.