JP4648398B2 - Formulation and characterization of formulations in high-speed mass processing mode - Google Patents

Description

  The present invention generally relates to an automated robotic system for manufacturing and testing formulations with very high volume processing. In particular, this system is an integrated hardware and software system capable of formulating and evaluating hundreds of dispersed multiphase solutions per day. This system can automatically and quickly process the formulation and can introduce a very flexible formulation recipe. From 1 milliliter to 20 milliliter scale, up to 1200 formulations per day are possible. The system includes the progress of the process from start to finish, and includes integrating analytical data with the experimental results in the design state and the experimental results in the formulation state. Materials and consumables can be delivered from the storage system to the work station where the supply of components in various states such as solids, liquids, gels, pastes, suspensions and waxes. Is possible. The formed emulsion, dispersion, and / or solution can be characterized using methods including phase analysis, turbidity analysis, viscosity, and particle sizing. The modular system allows future processes and tests to be added to the station or added as a new station.

  In order to assess the impact of various variables on the performance, shelf life, delivery, contamination susceptibility, and customer satisfaction of the product's formulation chemist and the agrochemical market, surfactant materials (surfactants) Demonstrate the ability to apply design of experiments (DOE). Due to the complexity of formulation prescriptions and the large number of variables to be evaluated, the DOE method generates a matrix of tens of thousands of experiments that must be performed to open up and refine the experimental space of these products. The considerable number of experiments required wastes common bench chemistry techniques. The invention described herein provides pharmaceutical chemists with a means to tackle these large DOE matrices in an automated fashion.

  Following the overview of the invention is a detailed description of the system. Finally, the process description describes step by step the formulation and test method for a typical aqueous solution (SL) and suspension (SC) formulation formulated and tested in the present invention.

  The present invention is an automated robotic system that manufactures and tests formulations at very high speed and high throughput. This system is an integrated hardware and software system capable of formulating and evaluating hundreds of dispersed multiphase solutions per day. This system can be used on a 1 to 25 milliliter scale with aqueous solutions (SL), oil-in-water emulsions (EW), suspoemulsions (SE), microcapsule suspensions (CS), microemulsions (ME), and suspensions. (SC) formulations are possible. This system can automatically and quickly process the emulsion and introduce a very flexible formulation.

  This system allows chemists to create and introduce experimental samples of various prescriptions and methods, simultaneously with a planned process of processing and characterizing 1200 formulations per day. Materials and consumables can be delivered from the storage system to the work station where the supply of components in various states such as solids, liquids, gels, pastes, suspensions and waxes. Is possible. The formed emulsion can be characterized using automated test equipment using methods including phase analysis, turbidity analysis, viscosity, and particle sizing. The integrated module can also perform tank mix suitability tests in a high speed, high throughput mode. The modular system allows future processes and tests to be added to the station or added as a new station. The software includes the progress of the process from start to finish, and may include integrating analytical data with the experimental results in the design state and the experimental results in the formulation state.

  The object of the present invention is to provide an automated robotic system for the production and testing of formulations.

  A further object of the present invention is for use in agriculture, horticulture, forestry and protection during transport or storage, or for the use of agricultural, horticulture or forestry crops and for the public. To provide a system for product research, development, manufacturing, and sales for environmental treatment that combats the spread of pests that are detrimental to hygiene, safety, or convenience.

  A further object of the present invention is to provide products for crop protection or yield enhancement and for environmental treatments that combat the spread of pests that are harmful to public health, safety, or convenience. To provide a system for discovery and development.

  Further objects of the present invention are in formulations for fabric protection, body protection, textiles, mining, mineral coating, asphalt, petroleum, fuel, viscose, cleaning, construction, coating, paper processing and papermaking, and nitrogen To provide a system for research, development, manufacture, and / or sale of surfactants, fatty acids, and rheology control agents in all applications of derivatized surfactants.

  Disclosed herein is an automated robotic system that manufactures and tests formulations with very high volume processing. In a preferred embodiment, a single run is considered to be a system run of 24 hours or more, including a run period of about 20 hours and a set period of about 4 hours. Furthermore, the disclosed and preferred embodiment is based on the use of a 25 milliliter vial that holds about 10 milliliters of the test formulation. The embodiments disclosed herein are disclosed for illustrative purposes only, and other embodiments are contemplated.

  FIG. 1 shows a rack and vial storage system 100 that includes a rack 102 and a vial 104. The medicine bottle is about 25 milliliters, has a diameter of 24 mm and a height of 73 mm. This medicine bottle is a perforated plate “well plate” that contains six medicine bottles per rack, and is accommodated in the rack. Each medicine bottle has a barcode, and each rack has a barcode. Since this rack is a custom-made rack, there seems to be no cost difference between a molded plastic rack and a rack machined from metal. In fact, placing a rack of medicine bottles on a hot plate is faster than moving a medicine bottle from the rack to the heating block, so a metal rack provides an easier and faster way to heat the medicine bottle. can do. This example also requires less space on the robot deck because no empty racks are generated and the need for storage is reduced.

  FIG. 2 shows a consumable station 200. This consumable station is used to supply the materials needed for operation and includes a vial, a pipette tip, and any material to be supplied. The number and size of the storage system depends on the manufacturer, the size of the vial and the above-mentioned functions selected by the customer.

  There are many manufacturers of these storage systems or stations (eg, Zymark, CRS, TomTek, STRbotics, etc.) and can be customized. The standard model works with the “well plate” everywhere, and the system disclosed herein delivers the material in the same manner, whether it is a vial, pipette tip, or a solid to feed. It is considered to be housed in a rack. This rack can also be referred to as a “plate”, but the height is not the height of a standard well plate.

  This station is designed to house and pass each plate at a defined position to an arm or gantry robot. At the beginning of the run, the station is properly loaded with plates, and at the end of the run, the station uses the finished product, grouped as needed (pass, fail, etc.) with an empty rack. Accommodates with the raw material container and prepares for removal.

  The required processing power depends on the desired application. For example, in one embodiment, 2000 positions are provided to hold 1500 vials (leaving 500 empty), and in a second embodiment, 1000 positions are 600 The medicine bottle (400 pieces are left empty) is provided. In addition, a place for consumables (eg, 5000 pipette tips) and a place for compound supply are provided.

  FIG. 3 is an explanatory diagram of the robot arm 300, in which an arm 302 and a rail 304 are shown. There are a number of robot arm manufacturers, and the most suitable arm and manufacturer are selected at the design stage for each application. The robotic arm provides a transport connection between all stations that prepare and characterize the emulsion by moving the vials contained in the rack between the necessary stations. In certain embodiments, a second arm is added to the system. If a second arm is not added to the system, one arm also performs the task of loading individual vials into the mixing system, but the one arm system can either replace the gripper tool, or Requires a dual-function gripper design for both vial and rack operation.

  The operation of the robot arm is made up of three parts: a set part where materials and racks are distributed around the system, an operating part where the sample and feed are conveyed during the formulation of the emulsion, and the completion of the operation. Sometimes it can be thought of as a separate piece of material that has been dispersed and a tidy part where the sample is returned to its proper position. The use of such an arm allows for "random access" type process ordering provided by stations around the rail. In a preferred embodiment, the robot arm has the ability to read rack identification information by bar code.

  FIG. 4 shows a solid supply station 400. This station is available from several manufacturers including Chemspeed, Autodose, and Flexiweight. This platform is adapted to meet individual requirements. The supply accuracy of each system depends on the material supplied. In addition, a representative sample with respect to particle size and chemical composition must be supplied from the container. If necessary, sample preparation such as grinding and sieving can be utilized to prepare the powder. The supply of 1 mg can be performed easily, and the accuracy and precision are increased if the powder is pretreated.

  The solid supply station 400 can accept empty vial racks, or vials from other supply stations in the rack, and can be pre-loaded or supplied with materials for operation. Can accept racks of materials. The station lifts the entire vial rack or individual vials, places them on the mass balance 402, and supplies the solids obtained from the solid source hopper 404 into each vial based on weight, Return the vials to the rack before sending the rack to the delivery and collection point. The station also moves the rack of material to be supplied from the delivery and collection point to a distribution point on the deck. The station also includes a bar code reader 406.

  FIG. 5 shows an embodiment of a liquid, suspension, gel and meltable supply station 500. This station is based on a gantry or Cartesian laboratory robot. Again, there are many manufacturers of such systems, such as the Gilson “Cyberlab” 230/240/400 platform. These robotic systems can attach up to six tools to the tool head above the deck, and the deck can be fitted with custom equipment including substations with other built-in tools. In preferred embodiments, for example, rack and plate grippers, vials and cap grippers, gel dispenser grippers if necessary, pipettes for small plastic disposable pipette tips, any pipettor for glass disposable pipette tips, and A device such as a vacuum cannula for the supply of crushed beads can be attached to the tool head, but is not limited thereto.

  Some tools may require more than one tool position. Some of such devices are multifunctional. For example, the vial gripper can also function as a gel dispenser gripper. Further, in various embodiments, one or more sized pipettes may be required for delivery precision and accuracy. It is conceivable to use both a 5 milliliter tip and a 500 microliter tip.

  The deck includes, for example, a movable gel dispenser 502, a rack or supply location 504, a pre-loaded bead supply source 506 with a bead, a barcode reader and decapper 508, an orbital shaker 510, one or more heating blocks 512, a heated glass pipette tip 514, second mass balance 516, pipette tip rack location 518, liquid drug vial deck location where other sources of normal solution are placed on the deck, transported empty to other deck units Related devices such as, but not limited to, sufficient space to accommodate (e.g., stacked), a pipette tip and a garbage collection chute 520 for a vial cap. Bar code reader and decapper 508 is used to identify and open containers that arrive capped. Mixtures that require stirring, such as unstable suspensions, are sent to orbital shaker 510 after the cap is removed. Orbital shaker 510 is also used for slow mixing such as dissolution and can be used for vigorous stirring if the shaker is carefully selected. If necessary, the material is placed on or in one or more heating blocks 512 to melt and prepare to feed. A heated glass pipette tip 514 can be preloaded and heated to deliver a small amount of meltable. The second mass balance 516 is used to confirm the supply by weighing.

  Because of the distribution of tools on the robot's head (fixed tools are in a fixed position on the head), not all tools can access all deck spaces. In particular, for example, in certain cases, the right tool cannot access the left side of the deck, and vice versa. This limits the position and proximity of each tool to the floor. Alternatively, the supply of gels, pastes and highly viscous fluids or the supply of meltables may require a separate station or substation, especially when combined or supplied with mixing. This is possible if the volume exceeds 2 ml. If mixing is not required, the feed volume can be checked using a balance. However, due to the order of addition and mixing, the dispenser tip cannot be contacted with the mixed formulation, so feeding must be done without accurate metering.

  When a mixer is used with a supply, the station uses predetermined milliliter and 500 microliter tips (designated during the design phase), so that a cleaning fluid reservoir, pump, drain, and valve are used. A dedicated washing station for washing the mixer is also provided.

  FIG. 6 shows a normal liquid supply and pipette dispensing and characterization station 600, which may be included in another embodiment. This station comprises a pair of disposal stations where two different types of fluid are pumped for disposal, and is preferred when the fluids are incompatible with each other. The tool head includes, for example, a rack and plate gripper, a medicine bottle, a filter and cap gripper, a pipettor at the tip of a plastic disposable pipette, a supply pump to the outside of the deck, a valve and a manifold, a supply needle for supplying ordinary cleaning fluid, etc. These members can be attached.

  Again, some tools may require more than one tool placement, and some devices are preferably multifunctional. As previously mentioned, one or more sized pipettes are required for precision and accuracy of delivery. It is conceivable to use both 5 milliliter and 500 microliter tips. In addition, a pipetter suitable for higher viscosity samples can require a separate tool or can be replaced with a 5 milliliter tip rack pipettor.

Devices are attached to the deck and the number and location of the devices is based on the application. The apparatus consists of a barcode reader and capper and decapper 602, a cap supply source, a rack space 604 at the tip of the second pipette, a deck space for the liquid vial, a second orbital shaker 606, a tank mixing test unit 608, a particle size note. Inlet 610, dilution port 611, viscometer inlet 612, filtration device, filter element supply 614, particle size detector 618, viscosity detector 620, cap supply 622, disposal station 628, bead collection 630, trash can 632, Including but not limited to photography system 624 and particle microscopy system 638.

  Bar code reader and capper and decapper 602 are used to identify and open containers that have been capped and used to close the vials before they are sent to the reservoir. In a preferred embodiment, a source of about 2000 caps is provided. In a preferred embodiment, the pipette tip rack space 604 comprises a special slotted tip source that aspirates the powdered mixture from the beads. The liquid vial bottle space allows other sources of normal liquid to be placed on the deck. Similarly, the preferred embodiment provides sufficient space to accommodate the racks and to provide a space for classifying the sample vials into grades (eg, one pass or fail criteria applied). Space is provided. Orbital shaker 606 provides normal to moderate to moderate mixing, but is also used for tank mixing test 608. The sample is pipetted into the particle size inlet 610 and the actual particle size detector 618 is mounted outside the deck. The dilution port 611 allows for dilution of the formulation for particle photography. Viscometer inlet 612 allows for the measurement of viscosity at different shear rates. The filtration device can time the filtration of the tank mix test sample. The filter element obtained from the filter element source 614 is used for tank mixing tests. The photography system 624 is used to photograph the surface of the tank mixing test filter.

  Outside the robot deck, a large element of processing or measuring device is attached, a particle size detector 618, a photography system 624, a viscosity measuring electronic device 620, a small volume (several tens of microliters) of sample “main”. This includes, but is not limited to, a valve and pump system 626 that feeds the supply needle with a “solvent” flow, a pump connected to the needle and a source 616 of common cleaning fluid.

  FIG. 7 shows a mixer and homogenizer station 700 with liquid addition. This station has the ability to mix in both high and low shear modes in parallel. Station 702 includes a two-axis (one vertical axis and one horizontal axis) Cartesian robot system that includes up to six mixers and homogenizers 704 mounted linearly on an arm. Can be moved between several rows (n × 6) of up to six containers to an ultrasonic cleaning station 706 and a rinsing station 708. Furthermore, the container in which the mixing occurs can be heated or cooled by a temperature-controlled fluid jacket and a cooling device, a heating device and a circulation device 710. The mixer includes hardware that attaches three 1/8 inch diameter probes with working ends to the blades of the mixer. These probes can be for pH measurements, or can be tubes that are determined by application requirements and connected to a liquid addition unit 712 to supply fluid into the mixture.

  The mixer and homogenizer 704 has the ability to mix in high shear mode and low shear mode, the ability to determine torque, eg current, and velocity relative to it to roughly measure viscosity, and a head diameter of 15 mm or less. It is preferable that can be provided.

  The liquid addition unit 712 can supply a predetermined liquid during mixing. The liquid addition unit is made from common elements available from companies such as Hamilton, Cavro, Rheodyne, and Valco, for example. The number of designs for such devices is infinite, and the devices described herein can meet the set requirements with the understanding that other combinations of elements can provide adequate functionality. It should be considered as a plan to satisfy.

  In the first embodiment of the liquid addition unit, each mixer head includes one supply tube, and each supply tube is supplied from a separate pump 714 and raw material bottle 716. This configuration allows for the addition of up to six different liquids, selected by the position of the mixer row where the target vials are loaded. These pumps can quantitatively supply medium and low viscosity materials (flow at room temperature).

  In a second embodiment of the liquid addition unit, the mixer system comprises two tubes along the combined pH electrode. In a preferred embodiment, an electrode of 38.1 mm (1/8 ft) diameter including a temperature probe is used. Fluid is supplied from valve 718 to each mixer and homogenizer head, one at a time. As described above, the present embodiment can be used for pH adjustment. However, when pH adjustment is not required, this embodiment can be used for the supply of other normal liquids.

  In addition, a pH multimeter 720, available from, for example, NICO 2000, can be installed outside the deck. Models with up to 24 pH probes and up to 24 temperature probes are available.

  FIG. 8 shows a flexible arm station 800 used in another embodiment. The flexible arm 802 receives a vial rack from the robot arm 302 delivery point and supplies each vial to a capping, decapping, barcode reading, and cap supply station 804. To mix, if capped, the cap is removed and discarded into the trash can 806, and the vial is placed in the appropriate mixer location 704. Alternatively, the cap can be placed on the medicine bottle before it is put into the grinder 902 by the flexible arm 802. After processing, flexible arm 802 moves the vials to capping, decapping, barcode reading, and cap supply stations 804 as needed, and returns the vials to the appropriate rack.

  The system within the reach of the flexible arm 802 includes a rack delivery and receiving transfer area for the vial 808, a rack storage space 810 for the empty rack, capping, decapping, barcode reading, and cap supply. Station 804 (only the vials and no racks), and if the flexible arm 802 is used while the cap is removed, the trash can chute 806, the station outside the mixer, and the crusher loading receptacle 904, but is not limited thereto. The reach of the selected robot depends on the dimensions of the system, in particular the dimensions of the rack storage space and the crusher.

  FIG. 9 shows a grinding station 900 used in another embodiment. In this embodiment, the planetary ball mill 902 is partially modified, and a small medicine bottle of about 25 milliliters is arranged around the medicine bottle holder 906, and the grinding operation required for up to 32 medicine bottles in parallel. I do. The capped vial is sent to a mill that contains solids, liquids and beads. Planetary operation causes the beads to rotate in the vial to “fly” and pulverize the solid particles. After the set time, the mill returns to the predetermined stop position 908, and the medicine bottle is taken out by the arm 802 and stored in the rack. The vial cap can be removed prior to storage in the rack. Whether to remove the cap depends on what to do next with the vial. In addition, the vial can be stored in a given location and the removal of the cap can be delayed until the material lid can be removed.

  FIG. 10 shows a phase stability and cloud point station 1000. Apart from torque feedback from the mixing station, the phase stability and cloud point station 1000 is the first station where the majority of samples arrive and are characterized. This is based on a Cartesian robot system 1002, for example provided by Gilson. In the preferred embodiment, the only tool on the head 1004 is the gripper 1006. This gripper can invert the vial if necessary. A turbidity analyzer 1008, for example Turbicscan (from Formulation) or similar system, a barcode reader 1010, a heating and cooling zone 1012 and at least three rack spaces are mounted on the deck. The sample is delivered into the rack by the arm 302 and the vials are removed and placed in the heating and cooling zone and then placed into a turbidity analyzer system or, for example, turbidity, phase separation, homogeneity, Immediately put into a turbidity analyzer system that characterizes sedimentation, creaming, foaming, etc. The ability to invert the vial just before the measurement also makes it possible to examine foaming and settling. The vial is then removed and returned to the original rack, or determined by selection criteria, and placed in a “pass” rack and a “fail” rack. The arm 302 then removes the vial rack.

  FIG. 11 shows a temperature buffer 1100. Typically, such complex automated systems require space to buffer stations in order to synchronize processes occurring at different times and speeds. A solid supply station 400, a liquid, suspension, gel and meltable station 500, a normal liquid supply and pipette dispensing and characterization station 600, a flexible arm station 800, a phase stability and cloud point station 10000 The separate feed and pipette dispensing and characterization station 1200 inherently has some buffering capacity and some space in the storage system 100 that is also available during experimental activities. However, additional space may be required. For example, two embodiments can each include an ambient temperature buffer 1102 and a temperature controlled buffer 1104. Thus, the arm 302 is the only operation required for the shock absorbers when these shock absorbers are “silent”.

  FIG. 12 shows another supply and pipette dispensing and characterization station 1200 that can be included in another embodiment. This station is based on a gantry or Cartesian laboratory robot. Again, there are many manufacturers of systems such as the Gibson “Cyberlab” 230/240/400 platform. This robotic system can attach up to six tools to the tool head above the deck, and the deck can be fitted with custom equipment including substations with other built-in tools.

  The tool head includes, for example, a rack and plate gripper, a vial and cap gripper, a gel dispenser gripper, a pipettor for a plastic disposable pipette tip, a pipetter for a glass disposable pipette tip, a supply attached to a supply pump outside the deck Members such as needles, valves and manifolds, supply needles for supplying common cleaning fluids can be attached.

  Again, some tools may require more than one tool position, and in a preferred embodiment, some devices are multifunctional. As mentioned above, one or more sized pipettes are required for delivery precision and accuracy. The use of both 5 milliliter and 500 microliter tips is contemplated. In addition, a pipetter suitable for higher viscosity samples can be a separate tool or can be replaced with a 5 ml tip rack pipettor.

The deck includes the following related equipment: bar code reader and capper and decapper 1202, cap supply source 1232, pipette tip rack space 1204, balance 1206, liquid vial deck space, particle size inlet 1208, viscometer injection. An inlet 1210, a waste disposal station 1212, a gel dispenser 1220, an orbital shaker 1214, a heating block 1216, and a heating pipette tip 1218 can be attached according to the number and position of the application.

  Barcode reader and capper and decapper 1202 are used to identify and open the capped container and close the vial before it is sent to the reservoir. In a preferred embodiment, the cap source 1232 comprises a source of about 2000 caps. The balance 1206 is used to check the supply by weight. The liquid vial deck space allows other sources of normal liquid to be placed on the deck. Similarly, in the preferred embodiment, sufficient space is provided to accommodate the rack and to sort the vials by grade. The sample is pipetted into a particle size inlet 1208. Viscometer inlet 1210 allows for the measurement of viscosity at different shear rates. The orbital shaker 1214 with heating and cooling capabilities is where a mixture that requires agitation, such as an unstable suspension, is delivered after the cap is removed. Orbital shaker 1214 can also be used for slow mixing such as dissolution. By carefully selecting the orbital shaker, even more intense agitation can be achieved. The material is placed on or in the heating block 1216 for melting. Thus, the material is ready for supply. A heated pipette tip 1218 can be preloaded and heated to deliver a small amount of meltable.

  Outside the deck is a second particle size detector 1222 and a water wash system, a second viscometer electronics 1224, a valve that feeds a small volume (several tens of microliters) of sample along with the "main solvent" stream to the supply needle. And a system including, but not limited to, a pump system 1226, a waste container 1234, a dilution port 1236, a second particle microscope system 1238, a pump connected to the needle and a source 1228 of common cleaning fluid. Not.

  In this embodiment, the gel, paste, and high viscosity fluid supply or meltable supply (see FIG. 5) may require a separate mixing station 1230. If mixing is not required, the feed volume is confirmed using a balance 1206. However, due to the order of addition and mixing, the dispenser tip cannot be contacted with the mixed formulation, so feeding must be done without accurate metering.

Process Description An automated robotic system is a minimum of one day (not limited to one day) after the robotic system is initialized in the preparation phase and loaded with relevant components (raw materials, consumables, vials, and racks). ) Is designed to operate without human intervention. Each vial 104 in any given rack 102 represents a particular experiment and has a set of parameters such as number of elements, type and amount of each element, mixing time, grinding time, etc. It is not limited to. Tool heads on solid supply station 400, liquid, suspension, gel and meltable supply station 500, normal liquid supply, pipette dispensing and characterization station 600, and flexible arm station 800 are racks 102. And a single medicine bottle 104 can be operated. However, the arm 302 used to move between stations in one embodiment can only operate the rack 102. Thus, vials 104 are always grouped within rack 102 when moved between stations. Once placed on the station, the vial 104 can be lifted by the tool head and sent to the desired location for processing.

  In this section, the actual working of this system is illustrated by two examples: a first experiment in which an aqueous solution (SL) emulsion formulation is formulated and tested, and a first experiment in which a suspension (SC) emulsion formulation is formulated and tested. This will be described using the experiment of 2.

  In the first example, the initialization and preparation steps are described in detail to show the steps involved in preparing the system for a single experiment.

Example 1: Experiment to formulate and test an aqueous (SL) emulsion formulation The purpose of this experiment was to formulate a clear formulation within a specific pH range containing one active ingredient and three different additives. is there. The finished formulation is then tested for its chemical and / or biological activity. The steps involved in this experiment are as follows.
1) Add the additive into the vial.
2) Add the active ingredient into the vial.
3) Add water into the medicine bottle.
4) Mix for 30 seconds at low shear.
5) Heat the mixture for 10 minutes at 60 ° C.
6) Mix for 2 minutes at high shear.
7) Perform phase analysis.
8) Store clear samples for 24 hours and reject other samples.
9) After 24 hours, perform phase analysis on the stored sample.
10) Store clear sample for further analysis and reject other samples.

  In this example, it is assumed that the properties and amounts of the components in one particular experiment are the properties and amounts shown in the table below.

Before this experiment can be started, the system goes through a preparatory stage with the following steps.
1) Load racks and vials into the rack and vial storage system 100.
2) Load consumables into the consumable station 200.
3) Load consumables in appropriate stations.
4) Move the consumable to the appropriate station.

  The entire preparatory procedure for this experiment is shown in FIG. 13 in the form of a workflow diagram and is described in further detail herein.

  FIG. 13 shows the steps involved in the system preparation phase before the experiment to prepare and test the aqueous solution (SL) emulsion formulation can begin. The various steps involved in the execution of each block of this flow diagram are described in detail below, but this description has shown that various embodiments require different steps in different orders. It should be noted that this is intended to be easily understood by an expert and is merely for illustrative purposes.

  The system initialization start process 1302 is the first process of initialization. In this process, the entire system is switched on and an initial system check is performed by the operator.

  The next step is a rack and vial loading step 1304 in which the desired number of racks 102 and vials 104 are loaded into the rack and vial storage system 100.

  In the consumable loading step 1306, all consumables such as, but not limited to, pipette tips are loaded into the consumable storage system 200.

  In the active ingredient loading step 1308, the active ingredient is loaded into the liquid supply, pipette dispensing, and characterization station 600. In a preferred embodiment, the active ingredient is loaded via a bottle connected to a valve and pump system 626.

  In the additive 1 loading step 1310, additive 1 is loaded into a liquid, suspension, gel, and meltable supply station 500. In the preferred embodiment, this loading occurs at a rack or supply location 504.

  In the Additive 2 loading step 1312, Additive 2, which is a high viscosity liquid, can be supplied by the movable gel dispenser 502 on the liquid, suspension, gel and meltable supply station 500, thus Additive 2 is loaded into one gel dispenser 502.

  In the additive 3 loading step 1314, the additive 3 that is a solid is supplied at the solid supply station 400. Additive 3 can be loaded into one of the solid source hoppers 404 and placed directly on the solids supply station 400 or placed on the rack 102 in the consumable storage system 200. The rack 102 including the hopper 404 can then be lifted from the consumable storage system 200 by the robot arm 302 and transported on the rail 304 to the solid supply station 400.

  In the water loading step 1316, water is loaded into the liquid supply, pipette dispense, and characterization station 500 via a bottle connected to a valve and pump system 626.

  In the consumables transfer step 1318, consumables such as, but not limited to, pipette tips, are lifted from the consumable storage system 200 by the robot arm 302 and supplied with a liquid, suspension, gel, meltable supply station 500. Then, it is transferred on the rail 304 to the station 600 for normal supply, pipette dispensing and characterization.

  Finally, in the system initialization completion step 1320, after all the elements have been loaded and the consumables have been transferred, the system is ready for experimentation.

  FIG. 14 shows an experimental flow diagram for formulating and testing an aqueous solution (SL) formulation. The various steps for executing each block of this flow diagram are described in detail below. As mentioned above, this description is intended to make it easy for experienced professionals to understand that different embodiments require different steps in different orders, and are for illustrative purposes only. It should be noted that this is not too much.

  At the beginning of the experimental process 1402, although not limited to six, the rack 102 containing six empty vials 104 is lifted by an arm 302 to provide a liquid, suspension, gel and meltable supply station 500. To the entry point of the rack 102. From here, the rack 102 is transferred to the rack or supply location 504 by the tool head on the liquid, suspension, gel and meltable supply station 500.

  In the additive 1 addition step 1404, the tool head lifts the vial 104 from the rack 102, sends the vial 104 to the barcode reader and decapper 508 for barcode scanning, and returns the vial 104 back into the rack 102. . Based on the bar code, the control software determines the element to be supplied to the vial 104, additive 1 in this example. In this experiment, the tool head lifts the disposable pipette from the pipette tip rack space 518 and aspirates 0.6 milliliters of Additive 1 and delivers it to the appropriate vial 104 in the rack 102. The tool head then moves over the dust collection chute 520 to discard its pipette tip.

  In the additive 2 addition step 1406, the additive 2 that is a highly viscous liquid is supplied based on weight measurement. The tool head transfers the vial 104 from the rack 102 to the mass balance 516, which is then initialized and measures the tare weight by the control software. The tool head then lifts the movable gel dispenser 502 containing Additive 2 and moves it above the vial 104, with a slight injection of 0.1 g until the balance points to 0.6 g. Agent 2 is supplied. The tool head then returns the movable gel dispenser 502 to its original location and returns the vial 104 to the rack 102. When all the supply operations of the liquid, suspension, gel and meltable supply station 500 have been completed, the rack 102 containing all the vials 104 is the liquid, suspension, gel and meltable supply station. It is transferred to the rack 102 exit point above 500.

  In the additive 3 addition step 1408, the rack 102 is lifted by the arm 302 from the rack 102 exit point above the liquid, suspension, gel, and meltable supply station 500 to supply the additive 3 solid supply station 400. To the rack 102 entry point. From there, the vial 104 is first sent to the barcode reader 406 for barcode scanning and then placed on the mass balance 402 by the tool head on the solid supply station 400. The control software confirms from the barcode the solid that needs to be supplied to the vial 104, additive 3 in this example. In this embodiment, the hopper 404 containing the additive 3 is lifted by the tool head, and 0.6 g of the additive 3 is added into the medicine bottle 104 on the mass balance 406. When all the solid supply operations have been completed, the rack 102 is transferred to the rack 102 exit point on the solid supply station 400.

  In the active ingredient addition process 1410, the arm 302 lifts the rack 102 from the exit point on the solid supply station 400 and moves the rack 102 to the rack 102 entry point on the normal liquid supply, pipette dispensing and characterization station 600. The tool head lifts the rack 102 from the entry point and moves the rack 102 to the rack 102 buffer zone. There, 7.6 milliliters of active ingredient is added by volumetric measurement into the vial 104 from the active ingredient reservoir connected to the valve and pump system 626 by a needle on the tool head.

  In the water addition step 1412, after adding the active ingredient, the needle on the tool head is rinsed in the wash station 628 and then 1 milliliter of water is supplied from a water reservoir connected to the valve and pump system 626. The The rack 102 is then transferred to the rack 102 exit point on the normal liquid supply, pipette dispensing and characterization station 600.

  In the vial mixing step 1414, the arm 302 moves the rack 102 from the normal liquid supply, pipette dispensing and characterization station 600 exit point to the rack 102 entry point 808 adjacent to the flexible arm 802. The flexible arm 802 moves the rack 102 from there to the rack storage space 810 of an empty rack. The vial 104 is lifted by the flexible arm 802 and sent to the barcode reading station 804 for identification and then placed on the mixer and homogenizer station 704 on the mixer and homogenizer station 700. The parallel mixing station 702 moves over up to six vials 104 placed on six parallel mixer and homogenizer stations 704, descends vertically until the mixer enters the vial 104, and then Begin mixing at low shear for 30 seconds. When the mixing time is complete, the six parallel mixer and homogenizer stations 704 rise vertically until they exit the vial 104, move to the ultrasonic bath 706 for cleaning, and then rinse. Move to rinse station 708. The vials are returned from the mixer and homogenizer station 704 back to the rack 102 in the rack storage space 810 for an empty rack. The rack 102 is then moved to the rack 102 exit point.

  In the vial heating step 1416, the arm 302 moves the rack 102 from the rack 102 exit point on the flexible arm station 800 to a temperature buffer 1100 where the rack is held at 60 ° C. for 10 minutes.

  In the pH adjustment step 1418, the rack 102 is moved again to the rack 102 entry point 808 adjacent to the flexible arm 802 after 10 minutes. The flexible arm 802 moves the rack 102 from there to the rack storage space 810 of an empty rack. The vial 104 is lifted by the flexible arm 802 and sent to the barcode reading station 804 for identification and then placed on the mixer and homogenizer station 700 for pH adjustment. The axis of the mixer and homogenizer 704 has a pH probe coupled to it on the pH multimeter 720, which measures the pH of the mixture in the vial 104 and reaches the setpoint value. Adjust acid and base addition via two valves 718.

  In the vial mixing step 1420, if the pH of the mixture is within the desired range, the mixture in the vial 104 is mixed at high shear for 2 minutes by the mixer and homogenizer 704. After mixing, the mixer and homogenizer 704 rises vertically until it exits the vial 104, moves to an ultrasonic bath 706 for cleaning, and then is transferred to a rinse station 708 for rinsing. The The vial 104 is returned by the flexible arm 802 to the rack 102 above the rack storage space 810 of the empty rack. The rack 102 is then moved to the rack 102 exit point by the flexible arm 802.

  In the phase analysis step 1422, the arm 302 moves the rack 102 from the rack 102 exit point to the phase stability and rack 102 entry point on the cloud point station 1000 by the flexible arm 802. The tool head 1004 on this station lifts the vial 104 from the rack 102 by the gripper 1006, sends the vial 104 to the barcode reader 1010 for identification, and then the turbidity analyzer 1008 for phase analysis. put on top.

  In the determination step 1424, the analysis result is analyzed by the software, and the mixture is classified into categories such as “transparent”, “turbid”, “foam”, “two-phase”, but is limited to these categories. It is not a thing.

  If the mixture in vial 104 is not identified as “clear”, rejection step 1426 will flag the vial as “failed” and the tool head 1004 will provide the rack 102 provided for the failed sample. Moved to. When the rack 102 is full, it is moved by the tool head 1004 to the rack 102 exit point, lifted by the arm 302 and returned to the rack and vial storage system 100.

  This operation causes the system to move to the end point 1438 and is considered to have ended the experimental run in the system.

  However, if the mixture in the vial 104 is identified as “transparent” by the device 1008, the vial is flagged as “passed” in the storage step 1428, and the tool head 1004 sets the “pass” sample for the “pass” sample. It is moved to the rack 102 provided. When this rack 102 is full, it is moved by the tool head 1004 to the rack 102 exit point, lifted by the arm 302, and returned to the rack and vial storage system 100 in the space provided for the “pass” sample, Housed for 24 hours. In this phase analysis step 1430, after 24 hours, the arm 302 again lifts the rack 102 containing the “pass” sample from the rack and vial storage system 100 and lifts the rack to the phase stability and cloud point station 1000. Move to upper rack 102 entry point. The tool head 1004 on this station lifts the vial 104 from the rack 102 with the gripper 1006, sends the vial to the barcode reader 1010 for identification, and then the vial is turbid for phase analysis. Place on analyzer 1008.

  In the second determination step 1432, the analysis result is analyzed again by the software, and the mixture is classified into categories such as “transparent”, “turbid”, “foam”, “two-phase”, etc. It is not limited to the category.

  As mentioned above, if the mixture in vial 104 is not identified as “transparent”, then in a second rejection step 1434, the mixture is flagged as “failed” and rejected by tool head 1004. The sample is transferred to the rack 102 reserved for the sample. When the rack 102 is full, it is moved by the tool head 1004 to the rack 102 exit point, lifted by the arm 302 and returned to the rack and vial storage system 100.

  This operation causes the system to move to the end point 1438 and is considered to have ended the experimental run in the system.

  However, if the mixture in the vial 104 is identified as “transparent” by the device 1008, the vial is flagged as “passed” in the storage step 1428 and the tool head 1004 causes the “passed” sample. It is transferred to a rack 102 provided for use. When this rack 102 is full, it is moved by the tool head 1004 to the rack 102 exit point, lifted by the arm 302, and returned to the rack and vial storage system 100 in the space provided for the “pass” sample, Stored for future analysis.

  This operation causes the system to move to the end point 1438 and is considered to have ended the experimental run in the system.

Example 2: Experiments for Formulating and Testing Suspension (SC) Emulsion Formulations The purpose of this experiment is a suspension within a specific particle size distribution and viscosity range containing one active ingredient and two different additives It is to prepare an emulsion formulation. The finished formulation is then tested for its chemical and / or biological activity. The steps included in this experiment are as follows.
1) Add the additive into the vial.
2) Add the active ingredient into the vial.
3) Add water to the medicine bottle.
4) Grind the mixture for 60 minutes.
5) Measure the particle size distribution.
6) If the sample is within the desired particle size range, then measure the viscosity. Otherwise, reject the sample.
7) If the sample is within the desired viscosity range, the sample is then stored for further analysis. Otherwise, reject the sample.

  In this experiment, it is assumed that the nature and quantity of the elements are as shown in the table below.

  As explained in the previous example, before starting the experiment, the automated robotic system goes through an initialization and preparation phase.

  FIG. 15 shows a flow diagram of an experiment for formulating and testing a suspension (SC) emulsion formulation. The various steps involved in the execution of each block of this flow diagram are described in detail below. This description is also intended to be easily understood by experienced professionals that the various embodiments require various steps in various orders and is merely for illustrative purposes. You should be careful.

  At the beginning of the experimental process 1502, but not limited to six, the rack 102 containing six empty vials 104 is lifted by the arm 302 to provide a liquid, suspension, gel and meltable supply station 500. To the rack 102 entry point above. From here, the rack 102 is moved to the rack or supply location 504 by the tool head on the liquid, suspension, gel, and meltable supply station 500.

  In the additive 1 addition step 1504, the tool head lifts the vial 104 from the rack 102, sends the vial 104 to a barcode reader and decapper 508 for barcode scanning, and places the vial 104 into the rack 102. return. Based on the barcode, the control software determines the elements to be supplied in the vial 104, in this example additive 1. In this experiment, the tool head lifts the disposable pipette from the pipette tip rack space 518 and aspirates 1.0 milliliter of Additive 1 and delivers it into the appropriate vial 104 in the rack 102. The tool head then moves above the garbage collection chute 520 to discard its pipette tip.

  In the additive 2 addition step 1506, the additive 2 that is a high-viscosity liquid is supplied based on weight measurement. The tool head transfers the vial 104 from the rack 102 to the mass balance 516, which is then initialized and the tare weight is measured by the control software. The tool head then lifts the movable gel dispenser 502 containing Additive 2 and moves it above the vial 104 to add Additive 2 with a slight injection of 0.1 g until the balance points to 1.0 g. Supply. The tool head then returns the movable gel dispenser 502 to its original location and returns the vial 104 to the rack 102. When all the supply operations of the liquid, suspension, gel, and meltable supply station 500 are completed, the rack 102 containing all the vials 104 supplies liquid, suspension, gel, and meltable. It is transferred to the rack 102 exit point on the station 500.

  In the active ingredient addition step 1508, the rack 102 is lifted from the rack 102 exit point on the liquid, suspension, gel, and meltable supply station 500 by the arm 302 and the solid supply station 400 is supplied to supply the active ingredient. Transferred to the rack 102 entry point. From there, the vial 104 is first sent to the barcode reader 406 for barcode scanning and then placed on the mass balance 402 by the tool head on the solid supply station 400. From the bar code, the control software determines the solid to be delivered into the vial 104, in this example the active ingredient. In this example, the hopper 404 containing the active ingredient is lifted by the tool head and 4.0 g of the active ingredient is added into the appropriate vial 104. When all the solid supply operations have been completed, the rack 102 is transferred to the rack 102 exit point 102 on the solid supply station 400.

  In the water addition step 1510, the arm 102 lifts the rack 102 from the exit point on the solid supply station 400 and moves the rack 102 to the rack 102 entry point on the normal liquid supply and pipette dispensing and characterization station 600. The tool head lifts the rack 102 from the entry point and moves the rack 102 to the rack 102 buffer zone. Here, 4.0 milliliters of water is added volumetrically into the vial 104 from the active ingredient reservoir connected to the valve and pump system 626 by a needle on the tool head. After adding water, the needle on the tool head is rinsed in the wash station 628 and the rack 102 is then moved to the rack 102 exit point above the normal liquid supply and pipette dispensing and characterization station 600. .

  In the grinding step 1512, the beads are first added into the vial 104 using a solid cannula on the liquid, suspension, gel, meltable supply station 500. The arm 302 transfers the rack 102 from the normal liquid supply and pipette dispensing and characterization station 600 exit point to the rack 102 entry point on the liquid, suspension, gel and meltable supply station 500 and the rack From the 102 entry point, the rack 102 is moved to the rack or supply location 504. A cannula on the tool head of the liquid, suspension, gel and meltable supply station 500 aspirates the required amount of beads from the milled bead source 506 and delivers the beads into the vial 104 based on volumetric measurements. To do. The rack is then moved by the tool head to the rack 102 exit point on the liquid, suspension, gel and meltable supply station 500 and transferred by the arm 302 to the rack 102 entry point 808 adjacent to the flexible arm 802. . Flexible arm 802 then moves rack 102 to rack storage space 810 for an empty rack. The vial 104 is lifted by the flexible arm 802 and sent to the capping and decapping and bar code reading and cap supply station 804 for identification and capping. In the capping and decapping and barcode reading and cap supply station 804, in one embodiment, when the vial 104 is capped, the cap is supplied from the cap source and over the mouth of the vial 104 by the tool head. Retained. The vial 104 is capped by rotating the vial around its central vertical axis, and then the crushing location 904 at the stop position 908 set on the vial holder 906 of the crushing station 900 by the flexible arm 802. Arranged in one of the The lid on the grinding station 900 is closed and the vial holder 906 is then rotated for 60 minutes in planetary motion. At the end of the crushing time, the vial holder 906 stops at the set stop position 908 and the vial 104 is lifted by the flexible arm 802 and returned to the rack 102 in the rack storage space 810 for an empty rack. It is. When the rack 102 is full, it is moved by the flexible arm 802 to the rack 102 exit point 808, from which it is typically moved to the rack 102 entry point on the liquid supply and pipette dispensing and characterization station 600 for bead removal. It is transferred by the arm 302. The vial 104 is moved to the barcode reader and capper and decapper 602 by the tool head on the normal liquid supply and pipette dispensing and characterization station 600. In one embodiment, the cap on the vial 104 is gripped by the barcode reader and capper and decapper 602 tool head, and the vial 104 is rotated for cap removal. The cap is discarded in the trash can 632, and the medicine bottle 104 is returned to the rack 102. By using a special pipette from the pipette tip rack space 604, only the suspension in the vial 102 is aspirated and supplied to a new vial 104 in a different rack 102 in the rack buffer space. The barcode of the new vial 104 containing the suspension is read by the barcode reader / capper / decapper 602. The original vial 104 and rack 102 can then be sent to the rack and vial storage system 100 using the arm 302 or can remain at that station for characterization.

  In a particle size distribution measurement step 1514 to measure the particle size distribution, the tool head lifts the pipette from the pipette tip rack space 604 and draws 0.5 to 1.0 milliliter of suspension from the vial 104, The suspension is injected into the inlet 610 of the particle size detector. This inlet allows for dilution of the sample prior to measurement.

  In decision step 1516, the injected sample is analyzed with a particle analyzer 618 mounted outside the deck to generate a particle size distribution profile. This profile is then compared with the desired profile by the software, and based on this comparison, the sample is classified as “failed” or “passed”.

  In the rejection step 1518, if the measured particle size distribution of the sample from the vial 104 exceeds the desired range, the formulation in that vial 104 is classified as “failed” and further tested. There is no. The vial is transferred to another rack 102 provided for the “failed” formulation, and if the rack 102 is full of vials 104, it is transferred to the rack and vial storage system 100.

  This operation causes the system to move to the end point 1530, and the experimental operation is considered to have ended in the system.

  If the measured particle size distribution of the sample from vial 104 is within the desired range, the formulation in that vial 104 is classified as “pass” and its viscosity is measured at both high and low shear. The In the high shear viscosity measurement step 1520 and the low shear viscosity measurement step 1522, the tool head lifts the pipette from the pipette tip rack space 604 and draws 0.5 ml to 1.0 ml of suspension from the vial 104. The suspension is injected into the viscometer inlet 612. High and low shear measurements are made in two different viscosity detectors 620. After this measurement is complete, the viscometer inlet 620 is automatically cleaned and cleaned.

  In the viscosity determination step 1524, the measured viscosity is compared with a desired value. If the measurement is within the desired range, the sample is classified as “pass”. Otherwise, the sample is classified as “failed”.

  In the viscosity rejection step 1526, samples classified as “failed” are not further tested and can be moved to another rack 102 provided for “failed” formulations. The rack is moved to a vial storage system when the vial 104 is full.

  This operation causes the system to move to the end point 1530, and the experimental operation is considered to have ended in the system.

  If the formulation in vial 104 is classified as “pass”, in storage step 1528, the formulation is moved by the tool head to rack 102 provided for “pass” samples. When this rack 102 is full, it is moved by the tool head to the rack 102 exit point and lifted by the arm 302 to the rack and vial storage system 100 in the space provided for the “pass” sample. Returned and stored for further analysis.

  This operation causes the system to move to the end point 1530, and the experimental operation is considered to have ended in the system.

  Although the apparatus and process of the present invention have been described in detail for purposes of illustration, such detailed description is for purposes of illustration only and may be modified by those skilled in the art without departing from the scope of the invention. It must be understood that it is possible to add. The apparatus and operation of the invention are defined by the claims.

FIG. 1 shows a rack and vial storage system 100. FIG. 2 shows a consumable store 200. FIG. 3 shows the robot arm 300. FIG. 4 shows a solid supply station 400. FIG. 5 shows a liquid, suspension, gel, and meltable supply station 500. FIG. 6 shows a normal liquid supply and pipette dispensing and characterization station 600. FIG. 7 shows a mixing or homogenizing station 700. FIG. 8 shows a flexible arm station 800 used in another embodiment. FIG. 9 shows a crusher station used in another embodiment 900. FIG. 10 shows a stable and cloud point station 1000. FIG. 11 shows the shock absorber 1100. FIG. 12 shows a supply, pipette dispensing and characterization station 1200 included in another embodiment. FIG. 13 shows a typical flow diagram for the preparation of the system. FIG. 14 shows a flow diagram of an experiment for formulating and testing an aqueous solution (SL) formulation. FIG. 15 shows a flow diagram of an experiment for formulating and testing a suspension (SC) emulsion formulation. FIG. 16 illustrates a rack and vial storage system 100, a consumables store 200, a robot arm 300, a mixing or homogenizing station 700, a phase stabilization and cloud point station 1000, a buffer 1100, a supply, 1 shows an embodiment of the invention comprising a pipette dispenser and a characterization station 1200. FIG. 17 illustrates a rack and vial storage system 100, a consumable store 200, a robot arm 300, a solid supply station 400, a liquid, suspension, gel and meltable supply station 500, a liquid supply and Of the present invention comprising a pipette dispensing and characterization station 600, a mixing or homogenizing station 700, a flexible arm station 800, a crusher station 900, a phase stabilization and cloud point station 1000, and a buffer 1100. An embodiment is shown.

Claims (9)

A modular robot system,
A rack and vial storage system for storing a plurality of racks and vials;
A consumable storage system for storing materials;
First, second and third locations;
A first robot arm for moving the vial from the first location to the second location, or for moving the rack from the first location to the second location;
A supply, pipette dispensing, or characterization station, or a solid supply station that supplies an active ingredient, water, or additive to the vial to produce a formulation, the first robot arm comprising: A supply, pipette dispense, or characterization station, or solid supply station that moves material from the consumable storage system to the supply, pipette dispense, or characterization station, or the solid supply station;
A mixing or homogenizing station that mixes or homogenizes the formulation to yield a mixture;
A phase stabilization station for phase analysis of the mixture,
And optionally, a liquid, suspension, gel or meltable station;
Optionally, a cap, decap, barcode reading, or cap supply station,
The first location is
The rack and vial storage system,
Said supply, pipette dispensing or characterization station;
The mixing or homogenizing station, or
The phase stabilization station,
The second location is
The rack and vial storage system,
Said supply, pipette dispensing or characterization station;
The mixing or homogenizing station, or
The phase stabilization station,
A flexible second robot arm that moves the rack or the vial from the first robot arm to the third location on the modular robotic system; Let
The third place is
Cap or decap, or barcode reading, or cap supply station,
The rack and vial storage system,
Said supply, pipette dispensing or characterization station;
The mixing or homogenizing station,
Said phase stabilization station,
The solids supply station, or
The liquid, suspension, gel or meltable station,
Modular robot system.   A crushing station for crushing solid particles, wherein the solid particles are active ingredients or additives, and the flexible second robot arm moves the rack from the first robot arm to the crushing station. The modular robot system according to claim 1, which is moved. Each of the racks holds up to six vials, each of the racks is barcoded, each of the vials is barcoded,
The material is selected from the group consisting of the vial, pipette tip, the active ingredient and the additive;
The supply, pipette dispensing or characterization station is
A disposal station where the fluid is pumped for disposal;
A tool head to which is attached at least one member selected from the group of members consisting of a rack gripper, a plate gripper, a vial gripper, a filter gripper, a cap gripper, a pipettor and a supply needle; Further comprising
The modular robot system according to claim 1. A modular robot system,
A rack and vial storage system for storing a plurality of racks and vials;
A consumable storage system for storing materials;
First, second and third locations;
A first robot arm for moving the vial from the first location to the second location, or for moving the rack from the first location to the second location;
Supply, pipette dispensing, or characterization station for supplying active ingredients, water, or additives to the vial;
A solid supply station for supplying solids, which are active ingredients or additives, into the vial based on weight;
A liquid, suspension, gel or meltable station for supplying viscous fluid, gel, paste or meltable, wherein the viscous fluid, gel, paste and meltable is an active ingredient or additive, A suspension, gel or meltable station,
A combination of the active ingredient, the water and the additive from the feed, pipette dispense, or characterization station, the solid feed station, or the liquid, suspension, gel or meltable station is a formulation. Produces
And a mixing or homogenizing station that mixes or homogenizes the formulation to produce a mixture;
A phase stabilization station for phase analysis of the mixture;
A flexible robot arm station comprising a flexible second robot arm, wherein the flexible second robot arm is moved from the first robot arm to the third location on the modular robot system in the rack. A flexible robot arm station that moves
A crushing station for crushing solid particles,
The first location is
The rack and vial storage system,
Said supply, pipette dispensing or characterization station;
The mixing or homogenizing station,
Said phase stabilization station,
The solids supply station,
The liquid, suspension, gel or meltable station, or
Said crushing station,
The second location is
The rack and vial storage system,
Said supply, pipette dispensing or characterization station;
The mixing or homogenizing station,
Said phase stabilization station,
The solids supply station,
The liquid, suspension, gel or meltable station,
The flexible second arm, or
Said crushing station,
The third place is
The rack and vial storage system,
Said supply, pipette dispensing or characterization station;
The mixing or homogenizing station,
Said phase stabilization station,
The solids supply station,
The liquid, suspension, gel or meltable station, or
The crushing station,
Modular robot system. Each of the racks holds up to six vials, each of the racks is barcoded, each of the vials is barcoded,
The material is selected from the group consisting of the vial, pipette tip, the active ingredient and the additive;
The supply, pipette dispensing or characterization station is
A disposal station where the fluid is pumped for disposal;
A tool head to which is attached at least one member selected from the group of members consisting of a rack gripper, a plate gripper, a vial gripper, a filter gripper, a cap gripper, a pipettor and a supply needle;
Deck, barcode reader, decapper, cap supply source, orbital shaker, tank mixing test unit, inlet, dilution port, filtration device, particle size detector, viscometer, disposal station, bead collector and photography system And a deck on which at least one device is selected, selected from the group of devices consisting of a dust collection chute and a particle microscopy system.
The modular robot system according to claim 4. Each of the racks identifies a barcode;
The barcode is read by the first robot arm;
The modular robot system according to claim 4. The liquid, suspension, gel, or meltable station is
A second tool head to which at least one member selected from the group of members consisting of a rack gripper, a plate gripper, a medicine bottle gripper, a gel dispenser gripper, a cap gripper, a pipettor and a vacuum cannula is attached; Tool head,
A second deck, at least one device selected from the group of devices consisting of a movable gel dispenser, a grinding bead source, a barcode reader, a decapper, an orbital shaker, a heating block, a mass balance, and a garbage collection chute; A second deck to be attached;
The modular robot system according to claim 5. A second supply, pipette dispensing, or characterization station, further comprising a third deck and a third tool head;
At least one member selected from the group of members consisting of a rack gripper, a plate gripper, a medicine bottle gripper, a gel dispenser gripper, a cap gripper, a pipettor and a supply needle is attached to the third tool head,
The third deck includes at least one selected from the group of devices consisting of a bar code reader, a capper, a decapper, a cap supply, a balance, an inlet, a drain disposal station, a gel dispenser, an orbital shaker, and a heating block. One device is attached,
Further comprising a second supply, pipette dispensing, or characterization station;
The modular robot system according to claim 7. An external deck,
Further comprising an external deck to which is attached at least one device selected from a list of devices consisting of a second particle size detector, a running water system, a second viscometer, and a second particle microscopy system.
The modular robot system according to claim 8.

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