A dry powder particle processing apparatus

Abstract

A dry powder particle processing apparatus for coating carrier particles with guest particles including: a vessel supported for rotation about an axis A, the vessel including a first end wall, a second end wall and a side wall extending therebetween to define a chamber within which said particles are retained during processing; a motor connected to the vessel and adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall which is at least equal to 0.5g during use; a gas outlet member defining a gas flow path extending into the vessel and connectable to a gas supply for introducing gas into the chamber, wherein the gas outlet member has an outlet portion which is spaced apart from, and extends in a direction parallel to the axis A, and the outlet portion includes at least one or more outlet apertures in communication with the gas flow path for directing gas from the gas outlet member into the chamber in a direction towards the side wall.

Description

[0001] Title: A dry powder particle processing apparatus

[0002] Description of Invention

[0003] The present invention relates to a dry powder particle processing apparatus, system and process for coating carrier particles with guest particles.

[0004] It is known to coat carrier particles with guest particles for the purpose of modifying the physical, chemical and / or functional properties of the carrier and / or guest particle. Generally speaking, the guest particles are fine, i.e. relatively small, particles and the carrier particles are coarse, i.e. relatively large, particles and the guest particles attach to the external surfaces of the carrier particles. Coating of carrier particles in this way is used in the pharmaceutical and food industries, for example, so that an active pharmaceutical or food ingredient may coat a substantially inert carrier particle, or alternatively, an inert substance may coat a substantially active carrier particle so that the active carrier particle is protected by the inert substance prior to its digestion in the human body for example.

[0005] Coating of carrier particles with guest particles can broadly be carried out using what can be described as “wet” or “dry” processes.

[0006] For wet processes, the guest particles may be provided in the form of a liquid, or particles suspended within a liquid, with liquid applied, typically by spraying, to the carrier particles and then the coated carrier particles are subsequently dried through the application of a hot gas, for example, so that the guest particles remain attached to the carrier particles. The drying process may also involve the coated carrier particles being rotated in a vessel. The vessel may be a closed vessel into which the hot gas is directed, or the vessel may be formed from perforated walls and the hot gas is directed into the vessel through the perforated walls. In such processes it is important that the vessel is rotated relatively slowly so that the time of exposure of the coated particles is maximised and so as to avoid the guest particles being detached from the surfaces of the carrier particles.

[0007] For dry processes, both the carrier and the guest particles are provided in powder form (i.e. are not liquid, or suspended in liquid).

[0008] In other known dry coating processes, devices are known which may permit the application of high shear, mechanical and compaction forces on a mixture of guest and carrier particles so as to increase the adhesion of the fine guest particles to the carrier particles and cause the guest particles to become embedded onto the external surfaces of the carrier particles. In order to do so, the devices first de-agglomerate the fine guest particles prior to mixing the guest particles and the carrier particles and then finally causing the guest particles to adhere to the carrier particle through high shear, mechanical and compaction forces. Early devices (such as the Mechanofusion high shear mill and the Hybridizer dry impactor) were able to produce the required forces but they suffered from disadvantages. The devices often caused weakening and / or fracturing of the carrier particles. The devices also generated heat during the process which made them unsuitable for use with thermo-labile particles.

[0009] Another known dry coating process and system for the same is disclosed by WO2016 / 066462. Figure 1 shows the system 1 of WO2016 / 066462. The system includes an apparatus including a cylindrical vessel 2 defining a chamber 3. The vessel 2 is connected to a motor 10 by a belt 12 to drive rotation of the vessel 2. The apparatus includes a gas outlet member in the form of a hollow shaft 4 that extends into the vessel 2 along the vessel axis. The shaft 4 is connected to a gas supply 14 by a gas inlet 5. The shaft 4 includes apertures 9, 9’ that extend axially along the shaft along respective lines that are circumferentially spaced about the shaft 4. A gas outlet 7 is provided at an opposing axial end of the vessel to which the gas inlet 5 is connected.

[0010] The system is configured so that, during use, the vessel is rotated relatively fast so that the guest and carrier particles are held against the inner surface of the side wall due to the induced centrifugal forces acting upon them. The hollow shaft introduces the gas into the vessel through apertures 9, 9’ and effectively creates a number of axially extending “gas blades” which direct the gas radially upon the particles that are held against the side wall of the vessel. This is a lower I low shear process and produces strong adhesion between the particles without any substantial heat and / or shear being generated and / or reducing any contamination risk.

[0011] The present invention seeks to provide an improved apparatus, system and process.

[0012] According to an aspect of the present disclosure we provide a dry powder particle processing apparatus for coating carrier particles with guest particles including: a vessel supported for rotation about an axis A, the vessel including a first end wall, a second end wall and a side wall extending therebetween to define a chamber within which said particles are retained during processing; a motor connected to the vessel and adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall which is at least equal to 0.5g during use; a gas outlet member defining a gas flow path extending into the vessel and connectable to a gas supply for introducing gas into the chamber, wherein the gas outlet member has an outlet portion which is spaced apart from, and extends in a direction parallel to the axis A, and the outlet portion includes at least one or more outlet apertures in communication with the gas flow path for directing gas from the gas outlet member into the chamber in a direction towards the side wall.

[0013] According to an aspect of the present disclosure we provide a dry powder particle processing apparatus for coating carrier particles with guest particles including: a vessel supported for rotation about an axis A, the vessel including a first end wall, a second end wall and a side wall extending therebetween to define a chamber within which said particles are retained during processing; a motor connected to the vessel, optionally or preferably the motor is adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall which is at least equal to 0.5g during use; a gas outlet member defining a gas flow path extending into the vessel and connectable to a gas supply for introducing gas into the chamber, wherein the gas outlet member has an outlet portion which is spaced apart from, and extends in a direction parallel to the axis A, and the outlet portion includes at least one or more outlet apertures in communication with the gas flow path for directing gas from the gas outlet member into the chamber in a direction towards the side wall.

[0014] According to an aspect of the present disclosure we provide a dry powder particle processing system for coating carrier particles with guest particles, the system including: a processing apparatus including: a vessel supported for rotation about an axis A, the vessel including a first end wall, a second end wall and a side wall extending therebetween to define a chamber within which said particles are retained during processing; a motor connected to the vessel and adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall which is at least equal to 0.5g during use; a gas outlet member defining a gas flow path extending into the vessel and connected to a gas supply for introducing gas into the chamber, wherein the gas outlet member has an outlet portion which is spaced apart from, and extends in a direction parallel to the axis A, and the outlet portion includes at least one or more outlet apertures in communication with the gas flow path for directing gas from the gas outlet member into the chamber in a direction towards the side wall, and wherein the system is arranged with no means for introducing liquid into the chamber during use of the system.

[0015] According to an aspect of the present disclosure we provide a dry powder particle processing system for coating carrier particles with guest particles, the system including: a processing apparatus including: a vessel supported for rotation about an axis A, the vessel including a first end wall, a second end wall and a side wall extending therebetween to define a chamber within which said particles are retained during processing; a motor connected to the vessel and optionally or preferably adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall which is at least equal to 0.5g during use; a gas outlet member defining a gas flow path extending into the vessel and connected to a gas supply for introducing gas into the chamber, wherein the gas outlet member has an outlet portion which is spaced apart from, and extends in a direction parallel to the axis A, and the outlet portion includes at least one or more outlet apertures in communication with the gas flow path for directing gas from the gas outlet member into the chamber in a direction towards the side wall, and wherein the system is arranged with no means for introducing liquid into the chamber during use of the system.

[0016] According to an aspect of the present disclosure we provide a dry powder particle processing apparatus for coating carrier particles with guest particles including: a vessel supported for rotation about an axis A, the vessel including a first end wall, a second end wall and a side wall extending therebetween to define a chamber within which said particles are retained during processing; a motor connected to the vessel and adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall which is at least equal to 0.5g during use; a gas outlet member connected to the first end wall and defining a gas flow path extending into the vessel and connectable to a gas supply for introducing gas into the chamber, wherein the gas outlet member has an outlet portion including at least one or more outlet apertures in communication with the gas flow path for directing gas from the gas outlet member into the chamber in a direction towards the side wall; and the vessel includes a gas exhaust outlet provided on the first end wall and in communication with the chamber. According to an aspect of the present disclosure we provide a dry powder particle processing apparatus for coating carrier particles with guest particles including: a vessel supported for rotation about an axis A, the vessel including a first end wall, a second end wall and a side wall extending therebetween to define a chamber within which said particles are retained during processing; a motor connected to the vessel and optionally or preferably adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall which is at least equal to 0.5g during use; a gas outlet member connected to the first end wall and defining a gas flow path extending into the vessel and connectable to a gas supply for introducing gas into the chamber, wherein the gas outlet member has an outlet portion including at least one or more outlet apertures in communication with the gas flow path for directing gas from the gas outlet member into the chamber in a direction towards the side wall; and the vessel includes a gas exhaust outlet provided on the first end wall and in communication with the chamber.

[0017] The outlet portion may be generally elongate or is elongate, and / or extend parallel to the side wall.

[0018] The outlet portion may be positioned closer to the side wall than the axis A.

[0019] The gas outlet member may include a first portion in communication with the outlet portion and the first portion is spaced apart from the outlet portion, optionally or preferably the first portion extends in a direction parallel to axis A and / or is closer to axis A than the outlet portion.

[0020] The first portion may be generally elongate or is elongate and / or extend parallel to the side wall.

[0021] The gas outlet member may include a second portion which extends between the outlet portion and the first portion, optionally or preferably the second portion is positioned adjacent to the second wall.

[0022] The outlet portion may be generally elongate or is elongate, and the outlet portion may terminate in first and / or second free ends, optionally or preferably the first and / or second free ends are positioned in the chamber. The first free end may be adjacent or near the first end wall and / or the second free end may be adjacent or near the second end wall. The first portion may be connected to the outlet portion by a connecting portion which extends generally radially or radially away from the first portion. The first portion may extend into the chamber, and the outlet portion may have a length which is longer than the distance the first portion extends into the chamber. The connecting portion and the outlet portion may generally form a T-shape.

[0023] The outlet portion may have first and / or second end portions which terminate in the respective first and / or second free ends. The first and / or second end portions may extend transversely with respect to the rest of the outlet portion, optionally or preferably the first and / or second end portions may extend inwardly towards axis A.

[0024] The first portion may extend through the first wall.

[0025] The gas outlet member may include a third portion that extends away from the outlet portion, and optionally or preferably the third portion forms a free end of the gas outlet member.

[0026] The first wall may be connected to the side wall and may be opened to permit access to the chamber.

[0027] The first wall may be releasably connected to the side wall.

[0028] The gas outlet member may be connected to the first wall.

[0029] The vessel may include a gas exhaust outlet in communication with the chamber. Optionally or preferably the gas exhaust outlet is separate from the gas outlet member. Optionally or preferably the gas exhaust outlet is provided in the first wall. Optionally or preferably the gas outlet member terminates in the chamber.

[0030] The apparatus or system may include a pressure regulation system for regulating pressure within the chamber. Optionally or preferably the system is for extracting gas from the chamber. Optionally or preferably the pressure regulation system is connected to the gas exhaust outlet.

[0031] The apparatus or system may include a gas recirculation system for extracting gas from the chamber and providing the extracted gas to the gas outlet member. Optionally or preferably the system includes a pump for extracting the gas. Optionally or preferably the system provides the extracted gas to the gas outlet member. Optionally or preferably the gas recirculation system is connected to the gas exhaust outlet and / or the gas outlet member.

[0032] The dry powder particles may be sealed within the chamber during use and / or may only be removed when the vessel has been opened. The motor may be adapted to rotate the vessel to create a centrifugal acceleration (a at the side wall in the range 0.5g < (a) < 800g.

[0033] The motor may be adapted to rotate the vessel at R rotational revolutions per minute of between 100 and 4000 RPM, optionally or preferably between 500 and 3000 RPM, optionally or preferably between 750 and 2000 RPM.

[0034] The vessel may have a radius (r) and the motor may be adapted to rotate the vessel at R revolutions per minute such that:

[0035] 0.5g < ([R / 60]*2TT)2* r < 800g

[0036] The gas flow rate to the gas outlet member may be up to 120 L / min, preferably or optionally up to 90 L / min, preferably or optionally up to 60 L / m, preferably or optionally 5 - 50L / min.

[0037] Herein at least one or more outlet apertures in communication with the gas flow path may direct gas from the gas outlet member into the chamber in a direction radially towards the side wall.

[0038] According to an aspect of the present disclosure we provide a dry powder particle process for coating carrier particles with guest particles, the process comprising the steps of: a. providing an apparatus or system according to any one of the preceding aspects; b. adding the particles to the chamber and sealing the vessel so that only the gas outlet member and / gas exhaust outlet are in communication with the vessel; c. rotating the cylindrical processing vessel about its axis at a rotational speed to create a centrifugal acceleration (a) at the side wall of at least 0.5g; d. flowing gas from the gas outlet member and into the chamber through the one or more outlet apertures; and e. retaining the particles in the chamber until the process has been completed.

[0039] According to an aspect of the present disclosure we provide a dry powder particle process for coating carrier particles with guest particles, the process comprising the steps of: a. providing an apparatus or system according to any one of the preceding aspects; b. adding the particles to the chamber and sealing the vessel so that only the gas outlet member and / gas exhaust outlet are in communication with the vessel; c. rotating the cylindrical processing vessel about its axis, optionally or preferably at a rotational speed to create a centrifugal acceleration (a) at the side wall of at least 0.5g; d. flowing gas from the gas outlet member and into the chamber through the one or more outlet apertures; and e. retaining the particles in the chamber until the process has been completed.

[0040] No liquid or solvents are introduced into the chamber during the process.

[0041] Examples of the present disclosure will now be described by way of example with reference to the accompanying drawings in which:

[0042] Figure 1 shows a schematic representation of a prior art system disclosed by WO2016 / 066462;

[0043] Figure 2 is a perspective view showing a system according to examples of the present disclosure;

[0044] Figure 3 is a cross-section view showing certain components of the system shown in figure 2;

[0045] Figure 4 is a perspective view of a component of an apparatus of the system shown in figure 2;

[0046] Figure 5 is an end view of the component of figure 4;

[0047] Figure 6 is a cross-section view of the component of figure 4 through the plane B-B;

[0048] Figures 7a-d are Scanning Electron Microscopy images taken at varying magnifications of particles having been processed in the system shown in Figure 2;

[0049] Figure 8 is a perspective view showing a component according to another example of the present disclosure for use with the system of figure 2; and

[0050] Figure 9 is a perspective view of the component of figure 8 connected to other component parts of the system of figure 2.

[0051] Referring to figures 2 and 3, these show a dry powder particle processing system 100 and certain components thereof respectively for coating carrier particles with guest particles. The system 100 is similar to the prior art system shown in figure 1 but includes a number of modifications thereto. It will be appreciated that the system 100 may include one or more of the features of the system shown in figure 1 without departing from the scope of the present disclosure. The system 100 includes a processing apparatus 110 including a vessel 120 supported for rotation about an axis A. The vessel 120 has a first end 120a and a second end 120b. The vessel 120 includes a first end wall 122, a second end wall 124 and a side wall 126 extending therebetween to define a chamber 128 within which carrier and guest particles are retained during processing. The vessel 120 may be generally cylindrical in shape. The vessel 120 is made from stainless steel but may be made from other suitable rigid materials in examples, e.g. other metals, or plastics materials such as acrylic or polytetrafluoroethylene (PTFE). The inner surfaces of the walls 122, 124 and 126 defining the chamber 128 are preferably smooth. The apparatus 110 includes a motor 130 connected to the vessel 120, e.g. through a drive belt or the like, and the motor is adapted to rotate the vessel 120 to create a centrifugal acceleration (a) at the side wall 126 which is at least equal to 0.5g during use. The walls 122, 124 and 126 are solid, unperforated, walls so that the particles are retained in the chamber 128 during processing, i.e. the particles cannot leave the chamber 128 by passing through any of the walls 122, 124 and 126. The apparatus 110 includes a gas outlet member 132, in the form of a hollow shaft, which defines a gas flow path. The gas outlet member 132 extends into the vessel 120 and is connected to a gas supply 134 to introduce gas into the chamber 128. The gas outlet member 132 may be made from stainless steel or other suitable materials, e.g. other metals or plastics. The gas supply 134 may be provided as part of a gas recirculation system including a pump for use in extracting gas from the chamber 128 and then circulating the gas back to the gas outlet member 132 for reintroduction to the chamber 128. The gas recirculation system may be configured to selectively permit gas into the chamber 128 that has not been recirculated, i.e. directly from the gas supply.

[0052] The system 100 includes a control panel 150 for a user to operate the system 100, and a supporting frame 151 defining a space 158 in which the vessel 120 is positioned. The control panel 150 is connected to a control system 152 that includes various electronic circuits and / or computer processing components for controlling operation and / or monitoring operation of the various components of the system 100. The system 100 includes a safety cover 160 that is pivotally movable to selectively close or open the space 158 to inhibit or permit access thereto respectively. The system 100 is arranged with no means for introducing liquid into the chamber 128 during use of the system 100.

[0053] Referring to figures 3, 4, 5 and 6, the gas outlet member 132 is generally an elongate shaft that has been bended back on itself to define an open generally rectangular or lozenge shaped loop. The gas outlet member 132 extends from the first end wall 122 towards the second end wall 124. The gas outlet member 132 extends across effectively the whole length of the chamber. The gas outlet member 132 has an outlet portion 136 which is spaced apart from, and extends in a direction parallel to the axis A. The outlet portion 136 is generally elongate and extends parallel to the side wall 126. The outlet portion 136 has a first end 136a which is positioned towards the first end wall 122 and a second end 136b which is positioned towards the second end wall 124. The outlet portion 136 includes outlet apertures 138 in communication with the gas flow path for directing gas from the gas outlet member 132 into the chamber 128 in a radial direction towards the side wall 126. In examples, the outlet apertures 138 may be arranged in an axially extending row. This causes the gas to be incident perpendicular to the surface of the side wall 126. In examples, the outlet apertures 138 may direct the gas at a different angle towards the side wall 126. In examples, there may be one or more axially extending outlet apertures 138, e.g. slot(s). The gas outlet member 132 includes a first portion 140, a second portion 142 and a third portion 144.

[0054] The first portion 140 has a first end 140a including an inlet 145 for connection to the gas supply 134. The first end 140a is positioned externally of the vessel 120 and is spaced away from the outer surface of the first end wall 122. The first portion 140 extends through the first end wall 122 and has a second end 140b which is positioned near the second end wall 124. The outlet and first portions 136, 140 are generally elongate and have respective axes that are spaced apart from each other. The first portion 140 extends in a direction parallel to axis A and is positioned near axis A. The first portion 140 is parallel to the side wall 126. The outlet and first portions 136, 140 each extend between the first and second ends 120a, 120b. The outlet portion 136 is positioned closer to the side wall 126 than the axis A. The first portion 140 is greater in length than the outlet portion 136.

[0055] The second portion 142 has respective ends 142a, 142b which are arcuate and curve towards the respective second ends 136b, 140b and the second portion 142 has an elongate section 142c which extends radially between them. The third portion 144 is connected to the first end 136a and is positioned near the first end wall 122. The third portion 144 extends away from the first end 136a inwardly towards the first portion 140 along an arcuate connecting portion 144a which connects to an elongate portion 144b that terminates short of the first portion 140 to form a free end. The third portion 144 is closed at its free end. The second and third portions 142, 144 are thus positioned at respective first and second ends 120a, 120b of the chamber 128.

[0056] The gas flow path extends through each of the outlet, first, second and third portions 136, 140, 142, 144. The gas flow path extends from the inlet 145 along the length of the gas outlet member 132 before terminating at the closed free end of the third portion 144. The apertures 138 are arranged on a surface of the outlet portion 136 that faces towards the side wall 126. The apertures 138 are arranged along a line and are uniformly spaced along the line. The apertures 138 also extend along the outer surfaces of the arcuate end portion 142b, and the arcuate connecting portion 144a. The apertures 138 thus effectively cover the length of the side wall 126.

[0057] In examples, the gas outlet member 132 may be shaped differently and all that is required is that the gas outlet member 132 has the outlet portion 136 extending in a direction parallel to, and spaced apart from, the axis A. For example, the outlet portion 136 may be curved. In examples, the member 132 may have a first portion 140 that extends radially towards the outlet portion 136 and a second portion 142 that terminates at a free end, i.e. the member 132 has no elongate portion extending into the vessel 128 positioned near the axis A.

[0058] The first end wall 122 of the vessel 120 is connected to the side wall 126 and may be opened to permit access to the chamber 128 for placing powder particles into the chamber 128 and for removing processed powder particles from the chamber 128. The first end wall 122 may be configured as a lid which can be releasably connected to the end of the vessel 120, e.g. by fasteners to a flange provided along the end 120a of the side wall 126. The first end wall 122 includes a manifold member 170 which extends centrally through the first end wall 122. The manifold member 170 has a first end 170a which sits outside of the chamber 128 and a second end 170b which is positioned within the chamber 128. The second end 170b extends a relatively small distance into the chamber 128. The manifold member 170 is connected to the first end wall 122 by a member 171 that is part of the first end wall 122 and there is a rotatable connection 172 between the member 171 and the manifold member 170. This arrangement means that the gas outlet member 132 and manifold member 170 are stationary whilst the rest of the vessel 120 rotates during operation. The rotatable connection 172 may be a bearing in examples. In examples, the member 171 may be integrally formed as part of the first end wall 122 or it may be a separate component which is fixed to the first end wall 122.

[0059] The manifold member 170 includes a first passage 174 which extends the entire length of the manifold member 170. The first passage 174 is a cylindrical shape which is open at its ends. The gas outlet member 132 extends through the first passage 174. In more detail, the first portion 140 has a radially extending flange 146 positioned towards its first end 140a and the first portion 140 extends through the first passage 174 with the flange 146 abutting an inwardly facing surface at the first end 170a. The first end 140a sits proud of the first passage 174 to permit connection of the gas supply 134 to the inlet 145. In examples, the gas outlet member 132 is connected to the first end wall 122 and in examples they may be fixed relative to one another, e.g. through fasteners or the like, so that when the first end wall 122 is removed (in certain examples), the gas outlet member 132 comes away with it.

[0060] The manifold member 170 includes a second passage 176 which extends the length of the manifold member 170. The second passage 176 is a cylindrical shape that is open at its ends. The second passage 176 is spaced part and parallel to the first passage 174. The second passage 176 has a first end 176a positioned outside of the chamber 128 and a second end 176b positioned inside the chamber 128. The second passage 176 defines a gas exhaust outlet 178 in communication with the chamber 128. The gas exhaust outlet 178 is separate from the gas outlet member and terminates (at its second end 176b) in the chamber 128. The first end 176a is fluidly connected to a pressure regulation system (not shown) for regulating the pressure within the chamber 128 and it may connected to a gas recirculation system (where provided) for extracting gas from the chamber 128 prior to recirculation into the chamber 128. In the examples, the chamber 128 is sealed other than the fluid communication with the outlet member 132 and the gas exhaust outlet 178 (where provided).

[0061] The gas supply 134 may provide nitrogen or other inert gas that will not interact with or oxidise the particles being processed. The gas may be heated prior to introduction into the gas outlet member 132 in examples. In examples, the gas flow rate may be up to 120 L / min. The gas flow rate may be up to 90 L / min. The gas flow rate may be up to 60 L / m. In examples, the gas flow rate may be 5 - 50L / min.

[0062] The second end wall 124 includes a driving formation 129 for connection to a drive member (not shown), e.g. a shaft or the like, connected to the motor 130 so that the motor can drive rotation of the vessel 120. The driving formation 129 is formed centrally of the second end wall 124 and is generally annular in shape. The driving formation 129 includes an outwardly extending boss having an internal passage for engagement with the drive member.

[0063] Operation of the system 100 will now be described for processing of pharmaceutical substances alpha lactose monohydrate (Grade - Lactohale 100) as the carrier particles (i.e. relatively large I coarse particles), and fluticasone propionate (FP) as the guest particles (i.e. relatively small I fine particles). It should be noted that although a specific example is being described for the purpose of explaining operation of system 100, the carrier and guest particles may be other materials that have been selected according to the application and may include any of the particles described in WO2016 / 066462, including the various parameters of particles described therein. In examples, mixtures of dry powders of diverse particle size may be used. The particles may be of diverse agglomerated states that may be cohesive and have poor flow properties or could be free flowing. The particles may be hydrophobic or hydrophilic. They may be particles of amphipathic materials; may be biological in nature, proteins, enzymes, monoclonal antibodies, hormones; may be endogenous or not; may be crystalline or amorphous; may contain small molecules or large molecules; may be organic or inorganic; may be charged or neutral; may be physically or chemically labile.

[0064] The safety cover 160 is opened and the vessel 120 is removed from the frame 151 to load with the carrier and guest particles.

[0065] The carrier and guest particles (in their powder form) are placed into the chamber 128 of the vessel 120 by opening the first end wall 122. The first end wall 122 is then fastened into place so that the gas outlet member 132 extends in the chamber 128 as shown in figure 3. The vessel 120 is then placed into the space 158 and attached to the respective connections that support the vessel 120. The cover 160 is then closed. The pressure regulation system and gas recirculation system (where provided) and gas supply 134 are connected to the second passage 176 and inlet 145 respectively. The chamber 128 is now sealed other than for the fluid communication with the gas outlet member 132 and the gas exhaust outlet 178.

[0066] The control panel 150 is then operated to input the desired rotational speed in RPM, the desired gas flow rate to the gas outlet member 132 and other process parameters as required. Once this information has been inputted, the user operates the control panel 150 to start the process.

[0067] The control system 152 then automatically operates the various components of the system 100 in accordance with the process parameters selected by the user. The process parameters may include specifying the rotational speed of the vessel 120, the flow rate of the gas passing through the gas outlet member 132, the atmospheric pressure to be maintained within the chamber 128, the temperature of the gas passing through the gas outlet member 132, the temperature within the chamber 128, and / or whether to supply non-circulated gas to the gas outlet member 132. For example, the control system 152 may control the pressure within the chamber 128, e.g. via a pressure regulation system and I or gas recirculation system (where provided in examples), to be close to or at atmospheric pressure, e.g. in the range 1.0 - 1.5 Bar. For example, in examples, the temperature within the chamber 128 may be between 18° and 30°C, optionally or preferably 20° and 28°C, and optionally or preferably between 22° and 28°C. In particular, for materials that are non-thermolabile, the temperature in the chamber 128 may be deliberately raised or lowered, e.g. through heating of gas supplied to the gas outlet member 132 prior to it being outputted into the chamber 128 or by other means in examples.

[0068] The selection of the desired rotational speed will depend on the size of the vessel 120, and in particular, on its radius (r). This is because the process of coating the carrier particles with the guest particles involves applying centrifugal acceleration to the particles so that a thin layer of the particles is formed on the inner surface of the side wall 126 and gas from the gas outlet member 132 is directed into the particles to cause thin layer fluidisation to occur. In order for the thin layer of particles to be formed in this way, the particles must be urged against the inner surface of the side wall 126 and this is achieved through relatively fast rotation of the vessel 120 to create a sufficient centrifugal acceleration (a) at the side wall 126 to retain the particles against the side wall 126. It has been realised that a minimum centrifugal acceleration (a) of 0.5g is required for this purpose. The centrifugal acceleration (a) is linked to the rotational speed in RPM (R) and radius of the vessel (r) by the formula: a = (angular velocity)2*r =([R / 60]*2n)2*r

[0069] In examples, the motor 130 may be adapted to rotate the vessel 120 to create a centrifugal acceleration (a) at the side wall 126 in the range 0.5g < (a) < 800g. In other words, the motor 130 is adapted to rotate the vessel at R revolutions per minute such that:

[0070] 0.5g < ([R / 60]*2TT)2* r < 800g

[0071] The motor 130 may be adapted to rotate the vessel 120 at R rotational revolutions per minute of between 100 and 4000 RPM, optionally or preferably between 500 and 3000 RPM, optionally or preferably between 750 and 2000 RPM. In examples, the control system 152 may be configured to provide control instructions to operate the motor 130 at the rotational speeds required, e.g. to create the centrifugal acceleration (a).

[0072] On commencement of the process, the vessel 120 is rotated and gas is supplied to the gas outlet member 132. In doing so, the guest and carrier particles de-agglomerate underthe effects of the centrifugal forces generated on them and a relatively thin layer of dry powder comprising the guest and carrier particles is formed at the side wall 126. The gas outputted from the apertures 138 of the gas outlet member 132 acts upon the layer of powder formed at the side wall 126 forming what can be thought of as a “gas blade” or “gas curtain”. The gas thereby disrupts the layer of powder and causes the fine guest particles to be distributed uniformly around the coarse carrier particles (because the fine guest particles are lighter they experience a smaller centrifugal force and so are freer to move compared to the coarse guest particles). Due to the dual forces of the centrifugal force and that of the gas acting upon them the fine particles become distributed around the surfaces of the coarse particles before becoming adsorbed thereon. The adsorption of the guest particles onto the surfaces of the carrier particles may occur through physical attractive forces such as van der Waals and electrostatic interactions. Due to the high degree of adsorption and distribution of the fine guest particles on the surfaces of the coarse carrier particles, a uniformly coated powder may be produced. In examples, these described mechanisms - de-agglomeration of fine and coarse particles, disruption of the powder layer, and adsorption of the fine particles onto the surfaces of the coarse particles - may occur concurrently.

[0073] The process continues for a pre-determined length of time until the fine particles have been adsorbed to the coarse particles in a sufficiently high number as required for the desired application. The length of time will depend on the particles being processed, e.g. their chemical composition, structure, size, and the desired application of the coated particles. During the process, no liquid is introduced into the chamber 128 and only the gas output by the gas outlet member 132 is introduced. The particles are retained in the chamber 128 until the process is complete.

[0074] For the present example that produces the results shown in the images of figures 7a-d, the process parameters include a vessel radius r = 0.175m, a rotational speed R being 760 RPM I ~1 13g, a gas flow rate of 33 L / min and a processing time of 15 minutes.

[0075] On completion of the process, the vessel 120 is removed and opened to permit removal of the processed powder.

[0076] Figures 7a - d show the adsorption of the fine guest particles, fluticasone propionate, to the surfaces of the coarse carrier particles, alpha lactose monohydrate at respectively higher magnifications. It can be seen that the fine guest particles are generally uniformly distributed over the surfaces of the coarse carrier particles and over all of the carrier particles to which they have been adsorbed.

[0077] It has been demonstrated that the system 100 can replicate the adsorption of guest particles to carrier particles in a dry process, i.e. without the introduction of liquid to coat or spray the particles. In particular, the system 100 is configured in examples so that no liquid or solvent, e.g. coating solution or suspended solutions, can be introduced into the chamber 128. The described examples provide a process that is low shear thereby preserving the original properties of the powder particles regardless of the scale of the process, e.g. the particle sizes, physical, chemical and biological properties of the particles being processed, and it also does not cause any charge separation during the process.

[0078] Furthermore, the process is successfully achieved with a gas outlet member 132 that is spaced away from the rotational axis A of the chamber 120 which is contrast to the system of the prior art system of figure 1 that has a gas outlet member 132 extending along the rotational axis A. The present configuration of gas outlet member 132 is advantageous as the outlet apertures 138 are provided closer to the side wall 126 in comparison to the corresponding apertures of the prior art system. The configuration may provide advantages in that it may permit larger scale processing vessels to be easily employed for larger manufacturing processes. Advantages may also include there being a lower pressure drop of the gas between the outlet apertures 138 and at the side wall 126. Although the gas outlet member 132 is provided in the shape as shown in figure 3, resembling a trombone slide, the shape could be varied in examples. All that is required is that the outlet portion 136 is spaced away from the axis A so as to be closer to the side wall 126.

[0079] In examples according to another aspect of the present disclosure, the gas outlet member may be configured or shaped differently, e.g. it may take the shape shown in the examples of WO2016 / 066462. The gas outlet member is connected to the first end wall similar to the previous examples and the gas exhaust outlet is provided on the same wall, i.e. the first end wall and separately from the gas outlet member. This is different to the examples of WO2016 / 066462 for which the gas exhaust outlet is provided at an opposite end wall of the vessel to the end wall to which the gas outlet member is connected. Examples described according to the present disclosure may be advantageous over the arrangement of WO’462 in that, for the present examples, only one of the end walls of the vessel has fluid conduits passing therethrough (e.g. such as the gas outlet member or the gas exhaust outlet) or fluid conduits which are directly or indirectly connected thereto. This permits for a simpler design of vessel and system in comparison to the prior art as connections do not have to be provided at both end walls of the vessel. Accordingly, it is easier and less costly to provide larger scale manufacturing systems and apparatus made according to the present disclosure.

[0080] With reference to figures 8 and 9, these show a gas outlet member 232 according to a further example of the present disclosure. The gas outlet member 232 is an alternative to the examples of the gas outlet member 132 described for use with the previously described examples of systems and apparatus. The gas outlet member 232 is for use with the vessel 120. Figure 9 shows the gas outlet member 232 connected to the manifold member 170 and the first end wall 122 in the example for which the wall 122 forms a lid of the vessel 120. The gas outlet member 232 has certain features in common with the gas outlet member 132. For example, the gas outlet member 232 defines a gas flow path extending into the vessel 120 and is connectable to the gas supply 134 for introducing gas into the chamber 128. The gas outlet member 232 includes an outlet portion 236 which is spaced apart from, and extends in a direction parallel to axis A. The outlet portion 236 includes one or more outlet apertures (not shown) in communication with the gas flow path for directing gas from the gas outlet member 232 into the chamber 128 in a direction towards the side wall 126. In this example, the apertures extend along the length of the outlet portion 236. The apertures may be equally spaced apart along the outlet portion 236. According to examples of the present disclosure, the apertures may share one or more features or configurations in common with the features or configurations of the previously described examples of the outlet apertures 138 in relation to the outlet portion 136.

[0081] In this example, the outlet portion 236 is generally elongate. The outlet portion 236 terminates in first and second free ends 236a, 236b. The ends 236a, 236b may be located within the chamber 128. The first free end 236a is adjacent or near the first end wall 122 and the second free end 236b is adjacent or near the second end wall 124 when the gas outlet member 232 is connected to the vessel 120. In examples, only one of the ends of the outlet portion 236 may terminate in a free end and the other end may, for example, be connected to another portion of the gas outlet member 232. The outlet portion 236 may be a straight member with no portions extending transversely away from one or both of its ends 236a, 236b. One or both of the free ends 236a, 236b of the outlet portion 236 may face in an axial direction, e.g. parallel to axis A. In examples, the end portions of the outlet portion 236 which terminate in the respective free ends 236a, 236b may extend transversely, e.g. be inclined, with respect to the rest of the outlet portion 236, e.g. with respect to a central portion of the outlet portion 236. For example, each of the end portions of the outlet portion 236 may extend generally radially inwardly towards the axis A at an angle. This may be effective in directing gas into the respective corners of the vessel formed between the end walls 122, 124 and the side wall 126.

[0082] The gas outlet member 232 may include a first portion 240. The first portion 240 may be in communication with the outlet portion 236. The first portion 240 is spaced apart from the outlet portion 236. The first portion 240 may extend in a direction parallel to axis A and / or is closer to axis A than the outlet portion 236. The first portion 240 is generally elongate. The first portion 240 is connected to the outlet portion 236. The first portion 240 may be connected to the outlet portion 236 at a position which is between the ends 236a, 236b of the outlet portion 236. For example, the first portion 240 may be connected midway along the length of the outlet portion 236. In examples, the first portion 240 may be connected to the outlet portion 236 by a connecting portion 300. An arcuate section may connect a distal end of the first portion 240 to the connecting portion 300. The first portion 240 and connecting portion 300 are generally perpendicular to each other. In examples they may not be perpendicular to each other and may extend at a different angle relative to each other. The connecting portion 300 may extend radially away, e.g. radially away from the axis A, from the first portion 240.

[0083] The first portion 240 is received in the manifold member 170 in a similar way to the first portion 140 of the previously described examples and has a flange 246 which is similar to the flange 146 for abutting the manifold member 170 in the same way. The main difference between the first portion 240 and the first portion 140 is that the first portion 240 does not extend substantially the length of the chamber 128. The first portion 240 extends a distance into the chamber 128 which is less than the length of the outlet portion 236. In examples, the first portion 240 may extend generally halfway along the length of the chamber 128. The connecting portion 300 and the outlet portion 236 generally form a T-shape. The connecting portion 300 has a length which is shorter than the radius of the chamber 128.

[0084] A pair of inclined support members, 302, 304 may be provided, e.g. in the form of struts, to provide support to the gas outlet member 232 so that the member 232 retains its overall shape and mechanical integrity during operation. The support members 302, 304 extend from respective sides of the connecting portion 300 to respective points on the outlet portion 236 on either side of the point at which the connecting portion 300 connects to the outlet portion 234.

[0085] An advantage of the gas outlet member 232 having configuration described in relation to these examples is that outlet portion 236 may terminate in free ends which, as opposed to the gas outlet member 132 shown in the previously described examples, means that the free ends may be located closer to the respective end walls 122, 124. This may ensure, in certain examples configured so that outlet portion 236 extends substantially, or all of the length of the side wall 126 to maximise the area over which gas is directed during use. Another advantage may be that the apparatus requires a smaller footprint to accommodate removal of the gas outlet member 232 compared to the gas outlet member 132. Such advantages may be particularly applicable to larger capacity apparatus. Representative features are set out in the following clauses / claims, which stand alone or may be combined, in any combination, with one or more features disclosed in the text and / or drawings of the specification. When used in this specification and claims, the terms "comprises" and "comprising" and variations thereof mean that the specified features, steps or integers are included. The terms are not to be interpreted to exclude the presence of other features, steps or components.

[0086] The features disclosed in the foregoing description, orthe following claims, orthe accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for attaining the disclosed result, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof. Although certain example examples of the invention have been described, the scope of the appended claims is not intended to be limited solely to these examples. The claims are to be construed literally, purposively, and / or to encompass equivalents.

Claims

CLAIMS1 . A dry powder particle processing apparatus for coating carrier particles with guest particles including: a vessel supported for rotation about an axis A, the vessel including a first end wall, a second end wall and a side wall extending therebetween to define a chamber within which said particles are retained during processing; a motor connected to the vessel and adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall which is at least equal to 0.5g during use; a gas outlet member defining a gas flow path extending into the vessel and connectable to a gas supply for introducing gas into the chamber, wherein the gas outlet member has an outlet portion which is spaced apart from, and extends in a direction parallel to the axis A, and the outlet portion includes at least one or more outlet apertures in communication with the gas flow path for directing gas from the gas outlet member into the chamber in a direction towards the side wall.

2. A dry powder particle processing system for coating carrier particles with guest particles, the system including: a processing apparatus including: a vessel supported for rotation about an axis A, the vessel including a first end wall, a second end wall and a side wall extending therebetween to define a chamber within which said particles are retained during processing; a motor connected to the vessel and adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall which is at least equal to 0.5g during use; a gas outlet member defining a gas flow path extending into the vessel and connected to a gas supply for introducing gas into the chamber, wherein the gas outlet member has an outlet portion which is spaced apart from, and extends in a direction parallel to the axis A, and the outlet portion includes at least one or more outlet apertures in communication with the gas flow path for directing gas from the gas outlet member into the chamber in a direction towards the side wall, and wherein the system is arranged with no means for introducing liquid into the chamber during use of the system.

3. A dry powder particle processing apparatus for coating carrier particles with guest particles including:a vessel supported for rotation about an axis A, the vessel including a first end wall, a second end wall and a side wall extending therebetween to define a chamber within which said particles are retained during processing; a motor connected to the vessel and adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall which is at least equal to 0.5g during use; a gas outlet member connected to the first end wall and defining a gas flow path extending into the vessel and connectable to a gas supply for introducing gas into the chamber, wherein the gas outlet member has an outlet portion including at least one or more outlet apertures in communication with the gas flow path for directing gas from the gas outlet member into the chamber in a direction towards the side wall; and the vessel includes a gas exhaust outlet provided on the first end wall and in communication with the chamber.

4. An apparatus or system according to claim 1 , 2 or 3, wherein the outlet portion is generally elongate or is elongate, and / or extends parallel to the side wall.

5. An apparatus or system according to any one of claims 1 to 4, wherein the outlet portion is positioned closer to the side wall than the axis A.

6. An apparatus according to any one of claims 1 to 5 wherein the gas outlet member includes a first portion in communication with the outlet portion and the first portion is spaced apart from the outlet portion, optionally or preferably the first portion extends in a direction parallel to axis A and / or is closer to axis A than the outlet portion.

7. An apparatus or system according to claim 6, wherein the first portion is generally elongate or is elongate and extends parallel to the side wall.

8. An apparatus or system according to claim 6 or 7, wherein the gas outlet member includes a second portion which extends between the outlet portion and the first portion, optionally or preferably the second portion is positioned adjacent to the second wall.

9. An apparatus or system according to any one of claims 1 to 7 including one or more of the following: a) wherein the outlet portion is generally elongate or is elongate, and the outlet portion terminates in first and / or second free ends, b) optionally or preferably the first and / or second free ends are positioned in the chamber,c) optionally or preferably wherein the first free end is adjacent or near the first end wall and / or the second free end is adjacent or near the second end wall; and / or d) when directly or indirectly dependent on claim 6 or 7, wherein the first portion is connected to the outlet portion by a connecting portion which extends generally radially or radially away from the first portion.

10. An apparatus according to claim 9, when directly or indirectly dependent on claim 6 or 7, wherein the first portion extends into the chamber, and the outlet portion has a length which is longer than the distance the first portion extends into the chamber.

11. An apparatus according to claim 9 or 10 wherein the connecting portion and the outlet portion generally form a T-shape.

12. An apparatus according to any one of claims 9 to 11 , wherein the outlet portion has first and / or second end portions which terminate in the respective first and / or second free ends, and wherein the first and / or second end portions extend transversely with respect to the rest of the outlet portion, optionally or preferably the first and / or second end portions may extend inwardly towards axis A.

13. An apparatus or system according to any one of claims 6 to 12, wherein the first portion extends through the first wall.

14. An apparatus or system according to any one of claims 1 to 8 wherein the gas outlet member includes a third portion that extends away from the outlet portion, and optionally or preferably the third portion forms a free end of the gas outlet member.

15. An apparatus or system according to any preceding claim wherein the first wall is connected to the side wall and may be opened to permit access to the chamber, optionally or preferably wherein the first wall is releasably connected to the side wall.

16. An apparatus or system according to any preceding claim wherein the gas outlet member is connected to the first wall and / or wherein the vessel includes a gas exhaust outlet in communication with the chamber, optionally or preferably the gas exhaust outlet is separate from the gas outlet member, and optionally or preferably the gas exhaust outlet is provided in the first wall, and / or the gas outlet member terminates in the chamber.

17. An apparatus or system according to any preceding claim including a pressure regulation system for regulating pressure within the chamber, optionally or preferably for extracting gas from the chamber, and / or optionally or preferably the pressure regulation system is connected to the gas exhaust outlet.

18. An apparatus or system according to any preceding claim including a gas recirculation system for extracting gas from the chamber and providing the extracted gas to the gas outlet member, optionally or preferably including a pump for extracting the gas and / or providing the extracted gas to the gas outlet member, and / or optionally or preferably the gas recirculation system is connected to the gas exhaust outlet and / or the gas outlet member.

19. An apparatus or system according to any preceding claim wherein the dry powder particles are sealed within the chamber during use and may only be removed when the vessel has been opened.

20. An apparatus or system according to any preceding claim wherein the motor is adapted to rotate the vessel to create a centrifugal acceleration (a) at the side wall in the range 0.5g < (a) < 800g.

21. An apparatus or system according to any preceding claim wherein the vessel has a radius (r) and the motor is adapted to rotate the vessel at R revolutions per minute such that:0.5g < ([R / 60]*2TT)2* r < 800g22. An apparatus or system according to any preceding claim wherein the gas flow rate to the gas outlet member is up to 120 L / min, preferably or optionally up to 90 L / min, preferably or optionally up to 60 L / m, preferably or optionally 5 - 50L / min.

23. An apparatus or system according to any preceding claim, wherein the at least one or more outlet apertures in communication with the gas flow path direct gas from the gas outlet member into the chamber in a direction radially towards the side wall.

24. A dry powder particle process for coating carrier particles with guest particles, the process comprising the steps of: a. providing an apparatus or system according to any one of the preceding claims; b. adding the particles to the chamber and sealing the vessel so that only the gas outlet member and / gas exhaust outlet are in communication with the vessel; c. rotating the cylindrical processing vessel about its axis at a rotational speed to create a centrifugal acceleration (a) at the side wall of at least 0.5g;d. flowing gas from the gas outlet member and into the chamber through the one or more outlet apertures; and e. retaining the particles in the chamber until the process has been completed.

25. A process according to claim 24 wherein no liquid or solvents are introduced into the chamber during the process.

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