Methods and systems for transferring viscous fluid to containers

Abstract

A method for transferring a fluid into a container is provided. The method includes connecting a capillator to a fluid so that a portion of the fluid is transferred into the capillator by capillary action and transferring the portion of the fluid from the capillator to the container using a centrifuge.

Description

GLAUKO.278WO PATENT METHODS AND SYSTEMS FOR TRANSFERRING VISCOUS FLUID TO CONTAINERS INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

[0001] Any and all applications for which a foreign or domestic priority claim is identified in the Application Data Sheet as filed with the present application are hereby incorporated by reference under 37 CFR 1.57. For example, this application claims the benefit of priority to U.S. Provisional Application No. 63 / 760341, filed February 19, 2025, U.S. Provisional Application No. 63 / 760344, filed February 19, 2025, and U.S. Provisional Application No. 63 / 760352, filed February 19, 2025, each of which are hereby expressly- incorporated by reference in their entireties.BACKGROUNDField

[0002] This disclosure generally relates to implantable intraocular drug delivery devices structured to provide targeted and / or controlled release of a drug to a desired intraocular tissue. In certain embodiments, this disclosure relates to methods of filling a container (e.g., the drug delivery devices) with a fluid (e.g., a viscous fluid).Description of the Related Art

[0003] Methods of filling containers with fluid can often result in over or underfilling of the container. To prevent underfilling, many methods over fill and wipe away the excess fluid. This approach can link the fluid volume to the size of the container, which may be undesirable due to manufacturing tolerances. Additionally, in some cases over filling and wiping away excess fluid will not work when the target fluid volume is less than the size of the container.SUMMARY

[0004] The embodiments disclosed herein each have several aspects no single one of which is solely responsible for the disclosure’s desirable attributes. Without limiting the scope of this disclosure, its more prominent features will now be briefly discussed. After considering this discussion, and particularly after reading the section entitled ‘‘Detailed Description” one will understand how the features of the embodiments described hereinprovide advantages over existing approaches or over existing systems for filling containers with a viscous fluid.

[0005] In one aspect, a method of transferring a fluid to a container includes priming a tube with the fluid. The method also includes cutting the tube to provide a tube segment having a length based at least in part on a target amount of the fluid. The method also includes assembling a transfer assembly by inserting the tube segment into a corresponding funnel aligned with a container mount holding the container. The method also includes transferring the fluid from the tube segment into the container.

[0006] In some embodiments, the method includes inserting the transfer assembly into a centrifuge and operating the centrifuge to spin the transfer assembly to drive the fluid from the tube segment into the funnel and from the funnel into the container. In some embodiments, the fluid includes travoprost. In some embodiments, the container is an ocular implant. In some embodiments, priming the tubing includes using pressure to drive the fluid into the tube. In some embodiments, the method includes using a pressurized gas to provide the pressure to drive the fluid into the tube. In some embodiments, the method includes using pressure between about 100 psi and about 3500 psi to drive the fluid into the tube. In some embodiments, the method includes heating the fluid. In some embodiments, the method includes heating the fluid to a temperature between about 33 degrees Celsius and about 40 degrees Celsius. In some embodiments, the method includes determining a length for the tube segment before cutting the tube segment. Determining the length for the tube segment includes cutting the tube to provide a calibration tube segment having a calibration length, measuring a first weight of the calibration tube segment with the fluid therein, removing the fluid from the calibration tube segment, measuring a second weight of the calibration tube segment without the fluid, and determining the length of the tube segment based at least in part on the calibration length, the first weight, and the second weight of the calibration tube segment. In some embodiments, the method includes calculating an amount of fluid per unit length for the tube based at least in part on the calibration length, the first weight, and the second weight of the calibration tube segment, and determining the length of the tube segment based at least in part on the calculated amount of fluid per unit length and the target amount of the fluid. In some embodiments, the fluid has a viscosity greater than about 500 cPs at 25 degrees C.

[0007] In another aspect, a system for transferring fluid to a container includes a transfer assembly and a centrifuge spin fixture. The transfer assembly includes a container mount configured to retain a container, a funnel comprising an opening extending from a first end to a second end, the second end configured to align with the container mount, and a tubesegment positioned within the first end of the funnel and configured to retain a fluid, the tube segment having a length based at least in part on a target amount of fluid. The centrifuge spin fixture includes an opening configured to receive the transfer assembly.

[0008] In some embodiments, the opening of the funnel has a width that decreases from the first end to the second end. In some embodiments, the container mount comprises the container received within an opening sized and shaped to retain the container within the container mount. In some embodiments, the container is an ocular implant. In some embodiments, tube segment contains a viscous fluid. In some embodiments, the fluid comprises travoprost. In some embodiments, the centrifuge spin fixture comprises a base portion and a lid portion removable from the base and wherein the base portion and lid portion retain the transfer assembly within the opening of the centrifuge spin fixture. In some embodiments, the container includes an opening, and wherein the opening of the container aligns with the second end of the opening of the funnel.

[0009] In another aspect, a system for priming a tube includes a connector, a fluid reservoir, a pressure connection, and a tube connector. The connector includes a first end and a second end. The fluid reservoir is formed at the second end of the connector. The pressure connection is at the first end of the connector and configured to couple to a pressure device. The tube connector is coupled to a second end of the connector to couple the tube to the connector so that the tube is in fluid communication with the fluid reservoir. The pressure device is configured to apply pressure to the fluid reservoir to drive fluid from the fluid reservoir into the tube.

[0010] In some embodiments, the connector and the tube are disposed in a thermally controlled enclosure.

[0011] In another aspect a method of transferring a fluid to a container includes priming a tube with the fluid, cutting the tube to provide a tube segment having a length based at least in part on a target amount of the fluid, assembling a transfer assembly by coupling the tube segment to a container mount holding the container, and transferring the fluid from the tube segment into the container.

[0012] In some embodiments, the method includes inserting the transfer assembly into a centrifuge and operating the centrifuge to spin the transfer assembly to drive the fluid from the tube segment into the container. In some embodiments, the fluid includes travoprost. In some embodiments, the container is an ocular implant. In some embodiments, priming the tubing includes using pressure to drive the fluid into the tube. In some embodiments, the method includes using a pressurized gas to provide the pressure to drive the fluid into the tube.In some embodiments, the method includes using pressure between about 100 psi and about 3500 psi to drive the fluid into the tube. In some embodiments, the method includes heating the fluid. In some embodiments, the method includes heating the fluid to a temperature between about 33 degrees Celsius and about 40 degrees Celsius. In some embodiments, the method includes determining a length for the tube segment before cutting the tube segment. Determining the length for the tube segment includes cutting the tube to provide a calibration tube segment having a calibration length, measuring a first weight of the calibration tube segment with the fluid therein, removing the fluid from the calibration tube segment, measuring a second weight of the calibration tube segment without the fluid, and determining the length of the tube segment based at least in part on the calibration length, the first weight, and the second weight of the calibration tube segment. In some embodiments, the method includes calculating an amount of fluid per unit length for the tube based at least in part on the calibration length, the first weight, and the second weight of the calibration tube segment, and determining the length of the tube segment based at least in part on the calculated amount of fluid per unit length and the target amount of the fluid. In some embodiments, the method includes determining an amount of the fluid by weighing the tube before priming the tube with the fluid to identify a first weight and weighing the tube after priming the tube with the fluid to identify a second weight, wherein a difference between the second weight and the first weight corresponds to the amount of the fluid.

[0013] In another aspect a system for transferring fluid to a container includes a transfer assembly and a centrifuge spin fixture. The transfer assembly includes a container mount configured to retain a container and a tube segment configured to retain a fluid, the tube segment having a length based at least in part on a target amount of fluid. The centrifuge spin fixture includes an opening configured to receive the transfer assembly.

[0014] In some embodiments, the container mount comprises the container received within an opening sized and shaped to retain the container within the container mount. In some embodiments, the container is an ocular implant. In some embodiments, tube segment contains a viscous fluid. In some embodiments, the fluid comprises travoprost. In some embodiments, the centrifuge spin fixture comprises a base portion and a lid portion removable from the base and wherein the base portion and lid portion retain the transfer assembly within the opening of the centrifuge spin fixture.

[0015] In another aspect, a method of transferring a fluid to a container includes aligning a spin adapter with an aliquoter in a first configuration. The method also includes depositing a fluid in the spin adapter. The method also includes transferring the fluid from thespin adapter to the aliquoter. The method also includes aligning the aliquoter and a container mount in a second configuration, wherein the container mount includes the container. The method also includes transferring the fluid from the aliquoter to the container.

[0016] In some embodiments, the fluid includes travoprost. In some embodiments, the container comprises an ocular implant. In some embodiments, transferring the fluid from the spin adapter to the aliquoter includes inserting the spin adapter and the aliquoter in a centrifuge and operating the centrifuge. In some embodiments, transferring the fluid from the aliquoter to the container further includes inserting the aliquoter, and the container mount in the centrifuge and operating the centrifuge. In some embodiments, aligning in the second configuration includes aligning the spin adapter, the aliquoter, and the container mount in the second configuration. Transferring the fluid from the aliquoter to the container includes first transferring the fluid from the aliquoter to the spin adapter. In some embodiments, transferring the fluid from the aliquoter to the container includes transferring the fluid from the spin adapter to the container. In some embodiments, the method includes aligning the spin adapter to the aliquoter comprises aligning a plurality of spin adapters with a plurality of aliquoters, depositing a fluid in the spin adapter further comprises depositing fluid in the plurality of spin adapters, transferring fluid from the spin adapter to the aliquoter further comprises transferring fluid from the plurality' of spin adapters to the plurality' of aliquoters, aligning the aliquoter, and the container mount in the second configuration further comprises aligning the plurality of aliquoters, and the plurality of container mounts in the second configuration, wherein the plurality of container mounts include a plurality' of containers, and, transferring the fluid from the aliquoter to the container further comprises transferring the fluid form the plurality' of aliquoters to the plurality of containers. In some embodiments, the method includes heating the fluid. In some embodiments, the method includes heating the fluid to a temperature between about 33 degrees Celsius and about 40 degrees Celsius. In some embodiments, the aliquoter includes a body having a first surface at a first end and a second surface at a second end opposite the first end, a first channel extending from the first end partially into the body towards the second end, a second channel extending from the second end partially into the body towards the first end. a wall separating the first channel from the second channel, and an opening through the wall to fluidly couple the first channel to the second channel. In some embodiments, transferring the fluid from the spin adapter to the aliquoter includes transferring a first portion of the fluid from the spin adapter into the first channel of the aliquoter to fill the first channel up to the opening, and transferring a second portion of the fluid from the spin adapter into the first channel of the aliquoter, wherein at least some of the second portion ofthe fluid passes from the first channel, through the opening, into the second channel, and out of the second channel at the second end of the body of the aliquoter. In some embodiments, aligning the spin adapter with the aliquoter in the first configuration includes positioning the spin adapter over the aliquoter, and aligning the aliquoter, and the container mount in the second configuration includes inverting the aliquoter, positioning the inverted aliquoter over the spin adapter, and positioning the spin adapter over the container mount. In some embodiments, the aligning in the second configuration includes aligning the spin adapter, the aliquoter, and the container mount in the second configuration, wherein the aliquoter has a first end and a second end opposite the first end, wherein the spin adapter has a first end and a second end opposite the first end, wherein in the first configuration the first end of the aliquoter is positioned towards the second end of the spin adapter, and wherein in the second configuration the first end of the aliquoter is positioned towards the first end of the spin adapter.

[0017] In another aspect, an aliquoter includes a body having a first surface at a first end and a second surface at a second end opposite the first end, a first channel extending from the first end partially into the body towards the second end. a second channel extending from the second end partially into the body towards the first end, a wall separating the first channel from the second channel, and an opening through the wall to fluidly couple the first channel to the second channel.

[0018] In some embodiments, the aliquoter includes a third channel aligned with the opening. In some embodiments, the third channel is substantially perpendicular to the first channel or to the second channel. In some embodiments, the first channel is substantially parallel to the second channel. In some embodiments, the first channel is substantially aligned with a central axis of the aliquoter, and the second channel is offset from the central axis of the aliquoter. In some embodiments, a system includes the aliquoter and a spin adapter that includes a body having a first surface at a first end and a second surface at a second end opposite the first end, a funnel extending from the first end and narrowing towards the second end, and a channel extending from a narrow end of the funnel to the second end to thereby provide a fluid path through the body. In some embodiments, the channel of the spin adapter is aligned with the first channel of the aliquoter. In some embodiments, the system includes a container mount that includes a recess with the container positioned in the recess, wherein the container aligned with the channel of the spin adapter.

[0019] In another aspect, a system for transferring a fluid to a container includes a spin adapter comprising an opening extending from a first end to a second end of the spin adapter, the spin adapter configured to receive a fluid in the first end, an aliquoter including afirst channel extending from an opening in a first end of the aliquoter, the first channel having a closed second end. a second channel offset from the first channel and fluidly coupled to the first channel via an opening in a sidewall of the first channel, the second channel extending through a second end of the aliquoter, and a third channel fluidly coupled to the first channel and the second channel, the third channel extending generally perpendicular to the first channel and the second channel, the third channel extending through a side wall of the aliquoter, and a container mount having a top surface configured to retain a container, wherein in a first configuration the second end of the spin adapter is aligned with the first end of the aliquoter, and wherein in a second configuration the first end of the aliquoter is aligned with the first end of the spin adapter, and the second end of the spin adapter is aligned with the top surface of the container mount.

[0020] In some embodiments, the opening of the spin adapter has a diameter or width that decreases from the first end to the second end. In some embodiments, the container mount comprises the container received within an opening sized and shaped to retain the container within the container mount. In some embodiments, the container is an ocular implant. In some embodiments, a centrifuge mount configured to receive the first configuration. In some embodiments, a centrifuge mount configured to receive the second configuration.

[0021] In another aspect a method for transferring fluid into a container includes connecting a capillator to a fluid so that a portion of the fluid is transferred into the capillator by capillary action and transferring the portion of the fluid from the capillator to the container using a centrifuge.

[0022] In some embodiments, the capillator includes a channel that is sized so that the capillator holds a target volume of fluid that corresponds to filling the container, and the capillator is configured to stop transferring fluid by capillary action once the target volume is transferred to the capillator. In some embodiments, the method includes depositing a volume of the fluid into a capillary loader. In some embodiments, the method includes applying pressure to the capillary loader to push some of the fluid out of an opening of the capillary loader to form a layer of fluid on an outside surface of the capillary loader. In some embodiments, the method includes coupling the capillator to the capillary loader so that the capillator contacts fluid. In some embodiments, the deposited volume of fluid in the capillary loader is sufficient to fill multiple capillators, and the method includes coupling an additional capillator to the capillary loader so that an additional portion of the fluid is transferred from the capillary loader into the additional capillator. In some embodiments, the additional portion of the fluid is transferred from the capillary' loader into the additional capillator while the portionof the fluid is being transferred from the capillator to the container using the centrifuge. In some embodiments, the method includes inserting a nozzle of a vial containing the fluid into a funnel of the capillary loader and applying pressure to the vial to drive the portion of the fluid out of the nozzle and into the funnel of the capillary loader. In some embodiments, the method includes inserting a nozzle of a vial containing the fluid into a funnel of the capillary loader and using gravity to transfer the portion of the fluid out of the nozzle and into the funnel of the capillary loader. In some embodiments, the method includes inserting a nozzle of a vial containing the fluid into a funnel of the capillary loader, and using at least one of a needle, syringe, or robotic fluid dispensing system to transfer the portion of the fluid out of the nozzle and into the capillary' loader. In some embodiments, the method includes installing multiple capillary loaders into a loader module, inverting the loader module, and inserting a nozzle of a vial containing the fluid through an opening in the loader module and into a funnel of the capillary loader. In some embodiments, the method includes heating the fluid. In some embodiments, the method includes heating the fluid to a temperature between about 33 degrees Celsius and about 40 degrees Celsius. In some embodiments, the method includes applying pressure to the vial to drive the portion of the fluid out of the nozzle and into the funnel of the capillary loader. In some embodiments, the method includes using gravity to transfer the portion of the fluid out of the nozzle and into the funnel of the capillary' loader. In some embodiments, the method includes un-inverting the loader module before coupling the capillator to the capillary loader. In some embodiments, the method includes heating the fluid. In some embodiments, the method includes heating the fluid to a temperature between about 33 degrees Celsius and about 40 degrees Celsius. In some embodiments, the capillator includes a body that has a first end, a second end opposite the first end, and a first length that extends from the first end to the second end, a recess extending from the first end toward the second end and having a base, wherein the recess has a depth extending from the first end to the base of the recess, and a channel extending from the base of the recess toward the second end, wherein the channel has a second length that is shorter than the first length. In some embodiments, the channel extends from the base of the recess to the second end of the capillator. In some embodiments, the channel is sized so that the capillator holds a target volume of fluid that corresponds to filling the container. In some embodiments, the channel is configured to draw the portion of the fluid into the channel by capillary' action, and wherein the channel is configured to stop drawing fluid when the channel is substantially full. In some embodiments, the capillator includes an additional recess extending from the second endtowards the first end of the capillator, and the channel extends into the additional recess toward the second end forming a raised lip.

[0023] In another aspect, a method of making a capillator includes forming a channel through a body having a first end and a second end opposite the first end, wherein the channel has a first length, and wherein the channel is along a direction that extends from the first end to the second end of the body; measuring a first volume of fluid held by the channel with the first length; and forming a recess in the first end of the body, the recess having a depth to shorten the channel to have a second length, wherein the depth of the channel is based at least in part on the measured first volume of fluid and a target volume of fluid for the capillator.

[0024] In some embodiments, the channel is sized so that the capillator holds the target volume of fluid that corresponds to filling a container. In some embodiments, the channel is configured to draw the portion of the fluid into the channel by capillary' action. In some embodiments, the channel is configured to stop drawing fluid when the channel is substantially full. In some embodiments, the method includes forming an additional recess extending from the second end towards the first end of the capillator. In some embodiments, the channel extends into the additional recess toward the second end forming a raised lip.

[0025] In another aspect, a capillator includes a body that has a first end, a second end opposite the first end, and a first length that extends from the first end to the second end; a recess extending from the first end toward the second end and having a base, wherein the recess has a depth extending from the first end to the base of the recess; and a channel extending from the base of the recess toward the second end, wherein the channel has a second length that is shorter than the first length.

[0026] In some embodiments, the channel extends from the base of the recess to the second end of the capillator. In some embodiments, the channel is sized so that the capillator holds a target volume of fluid that corresponds to filling a container. In some embodiments, the channel is configured to draw the portion of the fluid into the channel by capillary' action. In some embodiments the channel is configured to stop drawing fluid when the channel is substantially full. In some embodiments, the capillator includes an additional recess extending from the second end towards the first end of the capillator. In some embodiments, the channel extends into the additional recess toward the second end forming a raised lip.

[0027] In another aspect, a capillator includes a body that has a first end, a second end opposite the first end, and a first length that extends from the first end to the second end; and a channel extending from the first end toward the second end. wherein the channel has a second length that is equal to or less than the first length.

[0028] In some embodiments, the channel is sized so that the capillator holds a target volume of fluid that corresponds to filling a container. In some embodiments, the channel is configured to draw the portion of the fluid into the channel by capillary action. In some embodiments the channel is configured to stop drawing fluid when the channel is substantially full. In some embodiments, the capillator includes a recess extending from the second end towards the first end of the capillator. In some embodiments, the channel extends into the recess toward the second end forming a raised lip.

[0029] In another aspect, a system for transferring a fluid to a container includes a capillary loader comprising an opening extending from a first end to a second end, the opening comprising a funnel portion extending from the first end and a receiving portion extending from the second end; a capillator comprising a channel extending at least partially through the length of the capillator; and a container mount retaining a container; wherein in a first configuration the capillator is received within the receiving portion of the capillary loader; and wherein in a second configuration the channel of the capillator is aligned with the container.

[0030] In some embodiments, the system includes a vial containing a viscous fluid configured to deposit the viscous fluid into the funnel portion of the capillary loader. In some embodiments, the system includes a dispensing system fluidly coupled to the vial, wherein the dispensing system is configured to apply a pressure to the vial to assist in depositing the viscous fluid into the funnel portion of the capillary loader. In some embodiments, the funnel portion has a diameter that decreases from the first end to the second end. In some embodiments, the container mount comprises the container received within an opening sized and shaped to retain the container within the container mount. In some embodiments, the container is an ocular implant. In some embodiments, the system includes a centrifuge mount configured to receive the second configuration.

[0031] In another aspect, a method of transferring a fluid includes installing a plurality of capillary loaders in a base; installing a dispensing cap to a vial containing the fluid; inverting the base; aligning the vial with a first capillary loader; dispensing a portion of the fluid from the vial to the first capillary loader; repeating the aligning and dispensing steps for each of the plurality of capillary loaders; aligning respective empty capillators with the plurality of capillary loaders; and transferring the fluid from the capillary loaders to the capillators.

[0032] In some embodiments, the method includes transferring the fluid from the capillators to containers. In some embodiments, transferring the fluid from the capillators to the containers further comprises inserting the capillators and the containers into a centrifuge, and operating the centrifuge to spin the capillators and the containers to drive the fluid fromthe capillators into the containers. In some embodiments, the fluid comprises travoprost. In some embodiments, the containers are ocular implants. In some embodiments, the method includes applying a pressure pulse to the capillary loaders causing the fluid to billow onto atop surface of the capillary loaders. In some embodiments, the method includes applying a top cap to the vial, the top cap configured to connect the vial to a pressure controller. In some embodiments, transferring the fluid from the capillary loaders to the capillators comprises applying heat or a dry bath. In some embodiments, transferring the fluid from the capillary loaders to the capillators comprises heating the fluid. In some embodiments, the fluid is transferred from the capillary loaders to the capillators by capillary action.BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The foregoing and other features of the present disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments in accordance with the disclosure and are not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings. In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here. In some drawings, various structures according to embodiments of the present disclosure are schematically shown. However, the drawings are not necessarily drawn to scale, and some features may be enlarged while some features may be omitted for the sake of clarity. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the figures, can be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and make part of this disclosure.

[0034] FIG. 1 is a flow chart illustrating an example method of filling a container with a fluid according to the present disclosure.

[0035] FIG. 2 illustrates example tubes inside a container according to the present disclosure.

[0036] FIG. 3 is an example priming assembly used to prime the tube according to the present disclosure.

[0037] FIG. 4 illustrates a fluid reservoir and pressure connection of the example priming assembly of FIG. 3 according to the present disclosure.

[0038] FIGS. 5A-C illustrate an example method of priming the tube according to the present disclosure.

[0039] FIG. 6A shows an example tube wi th calibration tube segments cut off of both ends.

[0040] FIG. 6B illustrates example tube segments after being cut from the tube to a predetermined length according to the present disclosure.

[0041] FIG. 7 illustrates an example configuration of a transfer assembly including a container mount, container, funnel, and cut tube for processing in a centrifuge according to the present disclosure.

[0042] FIG. 8A is an exploded view of a centrifuge spin fixture and a plurality of transfer assemblies according to the present disclosure.

[0043] FIG. 8B is an assembled view of the centrifuge spin fixture and plurality' of transfer assemblies of FIG. 8A.

[0044] FIG. 8C illustrates the plurality of transfer assemblies positioned in the centrifuge spin fixture of FIG. 8A.

[0045] FIG. 9 illustrates an example centrifuge according to the present disclosure.

[0046] FIG. 10 is a flow chart illustrating an example method of filling a container with a fluid according to the present disclosure.

[0047] FIG. 11 A is a side cross-sectional view of an example aliquoter according to the present disclosure.

[0048] FIG. 1 IB is a top perspective view of the aliquoter of FIG. 11A.

[0049] FIG. 11C is a bottom perspective view of the aliquoter of FIG. 11A.

[0050] FIG. 12A is a side cross-sectional view of an example spin adapter according to the present disclosure.

[0051] FIG. 12B is a top perspective view of the spin adapter of FIG. 12A.

[0052] FIG. 12C is a bottom perspective view of the spin adapter of FIG. 12A.

[0053] FIG. 13A is a side cross-sectional view of an example container mount according to the present disclosure.

[0054] FIG. 13B is a top perspective view of the container mount of FIG. 13 A.

[0055] FIG. 13C is a bottom perspective view of the container mount of FIG. 13 A.

[0056] FIG. 14A illustrates the aliquoter of FIG. 11A and the spin adapter of FIG.12A assembled in a first configuration having the fluid loaded in the spin adapter according to the present disclosure.

[0057] FIG. 14B illustrates the aliquoter and spin adapter assembly of FIG. 14A after spinning the assembly to transfer the fluid from the spin adapter to the aliquoter.

[0058] FIG. 15A illustrates the aliquoter of FIG. 14B, the spin adapter of FIG. 12A, and the container mount of FIG. 13 A assembled in a second configuration having the fluid loaded in the aliquoter according to the present disclosure.

[0059] FIG. 15B illustrates the aliquoter, spin adapter, and container mount assembly of FIG. 15A after spinning the assembly to transfer the fluid from the aliquoter to the container mount.

[0060] FIG. 16 is a cross-sectional view of centrifuge mount holding a plurality of aliquoter and spin adapter assemblies of FIG. 14A according to the present disclosure.

[0061] FIG. 17 illustrates an example embodiment of a centrifuge according to the present disclosure.

[0062] FIG. 18 illustrates the transfer of fluid from the spin adapter to the aliquoter using the assembly of FIG. 14A.

[0063] FIG. 19 illustrates the transfer of fluid from the aliquoter, through the spin adapter, to the container mount using the assembly of FIG. 15 A.

[0064] FIG. 20 illustrates the removal of filled containers according to the present disclosure.

[0065] FIG. 21 is a flow chart illustrating an example method of filling a container with a fluid according to the present disclosure.

[0066] FIG. 22A illustrates the loading of capillary loaders in a base structure according to the present disclosure.

[0067] FIG. 22B is a cross-section of a capillary loader positioned in the base structure.

[0068] FIG. 22C shows a first (e.g., top) side of an example embodiment of a capillary loader.

[0069] FIG. 22D shows a second (e.g., bottom) side of the capillary loader.

[0070] FIG. 23A illustrates an example vial containing a fluid according to the present disclosure.

[0071] FIG. 23B is a cross-section of the vial of FIG. 23 A.

[0072] FIG. 24A illustrates a dispensing cap being installed on the vial of FIG. 23 A according to the present disclosure.

[0073] FIG. 24B illustrates the vial of FIG. 23A fluidly coupled to a dispenser system.

[0074] FIG. 25 illustrates a method of loading the capillary loaders of FIG. 22 using the vial and dispensing cap of FIG. 24.

[0075] FIG. 26 illustrates a method of positioning the base structure with capillary loaders of FIG. 22 into a capillary loader manifold according to the present disclosure.

[0076] FIG. 27 illustrates a pressure pulse being applied to the capillary loaders according to the present disclosure.

[0077] FIG. 28A illustrates capillators positioned atop the capillary loaders in the base structure of FIG. 22 according to the present disclosure.

[0078] FIG. 28B is cross-sections of the capillator and capillary loader assembly illustrating the filling of the capillator.

[0079] FIG. 28C illustrates an inside chamber of the capillator.

[0080] FIG. 28D shows a first (e.g., top) side of an example embodiment of a capillator.

[0081] FIG. 28E shows a second (e.g., bottom) side of the capillator.

[0082] FIG. 29A illustrates a filled capillator positioned above an empty container mount according to the present disclosure.

[0083] FIG. 29B illustrates the fluid in the filled capillator transferring to a container within the container mount of FIG. 29A during a centrifuge process according to the present disclosure.

[0084] FIG. 29C illustrates an example centrifuge according to the present disclosure.

[0085] FIG. 29D illustrates an example centrifuge mount according to the present disclosure.

[0086] FIG. 29E illustrates a close up view of the centrifuge mount containing container mounts according to the present disclosure.

[0087] FIG. 29F shows a first (e.g., top) side of an example embodiment of a container mount.

[0088] FIG. 29G shows a second (e.g., bottom) side of the container mount.DETAILED DESCRIPTION

[0089] The following detailed description is directed to certain specific embodiments of the present disclosure. Reference in this specification to ‘'one embodiment,” “an embodiment,” or “in some embodiments” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. The appearances of the phrases “one embodiment,” “an embodiment,” or “in some embodiments” in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments necessarily mutually exclusive of other embodiments. Moreover, various features are described which may be exhibited by some embodiments and not by others.

[0090] Various embodiments will now be described with reference to the accompanying figures, wherein like numerals refer to like elements throughout, unless context dictates otherwise. The terminology used in the description presented herein is not intended to be interpreted in any limited or restrictive manner, simply because it is being utilized in conjunction with a detailed description of certain specific embodiments of the present disclosure. Furthermore, embodiments of the present disclosure may include several novel features, no single one of which is solely responsible for its desirable attributes or which is essential to practicing the present disclosure.

[0091] The technology generally relates to implantable intraocular drug delivery devices, which can be structured to provide targeted and / or controlled release of a drug to a desired intraocular tissue. In certain embodiments, this disclosure relates to methods of filling the drug delivery devices with a fluid (e.g., a viscous fluid). In some embodiments, a viscous fluid has a viscosity greater than 500 cP at 25 degrees C, greater than 1000 cP at 25 degrees C, greater than 10000 cP at 25 degrees, or more, or less, or any value in between. The methods and devices described herein are advantageous as containers (e.g., ocular implants) can be filled with a target volume of fluid using methods that reduce the risk of overfilling or spillage. The methods and devices described herein are also beneficial in that the risk of operator error is reduced and the accuracy of filling the containers is increased. Additionally, the methods allow for a higher throughout of filled containers. In some cases, filling a container can include transferring a target amount of fluid into the container, even if additional space remains in the container, such as to accommodate a cap, seal member, fluid dispenser, etc. Various details regarding the ocular implants and other containers are disclosed in U.S. Patent Application Publication No 2018 / 0333296, which is titled DRUG DELIVERY IMPLANTS ASINTRAOCULAR DRUG DEPOTS AND METHODS OF USING SAME, which published on November 22, 2018, and which was filed as U.S. Patent Application No. 15 / 756,906. The US 2018 / 0333296 is hereby incorporated by reference and made a part of this specification for all that it discloses.

[0092] Drug delivery' ocular implants can be made to hold a variety' of different drug volumes. The methods and systems disclosed herein can be used to transfer various different volumes of fluid, such as about 10 nanoliters, about 20 nanoliters, about 30 nanoliters, about 40 nanoliters, about 50 nanoliters, about 60 nanoliters, about 70 nanoliters, about 80 nanoliters, about 90 nanoliters, about 100 nanoliters, about 110 nanoliters, about 120 nanoliters, about 130 nanoliters, about 140 nanoliters, about 150 nanoliters. about 160 nanoliters, about 170 nanoliters. about 180 nanoliters, about 190 nanoliters, about 200 nanoliters. about 225 nanoliters, about 250 nanoliters, about 300 nanoliters, about 350 nanoliters, about 400 nanoliters, about 450 nanoliters, about 500 nanoliters, or more, or any values therebetween, or any ranges between any of these values, although other volumes of fluid could be used in some cases. In some embodiments, the volume of fluid can be less than about 500 nanoliters, less than about 400 nanoliters, less than about 400 nanoliters, less than about 200 nanoliters, or less than about 100 nanoliters.

[0093] The drug delivery ocular implant or other container can have an opening to receive the fluid, and the opening can have a width or diameter of about 0.1 mm, about 0.15mm, about 0.2 mm, about 0.25 mm, about 0.3 mm. about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, about 0.55 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1 mm, about 1.2 mm, about 1.5 mm, about 2 mm, or any values therebetween, or any ranges between any of these values, although other sizes could be used in some cases. In some cases, the opening can have a width or diameter of less than or equal to about 1 mm. less than or equal to about 0.5 mm, or less than or equal to about 0.3 mm, although other sizes could be used in some cases.Example Filling Method Using Primed Tubes

[0094] FIG. 1 is a flow chart illustrating an example method 100 of filling a container with a fluid according to the present disclosure. FIGS. 2-9 illustrate corresponding parts, structures, and / or method steps related to the method 100.

[0095] Starting at block 104 a tube or tubing 120 can be obtained and primed with a fluid. The terms tube and tubing may be used interchangeably herein. For example, a portion of an empty tube 120 is shown in FIG. 2. FIG. 2 shows several tubes 120 inside a container,which can be used for shipping and / or storage of the tubes 120. In some embodiments, the tube 120 can be a Fluorinated Ethylene Propylene (FEP) tube, although various other polymers or other materials could be used, such as Perfluoroaloxy Alkanes (PF A), Polytetrafluoroethylene (PTFE), other fluoroplastic material, or other material such as polyetheretherketone (PEEK), silicone, glass, or other material. The tube 120 can include an inner coating (or another inner surface treatment) to have a hydrophilic, hydroscopic, or an electrostatic inner surface. The tube 120 can be primed in various lengths. Tubes of various lengths can be used, for example, about 6 inches, about 9 inches, a 1 foot length tube, a 2 foot length tube, a 3 foot length tube, a 4 foot length tube, a 5 foot length tube, a 6 foot length tube, a 7 foot length tube, an 8 foot length tube, a 9 foot length tube, a 10 foot length tube, a 12 foot length tube, a 15 foot length tube, a 20 foot length tube, or more, or any values therebetween, or any ranges between any of these values, although other sizes could also be used. The tube 120 can have an outer diameter of about 0.03125 inches, in some embodiments but other sizes could also be used. For example, the tube 120 can have an outer diameter of about 0.01 inches, about 0.02 inches, about 0.03 inches, about 0.04 inches, about 0.05 inches, or any value in between, or any ranges between any of these values, although other sizes could be used. The tube 120 can have an inner diameter of about 0.004 inches, in some embodiments but other sizes could also be used. For example, the tube 120 can have an inner diameter of about 0.001 inches, about 0.002 inches, about 0.003 inches, about 0.004 inches, about 0.005 inches, about 0.006 inches, about 0.007 inches, about 0.008 inches, or any value in between, or any ranges between any of these values, although other sizes could be used. The tube can have an inner diameter of about 0.05 mm, about 0.055 mm, about 0.06 mm, about 0.065, about 0.07 mm, about 0.075, about 0.08 mm, about 0.085, about 0.09 mm, about 0.095, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm. about 0.14 mm, about 0.15 mm, about 0.17, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, or any values therebetween, or any ranges between any of these values, although other sizes could be used in some cases. In some embodiments, the tube can have a thickness between about 0.01 inch to about 0.1 inch.

[0096] In some embodiments, the fluid can be a viscous fluid. In some embodiments, the fluid can be a drug, which can be formulated as an oil. The drug can include a prostaglandin, a prostaglandin analog, a prostaglandin inhibitor, a beta-adrenergic receptor antagonist, or combinations thereof, although other drugs can be used as discussed herein. In some embodiments, the drug can include travoprost. In some embodiments, antioxidants can help to extend the shelf-life (or therapeutic life-span) of a drug by reducing the oxidation rate of the active ingredient and / or an excipient compounded with the drug. Examples of suitableantioxidants include without limitation propyl gallate, tertiary' butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), butylated hydroxy toluene (BHT), beta carotene, vitamin E, vitamin C, sodium bisulphite, sodium salts of edetate (EDTA), butylated hydroxy ethylbenzene (BHEB), octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (e.g., Irganox 1076), pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxyhydrocinnamate) (e.g., Irganox 1010), other sterically hindered phenolic antioxidants (e.g., Irganox B900), tris(2,4-di-tert-butylphenyl) phosphite (e.g., Irgafos 168), oleamide, erucamide, N,N’-Ethylenebisoleamide (EBO), oleylpalmitamide (OP), and mixtures thereof. Various drug formulations can be used. Nonlimiting examples include a travoprost-propyl gallate formulation, a travoprost-TBHQ formulation, a travoprost-BHA formulation, a travoprost-beta carotene formulation, a travoprost vitamin E formulation, a travoprost-vitamin C formulation, a travoprost-sodium bisulphate formulation, and a travoprost-EDTA formulation.

[0097] FIG. 3 illustrates an exploded view of a portion of an example priming assembly 124. The priming assembly 124 can be used to fill the tube 120 with the fluid. As shown in FIG. 4, the priming assembly 124 can include a tube connector 128, a fluid reservoir 132, and a pressure connection 136. The tube 120 can be connected to the fluid reservoir 132 via the tube connector 128. The fluid reservoir 132 can contain the fluid (e.g., travoprost). The priming of the tube 120 can occur under pressure, such as through the use of pressurized nitrogen (or another gas) from a gas cylinder 138 (as labeled in FIG. 5B) attached to the pressure connection 136. The use of pressure can drive the fluid into the tube 120.

[0098] A connector 133 can be used to couple a pressure line to the tube 120. The connector 133 can include a housing 135. A first end of the connector 133 can be configured to couple to a pressure line, such as using the pressure connection 136. A second end of the connector 133 can be configured to couple to the tube 120, such as using the tube connector 128. The connector 133 can include the fluid reservoir 132. For example, the first end of the connector 133 can include a reservoir cavity (e.g., a bore), which can receive a volume of the fluid therein. The reservoir cavity can extend from the first end of the connector towards the second end of the connector. A tube cavity can extend from a floor of the reservoir cavity towards the second end of the connector. The tube cavity can have a width or diameter that is smaller than a width or diameter of the reservoir cavity. In some cases, the tube cavity can receive the tube therein. The second end of the connector can be threaded to receive the tube connector 128, which can configured to couple to the tube 120, such as using the tube connector 128. The first end of the connector 133 can be a compression-fit connector, such as a PEEK compression-fit connector. The tube connector 128 can be threaded to engage the threadingon the second end of the connector 133. The tube connector 128 can be a two-piece compression fitting. The outer piece can be threaded onto the connector 133 to drive the inner piece toward the connector 133. The inner piece can have a tapered end that can engage a tapered recess on the second end of the connector 133, and the tube 120 can extend through the tapered end of the inner piece. The inner piece can be pressed against the tube 120 as the inner piece is driven into the tapered recess, thereby securing the tube 120 to the tube connector 128 and coupling the tube to the connector 133. Various other suitable couplers can be used to connect the tube 120 to the connector 133. A pressure device (e g., the gas cylinder 138 or pump) can apply pressure to the first end of the connector 133, which can pressurize the fluid reservoir 132, which can drive the fluid into the tube 120.

[0099] In some embodiments, heating of the fluid may be used to reduce the overall time required to prime the tube 120. For example, the heating of the fluid may reduce the viscosity of the fluid. One or more tubes can be primed at a time using the priming assembly 124. FIGS. 5A-5C illustrate additional views of the priming assembly 124. The system can apply pressure to drive the fluid into the tube, such as pressure of about 100 psi, about 200 psi, about 300 psi, about 400 psi, about 500 psi, about 600 psi, about 700 psi, about 800 psi, about 900 psi, about 1000 psi, about 1200 psi, about 1400 psi, about 1600 psi, about 1800 psi, about 2000 psi, about 2200 psi, about 2400 psi, about 2500 psi, about 2600 psi, about 2700 psi, about 2800 psi, about 2900 psi. about 3000 psi, about 3250 psi, about 3500 psi, about 3750 psi, about 4000 psi. about 4500 psi, about 5000 psi, or more, or any values therebetween, or any ranges between any of these values, although other amounts of pressure could be used.

[0100] The tube 120 and / or the pressure reservoir 132 can be placed in a heater 121. The heater 121 can include a thermally controlled enclosure or housing. The enclosure can be insulated in some cases. The heater can include a heating element that is configured to provide heat to the enclosure so as to increase the temperature inside the enclosure. In some cases, the system can perform cooling as well as heating, such as to maintain the temperature of the thermally controlled enclosure at a temperature to temperature range, which can be specified by a user, in some cases. The heater can include a thermoelectric cooler and / or heater, such as a heat pump, a Peltier device, etc. The fluid can be heated, and / or the tube 120 can be primed, at a temperature above room temperature (e.g., about 37 degrees Celsius, in some embodiments). However, various temperatures can be used, such as about 20 degrees Celsius, about 22 degrees Celsius, about 25 degrees Celsius, about 30 degrees Celsius, about 33 degrees Celsius, about 34 degrees Celsius, about 35 degrees Celsius, about 36 degrees Celsius, about 37 degrees Celsius, about 38 degrees Celsius, about 39 degrees Celsius, about 40 degreesCelsius, about 45 degrees Celsius, about 50 degrees Celsius, about 60 degrees Celsius, about 70 degrees Celsius, about 80 degrees Celsius, about 90 degrees Celsius, about 100 degrees Celsius, or any value in between, or any ranges between any of these values, although other temperatures could be used. In some cases, the fluid can be heated to a temperature of greater than or equal to about 25 degrees Celsius, greater than or equal to about 30 degrees Celsius, greater than or equal to about 35 degrees Celsius, or greater than or equal to about 40 degrees Celsius, although other temperatures could be used in some cases.

[0101] The inside of the enclosure can have a connector 123, which can be configured to engage with the pressure connection 136, such as to couple the fluid reservoir 132 to the pressure device, such as the gas cylinder 138. Various other suitable pressure devices could be used in place of the gas cylinder 138. such as a pump, an actuated plunger, inbuilt facility compressed gas, etc. The pressure device (e.g., gas cylinder 138) can couple to a port 125, which can be outside of the enclosure. A pressure line 127 can extend from the port 125, through a wall of the enclosure, to the connector 123. A valve 129 can be configured to open and / or close the pressure line 127. For example, the user can close the valve 129 while the tube 120 is being attached to the priming assembly, and / or while the fluid is being heated. Then the user can open the valve 129 to start the priming process.

[0102] The enclosure can have a transparent lid or window, which can enable a user to see the tube 120 inside the enclosure. The enclosure can have lights 131, which can be configured to illuminate the tube 120, which can facilitate observation of the tube 120 to determine the progress made during priming of the tube 120. The lights 131 can be disposed along the periphery of the enclosed chamber of the heater 121, in some cases. The tube 120 can be wound around a spool, which can be positioned in a generally central region of the chamber. The lights 131 can be configured to directly light inwardly toward the tube 120 on the spool. Various different systems could be used for priming the tube 120.

[0103] By way of example, the priming process of filling the tube 120 can take about 2 hours for a 5 foot length of tubing using 1000 PSI of pressure at a temperature of 37 degrees C. Various other parameters could be used for priming the tube 120. The priming speed can depend on how far along the tube the priming process is, and the total length of tube. The priming process can become slower as the tube 120 is filled with the fluid and the fluidic resistance to flow increases. For example, the fill rate can start at a rate of several inches per minute at the very beginning and it can slow to a fraction of an inch per minute by the end of the process. In some cases, the longer the tube, the more the fill rate slows as it progresses. The tube can be primed at a rate of about 0.1 inches per minute, about 0.2 inches per minute,about 0.25 inches per minute, about 0.3 inches per minute, about 0.35 inches per minute, about 0.4 inches per minute, about 0.45 inches per minute, about 0.5 inches per minute, about 0.55 inches per minute, about 0.6 inches per minute, about 0.65 inches per minute, about 0.7 inches per minute, about 0.75 inches per minute, about 0.8 inches per minute, about 0.85 inches per minute, about 0.9 inches per minute, about 0.95 inches per minute, about 1 inch per minute, about 1.25 inches per minute, about 1.5 inches per minute, about 2 inches per minute, about 3 inches per minute, about 4 inches per minute, about 5 inches per minute, or any values therebetween, or any ranges bounded by any of these values. In some cases, these values can be an average fill rate for priming the tube 120.

[0104] The system can prime one tube 120 at a time, in some cases. Alternatively, multiple tubes 120 can be primed at the same time. The system can include multiple connectors 123, which can be coupled to multiple tubes 120. Pressure can be selectively sent to each tube, such as using separate valves 129, and separate pressure lines 127, which can branch off from a common pressure source, in some cases.

[0105] Moving to block 108. after priming the tube 120 with the fluid, the tube 120 can be cut into tube segments 140. The length of the tube segments 140 can be based at least in part on a target amount of the fluid (e g., measured by volume or by weight, etc.) that is intended to be used to fill a container. FIG. 6B illustrates the tube segments 140 after being cut from tube 120. Prior to cutting all tube segments 140 from a tube 120, at least one calibration tube segment 120a, 120b may be cut from one or both ends of the primed tube 120, as can be seen in FIG. 6 A. The calibration tube segment(s) 120a, 120b can be weighed using a precision balance. After weighing the calibration tube segment(s) 120a, 120b, the fluid from inside the calibration tube segments can be emptied from the calibration tube segments. The now-empty calibration tube segment(s) 120a, 120b can be weighed again and the amount of fluid that was held can be determined based on a comparison of the weight of the fdled calibration tube segment as compared to the weight of the emptied calibrations tube segment. The weight of the fluid per unit length (e.g., one mm) of the tube 120 can be calculated by finding the difference between the primed calibration tube segment and the empty calibration tube segment 120a or 120b, and by dividing that difference by the length of the calibration segment. If multiple calibration tube segments 120a, 120b are used, the determined amounts of fluid per unit length can be averaged. If the difference between the amount of fluid per unit length for one calibration tube segment 120a is different from the amount of fluid per unit length for another calibration tub segment 120b is above a threshold amount, that can indicate that the tube 120 is not sufficiently uniform to use for allocating amounts of the fluid, and that tube 120can be discarded for example. In some cases, the amount of fluid per unit length can be determined by averaging the results for the difference between the primed and empty weights from multiple calibration tube segments 120a, 120b (e.g., each calibration tube segment 120a, 120b from each end of the tube 120) and dividing the average by the length of the calibration tube segment(s) 120a, 120b (e.g., which can be of the same length). For example, this is shown in the equations below. Additional calibration segments beyond two segments can be used in a similar manner to improve characterization of tube 120 by, for example, cutting a calibration segment from near the middle of tube 120, or by cutting any number of calibration segments from any portions of the tube 120 (e.g., at periodic intervals). In some cases, a single calibration segment can be used. In some cases, no calibration segments are cut. For example, a total amount of fluid put into the tube 120 can be known or measured (e.g., by weighing the tube before and after priming). The total amount of fluid can be divided by the length of the tube 120 to get the amount of fluid (e.g., in weight) per unit length of the tube 120.Fluid in Cal. Segment 1 = (Weight of Cal. Segment 1 as cut — Weight of Cal. Segment 1 after emptying) Fluid in Cal. Segment 2 = (V cit / it of Cal. Segment 2 as cut — Weight of Cal. Segment 2 after emptying)Fluid in Cal. Segment 1 + Fluid in Cal. Segment 2 1Fluid per mm of tube = - - - x - - - — „ - 2 Length of Cal. SegmentsThe predetermined length (e.g., cut length) for each tube segment 140 of tube 120 can be based at least in part on the target fill amount or weight and the determined amount or weight of liquid per unit length, such as calculated using the equation below.Target fill weightCut Length — - - - - - - — - - Liquid weight per mm of tubing

[0106] Moving to block 112, the tube segments 140 of tube 120 can be at least partially inserted into a funnel 144 aligned with a container mount 148. In some embodiments, the funnel 144 and / or the container mount 148 can be made of titanium, although various other metals or other materials could be used. The funnel 144 can have atop surface 145 and a bottom surface 146. An opening 147 can extend from the top surface 145 to the bottom surface 146. The opening 147 can have a decreasing diameter as it extends from the top surface 145 toward the bottom surface 146.

[0107] The container mount 148 can have a top surface 149 and a bottom surface 150. The top surface 149 can have an opening or recess sized and shaped to receive a container152. Non-limiting examples of containers 152 include intraocular drug delivery devices such as drug delivery implants. The funnel member 144 can fit onto the container mount 148. For example, at least one of the funnel member 144 and / or the container mount 148 can have a protrusion, which can engage with a recess on the other of the container mount 148 or funnel member 144, which can align the funnel member 144 with the container mount 148. An opening of the container 152 can align with an opening at the bottom of the funnel 144. so that fluid can exit the bottom of the funnel 144 and enter the opening of the container 152, as discussed herein. The alignment of the funnel 144 with the container 152 can be accomplished using the fixture 160 that holds the two parts on top of each other. The funnel member 144 and the container mount 148 can be cylindrical parts (although other shapes could be used, such as if the openings in the fixture 160 have different shapes), which can be aligned by both parts being in the same hole or opening 170. In some cases, there can be a small clearance between the diameter of the hole or opening 170 and the diameters of the funnel member 144 and / or container mount 148 themselves. By way of example, a total clearance of about 50 microns can be used, such as with a diameter of about 4 mm for the funnel member 144 and / or the container mount 148, and a diameter of about 4.05 mm for the holes or openings 170. The tolerance of each dimension can be about + / - 0.02 mm. Various clearance amounts could be used, such as about 10 microns, about 20 microns, about 30 microns, about 40 microns, about 50 microns, about 60 microns, about 70 microns, about 80 microns, about 90 microns, about 100 microns, or more, or any values or ranges between any of these values. Various other alignment or engagement features can be used to couple to the funnel member 144 with the container mount 148, such as a friction fit, threading, a clamp, or any other suitable coupling mechanism. The top of the container 152 can be spaced apart from the bottom of the funnel 144. Alternatively, the bottom of the funnel 144 can have a protrusion or nozzle that extends into and below the top of the container 152. The top of the funnel 144 can be wider than the width of the tube 120. The bottom of the funnel 144 can be narrower than the width of the tube 120. The funnel member 144 can have a recess on the bottom side thereof, which can receive a portion of the container 152 into the recess when the funnel member 144 and the container mount 148 are coupled together. In some cases, the container 152 does not contact the funnel member 144. The funnel member 144 can be an adapter (e g., a spin adapter) for interfacing between the tube 120 and the container 152, such as during centrifuging. The opening at the bottom of the funnel 144 can be a channel that extends to the bottom of the adapter so that fluid can flow down the funnel, through the channel, and out of the adapter.

[0108] The narrow opening of the funnel 144 and / or the channel can have a width or diameter of about 0.05 mm. about 0.055 mm about 0.06 mm, about 0.065, about 0.07 mm, about 0.075, about 0.08 mm, about 0.085, about 0.09 mm, about 0.095, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, about 0.15 mm, about 0.17, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, or any values therebetween, or any ranges between any of these values, although other sizes could be used in some cases. The wide opening of the funnel 144 can have a width or diameter of about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1 mm, about 1.2 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, about 3.5 mm, about 4.0 mm, about 4.5 mm, about 5.0 mm, or any values therebetween, or any ranges between any of these values, although other sizes could be used in some cases. The opening at the end of the channel or funnel member 144 can be spaced apart from the container, such as by a distance of about 0.05 mm, about 0.055 mm, about 0.06 mm, about 0.065, about 0.07 mm, about 0.075, about 0.08 mm, about 0.085, about 0.09 mm, about 0.095, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm. about 0.14 mm, about 0.15 mm. about 0.17. about 0.2 mm, about 0.25 mm, or any values therebetween, or any ranges between any of these values, although other distances could be used in some cases. Alternatively, the bottom of the funnel member 144 can have a protrusion or nozzle that extends into and below the top of the container 152.

[0109] A transfer assembly 156 can be assembled by positioning the container 152 within the container mount 148. The container mount 148 holding the container 152 can be aligned with the funnel 144. For example, the bottom surface 146 of the funnel 144 can be aligned with the top surface 149 of the container mount 148. The container 152 can be aligned with the opening 147 that extends through the bottom surface of the funnel 144. In some embodiments, a tube segment 140 of tube 120 can be at least partially inserted into the funnel 144. The transfer assembly 156 can be used to transfer the fluid from within the tube segment 140 to container 152 via the funnel 144.

[0110] One or more transfer assemblies 156 can be disposed within a centrifuge spin fixture 160. FIG. 8 A illustrates an exploded view of the centrifuge spin fixture 160 and transfer assemblies 156. FIGS. 8B and 8C illustrate the centrifuge spin fixture 160 assembled and retaining a plurality of transfer assemblies 156. The centrifuge spin fixture 160 can include a base portion 164 and lid portion 168. The base portion 164 can include a plurality of openings 170. The openings 170 can be sized to receive a transfer assembly 156. While ten openings 170 are shown, there can be any number of openings 170. For example, 5 openings 10 openings,15 openings, 20 openings, or more, or any values or ranges therebetween. The number of openings 170 can determine how many containers 152 can be filled during a single centrifuge process as described herein. While a round centrifuge spin fixture is shown, other shapes and sizes, including larger shapes and sizes that contain many more openings, are possible. The spin fixture 160 may preferentially be designed to fit into and be contained within a vessel typically used for centrifugation, such as a 50 mL centrifuge tube. Alternatively, the spin fixture may, but not necessarily, be designed to fit into other vessels typically used for centrifugation, such as a 10 mL centrifuge tube, multiwell plate, etc.[OHl] In some embodiments, the transfer assemblies 156 can be assembled as they are inserted into the centrifuge spin fixture 160. For example, the container mount 148 can be inserted into the opening 170 of the base portion 164. The container 152 can be inserted into the container mount 148 prior to or after the container mount 148 are inserted into the base portion 164. After inserting the container mount 148 into the base portion 164, the funnel 144 can be inserted into the opening 170 and aligned on top of the counter mount 148. In some embodiments, the transfer assemblies 156 can be pre-assembled and then inserted into the centrifuge spin fixture 160.

[0112] In some embodiments, the transfer assemblies 156 can be inserted into the openings 170 prior to inserting the tube segment 140 of tube 120 into the funnel 144. The lid portion 168 can then be coupled to the base portion 164. After coupling the lid portion 168 and the base portion 164, the tube segments 140 of tube 120 can be inserted into corresponding funnels 144 of the transfer assemblies 156 through openings 174 in the lid portion 168. The openings 174 in the lid portion 168 can be smaller than the openings 170 in the base portion 164 to prevent the transfer assemblies from falling out of the centrifuge spin fixture 160.

[0113] In some embodiments, the transfer assemblies 156 can be inserted into the openings 170 with the tube segments 140 previously inserted in the funnels 144. Alternatively, the tube segments 140 of tube 120 can be inserted into the funnels 144 prior to attaching the lid portion 168 being coupled to the base portion 164.

[0114] Moving to block 116, the fluid can be transferred to the containers 152 using a centrifuge 182, for example as shown in FIG. 9. One or more centrifuge spin fixtures 160 can be inserted into the centrifuge 182. In some embodiments, an even number of centrifuge spin fixtures 160 can be inserted into the centrifuge 182. This can facilitate a uniform distribution of the centrifuge spin fixtures 160 within the centrifuge. For example, if two centrifuge spin fixtures 160 are used they can be positioned directly across from or opposite one another. If four centrifuge spin fixtures 160 are used they can be positioned such that each pair ofcentrifuge spin fixtures 160 are positioned directly across from or opposite one another. This can facilitate substantially even weight distribution for smooth operation of the centrifuge. In some cases, the centrifuge spin fixtures 160 can pivot (e.g., by about 90 degrees) between an insertion position (as shown in Figure 9) and a spinning position. When spinning the container 152 can be positioned radially outw ard of the funnel 144. The fluid can be driven radially outward by the centrifuge, out of the tube segment 140 and into the funnel 144, then through the bottom of the funnel 144 and into the container 152.

[0115] The centrifuge can operate for various operation times, such as about 1 minute, 5 minutes, 10 minutes, 15 minutes, 25 minutes, 35 minutes, or 40 minutes or any value in between, or any ranges between any of these values, although other operation times could be used as well. The centrifuge can operate at about 3,700 RPMs, generating about 3.000 xG RCF, for example. In some cases, the centrifuge can be operated at different speeds to generate a relative centrifugal force of greater than or equal to about 100 xG RCF, greater than or equal to about 500 xG RCF, greater than or equal to about 1000 xG RCF, greater than or equal to about 2,000 xG RCF, greater than or equal to about 3,000 xG RCF. greater than or equal to about 3,500 xG RCF, greater than or equal to about 4,000 xG RCF, greater than or equal to about 4,500 xG RCF, greater than or equal to about 5,000 xG RCF, greater than or equal to about 7,000 xG RCF, greater than or equal to about 10,000 xG RCF, up to about 50,000 xG RCF, up to about 100,000 xG RCF, or more, or less, or any values or ranges in between any of the list values, although other values could be used in some cases.

[0116] In some embodiments, the fluid can be heated during the centrifuging. For example, the centrifuge 182 can include a heater. In some cases, the centrifuge 182 can generate heat during the centrifuging process (e g., by operation of the motor or friction, etc.), and that heat generated by operation of the centrifuge can be used to heat the fluid. The centrifuge 182 can have a cooler, which can operate to control the temperature in the centrifuge 182. In some cases, the cooler and / or the operation of the centrifuge (or a dedicated heater) can be used to heat the fluid to a target temperature or temperature range during the centrifuging, such as a temperature above room temperature (e.g.. about 37 degrees Celsius, in some embodiments). However, various temperatures can be used, such as about 20 degrees Celsius, about 22 degrees Celsius, about 25 degrees Celsius, about 30 degrees Celsius, about 33 degrees Celsius, about 34 degrees Celsius, about 35 degrees Celsius, about 36 degrees Celsius, about 37 degrees Celsius, about 38 degrees Celsius, about 39 degrees Celsius, about 40 degrees Celsius, about 45 degrees Celsius, about 50 degrees Celsius, about 60 degrees Celsius, about 70 degrees Celsius, about 80 degrees Celsius, about 90 degrees Celsius, or anyvalue in between, or any ranges between any of these values, although other temperatures could be used as well. In some cases, a heater can be used to add heat beyond the heat produced by centrifuging. In some cases, the fluid is not heated above a temperature as disclosed herein so as to not negatively impact the fluid (e.g., drug) being transferred. In some cases, the container is an implant that will be implanted into an eye or other portion of a patient's body, so that the drug will experience a range of human body temperatures after being implanted. Accordingly, in some embodiments, the fluid is not heated beyond (or much beyond) the temperature of the human body during the fluid transfer process. Thus, the heat applied during the transfer process would not degrade the fluid any more than the body heat of the patient would after being implanted. Alternatively, the fluid may be heated beyond the temperature of the human body, such as a temperature of about 40 degrees Celsius, about 50 degrees Celsius, about 60 degrees Celsius, about 70 degrees Celsius, or even warmer, to further decrease viscosity. Such elevated temperatures may not substantially degrade the fluid depending on the properties of the fluid and / or when applied for short periods of time.

[0117] The number of centrifuge spin fixtures 160 and / or the number of transfer assemblies 156 per each centrifuge spin fixture 160 can determine how many containers 152 are filled at a time. In some cases, the centrifuge can be operated for about 20 minutes in order to transfer the fluid from the tube segments 140 to the containers 152. However, various operation times can be used, such as about 1 minute, about 2 minutes, about 3 minutes, about 5 minutes, about 10 minutes, about 15 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 60 minutes, or more, or any values in between, or any ranges between any of these values, although other operation times could be used as well. Generally, when the centrifuge is heated to higher temperature a shorter operation time can be used. The fluid can be transferred from the tube segments 140 to the containers 152 via the spinning of the centrifuge spin fixtures 160 within the centrifuge 182. The spinning of the centrifuge spin fixtures 160 can draw the fluid from the tube segment 140 into the funnel 144 and then into the container 152. Once the centrifuge cycle is complete, the centrifuge spin fixtures 160 can be disassembled and the filled containers 152 can be removed.Example Filling Method Using Aliquoters

[0118] FIG. 10 is a flow chart illustrating an example method 300 of filling a container with a fluid according to the present disclosure. FIGS. 11-20 illustrate corresponding parts, structures, and / or method steps related to the method 300. The method 300 may use analiquoter 304, a spin adapter 308, and a container mount 312. As used herein, the term "aliquoter" refers to a device configured to receive and hold a predetermined volume of fluid. In some embodiments, an aliquoter can include a fluid-receiving portion and an overflow portion configured to allow excess fluid beyond the predetermined volume to exit the fluidreceiving portion. In some cases, the dimensions and / or configuration of the fluid-receiving portion can be based on a desired amount of fluid to be transferred to a container. The aliquoter 304, spin adapter 308, and / or the container mount 312 can be assembled in various configurations during various stages of the method 300 according to the present disclosure during the execution of method 300.

[0119] FIGS. 11A-C illustrate an example embodiment of the aliquoter 304. The aliquoter 304 can have any shape cross-section. For example, the aliquoter 304 can have a generally cylindrical shape (e.g., with a generally circular cross-section), a generally square cross-section, and / or polygonal cross-section. The cross-sectional shape of the aliquoter 304 can correspond to the cross sectional shape of the spin adapter 308 and / or the cross-sectional shape of the container mount 312. The aliquoter 304 can have a first opening 305 extending through a top surface 306. The first opening 305 can be located along a central longitudinal axis of the aliquoter 304, in some embodiments. The first opening 305 can align with a channel 307. The channel 307 can extend from the top surface 306 toward a bottom surface 309 of the aliquoter 304. The channel 307 can extend from the top surface 306 about a distance equal to, less than, or greater than, about half a height of the aliquoter 304.

[0120] The channel 307 can have a closed end opposite the opening 305. The channel 307 can have an opening 310 extending through a sidewall of the channel 307. The opening 310 can fluidly couple the channel 307 to a first outlet channel 311 and / or a second outlet channel 313. The first outlet channel 311 can be offset of the channel 307 and can extend generally parallel to the channel 307. The first outlet channel 311 can have a closed end positioned closer to the top surface 306 than then bottom surface 309. The first outlet channel 311 can have an open end extending into a recess 314 of the bottom surface 309.

[0121] The second outlet channel 313 can extend generally perpendicular to the channel 307 and / or the channel 311. The second outlet channel 313 can extend from the opening 310 of the channel 307 to an opening in a sidewall of the aliquoter 304. The second outlet channel 313 can extend through the first outlet channel 311.

[0122] The channel 307 can be a bore, which can be formed by drilling a hole into the top surface 306 of the aliquoter 304. The channel 311 can be a bore, which can be formed by drilling a hole into the bottom surface 309 of the aliquoter 304. A wall 315 can separate thechannel 307 from the channel 311. The opening 310 can extend through the wall 315 to fluidically connect the channel 307 to the channel 311 at the opening 310. The opening 310 can be formed by drilling a hole into the side of the aliquoter 304 to form the channel 313. The channel 313 can be formed by advancing a drill from the side of the aliquoter 304 to the channel 311, and the drill can be advanced through the wall 315 and into the channel 307, thereby forming the opening 310. The channel 307 can extend substantially parallel to an axis of the aliquoter 304 (e.g., along a central axis). The channel 311 can extend substantially7parallel to the axis of the aliquoter 304 and / or substantially parallel to the channel 307. The channel 313 can extend laterally, such as substantially perpendicular to the axis of the aliquoter 304, the channel 307, and / or the channel 311. In some embodiments, the channel 313 can be formed at other angles, and the opening 310 could still be formed at the same location as illustrated. In some cases, the channel 313 can be substantially parallel to the channel 307. For example, the channel 313 could be at the location shown in dashed lines in Figure 11 A. The channel 313 can extend between channel 307 and channel 311 so that the channels 307 and 311 are joined by an opening that ends at the bottom of the bore or channel 313. The wall 315 can separate the channels 307 and 311 below the channel 313. In another example, the channel 307 can have a larger diameter or width at an upper portion, so that the channel 307 is open to channel 311 at the upper portion, and the channel 307 can have a smaller diameter or width at a lower portion, so that the lower portion of the channel 307 is separated from the channel 311 by the wall 315.

[0123] The dimensions of the channel 307 and / or the position of the opening 310 can be configured based on a desired amount (e.g., volume) of fluid to be transferred to the container 152. As discussed herein, fluid can be transferred into the channel 307. The fluid can fill the channel until the fluid level reaches the opening 310, and additional fluid can then flow through the opening 310 and out of the outlet channel 311. In some cases, the channel 313 can be used merely to form the opening 310 during construction of the device. The channel 313 could be filled or capped, or the channel 313 can remain open during use. In some cases, the channel 313 can be in fluid communication with the channel 307 and the channel 311 so that some fluid could flow out through the channel 313. such as depending on the angle of the channel 313. In some cases, the channel 311 can be the primary or only outflow path for the excess fluid. In some cases, the channel 313 can be the primary7or only outflow path for the excess fluid. For example, and channel 313 can be formed at an angle so that it intersects channel 307 to form the opening 310 and so that excess fluid can exit through the channel 313 (e.g., to the bottom side of the aliquoter 304), and in some cases channel 311 can be omitted.Viewed another way, the channel 313 can be omitted, and the channel 311 can be angled relative to the channel 307 so that the channel 311 intersects the channel 307 to form the opening 310.

[0124] The opening 305 to the channel 307 can be wider than the channel 307, such as to form a recess. The opening 305 or recess can be formed by drilling a wider hole than used to form the channel 307. A raised lip 303 can extend into the recess or opening 305 or from the top surface 306 of the aliquoter 304. The raised lip 303 can surround the channel 307 (e.g., extending the channel 307 into the recess or opening 305), such as to form a nipple. The recess or opening 305 and / or the raised lip 303 can facilitate the transfer of fluid out of the channel 307 (e.g., when the aliquoter 304 is inverted, as discussed herein). The recess or opening 305 can act to protect the raised lip 303 from contact with other components or tools (e.g., during manipulation or cleaning) that may damage it if not protected. In some cases, the recess or opening 305 can be omitted. In some cases, the raised lip 303 can be omitted.

[0125] The recess 314 can be wider than the channel 311, and can be formed by drilling a wider hole than used to form the channel 311. A raised lip 319 can extend into the recess 314 or from the bottom surface 309 of the aliquoter 304. The raised lip 319 can surround the channel 311 (e g., extending the channel 311 into the recess 314), such as to form a nipple. The recess 314 and / or the raised lip 319 can facilitate the transfer of fluid out of the channel 311, as discussed herein. In some cases, the recess 314 can be omitted. In some cases, the raised lip 319 can be omitted.

[0126] Although the channels, openings, and recesses are described as being formed by drilling, other techniques could be used, such as milling, machining, or injection molding, etc. In some cases, the channel 307, the channel 311, and the opening 310 can be formed without the channel 313, which could be omitted. The aliquoter 304 can be made of titanium, although various other metals or other materials could be used.

[0127] The channel 307 and / orthe channel 311, and / or the opening 310, and / orthe channel 313 can have a width or diameter of about 0.1 mm, about 0.12 mm, about 0.14 mm, about 0.17, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1 mm, or any values therebetween, or any ranges between any of these values, although other sizes could be used in some cases. The widths or diameters of each channel 307 and / or channel 311, and / or opening 310, and / or channel 313 can be the same or different from each other.

[0128] FIGS. 12A-C illustrate an example embodiment of the spin adapter 308. The spin adapter 308 can include a funnel and can include any of the features described herein withreference to any funnel or funnel member disclosed herein and vice versa. The spin adapter 308 can include a top surface 316 and a bottom surface 320. The spin adapter 308 can have any shape cross-section. For example, the spin adapter 308 can have a generally cylindrical shape (e.g., with a generally circular cross-section), a generally square cross-section, and / or polygonal cross-section. The cross-sectional shape of the spin adapter 308 can correspond to the cross sectional shape of the aliquoter 304 and / or the cross-sectional shape of the container mount 312. The spin adapter 308 can include a funnel 324 extending from an opening 328 in the top surface 316. The funnel 324 can have a decreasing diameter or width as the funnel 324 extends from the opening to a channel 332. For example, the diameter or width of the funnel 324 at the opening 328 can be larger than the diameter or width of the funnel 324 at the start of the channel 332. The diameter or width of the funnel 324 can gradually decrease along the longitudinal axis of the spin adapter 308 (e.g., in the downward direction).

[0129] The channel 332 can extend from the bottom of the funnel 324 (e.g., the smallest diameter or width of the funnel 324) to a recess 336 in the bottom surface 320. The channel 332 can extend into the recess 336 such that an outer wall of the channel 332 and an outer wall of the recess 336 form a generally donut shape recess 336. A raised lip 333 can extend into the recess 336 or from the bottom surface 320 of the adapter 308. The raised lip 333 can surround the channel 332 (e.g., extending the channel 332 into the recess 336), such as to form a nipple. The recess 336 and / or raised lip 333 can facilitate the transfer of fluid out of the channel 332. The recess 336 can act to protect the raised lip 333 from contact with other components or tools (e g., during manipulation or cleaning) that may damage it if not protected. In some cases, the recess 336 can be omitted. In some cases, the raised lip 333 can be omitted. In some cases, the recess 336 can be used to help couple the spin adapter 308 to the aliquoter 304 and / or the container mount 312 according to the present disclosure.

[0130] The adapter 308 can be made of titanium, although various other metals or other materials could be used. The channels, openings, and recesses can be formed by drilling, or techniques could be used, such as milling, machining, or injection molding, etc. to form the structures of the adapter 308.

[0131] The narrow opening of the funnel 324 and / or the channel 332 can have a width or diameter of about 0.05 mm, about 0.055 mm, about 0.06 mm, about 0.065, about 0.07 mm, about 0.075, about 0.08 mm, about 0.085, about 0.09 mm, about 0.095, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, about 0.15 mm, about 0.17, about 0.2 mm, about 0.25 mm, about 0.3 mm. about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, or any values therebetween, or any ranges between any of these values, althoughother sizes could be used in some cases. The wide opening of the funnel 324 can have a width or diameter of about 0.3 mm. about 0.4 mm, about 0.5 mm, about 0.6 mm. about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1 mm, about 1.2 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, about 3.5 mm, about 4.0 mm, about 4.5 mm, about 5.0 mm, or any values therebetween, or any ranges between any of these values, although other sizes could be used in some cases.

[0132] FIGS. 13A-C illustrate an example embodiment of the container mount 312. The container mount 312 can include any of the features described herein with reference to any container mount embodiments and vice versa. The container mount 312 can be used to hold the container 152 during the filling process. Non-limiting example containers 152 include ocular implants or drug delivery devices. The container mount can include a top surface 340 and a bottom surface 344. The container mount 312 can have any shape cross-section. For example, the container mount 312 can have a generally cylindrical shape (e.g., having a generally circular cross-section), a generally square cross-section, and / or polygonal crosssection. The cross-sectional shape of the container mount 312 can correspond to the cross sectional shape of the aliquoter 304 and / or the cross-sectional shape of the spin adapter 308, in some implementations.

[0133] The top surface 340 can include a recess 348. The recess can be formed by drilling into the top surface of the container mount 312. The recess 348 can include an opening 352 sized and shaped to receive at least a portion of the container 152. The opening 352 can extend downward from a surface of the recess 348 toward the bottom surface 344. The bottom surface 344 can be a solid surface with no openings and / or recesses, in some cases. The opening 352 can be a bore, which can be formed by drilling into the container mount 312. A hole 353 can be formed in the bottom of the opening 352. The hole 353 can be a bore, which can be formed by drilling. The recess 348, opening 352, and hole 353 can be formed by other techniques, such as milling or machining, etc. or injection molding can be used to form the container mount 312, or any other suitable technique. The container mount 312 can be made of titanium, although various other metals or other materials could be used. The hole 353 can have a smaller diameter or width than the opening 352. The opening 352 can have a smaller diameter or width than the recess 348. A portion of the container 152 (e.g., a spike or retention portion of an ocular implant) can extend into the hole 353. The bottom of the opening 352 can support the container 152. In some cases the container 152 can extend upward past the upper surface 340 of the container mount 312. For example, the container 152 can extend into the recess 336 of the aliquoter 304. In some cases, the container 152 can be flush with the uppersurface 340, or the top of the container 152 can be recessed below the upper surface 340 (e.g., in the recess 348).

[0134] Starting with block 350 of method 300 the spin adapter 308 can be aligned with and coupled to the aliquoter 304 in a first configuration to form an assembly 317, as shown in FIGS. 14A-14B. The bottom surface 320 of the spin adapter 308 can be coupled with the top surface 306 of the aliquoter 304. The recess 336 of the spin adapter 308 can be aligned with the opening 305 of the aliquoter 304. The opening at the end of the channel 332 or adapter 308 can be spaced apart from the opening to the channel 307, such as by a distance of about 0.05 mm, about 0.055 mm, about 0.06 mm, about 0.065, about 0.07 mm, about 0.075, about 0.08 mm, about 0.085, about 0.09 mm, about 0.095, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, about 0.15 mm, about 0.17. about 0.2 mm. about 0.25 mm, about 0.3 mm, about 0.4 mm, about 0.5 mm, or any values therebetween, or any ranges between any of these values, although other distances could be used in some cases. Alternatively, the opening at the end of the channel 332 can have a protrusion or nozzle that extends into and below the top of the channel 307.

[0135] Moving to block 352 of the method 300, a fluid 301 can be deposited in the spin adapter 308. The fluid 301 can be deposited via a manual method or a robotic method. In some embodiments, the spin adapter 308 can be preloaded with the fluid 301. In some embodiments, the spin adapter 308 can have the fluid 301 deposited into the funnel 324 after the spin adapter 308 and aliquoter are aligned 304 and / or assembled in a first configuration.

[0136] In some embodiments, the fluid 301 can be a viscous fluid. In some embodiments, the fluid can be a drug, which can be formulated as an oil. The drug can include a prostaglandin, a prostaglandin analog, a prostaglandin inhibitor, a beta-adrenergic receptor antagonist, or combinations thereof, although other drugs can be used as discussed herein. In some embodiments, the drug can include travoprost. In some embodiments, antioxidants can help to extend the shelf-life (or therapeutic life-span) of a drug by reducing the oxidation rate of the active ingredient and / or an excipient compounded with the drug. Examples of suitable antioxidants include without limitation propyl gallate, tertiary’ butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), but lated hydroxy toluene (BHT), beta carotene, vitamin E, vitamin C, sodium bisulphite, sodium salts of edetate (EDTA), butylated hydroxy ethylbenzene (BHEB), octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (e.g., Irganox 1076), pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxyhydrocinnamate) (e.g., Irganox 1010), other sterically hindered phenolic antioxidants (e.g., Irganox B900). tris(2,4-di-tert-butylphenyl) phosphite (e.g., Irgafos 168), oleamide, erucamide, N,N’-Ethylenebisoleamide (EBO),oleylpalmitamide (OP), and mixtures thereof. Various drug formulations can be used. Nonlimiting examples include a travoprost-propyl gallate formulation, a travoprost-TBHQ formulation, a travoprost-BHA formulation, a travoprost-beta carotene formulation, a travoprost vitamin E formulation, a travoprost-vitamin C formulation, a travoprost-sodium bisulphate formulation, and a travoprost-EDTA formulation. The viscosity of the fluid 301 can limit or prevent the fluid 301 from flowing into the aliquoter in response to gravity alone in a reasonable amount of time.

[0137] Moving to block 354 of the method 300, the fluid 301 can be transferred from the spin adapter 308 to the aliquoter 304, for example as shown in FIGS. 14A, 14B, and 18. In some embodiments, the fluid 301 can be transferred from the spin adapter 308 to the aliquoter 304 using a centrifuge 362, as shown in FIG. 17. One or more assemblies 317 can be positioned in a centrifuge mount 366 (for example, as shown in FIG. 16). The centrifuge mount 366 may have a plurality of spaces sized to receive the assemblies 317. In some embodiments, the assemblies 317 can be positioned in the centrifuge mount 366 after being assembled. In some embodiments, the assemblies 317 can be assembled as they are positioned in the centrifuge mount 366. For example, the aliquoter 304 can be inserted into a space of the centrifuge mount 366 and then a spin adapter 308 can be positioned over (e g., atop) the aliquoter 304 in the configurations according to the present disclosure. The assemblies 317 can be positioned and / or assembled in the centrifuge mount 366 in a uniform pattern. For example, in linear rows. While rows of three assemblies 317 are shown, any number of assemblies 317 can be aligned in a row. The centrifuge mount 366 can hold 75 assemblies 317, in the embodiment of Figure 1 . The centrifuge mount 366 can hold any other suitable number of the assemblies 317, such as 1, 2, 4, 8, 12, 16, 25, 30, 35, 40, 50, 60, 70. 80, 90, 100, 120, 150, 200, 250. 300, 400, 500, or more, or any values or ranges therebetween.

[0138] One or more centrifuge mounts 366 can be positioned within the centrifuge 362. For example, FIG. 17 illustrates the centrifuge 362 capable of receiving four centrifuge mounts 366. An even number of centrifuge mounts 366 can be positioned within the centrifuge 362. The even number of centrifuge mounts 366 can be uniformly disposed. For example, if two centrifuge mounts 366 are positioned in the centrifuge 362 they can be positioned directly opposite each other. The uniform positioning can facilitate substantially even weight distribution for smooth operation of the centrifuge. During operation of the centrifuge 362, the assemblies 317 will spin. The spinning of the assemblies 317 will assist in transferring the fluid 301 from the spin adapter 308 to the aliquoter 304. In some cases, the centrifuge mount 366 can pivot (e.g., by about 90 degrees) between an insertion position (as shown in Figure 17) anda spinning position. When spinning the container aliquoter 304 can be positioned radially outward of the adapter 308. The fluid can be driven radially outward by the centrifuge, down the funnel 324, through the channel 332, and into the channel 307 of the aliquoter 304.

[0139] In some embodiments, the fluid can be heated during the centrifuging. For example, the centrifuge 362 can include a heater. In some cases, the centrifuge 362 can generate heat during the centrifuging process (e.g., by operation of the motor or friction, etc.), and that heat generated by operation of the centrifuge can be used to heat the fluid. The centrifuge 362 can have a cooler, which can operate to control the temperature in the centrifuge 362. In some cases, the cooler and / or the operation of the centrifuge (or a dedicated heater) can be used to heat the fluid to a target temperature or temperature range during the centrifuging, such as a temperature above room temperature (e.g.. about 37 degrees Celsius, in some embodiments). However, various temperatures can be used, such as about 20 degrees Celsius, about 22 degrees Celsius, about 25 degrees Celsius, about 30 degrees Celsius, about 33 degrees Celsius, about 34 degrees Celsius, about 35 degrees Celsius, about 36 degrees Celsius, about 37 degrees Celsius, about 38 degrees Celsius, about 39 degrees Celsius, about 40 degrees Celsius, about 45 degrees Celsius, about 50 degrees Celsius, about 60 degrees Celsius, about 70 degrees Celsius, about 80 degrees Celsius, about 90 degrees Celsius, or any value in between, or any ranges between any of these values, although other temperatures could be used as well. In some cases, a heater can be used to add heat beyond the heat produced by centrifuging. In some cases, the fluid is not heated above a temperature as disclosed herein so as to not negatively impact the fluid (e.g., drug) being transferred. In some cases, the container is an implant that will be implanted into an eye or other portion of a patient's body, so that the drug will experience a range of human body temperatures after being implanted. Accordingly, in some embodiments, the fluid is not heated beyond (or much beyond) the temperature of the human body during the fluid transfer process. Thus, the heat applied during the transfer process would not degrade the fluid any more than the body heat of the patient would after being implanted. In some embodiments, the centrifuge 362 can operate at about 37 degrees Celsius. However, various temperatures can be used, such as about 20 degrees Celsius, about 22 degrees Celsius, about 25 degrees Celsius, about 30 degrees Celsius, about 33 degrees Celsius, about 34 degrees Celsius, about 35 degrees Celsius, about 36 degrees Celsius, about 37 degrees Celsius, about 38 degrees Celsius, about 39 degrees Celsius, about 40 degrees Celsius, about 45 degrees Celsius, about 50 degrees Celsius, about 60 degrees Celsius, about 70 degrees Celsius, about 80 degrees Celsius, about 90 degrees Celsius, or any value in between, or any ranges between any of these values, although other temperatures could be used as well.Alternatively, the fluid may be heated beyond the temperature of the human body, such as a temperature of about 50 degrees Celsius, 60 degrees Celsius, 70 degrees Celsius, or even warmer, such as to further decrease viscosity. Such elevated temperatures may not substantially degrade the fluid depending on the properties of the fluid and / or when applied for short periods of time. The centrifuge 362 can operate for about 40 minutes, for example, in order to transfer the fluid 301 from the spin adapter 308 to the aliquoter 304. However, various operation times can be used, such as about 5 minutes, 10 minutes, 15 minutes, 25 minutes, 30 minutes, 35 minutes, or 40 minutes or any value or ranges in between any of these values, or any ranges between any of these values, although other operation times could be used as well. Generally when the centrifuge is heated to higher temperature a shorter operation time can be used. The centrifuge can operate at about 3,700 RPMs, which can generate about 3,000 xG RCF (relative centrifugal force), for example. In some cases, the centrifuge can be operated at different speeds to generate a relative centrifugal force of greater than or equal to about 100 xG RCF, greater than or equal to about 500 xG RCF, greater than or equal to about 1000 xG RCF. greater than or equal to about 2000 xG RCF, greater than or equal to about 2500 xG RCF, greater than or equal to about 3000 xG RCF, greater than or equal to about 3500 xG RCF, or greater than or equal to about 4000 xG RCF, greater than or equal to about 4500 xG RCF, greater than or equal to about 5000 xG RCF, greater than or equal to about 7000 xG RCF, up to about 10,000 xG RCF, up to about 50,000 xG RCF, up to about 100,000 xG RCF, or more or less, or any values or ranges in between any of the listed values, although other values could be used in some cases.

[0140] During the transferring of the fluid 301 from the spin adapter 308 to the aliquoter 304, the fluid 301 will move down the funnel 324, enter the channel 332 and continue into the channel 307. The channel 307 can have a maximum capacity of a predetermined amount of the fluid 301 that can correspond to a target fluid volume for filling the container 152. The target fluid volume can be less than the amount of fluid 301 deposited or preloaded in the spin adapter 308. The target fluid volume can be determined in part by the location of the opening 310. For example, as the fluid 301 is transferred to the channel 307 any fluid that reaches or exceeds the opening 310 will flow through the opening 310 and into the first outlet channel 311 and / or the second outlet channel 313. This will allow removal of fluid 301 that exceeds the target fluid volume. The excess fluid 301 can then exit the first outlet channel 311 through the open end of the first outlet channel 311 and out the bottom surface 309 of the aliquoter 304 and / or exit the second outlet channel 313 through the open end in the sidewall of the aliquoter 304. FIG. 14B illustrates the channel 307 filled with the target fluid volume.

[0141] Moving to block 356, the aliquoter 304 containing the target fluid volume, the spin adapter 308. and the container mount 312 holding the container 152 can be assembled in a second configuration or assembly 370, for example, as shown in FIGS. 15A, 15B, and FIG.19. The aliquoter 304 containing the target fluid volume can be inverted as compared to the orientation of the aliquoter 304 during the steps associated with blocks 350, 352, and / or 354 of method 300. For example, the top surface 306 of the aliquoter 304 containing the target fluid volume can be aligned with the top surface 316 of the spin adapter 308. While illustrated as having a slight gap between the top surface 306 and top surface 316, the top surfaces 306, 316 can alternatively be in contact with each other. The top surface 340 of the container mount 312 can be aligned and / or coupled to the bottom surface 320 of the spin adapter 308. Prior to aligning the container mount 312 with the spin adapter 308 the container 152 can be inserted into the container mount 312 according to the present disclosure.

[0142] The opening at the end of the channel 332 of adapter 308 can be spaced apart from the container 152, such as by a distance of about 0.05 mm, about 0.055 mm, about 0.06 mm, about 0.065. about 0.07 mm, about 0.075, about 0.08 mm. about 0.085, about 0.09 mm, about 0.095, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, about 0.15 mm, about 0.17, about 0.2 mm, about 0.25 mm, or any values therebetween, or any ranges betw een any of these values, although other distances could be used in some cases. Alternatively, the opening at the end of the channel 332 can have protrusion or nozzle that extends into and below the top of the container 152.

[0143] One or more assemblies 370 can be positioned in a centrifuge mount 366A, which can be similar to the centrifuge mount 366 shown in FIG. 16, for example. The centrifuge mount 366A may be sized to receive the assemblies 370. For example, the centrifuge mount 366A may differ from the centrifuge mount 366 as the centrifuge mount 366A can receive the aliquoter 304, the spin adapter 308, and the container mount 312, while the centrifuge mount 366 may only receive the aliquoter 304 and the spin adapter 308. The depth of the spaces receiving the assemblies 370 in the container mount 366A can be larger than the depth of the spaces receiving the assemblies 317 in the container mount 366 to account for the larger assembly. The assemblies 370 can be positioned in the centrifuge mount 366A in a uniform pattern, for example, in linear rows. While rows of three assemblies 370 are shown, any number of assemblies 370 can be aligned in a row; The centrifuge mount 366A can hold any suitable number of the assemblies 370 such as 1, 2, 4, 8, 12, 16, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 150. 200, 250, 300, 400, 500. or more, or any values or ranges therebetween.

[0144] In some embodiments, the assemblies 370 can be positioned in the centrifuge mount 366A fully and / or partially assembled. In some embodiments, the assemblies 370 can be assembled as the individual parts (e.g., the container mount 312, the spin adapter 308, the aliquoter 304) are positioned in the centrifuge mount 366A. In some embodiments, the container mount 312 can be positioned in a space of the centrifuge mount 366A. The spin adapter 308 can then be positioned over (e.g., atop) the container mount 312 according to the present disclosure. The aliquoter 304 containing the target fluid volume can then be positioned over (e.g., atop) the spin adapter 308. In some embodiments, the aliquoter 304 containing the target fluid volume can be positioned in a second portion 367 removably attachable to centrifuge mount 366A, as shown in FIG. 19. The second portion 367 can be positioned over (e.g., atop of) the centrifuge mount 366A. The second portion 367 can facilitate the manipulation of the aliquoter 304, including manipulating aliquoter 304 into an inverted configuration. In some embodiments, the aliquoter 304 can be positioned in the space of the centrifuge mount 366 A.

[0145] Moving to block 358 of the method 300, the fluid 301 can be transferred from the aliquoter 304 to the container 152, for example as shown in FIGS. 15A, 15B, and 19. In some embodiments, the fluid 301 can be transferred from the aliquoter 304 using a centrifuge 362, as shown in FIG. 17. In some embodiments, the fluid 301 can be transferred directly from the aliquoter 304 to the container 152 without the use of a spin adapter 308. In some embodiments, the fluid 301 can be transferred from the aliquoter 304 to the spin adapter 308 and from the spin adapter 308 to the container 152, which can be held in the container mount 312. During operation of the centrifuge 362, the assemblies 370 will spin. The spinning of the assemblies 370 will assist in transferring the fluid 301 from the aliquoter 304 to the spin adapter 308 and / or the container 152. In some cases, the centrifuge mount 366 can pivot (e.g.. by about 90 degrees) between an insertion position (as shown in Figure 17) and a spinning position. In some embodiments, the fluid can be heated during the centrifuging, similar to the discussion in connection with block 354. In some embodiments, the centrifuge 362 can operate at a temperature above room temperature (e.g., about 37 degrees Celsius, or at other suitable temperatures as discussed herein). However, various temperatures can be used, such as about 20 degrees Celsius, about 22 degrees Celsius, about 25 degrees Celsius, about 30 degrees Celsius, about 33 degrees Celsius, about 34 degrees Celsius, about 35 degrees Celsius, about 36 degrees Celsius, about 37 degrees Celsius, about 38 degrees Celsius, about 39 degrees Celsius, about 40 degrees Celsius, about 45 degrees Celsius, about 50 degrees Celsius, about 60 degrees Celsius, about 70 degrees Celsius, about 80 degrees Celsius, about 90 degreesCelsius, or any value in between, or any ranges between any of these values, although other temperatures could be used as well. The centrifuge 362 can operate for about 40 minutes, for example, in order to transfer the fluid 301 from aliquoter 304 to the spin adapter 308 and / or container 152 in the container mount 312. The centrifuge can operate at about 3,700 RPMs, which can generate about 3,000 xG RCF, for example. In some cases, the centrifuge can be operated at different speeds to generate a relative centrifugal force of greater than or equal to about 100 xG RCF, greater than or equal to about 500 xG RCF, greater than or equal to about 1000 xG RCF, greater than or equal to about 2000 xG RCF, greater than or equal to about 2500 xG RCF, greater than or equal to about 3000 xG RCF, greater than or equal to about 3500 xG RCF, greater than or equal to about 4000 xG RCF, greater than or equal to 4500 xG RCF, greater than or equal to about 5000 xG RCF, greater than or equal to about 7000 xG RCF, up to about 10,000 xG RCF, up to about 50,000 xG RCF, up to about 100,000 xG RCF, or more or less, or any values or ranges in between any of the listed values, although other values could be used in some cases. The transferring of the fluid 301 to the container mount 312 can result in the filling of the container 152. The containers 152 can then be removed from the one or more assemblies 170, as shown in FIG. 20. In some embodiments, the fluid can be transferred from the aliquoter 304 to the container 152, without the spin adapter 308.

[0146] The centrifuge mount 366A can have openings on the bottom, which can be smaller than the container mounts 312, so that the container mounts 312 do not fall through the openings. An extractor 369 can have posts that extend upward and are sized and spaced to fit into the openings. The centrifuge mount 366A can be placed onto the extractor 369 so that the posts extend into the openings and push the container mounts 312 upward. The containers 152 can be removed from the container mounts 312.Example Filling Method Using Capillators

[0147] FIG. 21 is a flow chart illustrating an example method 500 of filling a container with a fluid according to the present disclosure. FIGS. 22A-29E illustrate corresponding parts, structure, and / or methods steps related to the method 500.

[0148] Starting at block 502 one or more capillary loaders 518 can be positioned or placed into a base 520, for example as shown in FIG. 22A. Each capillary loader 518 can be positioned within a space or receiving cell 522. The receiving cell 522 can be sized to retain the capillary loader 518. The receiving cells 522 can be uniformly distributed within the base 520, for example, in linear rows. The linear rows can include any number of receiving cells 522, and the base can be configured to hold any suitable number of the capillary loaders 518such as 1, 2, 4, 8, 12, 16, 18, 20, 22, 24, 25, 26, 28, 30, 32, 35, 40, 45, 50, 60, 70, 80, 90, 100, 120, 150. 200, 250. 300, 400, 500, or more, or any values or ranges therebetween.. A cover 523 can be placed over the base 520, which can create a loader module 525. One or more rotating screws 524 (e.g., thumb screws) can be rotated to secure the cover 523 to the base 520.

[0149] FIG. 22B is a cross-section of the capillary loader 518 positioned in a receiving cell 522 of the base 520 of the loader module 525. FIG. 22C shows a first (e.g., top) side of the capillary loader 518. FIG. 22D shows a second (e.g., bottom) side of the capillary loader. The receiving cell 522 can extend through the base 520 from a first surface 526 of the base 520 to a second surface 528 of the base 520. The receiving cell 522 can include an opening through the cover 523. The receiving cell 522 can have a stepped inner diameter or width. For example, a first portion of the receiving cell 522 extending from the first surface 526 can have a larger diameter or width than a second portion of the receiving cell 522 extending from the second surface 528. The first portion and the second portion of the receiving cell can connect at a step 530 where there is the change in diameter or width. The step 530 can prevent the capillary loader 518 from falling out of the base 520 when the capillary loader 518 is disposed in a receiving cell 522. Similarly, the cover 523, which can be secured by rotating screws 524, or any other suitable coupling mechanism, can prevent the capillary loader 518 from falling out of the base 520.

[0150] The capillary loader 518 can include a funnel 534. The funnel 534 can extend from an opening 538 at first end of the capillary loader 518. The funnel 534 can have a decreasing diameter or width as the funnel 534 extends from the opening 538 to a channel 542. For example, the diameter or width of the funnel 534 at the opening 538 can be larger than the diameter or width of the funnel 534 at the start of the channel 542. The diameter of the funnel 534 can gradually decrease along the longitudinal axis of the capillary loader 518 (e.g., in the direction from the first end to the second end of the capillary loader 518). The channel 542 can lead to an opening 546 or recess that can be sized to receive a capillator 550 (e.g., as show n in FIGS. 28A-28B) according to the present disclosure. As used herein, the term "capillator" refers to a device configured to receive fluid by capillary action. In some embodiments, a capillator can be configured to hold a target volume of fluid. In some cases, the capillator can be configured to stop receiving fluid once the target volume is transferred to the capillator. As shown in FIG. 22B, the capillary loader 518 can be inserted into the base 520 with the openings 538 entering the receiving cell 522 first. For example, the funnel 534 may appear upside down after being inserted into the loader module 525.

[0151] The narrow opening of the funnel 534 and / or the channel 542 can have a width or diameter of about 0.05 mm. about 0.055 mm. about 0.06 mm, about 0.065. about 0.07 mm, about 0.075, about 0.08 mm, about 0.085, about 0.09 mm, about 0.095, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, about 0.15 mm, about 0.17, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, or any values therebetween, or any ranges between any of these values, although other sizes could be used in some cases. The wide opening of the funnel 534 can have a width or diameter of about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1 mm, about 1.2 mm, about 1.5 mm, about 2.0 mm, about 2.5 mm, about 3.0 mm, about 3.5 mm, about 4.0 mm, about 4.5 mm, about 5.0 mm, about 6 mm, about 7 mm, or any values therebetween, or any ranges between any of these values, although other sizes could be used in some cases.

[0152] A raised lip 533 can extend into the recess or opening 546. The raised lip 533 can surround the channel 542 (e.g., extending the channel 542 into the recess or opening 546), such as to form a nipple. The raised lip 533 can facilitate the transfer of fluid out of the channel 542. In some cases, the raised hp 533 can be omitted.

[0153] The capillary loader 518 can be made of titanium, although various other metals or other materials could be used. The channels, openings, funnel, and recesses, etc. can be formed by drilling, or other techniques could be used, such as milling, machining, or injection molding, etc. to form the structures of the capillary loader 518.

[0154] Moving to block 504, the loader module 525 can be inverted, as shown in FIG. 25. The base 520 can be inverted before or after installing a dispensing cap 551 on the vial 554. The inverting of the base 520 can provide access to the opening 538 of the funnel 534 (e.g., through the second part of the receiving cell 522).

[0155] Moving to block 506 a dispensing cap 551 can be installed on a vial 554 containing a fluid 556, as shown in FIGS. 23 A, 23B, and 24A. In some embodiments, the fluid 556 can be a viscous fluid. In some embodiments, the fluid can be a drug, which can be formulated as an oil. The drug can include a prostaglandin, a prostaglandin analog, a prostaglandin inhibitor, a beta-adrenergic receptor antagonist, or combinations thereof, although other drugs can be used as discussed herein. In some embodiments, the drug can include travoprost. In some embodiments, antioxidants can help to extend the shelf-life (or therapeutic life-span) of a drug by reducing the oxidation rate of the active ingredient and / or an excipient compounded with the drug. Examples of suitable antioxidants include without limitation propyl gallate, tertiary butylhydroquinone (TBHQ), butylated hydroxyanisole(BHA), butylated hydroxytoluene (BHT), beta carotene, vitamin E, vitamin C, sodium bisulphite, sodium salts of edetate (EDTA). butylated hydroxy ethylbenzene (BEIEB), octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (e.g., Irganox 1076), pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxyhydrocinnamate) (e.g., Irganox 1010), other sterically hindered phenolic antioxidants (e.g., Irganox B900), tris(2.4-di-tcrt-but lpbcnyl) phosphite (e.g., Irgafos 168), oleamide, erucamide, N,N'-Ethylenebisoleamide (EBO), oleylpalmitamide (OP), and mixtures thereof. Various drug formulations can be used. Nonlimiting examples include a travoprost-propyl gallate formulation, a travoprost-TBHQ formulation, a travoprost-BHA formulation, a travoprost-beta carotene formulation, a travoprost vitamin E formulation, a travoprost-vitamin C formulation, a travoprost-sodium bisulphate formulation, and a travoprost-EDTA formulation.

[0156] The vial 554 can include a removable bottom cap 552 and / or a removable top cap 558. The bottom cap 552 can be removed and replaced with the dispensing cap 551. The dispensing cap 551 can include a dispensing channel 560. The dispensing channel 560 can extend past a bottom surface of the vial 554 body forming a nozzle 559 such that the dispensing channel 560 can be inserted into the receiving cells 522 and / or capillary loaders 518. The removable top cap 558 can be removed and replaced with a pressure connecting cap 562. The pressure connecting cap 562 can include a pressure channel 561. The pressure connecting cap 562 can be connected to a dispensing system 563 having a pressure source, such as via a nozzle 564, as shown in FIG. 24B.

[0157] Moving to block 508, the vial 554 can be aligned with one capillary loader 518. As shown in FIG. 25, the dispensing channel 560 can be at least partially inserted into the receiving cell 522 and / or the funnel 534. The end of nozzle 559 of dispensing cap 551 can abut against the funnel 534 of capillary loader 518 such that the weight of the vial 554 is supported and a seal or partial seal is created at the interface of the end of nozzle 559 and the funnel 534.

[0158] Moving to block 510, the fluid 556 can be dispensed into the capillary loader 518. The dispensing system 563 can be used to assist in dispensing fluid 556 from the vial 554 into the capillary loader(s) 518. Once inserted, the dispensing channel 560 can deposit the fluid 556 into the capillary loader 518. The fluid 556 can be dispensed from the vial through the dispensing channel 560 and into the capillary loader 518, such as by applying pressure to the vial 554 via the dispensing system 563. The seal or partial seal between the end of nozzle 559 and the funnel 534 can assist in dispensing the fluid 556 to the appropriate level without overfdling. Alternatively, gravity alone can be used to deposit the fluid 556 into capillaryloader 518 without the use of dispensing system 563. Gravity can act on fluid 556 to cause it to flow down dispensing channel 560 and into funnel 534 of capillary loader 518 and into channel 542. The flow of fluid 556 can self-arrest once it reaches the end of raised lip 533. An elevated temperature can speed this process along. In some cases, the device can be in a heated chamber, which can be heated to a temperature above room temperature (e.g., about 37 degrees C, or any of the other temperatures or ranges discussed herein). However, various temperatures can be used, such as about 20 degrees Celsius, about 22 degrees Celsius, about 25 degrees Celsius, about 30 degrees Celsius, about 33 degrees Celsius, about 34 degrees Celsius, about 35 degrees Celsius, about 36 degrees Celsius, about 37 degrees Celsius, about 38 degrees Celsius, about 39 degrees Celsius, about 40 degrees Celsius, about 45 degrees Celsius, about 50 degrees Celsius, about 60 degrees Celsius, about 70 degrees Celsius, about 80 degrees Celsius, about 90 degrees Celsius, or any value in between, or any ranges between any of these values, although other temperatures could be used as well. The steps of aligning the vial 554 and the capillary loader 518 and dispensing the fluid 556 into the capillary loader 518 can be repeated as needed to fill a predetermined number of capillary loaders 518. For example, the vial 554 can be slowly lifted or removed from the filled capillary loader 518 and moved to the next capillary loader 518 for filling according to the present disclosure. Alternatively, fluid can be deposited into the capillary' loader 518 by a variety' of other means such as a pressure-driven or displacement-driven syringe with dispensing needle or other dispensing tip, or other such fluid dispensing systems or mechanisms, or by methods such as using a wire, rod, dip stick, or tool to manually, or robotically, deposit amounts of fluid into the capillary loader(s). For example, with a robotic fluid dispensing system, such as pressure-driven or displacement-driven syringe. In some embodiments, fluid can be deposited into the capillary' loader 518 by using at least one of a needle, syringe, or robotic fluid dispensing system to transfer the portion of the fluid out of the nozzle and into the capillary loader.

[0159] The funnel 534 can be advantageous as the funnel 534 can wick the fluid towards the narrowing end of the funnel 534 due to adhesive forces (for example, surface wetting). In some instances, just simply placing a drop of fluid on the side of the funnel 534 can result in the funnel wicking the fluid.

[0160] During the dispensing process, the fluid 556 can be inspected for bubbles and / or particulates in the fluid 556 as a quality' control step. This can be completed by a user using a microscope to inspect the funnel 534 for the present of particulate or air bubbles in the fluid 556. The fluid 556 in multiple capillary loaders 518 in loader module 525 can be checked quickly and easily. The base 520 can be un-inverted to the original orientation to check theopening 546 for any damage, presence of particulates, or fluid spillage. For example, the orientation of FIG. 22B. Surface tension of the fluid 556 and adhesion of fluid 556 to the surface of funnel 534 can cause the fluid 556 to remain in place indefinitely against the force of gravity after base 520 is un-inverted, in some cases.

[0161] Moving to block 512, pressure can be applied to the capillary loaders 518. In some embodiments, the loader module 525 comprising the filled capillary loaders 518 can be placed in a capillary loader manifold 566, as shown in FIG. 26. The capillary loader manifold 566 can be connected to a pressure source 568 (e.g., which can be the same pressure source 563 used with the vial 554 or it can be a different pressure source). The pressure source 568 can be used to apply a pressure pulse to the capillary loaders 518. The pressure pulse can cause the fluid 556 to billow onto a surface outside the channel 542 of the capillary loader 518, for example as shown in FIG. 27. For example, the fluid 556 can billow onto the top surface of the raised lip 533. In some cases, after the pressure pulse stops, the fluid 556 can retract back into the channel 542 due to the surface tension. A film or layer 531 of the fluid 556 can remain on top of the channel 542, in some cases.

[0162] Moving to block 514, capillators 550 can be aligned with the capillary loaders 518 in the base 520, as shown in FIGS. 28A and 28B. FIG. 28D shows a first (e.g., top) side of an example embodiment of a capillator 550. FIG. 28E shows a second (e.g., bottom) side of the capillator 550. Prior to aligning each capillator 550 with a corresponding capillary loader 518. the base 520 can be un-inverted back to its original orientation. For example, the base 520 can be positioned such that the opening 546 is facing away from the surface that the base 520 is placed on. The capillator 550 can be inserted into the opening 546 of the capillary loader 518. The film of the fluid 556 formed by applying the pressure pulse at block 512 can facilitate a good fluid connection between the capillitor 550 and the capillary loader 518.

[0163] In some embodiments, the fluid can be heated, which can facilitate movement of the fluid from the capillary loader(s) 518 to the capillator(s) 550. For example, the assembled capillators 550 and capillary loaders 518 (e.g., the base 520 or module 525 containing the assembled capillators 550 and capillary loaders 518) can be placed in a dry bath, although any suitable type of heater can be used. In some instances, the assembly can be placed in the dry bath or heater for about 15 minutes. Various times can be used, for example, about 30 seconds, about 1 minute, about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, 30 minutes, 60 minutes, about 90 minutes, about 120 minutes, or more, or any value or range in between these values. The dry bath can be performed at a temperature of about 37 degrees Celsius. However, various temperatures can be used, such as about 20 degrees Celsius,about 22 degrees Celsius, about 25 degrees Celsius, about 30 degrees Celsius, about 33 degrees Celsius, about 34 degrees Celsius, about 35 degrees Celsius, about 36 degrees Celsius, about 37 degrees Celsius, about 38 degrees Celsius, about 39 degrees Celsius, about 40 degrees Celsius, about 45 degrees Celsius, about 50 degrees Celsius, about 60 degrees Celsius, about 70 degrees Celsius, about 80 degrees Celsius, about 90 degrees Celsius, or any value in between, or any ranges between any of these values, although other temperatures could be used as well. In some cases, the fluid is not heated above a temperature as disclosed herein so as to not negatively impact the fluid (e.g., drug) being transferred. In some cases, the container is an implant that will be implanted into an eye or other portion of a patient's body, so that the drug will experience a range of human body temperatures after being implanted. Accordingly, in some embodiments, the fluid is not heated beyond (or much beyond) the temperature of the human body during the fluid transfer process. Thus, the heat applied during the transfer process would not degrade the fluid any more than the body heat of the patient would after being implanted. Alternatively, the fluid may be heated well beyond the temperature of the human body, such as a temperature of about 50 degrees Celsius, 60 degrees Celsius, 70 degrees Celsius, or even warmer, to further decrease viscosity. In some cases, such elevated temperatures may not substantially degrade the fluid depending on the properties of the fluid and / or when applied for short periods of time.

[0164] The capillator 550 can cause the fluid from the capillary loaders 518 to flow into a channel 570 extending into or through the capillator 550, such as by capillary action. The size of the channel 570, including its cross-sectional area and length, can determined the amount of fluid transferred to the capillator 550, and eventually transferred to the container. After the channel 570 is filled with the fluid, the capillator 550 can be separated from the capillary loader 518. A user can inspect the filled capillators 550 (e.g., using a microscope) to ensure each capillator 550 is filled with the fluid. For example, FIG. 28C illustrates the appearance of the top opening of the channel 570 of a filled capillator 550 as viewed from above.

[0165] The capillator 550 can have a body with a first or upper end and a second or lower end. The channel 570 can extend through the body of the capillator 550, such as between the first and second ends. The first end can include a recess 565, which can be wider than the channel 570. In some embodiments, the capillator 550 can be made without the opening 565, with the channel 570 longer than as illustrated. The opening 565 or recess can be formed to shorten the length of the channel 570, which can reduce the amount of volume that the channel 570 holds. The amount of fluid that the channel 570 holds can be measured and the depth ofthe opening 565 can be increased until the channel 570 holds the target volume of fluid. In some cases, the amount of fluid that the channel holds can be measured before the recess 565 is formed, and a depth for the recess can be determined (e.g., based at least in part on the amount of volume that the channel holds, the length of the channel, and / or the target volume). The recess 565 can then be formed to have the determined depth, to thereby provide a channel 570 that can achieve the target volume for the fluid transfer. In some cases, the recess 565 can be formed with a first depth, and then the volume held by the channel can be measured. The recess depth can then be increased (e g., by further boring or machining, etc.) by a determined amount (e.g., based at least in part on the amount of volume that the channel holds, the length of the channel, and / or the target volume), for example so that the channel 570 can provide the target volume for fluid transfers. In some cases, the volume of fluid held by the channel 570 can be measured multiple times as the size of the recess 565 is increased gradually until the appropriate recess depth is reached to provide the target volume using the channel 570. Different capillators (e.g., for different sizes of implants or other containers) can be the same except for the depth of the opening 565. and therefore the length of the channel 570, which can yield the different volumes. In some cases two recesses can be formed on both ends of the capillator, where both recesses can shorten the length of the channel 570. For example, the raised lip 569 can be omitted or can be shorter to not extend to the second (e.g., bottom) end of the capillator, and / or the recess 567 can have a greater depth than in the illustrated embodiments.

[0166] In some cases, the volume of the fluid held by the channel can be measured by placing the capillary loader 518 in contact with fluid so that fluid is drawn into the channel by capillary action (e.g., using a capillary loader similar to Figure 28B). Then the fluid can be transferred out of the channel and into a measuring device (e.g.. using centrifuge, such as similar to Figures 29A-29E). The same type of fluid that will be transferred using the capillator (e.g., an oil or drug as discussed herein) can be used to measure the channel volume, or in some cases a different type of fluid can be used (e.g., a less viscous fluid, which can avoid the use of the centrifuge in some cases). The side walls around the opening 565 can also protect the channel 570 from accidental damage. The end of the channel 570 can have a sharp edge to facilitate appropriate capillary-wicking action (e g., that stops at the end of the channel 570). The capillator 550 can have a body with a length. The channel 570 can have a length that is less than the length of the body of the capillator 550. The capillator 550 can have a recess 567 at the second end. The recess 567 can be wider than the channel 570, and can be formed by drilling a wider hole than used to form the channel 570. A raised lip 569 can extendinto the recess 567 or from the bottom surface of the capillator 550. The raised lip 569 can surround the channel 570 (e.g., extending the channel 570 into the recess 567), such as to form a nipple. The recess 567 and / or the raised lip 569 can facilitate the transfer of fluid out of the channel 570, as discussed herein. The recess 567 can act to protect the raised lip 569 from contact with other components or tools (e.g., during manipulation or cleaning) that may damage it if not protected. In some cases, the recess 567 can be omitted. In some cases, the raised lip 569 can be omitted.

[0167] The channel 570 can have a width or diameter of about 0.05 mm, about 0.055 mm, about 0.06 mm, about 0.065, about 0.07 mm, about 0.075, about 0.08 mm, about 0.085, about 0.09 mm, about 0.095, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, about 0.15 mm, about 0.17, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, or any values therebetween, or any ranges between any of these values, although other sizes could be used in some cases. When the capillator 550 is coupled to the capillary loader 518, as shown in Figure 28B, the end of the channel 570 (e.g.. the raised lip 569) can be positioned sufficiently close to the end of the channel 542 (e.g., the raised lip 533) so that the fluid layer 531 can contact the channel 570. Capillary action can then draw the fluid into the channel 570. In some embodiments, the capillator nozzle 569 can extend past and end of the channel 570 (e.g., if the channel 570 were made wider than the capillator nozzle 569).

[0168] The capillator 550 can be made of titanium, although various other metals or other materials could be used. The channels, openings, and recesses, etc. can be formed by drilling, or other techniques could be used, such as milling, machining, or injection molding, etc. to form the structures of the capillator 550

[0169] Prior to, after, or during the transfer of the fluid from the capillary loaders 518 to the capillators 550, the container mounts 571 can be prepared. The container mounts 571 can include any of the features as described herein with reference to any container mounts embodiments and vice versa. For example, moving to block 516 container mounts 571 can be loaded into a centrifuge mount 572, as shown in FIGS. 29D and 29E. The container mount 571 can be used to hold the container 573 during the filling process. The container mount 571 can include an opening or recessed area sized to receive the container 573. Non-limiting example containers 573 include ocular implants or drug delivery’ devices. The container mount can include a top surface 574 and a bottom surface 575. The container mount 571 can have any shape cross-section. For example, the container mount 571 can have a generally cylindricalshape (e.g., with a generally circular cross-section), a generally square cross-section, and / or polygonal cross-section.

[0170] The top surface 574 can include a recess 579. The recess 579 can be formed by drilling into the to surface of the container mount 571. The recess 579 can include an opening 581, which can be sized and shaped to receive at least a portion of the container 573. The opening 581 can extend downward from a surface of the recess 579 toward the bottom surface 575. The bottom surface 575 can be a solid surface with no openings and / or recesses, in some cases. The opening 581 can be a bore, which can be formed by drilling into the container mount 571. A hole 583 can be formed in the bottom of the opening 581. The hole 583 can be a bore, which can be formed by drilling. The recess 579, opening 581, and hole 583 can be formed by other techniques, such as milling or machining, etc. or injection molding can be used to form the container mount 571, or any other suitable technique. The container mount 571 can be made of titanium, although various other metals or other materials could be used. The hole 583 can have a smaller diameter or width than the opening 581. The opening 581 can have a smaller diameter or width than the recess 579. A portion of the container 573 (e.g., a spike or retention portion of an ocular implant) can extend into the hole 583. The bottom of the opening 581 can support the container 573. In some cases the container 573 can extend upward past the upper surface 574 of the container mount 571. For example, the container 573 can extend into the recess 567 of the capillator 550. In some cases, the container 573 can be flush with the upper surface 574, or the top of the container 573 can be recessed below the upper surface 574 (e.g., in the recess 579).

[0171] The opening at the end of the channel 570 (e.g., the raised lip 569) can be spaced apart from the container 573, such as by a distance of about 0.05 mm, about 0.055 mm, about 0.06 mm, about 0.065. about 0.07 mm, about 0.075, about 0.08 mm, about 0.085, about 0.09 mm, about 0.095, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, about 0.15 mm, about 0.17, about 0.2 mm, about 0.25 mm, or any values therebetween, or any ranges between any of these values, although other distances could be used in some cases. Alternatively, the opening at the end of the channel 570 can have a protrusion or nozzle that extends into and below the top of the container 573.

[0172] Each container mount 571 can be positioned in a space or opening 576 of the centrifuge mount 572. The spaces or openings 576 of the centrifuge mount 572 can be uniformly spaced across the centrifuge mount 572. For example, the spaces or openings 576 can be disposed in linear rows. The containers 573 can be loaded into the container mounts 571 before or after the container mounts 571 are loaded into the centrifuge mount 572. Thecentrifuge mount 572 can hold any suitable number of the container mounts 573 or associated assemblies, such as 1, 2, 4. 8, 12, 16, 25, 30. 35. 40, 50, 60, 70, 75, 80, 90, 100. 120, 150, 200, 250, 300, 400, 500, or more, or any values or ranges therebetween.

[0173] Moving to block 517 the filled capillators 550 can be aligned with the container mounts 571 disposed in the centrifuge mount 572. For example, as shown in FIGS.29A and 29B. FIG. 29F shows a first (e.g., top) side of an example embodiment of a container mount 571. FIG. 29G shows a second (e.g., bottom) side of the container mount 571. The top surface 574 of the container mount 571 can be aligned with the bottom surface 577 of the capillator 550. The channel 570 of the capillator 550 can be aligned with the container 573 held within the container mount 571. In some embodiments, the channel 570 of the capillator 550 can be aligned with the container 573 by both parts being in the same hole or opening 576. In some cases, there can be a small clearance between the diameter of the hole or opening 576 and the diameter of the capillator 550 and / or container mount 571 themselves. By way of example, a total clearance of about 50 microns can be used, such as with a diameter of about 4 mm for both capillator 550 and / or the container mount 571, and a diameter of about 4.05 mm for the holes or openings 576. The tolerance of each dimension can be about + / - 0.02 mm. Various clearance amounts could be used, such as about 10 microns, about 20 microns, about 30 microns, about 40 microns, about 50 microns, about 60 microns, about 70 microns, about 80 microns, about 90 microns, about 100 microns, or more, or any values or ranges between any of these values. Various other alignment or engagement features can be used to couple and / or align capillator 550 with the container mount 571.

[0174] The opening at the end of the channel 570 (e.g., the raised lip 569) can be spaced apart from the container 573, such as by a distance of about 0.05 mm, about 0.055 mm, about 0.06 mm, about 0.065. about 0.07 mm, about 0.075, about 0.08 mm, about 0.085, about 0.09 mm, about 0.095, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, about 0.15 mm, about 0.17, about 0.2 mm, about 0.25 mm, about 0.5 mm, about 1 mm, or any values therebetween, or any ranges between any of these values, although other distances could be used in some cases. Alternatively, the opening at the end of the channel 570 can have a protrusion or nozzle that extends into and below the top of the container 573.

[0175] After assembling the fdled capillator(s) 550 with the container mount(s) 550 in the centrifuge mount 572, the centrifuge mount 572 can be secured in the centrifuge 578, as shown in FIG. 29C. A plurality of centrifuge mounts 572 can be prepared according to the present disclosure and secured in the centrifuge 578. The plurality of centrifuge mounts 572 can be uniformly positioned in the centrifuge 578. For example, if two centrifuge mounts 572are secured in the centrifuge 578, the two centrifuge mounts should be positioned directly across from or opposite each other. This can facilitate substantially even weight distribution for smooth operation of the centrifuge. In some cases, the centrifuge mounts 572 can pivot (e.g., by about 90 degrees) between an insertion position (as shown in Figure 29C) and a spinning position. When spinning, the container mount 571 (e g., and the container 573) can be positioned radially outward of the capillator 550. The fluid can be driven radially outward by the centrifuge, such as out of the channel 570 in the capillator 550 and into the container 573.

[0176] In some embodiments, the fluid can be heated during the centrifuging. For example, the centrifuge 578 can include a heater. In some cases, the centrifuge 578 can generate heat during the centrifuging process (e.g., by operation of the motor or friction, etc.), and that heat generated by operation of the centrifuge can be used to heat the fluid. The centrifuge 578 can have a cooler, which can operate to control the temperature in the centrifuge 578. In some cases, the cooler and / or the operation of the centrifuge (or a dedicated heater) can be used to heat the fluid to a target temperature or temperature range during the centrifuging, such as a temperature of about 37 degrees Celsius, in some embodiments. However, various temperatures can be used, such as about 20 degrees Celsius, about 22 degrees Celsius, about 25 degrees Celsius, about 30 degrees Celsius, about 33 degrees Celsius, about 34 degrees Celsius, about 35 degrees Celsius, about 36 degrees Celsius, about 37 degrees Celsius, about 38 degrees Celsius, about 39 degrees Celsius, about 40 degrees Celsius, about 45 degrees Celsius, about 50 degrees Celsius, about 60 degrees Celsius, about 70 degrees Celsius, about 80 degrees Celsius, about 90 degrees Celsius, or any value in between, or any ranges between any of these values, although other temperatures could be used as well. In some cases, a heater can be used to add heat beyond the heat produced by centrifuging. In some cases, the fluid is not heated above a temperature as disclosed herein so as to not negatively impact the fluid (e.g., drug) being transferred. In some cases, the container is an implant that will be implanted into an eye or other portion of a patient's body, so that the drug will experience a range of human body temperatures after being implanted. Accordingly, in some embodiments, the fluid is not heated beyond (or much beyond) the temperature of the human body during the fluid transfer process. Thus, the heat applied during the transfer process would not degrade the fluid any more than the body heat of the patient w ould after being implanted. Alternatively, the fluid may be heated well beyond the temperature of the human body, such as a temperature of about 50 degrees Celsius, 60 degrees Celsius, 70 degrees Celsius, or even warmer, to further decrease viscosity. Such elevated temperatures may notsubstantially degrade the fluid depending on the properties of the fluid and / or when applied for short periods of time.

[0177] Moving to block 519, the fluid can be transferred from the capillator 550 to the container 573 within the container mount 571, as shown in FIG. 29B. The spinning of the centrifuge 578 can transfer the fluid from the channel 570 of the capillator 550 to the container 573. The centrifuge 578 can operate for about 30 minutes, for example, to transfer the fluid from the capillators 550 to the containers 573. However, various operation times can be used, such as about 5 minutes, 30 minutes, 35 minutes, 25 minutes, 35 minutes, or 40 minutes or any value in between, or any ranges between any of these values, although other operation times could be used as well. Generally when the centrifuge is heated to higher temperature a shorter operation time can be used. The centrifuge can operate at about 3.700 RPMs, generating about 3,000 xG RCF, for example, although other parameter could be used. In some cases, the centrifuge can be operated to generate a relative centrifugal force of greater than or equal to about 100 xG RCF, greater than or equal to about 500 xG RCF, greater than or equal to about 1000 xG RCF, greater than or equal to about 2000 xG RCF, greater than or equal to about 2500 xG RCF, greater than or equal to about 3000 xG RCF, greater than or equal to about 3500 xG RCF, greater than or equal to about 4000 xG RCF, greater than or equal to about 4500 xG RCF, greater than or equal to 5000 xG RCF, greater than or equal to about 7000 xG RCF, up to about 10,000 xG RCF, up to about 50,000 xG RCF, up to about 100,000 xG RCF, or more or less, or any values or ranges in between any of the listed values, although other values could be used in some cases. Once filled, the centrifuge mounts 572 can be removed from the centrifuge 578 and the assemblies of the container mounts 571 and capillators 550 can be disassembled to remove the filled containers 573.

[0178] The capillators 550 can be recoupled to the capillary’ loaders 518. In some cases, as the capillator 550 is filled, the channel 542 can remain filled and a layer of fluid 531 can remain when the capillator 550 is removed from the capillary’ loader 518, so that a new capillator 550 can be coupled to capillary loader 518 right away. In some embodiments, the capillary loader 518 can be re-primed, such as with a new layer 531 of fluid, in some cases at the same time as the centrifuging step. The capillators 550 can be refilled, and the fluid can be transferred to additional containers (e.g., by’ centrifuging), as discussed herein. The capillary loaders 518 can have fluid (e.g., in the funnel) that is sufficient to fill several containers. Using the capillators 550 for filling the containers can produce less waste of the fluid and can be performed more efficiently and quickly than some other filling approaches. A next round of fluid transfers can be prepped while a prior round of transfers is still being performed. In somecases, additional capillators 550 can be used, and portions of the fluid can be transferred into the next set of capillators 550 while the centrifuge is transferring the fluid from the prior set of capillators 550 to the containers.

[0179] Surfaces of the capillary loaders 518, capillators 550, and / or containers 573 can be oleophilic and / or hydrophilic. Surfaces being oleophilic can be advantageous. For example, when the fluid is oil based (for example, travoprost) or another fluid having similar properties, the more oleophilic, the faster the capillators will self-prime and the taller and / or wider the capillators can be before priming is arrested by gravity. In embodiments where the liquid is aqueous based hydrophilic surfaces can result in the capillators self-priming faster and being capable of being taller and / or wider. The use of titanium is advantageous as titanium is both oleophilic and hydrophilic. Other advantageous materials include glass.

[0180] Various alternatives are possible. For example, in some cases, the individual capillary loaders can be omitted. A capillary loader system can have a reservoir for holding fluid (e.g., oil), and a plurality7of nozzles that each draw7from the same reservoir of fluid. In some cases, gravity can be used to transfer the fluid from the vial 554 to the capillary loader 518. In some cases, capillary loader(s) 518 can be used in a similar manner, but without use of, and independently of, loader module 525.Drugs

[0181] In some embodiments, the drug can be formulated as an oil. The drug can include a prostaglandin, a prostaglandin analog, a prostaglandin inhibitor, a beta-adrenergic receptor antagonist, or combinations thereof, although other drugs can be used as discussed herein. In some embodiments, the drug can include travoprost.

[0182] The therapeutic agents utilized with the drug delivery7implant, may include one or more drugs provided below, either alone or in combination. The drugs utilized may also be the equivalent of, derivatives of, or analogs of one or more of the drugs provided below. The drugs may7include but are not limited to pharmaceutical agents including anti-glaucoma medications, ocular agents, antimicrobial agents (e.g., antibiotic, antiviral, antiparasitic, antifungal agents), anti-inflammatory agents (including steroids or non-steroidal antiinflammatory ), biological agents including hormones, enzymes or enzyme-related components, antibodies or antibody-related components, oligonucleotides (including DNA, RNA, short-interfering RNA, antisense oligonucleotides, and the like), DNA / RNA vectors, viruses (either wild ty pe or genetically modified) or viral vectors, peptides, proteins, enzy mes, extracellular matrix components, and live cells configured to produce one or more biological components. The use of any particular drug is not limited to its primary7effect or regulatorybody -approved treatment indication or manner of use. Drugs also include compounds or other materials that reduce or treat one or more side effects of another drug or therapeutic agent. As many drugs have more than a single mode of action, the listing of any particular drug within any one therapeutic class below is only representative of one possible use of the drug and is not intended to limit the scope of its use with the ophthalmic implant system.

[0183] As discussed above, the therapeutic agents may be combined with any number of excipients as is known in the art. In addition to the biodegradable polymeric excipients discussed above, other excipients may be used, including, but not limited to, benzyl alcohol, ethylcellulose, methylcellulose, hydroxymethylcellulose, cetyl alcohol, croscarmellose sodium, dextrans, dextrose, fructose, gelatin, glycerin, monoglycerides, diglycerides, kaolin, calcium chloride, lactose, lactose monohydrate, maltodextrins, polysorbates, pregelatinized starch, calcium stearate, magnesium stearate, silcon dioxide, cornstarch, talc, and the like. The one or more excipients may be included in total amounts as low as about 1%, 5%, or 10% and in other embodiments may be included in total amounts as high as 50%, 70% or 90%.

[0184] Examples of drugs may include various anti-secretory agents; antimitotics and other anti-proliferative agents, including among others, anti-angiogenesis agents such as angiostatin, anecortave acetate, thrombospondin, VEGF receptor tyrosine kinase inhibitors and anti-vascular endothelial growth factor (anti-VEGF) drugs such as ranibizumab (LUCENTIS®) and bevacizumab (AVASTIN®), pegaptanib (MACUGEN®), sunitinib and sorafenib and any of a variety' of known small-molecule and transcription inhibitors having anti-angiogenesis effect; classes of know n ophthalmic drugs, including: glaucoma agents, such as adrenergic antagonists, including for example, beta-blocker agents such as atenolol propranolol, metipranolol, betaxolol, carteolol. levobetaxolol, levobunolol and timolol; adrenergic agonists or sympathomimetic agents such as epinephrine, dipivefrin, clonidine, aparclonidine, and brimonidine; parasympathomimetics or cholingeric agonists such as pilocarpine, carbachol, phospholine iodine, and physostigmine, salicylate, acetylcholine chloride, eserine, diisopropyl fluorophosphate, demecarium bromide); muscarinics; carbonic anhydrase inhibitor agents, including topical and / or systemic agents, for example acetozolamide, brinzolamide, dorzolamide and methazolamide, ethoxzolamide, diamox, and dichlorphenamide; mydriatic-cycloplegic agents such as atropine, cyclopentolate, succinylcholine, homatropine, phenylephrine, scopolamine and tropicamide; prostaglandins such as prostaglandin F2 alpha, antiprostaglandins, prostaglandin precursors, or prostaglandin analog agents such as bimatoprost, latanoprost, travoprost and unoprostone.

[0185] Other examples of drugs may also include anti-inflammatory agents including for example glucocorticoids and corticosteroids such as betamethasone, cortisone, dexamethasone, dexamethasone 21 -phosphate, methylprednisolone, prednisolone 21-phosphate, prednisolone acetate, prednisolone, fluroometholone, loteprednol, medrysone, fluocinolone acetonide, triamcinolone acetonide, triamcinolone, triamcinolone acetonide, beclomethasone, budesonide. flunisolide, fluoromethoIone, fluticasone, hydrocortisone, hydrocortisone acetate, loteprednol, rimexolone and non-steroidal anti-inflammatory agents including, for example, diclofenac, flurbiprofen, ibuprofen, bromfenac, nepafenac, and ketorolac, salicylate, indomethacin, ibuprofen, naxopren, piroxicam and nabumetone; anti-infective or antimicrobial agents such as antibiotics including, for example, tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, cephalexin, oxy tetracycline, chloramphenicol, rifampicin, ciprofloxacin, tobramycin, gentamycin, erythromycin, penicillin, sulfonamides, sulfadiazine, sulfacetamide, sulfamethizole, sulfisoxazole, nitrofurazone, sodium propionate, aminoglycosides such as gentamicin and tobramycin; fluoroquinolones such as ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin; bacitracin, erythromycin, fusidic acid, neomycin, polymyxin B, gramicidin, trimethoprim and sulfacetamide; antifungals such as amphotericin B and miconazole; antivirals such as idoxuridine trifluorothymidine, acyclovir, gancyclovir, interferon; antimicotics; immune-modulating agents such as antiallergenics, including, for example, sodium chromoglycate, antazoline. methapyriline, chlorpheniramine, cetrizine, pyrilamine. prophenpyridamine; antihistamine agents such as azelastine, emedastine and levocabastine; immunological drugs (such as vaccines, immune stimulants, and / or immunosuppressants); MAST cell stabilizer agents such as cromolyn sodium, ketotifen, lodoxamide, nedocrimil, olopatadine and pemirolastciliary body ablative agents, such as gentimicin and cidofovir; and other ophthalmic agents such as verteporfin, proparacaine, tetracaine, cyclosporine and pilocarpine; inhibitors of cell-surface glycoprotein receptors; decongestants such as phenylephrine, naphazoline, tetrahydrazoline; lipids or hypotensive lipids; dopaminergic agonists and / or antagonists such as quinpirole, fenoldopam, and ibopamine; vasospasm inhibitors; vasodilators; antihypertensive agents; angiotensin converting enzyme (ACE) inhibitors; angiotensin- 1 receptor antagonists such as olmesartan; microtubule inhibitors; molecular motor (dynein and / or kinesin) inhibitors; actin cytoskeleton regulatory agents such as cyctchalasin, latrunculin, swinholide A, ethacrynic acid, H-7, and Rho-kinase (ROCK) inhibitors; remodeling inhibitors; modulators of the extracellular matrix such as tert-butylhydro-quinolone and AL-3037A; adenosine receptor agonists and / or antagonists such as N-6-cylclophexyladenosine and (R)-phenylisopropyladenosine; serotonin agonists; hormonal agents such as estrogens, estradiol, progestational hormones, progesterone, insulin, calcitonin, parathyroid hormone, peptide and vasopressin hypothalamus releasing factor; growth factor antagonists or growth factors, including, for example, epidermal growth factor, fibroblast growth factor, platelet derived growth factor or antagonists thereof (such as those disclosed in United States Patent 7,759,472 or United States Patent Application Nos. 12 / 465,051, 12 / 564,863, or 12 / 641,270, each of which is incorporated in its entirety by reference herein), transforming growth factor beta, somatotrapin, fibronectin, connective tissue growth factor, bone morphogenic proteins (BMPs); cytokines such as interleukins, CD44, cochlin, and serum amyloids, such as serum amyloid A.

[0186] Other therapeutic agents may include neuroprotective agents such as lubezole, nimodipine and related compounds, and including blood flow enhancers such as dorzolamide or betaxolol; compounds that promote blood oxygenation such as erythropoeitin; sodium channels blockers; calcium channel blockers such as nilvadipine or lomerizine; glutamate inhibitors such as memantine nitromemantine, riluzole, dextromethorphan or agmatine; acetylcholinsterase inhibitors such as galantamine; hydroxylamines or derivatives thereof, such as the water soluble hydroxylamine derivative OT-440; synaptic modulators such as hydrogen sulfide compounds containing flavonoid glycosides and / or terpenoids, such as ginkgo biloba; neurotrophic factors such as glial cell-line derived neutrophic factor, brain derived neurotrophic factor; cytokines of the IL-6 family of proteins such as ciliary neurotrophic factor or leukemia inhibitory factor; compounds or factors that affect nitric oxide levels, such as nitric oxide, nitroglycerin, or nitric oxide synthase inhibitors; cannabinoid receptor agonsists such as WIN55-212-2; free radical scavengers such as methoxypolyethylene glycol thioester (MPDTE) or methoxypolyethlene glycol thiol coupled with EDTA methyl triester (MPSEDE); anti-oxidants such as astaxathin, dithiolethione, vitamin E, vitamin C, or metallocorroles (e.g., iron, manganese or gallium corroles), butylated hydroxyanisole (BHA), butylated hydroxy toluene (BHT), beta carotene, sodium bisulphite, and sodium salts of edetate (EDTA); compounds or factors involved in oxygen homeostasis such as neuroglobin or cytoglobin: inhibitors or factors that impact mitochondrial division or fission, such as Mdivi-1 (a selective inhibitor of dynamin related protein 1 (Drpl)); kinase inhibitors or modulators such as the Rho-kinase inhibitor H-1152 or the tyrosine kinase inhibitor AG1478; compounds or factors that affect integrin function, such as the Beta 1-integrin activating antibody HUTS-21; N-acyl-ethanaolamines and their precursors, N-acyl-ethanolamine phospholipids; stimulators of glucagon-like peptide 1 receptors (e.g., glucagon-like peptide 1); polyphenol containingcompounds such as resveratrol; chelating compounds; apoptosis-related protease inhibitors; compounds that reduce new protein synthesis; radiotherapeutic agents; photodynamic therapy agents; gene therapy agents; genetic modulators; auto-immune modulators that prevent damage to nerves or portions of nerves (e.g., demyelination) such as glatimir; myelin inhibitors such as anti-NgR Blocking Protein, NgR(310)ecto-Fc; other immune modulators such as FK506 binding proteins (e.g., FKBP51); and dry eye medications such as cyclosporine, cyclosporine A, delmulcents, and sodium hyaluronate.

[0187] Other therapeutic agents that may be used include: other beta-blocker agents such as acebutolol, atenolol, bisoprolol, carvedilol, asmolol, labetalol, nadolol, penbutolol, and pindolol; other corticosteroidal and non-steroidal anti-inflammatory agents such aspirin, betamethasone, cortisone, diflunisal, etodolac. fenoprofen, fludrocortisone, flurbiprofen, hydrocortisone, ibuprofen, indomethacine, ketoprofen, meclofenamate, mefenamic acid, meloxicam, methylprednisolone, nabumetone, naproxen, oxaprozin, prednisolone, pri oxicam, salsalate, sulindac and tolmetin; COX-2 inhibitors like celecoxib, rofecoxib and. Vai decoxib; other immune-modulating agents such as aldesleukin, adalimumab (HUMIRA®), azathiopnne, basiliximab, daclizumab, etanercept (ENBREL®), hydroxychloroquine, infliximab (REMICADE®), leflunomide, methotrexate, mycophenolate mofetil, and sulfasalazine; other anti-histamine agents such as loratadine, desloratadine, cetirizine, diphenhydramine, chlorpheniramine, dexchlorpheniramine, clemastine, cyproheptadine, fexofenadine, hydroxyzine and promethazine; other anti-infective agents such as aminoglycosides such as amikacin and streptomycin; anti-fungal agents such as amphotericin B, caspofungin, clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole, terbinafine and nystatin; anti-malarial agents such as chloroquine, atovaquone, mefloquine, primaquine, quinidine and quinine; anti-mycobacterium agents such as ethambutol, isoniazid, pyrazinamide, rifampin and rifabutin; anti-parasitic agents such as albendazole, mebendazole, thiobendazole, metronidazole, pyrantel, atovaquone, iodoquinaol, ivermectin, paromycin, praziquantel, and trimatrexate; other anti-viral agents, including anti-CMV or anti-herpetic agents such as acyclovir, cidofovir, famciclovir, gangciclovir, valacyclovir, valganciclovir, vidarabine, trifluridine and foscamet; protease inhibitors such as ritonavir, saquinavir, lopinavir, indinavir, atazanavir, amprenavir and nelfinavir; nucleotide / nucleoside / non-nucleoside reverse transcriptase inhibitors such as abacavir, ddl, 3TC, d4T, ddC, tenofovir and emtricitabine, delavirdine, efavirenz and nevirapine: other antiviral agents such as interferons, ribavirin and trifluri diene; other anti-bacterial agents, including cabapenems like ertapenem, imipenem and meropenem; cephalosporins such as cefadroxil,cefazolin, cefdinir, cefditoren, cephalexin, cefaclor, cefepime, cefoperazone, cefotaxime, cefotetan, cefoxitin, cefpodoxime, cefprozil. ceftaxidime, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime and loracarbef; other macrolides and ketolides such as azithromycin, clarithromycin, dirithromycin and telithromycin; penicillins (with and without clavulanate) including amoxicillin, ampicillin, pivampicillin, dicloxacillin, nafcillin, oxacillin, piperacillin, and ticarcillin; tetracyclines such as doxycycline, minocycline and tetracycline; other antibacterials such as aztreonam, chloramphenicol, clindamycin, linezolid, nitrofurantoin and vancomycin; alpha blocker agents such as doxazosin, prazosin and terazosin; calcium-channel blockers such as amlodipine, bepridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine and verapamil; other anti-hypertensive agents such as clonidine, diazoxide, fenoldopan, hydralazine, minoxidil, nitroprusside, phenoxybenzamine, epoprostenol, tolazoline, treprostinil and nitrate-based agents; anti-coagulant agents, including heparins and heparinoids such as heparin, dalteparin, enoxaparin, tinzaparin and fondaparinux; other anticoagulant agents such as hirudin, aprotinin, argatroban, bivalirudin, desirudin, lepirudin, warfarin and ximelagatran; anti-platelet agents such as abciximab, clopidogrel, dipyridamole, optifibatide, ticlopidine and tirofiban; prostaglandin PDE-5 inhibitors and other prostaglandin agents such as alprostadil, carboprost, sildenafil, tadalafil and vardenafil; thrombin inhibitors; antithrombogenic agents; anti-platelet aggregating agents; thrombolytic agents and / or fibrinolytic agents such as alteplase, anistreplase, reteplase, streptokinase, tenecteplase and urokinase; anti-proliferative agents such as sirolimus. tacrolimus, everolimus, zotarolimus, paclitaxel and mycophenolic acid; hormonal-related agents including levothyroxine, fluoxymestrone, methyltestosterone, nandrolone, oxandrolone, testosterone, estradiol, estrone, estropipate, clomiphene, gonadotropins, hydroxyprogesterone, levonorgestrel, medroxyprogesterone, megestrol, mifepristone, norethindrone, oxytocin, progesterone, raloxifene and tamoxifen; anti-neoplastic agents, including alkylating agents such as carmustine lomustine, melphalan, cisplatin, fluorouracils, and procarbazine antibiotic-like agents such as bleomycin, daunorubicin, doxorubicin, idarubicin, mitomycin and plicamycin; anti proliferative agents (such as 1,3-cis retinoic acid, 5-fluorouracil, taxol, rapamycin, mitomycin C and cisplatin); antimetabolite agents such as cytarabine, fludarabine, hydroxyurea, mercaptopurine and 5-fluorouracil (5-FU); immune modulating agents such as aldesleukin, imatinib, rituximab and tositumomab; mitotic inhibitors docetaxel, etoposide, vinblastine and vincristine; radioactive agents such as strontium-89; and other anti-neoplastic agents such as irinotecan, topotecan and mitotane.Conclusion

[0188] While the above detailed description has shown, described, and pointed out novel features of the present disclosure as applied to various embodiments, it will be understood that various omissions, substitutions, and changes in the form and details of the device or process illustrated may be made by those skilled in the art without departing from the spirit of the present disclosure. As will be recognized, the present disclosure may be embodied within a form that does not provide all of the features and benefits set forth herein, as some features may be used or practiced separately from others. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.

[0189] The term “comprising"’ as used herein is synonymous with “including,” “containing,” or “characterized by.” and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. With respect to the use of substantially any plural and / or singular terms herein, those having skill in the art may translate from the plural to the singular and / or from the singular to the plural as is appropriate to the context and / or application. The various singular / plural permutations may be expressly set forth herein for sake of clarity.

[0190] It will be understood by those within the art that, in general, terms used herein are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,"’ the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and "‘one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and / or “an” should typically be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations.

[0191] In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,”without other modifiers, typically means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together. A and C together, B and C together, and / or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A. B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and / or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.”

[0192] All numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches. For example, terms such as about, approximately, substantially, and the like may represent a percentage relative deviation, in various embodiments, of ±1%, ±5%, ±10%, or ±20%.

[0193] The above description discloses several methods and materials of the present disclosure. The present disclosure is susceptible to modifications in the methods and materials, as well as alterations in the fabrication methods and equipment. Such modifications will become apparent to those skilled in the art from a consideration of this disclosure. Consequently, it is not intended that the present disclosure be limited to the specific embodiments disclosed herein, but that it covers all modifications and alternatives coming within the true scope and spirit of the present disclosure.

Claims

WHAT IS CLAIMED IS:

1. A method of transferring a fluid to a container, the method comprising:priming a tube with the fluid;cutting the tube to provide a tube segment having a length based at least in part on a target amount of the fluid;assembling a transfer assembly by inserting the tube segment into a corresponding funnel aligned with a container mount holding the container; and transferring the fluid from the tube segment into the container.

2. The method of Claim 1, further comprising:inserting the transfer assembly into a centrifuge; andoperating the centrifuge to spin the transfer assembly to drive the fluid from the tube segment into the funnel and from the funnel into the container.

3. The method of Claim 1 or 2, wherein the fluid includes travoprost.

4. The method of any one of Claims 1-3, wherein the container is an ocular implant.

5. The method of any one of Claims 1-4, wherein priming the tube further comprises using pressure to drive the fluid into the tube.

6. The method of Claim 5, comprising using a pressurized gas to provide the pressure to drive the fluid into the tube.

7. The method of Claim 5, comprising using pressure between about 100 psi and about 3500 psi to drive the fluid into the tube.

8. The method of any one of Claims 1 -7, further comprising heating the fluid.

9. The method of Claim 8, comprising heating the fluid to a temperature between about 33 degrees Celsius and about 40 degrees Celsius.

10. The method of any one of Claims 1-9, further comprising determining a length for the tube segment before cutting the tube segment, wherein determining the length for the tube segment comprises:cutting the tube to provide a calibration tube segment having a calibration length;measuring a first weight of the calibration tube segment with the fluid therein; removing the fluid from the calibration tube segment;measuring a second weight of the calibration tube segment without the fluid; anddetermining the length of the tube segment based at least in part on the calibration length, the first weight, and the second weight of the calibration tube segment.

11. The method of Claim 10, comprising:calculating an amount of fluid per unit length for the tube based at least in part on the calibration length, the first weight, and the second weight of the calibration tube segment; anddetermining the length of the tube segment based at least in part on the calculated amount of fluid per unit length and the target amount of the fluid.

12. The method of any one of Claim 1-11 wherein the fluid has a viscosity' greater than about 500 cPs at 25 degrees C.

13. A system for transferring a fluid to a container, the system comprising:a transfer assembly comprising:a container mount configured to retain a container;a funnel comprising an opening extending from a first end to a second end, the second end configured to align with the container mount; anda tube segment positioned within the first end of the funnel and configured to retain a fluid, the tube segment having a length based at least in part on a target amount of fluid; anda centrifuge spin fixture comprising an opening configured to receive the transfer assembly.

14. The system of Claim 13, wherein the opening of the funnel has a width that decreases from the first end to the second end.

15. The system of Claim 13 or 14, wherein the container mount comprises the container received within an opening sized and shaped to retain the container within the container mount.

16. The system of Claim 15, wherein the container is an ocular implant.

17. The system of any one of Claims 13-16, wherein the tube segment contains a viscous fluid.

18. The system of any one of Claims 13-16, wherein the fluid comprises travoprost.

19. The system of any one of Claims 13-18, wherein the centrifuge spin fixture comprises a base portion and a lid portion removable from the base and wherein the base portion and lid portion retain the transfer assembly within the opening of the centrifuge spin fixture.

20. The system of any one of Claims 13-19, wherein the container includes an opening, and wherein the opening of the container aligns with the second end of the opening of the funnel.

21. A system for priming a tube, the system comprising:a connector comprising housing, a first end, and a second end;a fluid reservoir formed at the second end of the connector;a pressure connection at the first end of the connector and configured to couple to a pressure device; anda tube connector coupled to a second end of the connector to couple the tube to the connector so that the tube is in fluid communication with the fluid reservoir; wherein the pressure device is configured to apply pressure to the fluid reservoir to drive fluid from the fluid reservoir into the tube.

22. The system of Claim 21, wherein the connector and the tube are disposed in a thermally controlled enclosure.

23. A method of transferring a fluid to a container, the method comprising:priming a tube with the fluid;cutting the tube to provide a tube segment having a length based at least in part on a target amount of the fluid;assembling a transfer assembly by coupling the tube segment to a container mount holding the container; andtransferring the fluid from the tube segment into the container.

24. The method of Claim 23, further comprising:inserting the transfer assembly into a centrifuge; andoperating the centrifuge to spin the transfer assembly to drive the fluid from the tube segment into the container.

25. The method of Claim 23 or 24, wherein the fluid includes travoprost.

26. The method of any one of Claims 23-25, wherein the container is an ocular implant.

27. The method of any one of Claims 23-26, wherein priming the tube further comprises using pressure to drive the fluid into the tube.

28. The method of Claim 27, comprising using a pressurized gas to provide the pressure to drive the fluid into the tube.

29. The method of Claim 27 or 28, comprising using pressure between about 100 psi and about 3500 psi to drive the fluid into the tube.

30. The method of any one of Claims 23-29, further comprising heating the fluid.

31. The method of Claim 30, comprising heating the fluid to a temperature between about 33 degrees Celsius and about 40 degrees Celsius.

32. The method of any one of Claims 23-31, further comprising determining a length for the tube segment before cutting the tube segment, wherein determining the length for the tube segment comprises:cutting the tube to provide a calibration tube segment having a calibration length;measuring a first weight of the calibration tube segment with the fluid therein; removing the fluid from the calibration tube segment;measuring a second weight of the calibration tube segment without the fluid; anddetermining the length of the tube segment based at least in part on the calibration length, the first weight, and the second weight of the calibration tube segment.

33. The method of Claim 32. comprising:calculating an amount of fluid per unit length for the tube based at least in part on the calibration length, the first weight, and the second weight of the calibration tube segment; anddetermining the length of the tube segment based at least in part on the calculated amount of fluid per unit length and the target amount of the fluid.

34. The method of any one of Claims 23-31 further comprising determining an amount of the fluid by weighing the tube before priming the tube with the fluid to identify a first weight and weighing the tube after priming the tube with the fluid to identify' a second weight, wherein a difference between the second weight and the first weight corresponds to the amount of fluid.

35. A system for transferring a fluid to a container, the system comprising:a transfer assembly comprising:a container mount configured to retain a container; anda tube segment configured to retain a fluid, the tube segment having a length based at least in part on a target amount of fluid; anda centrifuge spin fixture comprising an opening configured to receive the transfer assembly.

36. The system of Claim 35, wherein the container mount comprises the container received within an opening sized and shaped to retain the container within the container mount.

37. The system of Claim 35 or 36, wherein the container is an ocular implant.

38. The system of any one of Claims 35-37, wherein the tube segment contains a viscous fluid.

39. The system of any one of Claims 35-38, wherein the fluid comprises travoprost.

40. The system of any one of Claims 35-39 wherein the centrifuge spin fixture comprises a base portion and a lid portion removable from the base and wherein the base portion and lid portion retain the transfer assembly within the opening of the centrifuge spin fixture.

41. A method of transferring a fluid to a container, the method comprising:aligning a spin adapter with an aliquoter in a first configuration; depositing a fluid in the spin adapter;transferring the fluid from the spin adapter to the aliquoter;aligning the aliquoter, and a container mount in a second configuration, wherein the container mount includes the container; andtransferring the fluid from the aliquoter to the container.

42. The method of Claim 41. wherein the fluid includes travoprost.

43. The method of Claim 41 or 42, wherein the container comprises an ocular implant.

44. The method of any one of Claims 41-43, wherein transferring the fluid from the spin adapter to the aliquoter comprises inserting the spin adapter and the aliquoter in a centrifuge and operating the centrifuge.

45. The method of Claim 44, wherein transferring the fluid from the aliquoter to the container further comprises inserting the spin adapter, the aliquoter, and the container mount in the centrifuge and operating the centrifuge.

46. The method of any one of Claims 31-45, wherein the aligning in the second configuration comprises aligning the aliquoter, the spin adapter, and the container mount in the second configuration, and wherein transferring the fluid from the aliquoter to the container comprises first transferring the fluid from the aliquoter to the spin adapter.

47. The method of Claim 46, wherein transferring the fluid from the aliquoter to the container further comprises transferring the fluid from the spin adapter to the container.

48. The method of any one of Claims 41-47, wherein:aligning the spin adapter to the aliquoter further comprises aligning a plurality of spin adapters with a plurality of aliquoters;depositing a fluid in the spin adapter further comprises depositing fluid in the plurality of spin adapters;transferring fluid from the spin adapter to the aliquoter further comprises transferring fluid from the plurality of spin adapters to the plurality of aliquoters; aligning the aliquoter, and the container mount in the second configuration further comprises aligning the plurality of aliquoters, and the plurality of container mounts in the second configuration, wherein the plurality of container mounts include a plurality of containers; andtransfernng the fluid from the aliquoter to the container further comprises transferring the fluid from the plurality’ of aliquoters to the plurality of containers.

49. The method of any one of Claims 41-48, further comprising heating the fluid.

50. The method of Claim 49, comprising heating the fluid to a temperature between about 33 degrees Celsius and about 40 degrees Celsius.

51. The method of any one of Claims 41-50, wherein the aliquoter comprises:a body having a first surface at a first end and a second surface at a second end opposite the first end;a first channel extending from the first end partially into the body towards the second end;a second channel extending from the second end partially into the body towards the first end;a wall separating the first channel from the second channel; and an opening through the wall to fluidly couple the first channel to the second channel.

52. The method of any one of Claims 41-51, wherein transferring the fluid from the spin adapter to the aliquoter comprises:transferring a first portion of the fluid from the spin adapter into the first channel of the aliquoter to fill the first channel up to the opening; andtransferring a second portion of the fluid from the spin adapter into the first channel of the aliquoter, wherein at least some of the second portion of the fluid passes from the first channel, through the opening, into the second channel, and out of the second channel at the second end of the body of the aliquoter.

53. The method of any one of Claims 41-52, wherein:aligning the spin adapter with the aliquoter in the first configuration includes positioning the spin adapter over the aliquoter; andaligning the aliquoter, and the container mount in the second configuration includes inverting the aliquoter, positioning the inverted aliquoter over the spin adapter, and positioning the spin adapter over the container mount.

54. The method of any one of Claims 41-53, wherein the aligning in the second configuration comprises aligning the aliquoter, the spin adapter, and the container mount in the second configuration, wherein the aliquoter has a first end and a second end opposite the first end, wherein the spin adapter has a first end and a second end opposite the first end, wherein in the first configuration the first end of the aliquoter is positioned towards the second end of the spin adapter, and wherein in the second configuration the first end of the aliquoter is positioned towards the first end of the spin adapter.

55. An aliquoter comprising:a body having a first surface at a first end and a second surface at a second end opposite the first end;a first channel extending from the first end partially into the body towards the second end;a second channel extending from the second end partially into the body towards the first end;a wall separating the first channel from the second channel; and an opening through the wall to fluidly couple the first channel to the second channel.

56. The aliquoter of Claim 55, further comprising a third channel aligned with the opening.

57. The aliquoter of Claim 56, wherein the third channel is substantially perpendicular to the first channel or to the second channel.

58. The aliquoter of any one of Claims 55-57, wherein the first channel is substantially parallel to the second channel.

59. The aliquoter of any one of Claims 55-58, wherein the first channel is substantially aligned with a central axis of the aliquoter, and wherein the second channel is offset from the central axis of the aliquoter.

60. A system comprising:the aliquoter of any one of Claims 55-59; anda spin adapter that comprises:a body having a first surface at a first end and a second surface at a second end opposite the first end;a funnel extending from the first end and narrowing towards the second end; anda channel extending from a narrow end of the funnel to the second end to thereby provide a fluid path through the body.

61. The system of Claim 60, wherein the channel of the spin adapter is aligned with the first channel of the aliquoter.

62. The system of Claim 60 or 61, further comprising a container mount that includes a recess with the container positioned in the recess, wherein the container aligned with the channel of the spin adapter.

63. A system for transferring a fluid to a container, the system comprising:a spin adapter comprising an opening extending from a first end to a second end of the spin adapter, the spin adapter configured to receive a fluid in the first end; an aliquoter comprising:a first channel extending from an opening in a first end of the aliquoter, the first channel having a closed second end:a second channel offset from the first channel and fluidly coupled to the first channel via an opening in a sidewall of the first channel, the second channel extending through a second end of the aliquoter; anda third channel fluidly coupled to the first channel and the second channel, the third channel extending generally perpendicular to the first channel and the second channel, the third channel extending through a side wall of the aliquoter; anda container mount having a top surface configured to retain a container; wherein in a first configuration the second end of the spin adapter is aligned with the first end of the aliquoter, andwherein in a second configuration the first end of the aliquoter is aligned with the first end of the spin adapter, and the second end of the spin adapter is aligned with the top surface of the container mount.

64. The system of Claim 63, wherein the opening of the spin adapter has a diameter or width that decreases from the first end to the second end.

65. The system of Claim 63 or 64, wherein the container mount comprises the container received within an opening sized and shaped to retain the container within the container mount.

66. The system of any one of Claims 63-65, wherein the container is an ocular implant.

67. The system of any one of Claims 63-66, further comprising a centrifuge mount configured to receive the first configuration.

68. The system of any one of Claims 63-67, further comprising a centrifuge mount configured to receive the second configuration.

69. A method for transferring a fluid into a container, the method comprising:connecting a capillator to a fluid so that a portion of the fluid is transferred into the capillator by capillary action; andtransferring the portion of the fluid from the capillator to the container using a centrifuge.

70. The method of Claim 69, wherein the capillator includes a channel that is sized so that the capillator holds a target volume of fluid that corresponds to filling the container, and wherein the capillator is configured to stop transferring fluid by capillary action once the target volume is transferred to the capillator.

71. The method of Claim 69 or 70, further comprising depositing a volume of the fluid into a capillary loader.

72. The method of Claim 71, further comprising applying pressure to the capillary loader to push some of the fluid out of an opening of the capillary loader to form a layer of fluid on an outside surface of the capillary' loader.

73. The method of Claim 71 or 72, comprising coupling the capillator to the capillary loader so that the capillator contacts the fluid.

74. The method of any one of Claims 71-73, wherein the deposited volume of fluid in the capi I lary loader is sufficient to fill multiple capillators, and wherein the method comprises repeatedly coupling one or more additional capillators to the capillary loader so that the fluid is transferred from the capillary loader into the one or more additional capillators.

75. The method of Claim 74, wherein the fluid is transferred from the capillary loader into the one or more additional capillators while the portion of the fluid is being transferred from the one or more additional capillators to the container using the centrifuge.

76. The method of any one of Claims 71, comprising:inserting a nozzle of a vial containing the fluid into a funnel of the capillary loader; andapplying pressure to the vial to drive the portion of the fluid out of the nozzle and into the funnel of the capillary loader.

77. The method of any one of Claims 71, comprising:inserting a nozzle of a vial containing the fluid into a funnel of the capillary loader; andusing gravity to transfer the portion of the fluid out of the nozzle and into the funnel of the capillary loader.

78. The method of any one of Claims 71, comprising:using at least one of a needle, syringe, or robotic fluid dispensing system to transfer the portion of the fluid into the capillary loader.

79. The method of any one of Claims 71-78, comprising:installing multiple capillary' loaders into a loader module;inverting the loader module; andinserting a nozzle of a vial containing the fluid through an opening in the loader module and into a funnel of the capillary loader.

80. The method of any one of Claims 69-79, further comprising heating the fluid.

81. The method of Claim 80, further comprising heating the fluid to a temperature between about 33 degrees Celsius and about 40 degrees Celsius.

82. The method of any one of Claims 79-81, further comprising applying pressure to the vial to drive the portion of the fluid out of the nozzle and into the funnel of the capillary loader.

83. The method of any one of Claims 79-81, further comprising using gravity to transfer the portion of the fluid out of the nozzle and into the funnel of the capillary loader.

84. The method of any one of Claims 79-83, comprising un-inverting the loader module before coupling the capillator to the capillary loader.

85. The method of any one of Claims 69-84, comprising heating the fluid.

86. The method of Claim 85, comprising heating the fluid to a temperature between about 33 degrees Celsius and about 40 degrees Celsius.

87. The method of any one of Claims 69-86, wherein the capillator includes:a body that has a first end, a second end opposite the first end, and a first length that extends from the first end to the second end;a recess extending from the first end toward the second end and having a base, wherein the recess has a depth extending from the first end to the base of the recess; anda channel extending from the base of the recess toward the second end, wherein the channel has a second length that is shorter than the first length.

88. The method of Claim 87, wherein the channel extends from the base of the recess to the second end of the capillator.

89. The method of Claim 87 or 88, wherein the channel is sized so that the capillator holds a target volume of fluid that corresponds to filling the container.

90. The method of any one of Claims 87-89, wherein the channel is configured to draw the portion of the fluid into the channel by capillary action, and wherein the channel is configured to stop drawing fluid when the channel is substantially full.

91. The method of any one of Claims 87-90, wherein the capillator includes an additional recess extending from the second end towards the first end of the capillator, wherein the channel extends into the additional recess toward the second end forming a raised lip.

92. A method of making a capillator, the method comprising:forming a channel through a body having a first end and a second end opposite the first end, wherein the channel has a first length, and wherein the channel is along a direction that extends from the first end to the second end of the body;measuring a first volume of fluid held by the channel with the first length; and forming a recess in the first end of the body, the recess having a depth to shorten the channel to have a second length, wherein the depth of the channel is based at least in part on the measured first volume of fluid and a target volume of fluid for the capillator.

93. The method of Claim 92, wherein the channel is sized so that the capillator holds the target volume of fluid that corresponds to filling a container.

94. The method of Claim 92 or 93, wherein the channel is configured to draw a portion of the fluid into the channel by capillary action, and wherein the channel is configured to stop drawing fluid when the channel is substantially full.

95. The method of any one of Claims 92-94, comprising forming an additional recess extending from the second end towards the first end of the capillator, wherein the channel extends into the additional recess toward the second end forming a raised lip.

96. A capillator comprising:a body that has a first end, a second end opposite the first end, and a first length that extends from the first end to the second end;a recess extending from the first end toward the second end and having a base, wherein the recess has a depth extending from the first end to the base of the recess; anda channel extending from the base of the recess toward the second end, wherein the channel has a second length that is shorter than the first length.

97. The capillator of Claim 96, wherein the channel extends from the base of the recess to the second end of the capillator.

98. The capillator of Claim 96 or 97, wherein the channel is sized so that the capillator holds a target volume of fluid that corresponds to filling a container.

99. The capillator of any one of Claims 96-98, wherein the channel is configured to draw a portion of a fluid into the channel by capillary action.

100. The capillator of Claim 99, wherein the channel is configured to stop drawing fluid when the channel is substantially full.

101. The capillator of any one of Claims 96-100. wherein the capillator includes an additional recess extending from the second end towards the first end of the capillator.

102. The capillator of Claim 101, wherein the channel extends into the additional recess toward the second end forming a raised lip.

103. A capillator comprising:a body that has a first end, a second end opposite the first end, and a first length that extends from the first end to the second end; anda channel extending from the first end toward the second end, wherein the channel has a second length that is equal to or less than the first length.

104. The capillator of Claim 103, wherein the channel is sized so that the capillator holds a target volume of fluid that corresponds to filling a container.

105. The capillator of Claim 103 or 104, wherein the channel is configured to draw a portion of a fluid into the channel by capillary action.

106. The capillator of any one of Claims 103-105. wherein the channel is configured to stop drawing fluid when the channel is substantially full.

107. The capillator of any one of Claims 103-106, wherein the capillator includes a recess extending from the second end towards the first end of the capillator.

108. The capillator of Claim 107, wherein the channel extends into the recess toward the second end forming a raised hp.

109. A system for transferring a fluid to a container, the system comprising:a capillary' loader comprising an opening extending from a first end to a second end, the opening comprising a funnel portion extending from the first end and a receiving portion extending from the second end;a capillator comprising a channel extending at least partially through a length of the capillator; anda container mount retaining a container;wherein in a first configuration the capillator is received within the receiving portion of the capillary loader; andwherein in a second configuration the channel of the capillator is aligned with the container.

110. The system of Claim 109, further comprising a vial containing a viscous fluid configured to deposit the viscous fluid into the funnel portion of the capillary' loader.

111. The system of Claim 110, further comprising a dispensing system fluidly coupled to the vial, wherein the dispensing system is configured to apply a pressure to the vial to assist in depositing the viscous fluid into the funnel portion of the capillary' loader.

112. The system of any one of Claims 109-111, wherein the funnel portion has a diameter that decreases from the first end to the second end.

113. The system of any one of Claims 109-112, wherein the container mount comprises the container received within an opening sized and shaped to retain the container within the container mount.

114. The system of any one of Claims 109-113, wherein the container is an ocular implant.

115. The system of any one of Claims 109-114, further comprising a centrifuge mount configured to receive the second configuration.

116. A method of transferring a fluid, the method comprising:installing a plurality' of capillary loaders in a base;installing a dispensing cap to a vial containing the fluid;inverting the base;aligning the vial with a first capillary' loader;dispensing a portion of the fluid from the vial to the first capillary loader; repeating the aligning and dispensing steps for each of the plurality of capillary loaders;aligning respective empty' capillators with the plurality' of capillary' loaders; and transferring the fluid from the capillary loaders to the capillators.

117. The method of Claim 116, further comprising transferring the fluid from the capillators to containers.

118. The method of Claim 117, wherein transferring the fluid from the capillators to the containers further comprises inserting the capillators and the containers into a centrifuge, and operating the centrifuge to spin the capillators and the containers to drive the fluid from the capillators into the containers.

119. The method of any one of Claims 116-118, wherein the fluid comprises travoprost.

120. The method of any one of Claims 117-119, wherein the containers are ocular implants.

121. The method of any one of Claims 116-120, further comprising applying a pressure pulse to the capillary loaders causing the fluid to billow onto a top surface of the capillary loaders.

122. The method of any one of Claims 116-121, further comprising applying a top cap to the vial, the top cap configured to connect the vial to a pressure controller.

123. The method of any one of Claims 116-122, wherein transferring the fluid from the capillary loaders to the capillators comprises applying heat or a dry bath.

124. The method of any one of Claims 116-122, wherein transferring the fluid from the capillary loaders to the capillators comprises heating the fluid.

125. The method of any one of Claims 116-124, wherein the fluid is transferred from the capillary loaders to the capillators by capillary action.

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