Method for producing multi-particles from a liquid feed using a spinning disk atomizer

Abstract

1. A process for making multiparticulates, comprising: providing a molten feed comprising an active ingredient and excipients; and providing a spinning disk atomizer (100), the spinning disk atomizer (100) comprising a rotatable disk (110) having a feed receiving surface (112) driven from above by a hollow drive shaft (A-A'), the axes of rotation of the hollow drive shaft (A-A') and the rotatable disk (B-B') being coaxial, the lower end (22) of the hollow drive shaft (200) being disposed with a distributor (204) for regulating the flow of the molten feed into a well (116), the distributor (204) and the well (116) together being configured to provide a substantially radially uniform outward flow of the molten feed across the feed receiving surface (112).

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Application No. 63 / 041,024, filed on Jun. 18, 2020. The prior application is hereby incorporated by reference in its entirety into this specification.

[0002] The devices and methods described herein are in the field of spinning disk atomizers, also known as spinning disk sprayers. In particular, they relate to spinning disk sprayers that are applied, for example, in the preparation of multi - particles from a melt feed in a melt - spray - congeal (MSC) process.

Background Art

[0003] A typical spinning disk atomizer receives a product feed onto a surface - rotating disk, and centrifugal force discharges the feed radially outward, where the feed leaves the surface as small particles. Spinning disk atomizers are used to create particles by solvent - based spray drying. One such device is described, for example, in WO2016 / 087261.

[0004] In many applications, the particle size must be within a defined range. In the melt - spray - congeal (MSC) process, for example, a rotating disk of a rotary atomizer is placed at the top of a large process vessel, and a melt feed is supplied onto a rotating disk that discharges particles that solidify in the air within the vessel and fall towards a base where they are collected as solid particles. Using the MSC process, lipid multi - particles for drug delivery can be produced, and control of the particle size is important for obtaining a uniform product containing a consistent amount of drug.

[0005] The aim herein is to provide a method and a spinning disk atomizer for generating particles having a narrower particle size distribution.

Summary of the Invention

[0006] Disclosed herein are various embodiments directed to a spinning disk atomizer for preparing multi-particles from a molten feed, and a method of forming multi-particles using the same.

[0007] Disclosed herein is a process for making multi-particles, comprising providing a molten feed comprising an active ingredient and an excipient, and providing a spinning disk atomizer (100) comprising a rotating disk (110) having a feed receiving surface (112) and a rotation axis (B-B'), and a drive hollow shaft (200) having a longitudinal shuttle lumen (202) and a rotation axis (A-A') and attached to the rotating disk (110). The feed receiving surface can define a well (116) centered about the rotation axis (B-B').

[0008] The molten feed is induced onto the feed receiving surface (112) through the lumen (202) and atomized from the rotating disk (110) to form solid multi-particles. The rotation axes of the hollow drive shaft (A-A') and the rotatable disk (B-B') can be coaxial, and the lower end (22) of the hollow drive shaft (200) can be provided with a distributor (204) for regulating the flow of the molten feed into the well (116) of the molten feed. The distributor (204) and the well (116) can be configured together to provide a substantially radially uniform outward flow of the molten feed across the entire feed receiving surface (112).

[0009] In some embodiments, the feed receiving surface (112) may comprise a peripheral flare portion (114) that gradually slopes in a central (30) and downward (22) direction towards the well (116), and the well (116) extends further downward (22) towards the well base end (117). At least a portion of the feed receiving surface of the well (116) can be steeper than at least a portion of the feed receiving surface of the flare portion (114).

[0010] In other embodiments, the flare portion (114) of the supply receiving surface (112) may comprise a plurality of radial channels (160, -a, -b), each channel being a conduit for the molten supply, open on the upper (20) side, open at both the peripheral (32) and central (30) ends, and configured to direct the molten supply from the well (116) to the periphery of the flare portion (114).

[0011] In yet other embodiments, the rotatable disk (110) may be disposed on the lower side (22) with a heating element (180) configured to regulate the temperature of the supply receiving surface. In some embodiments, the number of rotatable disks (110) and supply receiving surfaces (112) can be one.

[0012] In some embodiments, the distributor (204) can comprise a plurality of apertures (210) disposed around the circumference of the lower end (22) of the hollow drive shaft (200) for the outflow of the molten supply. In some embodiments, pillars (212, a, b) may be disposed between adjacent aperture pairs (210, a, b), the pillars (212, a, b) having, in cross-section, pillar outer edges (214, a), two pillar side edges (216, a, b; 218, a, b), and optionally pillar inner edges (220, a), the side edges (216, b and 218b) of the pillar (212, b) converging in a direction towards the center (30) of the hollow drive shaft (200).

[0013] The hollow drive shaft can be removably attached to the lower end (22) of the hollow drive shaft through an opening (130) in the well base end (117) of the rotatable disk (110). The hollow drive shaft (200) can be removably attached at its upper end (20) to a releasable mounting base (350). The spinning disk atomizer (100) can further include a hollow outer support shaft (270) having a longitudinal shaft lumen (272) for receiving the drive shaft (200). The spinning disk atomizer (100) can further include an optical camera configured to capture one or more images of at least a portion of the supply receiving surface and the supply particles being sprayed from the supply receiving surface (112) during spraying.

[0014] In some embodiments, the spinning disk atomizer (100) may be configured to be partially inserted into a process vessel (400) having a vessel volume (404) in which particles ejected from the rotatable disk (110) can undergo conversion, the rotatable disk (110) being embedded within the vessel volume and the upper end of the spinning disk atomizer being outside the vessel. The liquid supply can be a molten supply containing at least one active agent and at least one excipient, and optionally, the at least one excipient is an alkyl-containing glycerol such as a mixture of monoglyceryl behenate, diglyceryl behenate, and triglyceryl behenate (Compritol 888), glyceryl tristearate (Dynasan 118), hydrogenated cottonseed oil (Lubritab), hydrogenated castor oil (Kolliwax HCO), stearyl alcohol (Kolliwax SA), stearic acid and palmitic acid 50 (Kolliwax S), carnauba wax, candelilla wax, stearoyl polyoxyl glyceride (Gelucire 50 / 13), or a polyglycerol ester of a fatty acid. The molten supply may further include at least one of a pore former, a swelling agent, a release modifying material, and a viscosity modifying agent. The multi-particles may have a particle size range of 100 μm to a maximum of about 3 mm.

[0015] Additional features and embodiments of the disclosed spinning disk atomizer for preparing multi-particles from a molten feed, and methods of forming multi-particles using the same, are provided herein. The foregoing and other objects, features, and advantages of the present invention will become more apparent from the following detailed description which proceeds with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0016]

Figure 1

Figure 2A

Figure 2B

Figure 2C

Figure 3A

Figure 3B

Figure 3C

Figure 3D

Figure 4A

Figure 4B

Figure 4C

Figure 4D

Figure 5A

Figure 5B

Figure 5C

Figure 6A

Figure 6B

Figure 6C

Figure 6D

Figure 7A

Figure 7B

Figure 7C

Figure 8A

Figure 8B

Figure 9A

Figure 9B

Figure 9C

Figure 9D

Figure 9E

Figure 10

Figure 11

Figure 11A

Figure 11B

Figure 12

Figure 13A

Figure 13B

Figure 14A

Figure 14B

Figure 15A

Figure 15B

Figure 15C

Figure 16A

Figure 16B

Figure 16C

Figure 17A

Figure 17B

[0017] Before describing the present system and method of the present invention, it should be understood that the present invention is not limited to the specific systems and methods or combinations described, as such systems and methods and combinations can, of course, vary. It should also be understood that the terms used in this specification are not intended to be limiting. This is because the scope of the present invention is limited only by the appended claims.

[0018] As used in this specification, the singular forms "a", "an", and "the" include both singular and plural referents unless the context clearly dictates otherwise.

[0019] As used in this specification, the terms "comprising", "comprises", and "consisting of" are synonymous with "including", "includes", or "containing", "contains", and are inclusive or open-ended and do not exclude additional, unrecited members, elements, or method steps. It will be understood that the terms "comprising", "comprises", and "consisting of" used in this specification include the terms "consisting of", "consist", and "consist of".

[0020] The recitation of numerical ranges by endpoints includes all numbers and fractions within each range and the recited endpoints.

[0021] As used herein, the terms "about" or "approximately" when referring to measurable values such as parameters, amounts, and temporal durations mean that such variations are included as appropriate in the disclosed embodiments, within + / - 10% or less, preferably + / - 5% or less, more preferably + / - 1% or less, and still more preferably + / - 0.1% or less from the specified value. It should be understood that the value itself to which the modifier "about" or "approximately" refers is also specifically and preferably disclosed.

[0022] The term "one or more" or "at least one", e.g., one or more or at least one member of a group of members, is clear in itself, but by way of further illustration, this term includes references to any one of the members, or any two or more of the members, e.g., any ≧3, ≧4, ≧5, ≧6, or ≧7 etc. of the members, and up to all of the members.

[0023] All references cited herein are hereby incorporated by reference in their entirety. In particular, the teachings of all references specifically mentioned herein are incorporated by reference.

[0024] Unless otherwise defined, all terms used in this disclosure, including technical and scientific terms, have the meaning commonly understood by one of ordinary skill in the art to which this disclosure pertains. As a further guidance, definitions of terms are included to better understand the teachings of this disclosure.

[0025] In the following sections, different aspects of the present disclosure are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects, unless explicitly indicated to the contrary. In particular, any feature shown as being preferred or advantageous may be combined with any other feature or features shown as being preferred or advantageous.

[0026] References throughout this specification to "one embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, although they may. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments, as would be apparent to one of ordinary skill in the art from the present disclosure. Additionally, some embodiments described herein include some other features included in other embodiments and not others, but combinations of features of different embodiments are within the scope of the invention, as would be understood by one of ordinary skill in the art, and form different embodiments. For example, in the appended claims, any of the embodiments recited in the claims can be used in any combination.

[0027] In this disclosure, reference is made to the accompanying drawings, which form a part hereof and which illustrate, by way of example only, specific embodiments in which the disclosed subject matter may be practiced. The reference numbers, in parentheses or in boldface, attached to each element are illustrative of the element only and are not intended to limit each element. It is to be understood that other embodiments may be utilized and structural or logical changes may be made without departing from the scope of the invention. Accordingly, the following detailed description is not to be taken in a limiting sense, and the scope of the invention is defined by the appended claims.

[0028] The terms "upper" (20) and "lower" (22) are used herein to refer to opposite ends or sides of a spinning disk atomizer or a portion thereof, where the feed being atomized flows from a feed inlet in an upward direction to a downward direction. Upper typically refers to the upper end of a spinning disk atomizer or a part thereof, and lower refers to the proximal end of a spinning disk atomizer or a part thereof. A cross-section refers to a section taken across a plane perpendicular to the axis of rotation (e.g., A-A', B-B').

[0029] The term "central" (30) is used herein to refer to a lateral or transverse direction towards the central axis of rotation (A'A') of the hollow drive shaft (200), and "peripheral" (32) is used herein to refer to a lateral or transverse direction away from the central axis of rotation (A'A') of the axis of the hollow drive shaft (200). See, for example, FIG. 1.

[0030] Provided herein are a method and a spinning disk atomizer (100) for producing multi-particles from a liquid feed, particularly a melt feed. The spinning disk atomizer (100) atomizes the liquid feed to produce multi-particles. An exemplary spinning disk atomizer (100) is shown in FIG. 1.

[0031] Provided herein is a method for producing multi-particles by adding a liquid feed to a spinning disk atomizer (100). Exemplary methods are - providing a liquid feed, and - providing a spinning disk atomizer (100) as described herein, the spinning disk atomizer (100) comprising - a rotating disk (110) having a feed receiving surface (112) and a rotational axis (B-B'), the feed receiving surface defining a well centered on the rotational axis (B-B'), and - a drive shaft (200) attached to the rotating disk (110) and having a longitudinal shaft lumen (202) and a rotational axis (A-A'), and - inducing a liquid feed through the lumen (202) onto the feed receiving surface (112) and atomizing the liquid feed from the rotating disk (110) to form solid multi-particles.

[0032] A spinning disk atomizer (100) for generating multi-particles from a liquid supply is also provided herein. An exemplary spinning disk atomizer (100) includes a rotating disk (110) having a supply receiving surface (112) and a rotation axis (B-B'). The supply receiving surface (112) defines a well (116) centered on the rotation axis (B-B'). The spinning disk atomizer (100) further includes a drive shaft (200) attached to the rotating disk (110) and having a longitudinal shaft lumen (202) and a rotation axis (A-A'). The liquid supply is induced onto the supply receiving surface (112) through the lumen (202), and the liquid supply is atomized by the rotating disk (110) to form solid multi-particles. The rotation axes of the hollow drive shaft (A-A') and the rotatable disk (B-B') are coaxial.

[0033] The lower end (22) of the hollow drive shaft (200) is provided with a distributor for regulating the flow of the molten supply into the well of the molten supply, and the distributor is configured to regulate the outward flow of the molten supply across the entire supply receiving surface (112) in a substantially uniform manner. The lower end (22) of the hollow drive shaft (200) may be provided with a distributor for regulating the flow of the molten supply into the well of the molten supply, and the distributor (204) and the well (116) are configured together to provide a substantially radially uniform outward flow of the molten supply across the entire supply receiving surface (112). The distributor may be further configured to regulate the outward flow of the molten supply across the entire supply receiving surface (112) in a substantially radial manner.

[0034] The spinning disk atomizer (100) has upper (20) and lower (22) ends. The spinning disk atomizer includes a rotatable disk (110) having a supply receiving surface (112) facing upward (20). A hollow drive shaft (200) having a longitudinal shaft lumen (202) is attached (removably or non-removably) to the center of the rotatable disk (110).

[0035] Here, the spinning disk atomizer (100) and its parts, such as the outer support shaft 270, the hollow drive shaft (200), the heating element tube (236), and the rigid supply tube (232), have an axial direction (C-C') parallel to the rotation axis (A-A') of the hollow drive shaft (200).

[0036] The hollow drive shaft (200) extends upward (20). The motor unit (300) is disposed above (20) the rotatable disk (110) to apply torque to the drive shaft (200). The drive shaft (200) is removably connected to the torque output portion of the motor unit (300).

[0037] The lower end portion (22) of the hollow drive shaft (200) is provided with a distributor (204) for regulating the flow of liquid onto the supply receiving surface (112). The distributor (204) may include a plurality of apertures (210) connected to the drive shaft lumen (202) for an outward flow of the supply concentric with the rotation axis of the rotatable disk (110) on the supply receiving surface (112).

[0038] By providing the hollow drive shaft (200) attached to the rotatable disk (110) from above, and by providing a distributor (204) in the hollow drive shaft (200) lumen (202) for conveying the supply directly onto the supply receiving surface (112), the center of the supply outlet, the rotation axis (A-A') of the hollow drive shaft (200), and the rotation axis (B-B') of the rotatable disk (110) are coaxially aligned. This alignment causes the supply to be applied and propelled across the entire supply receiving surface (112) in a more uniform manner, resulting in a narrower size distribution of the particles, particularly for high throughput applications.

[0039] When the supply is not aligned with the axis of rotation (A-A') of the hollow drive shaft (200) and the axis of rotation (B-B') of the rotatable disk (110), i.e., when there is an eccentric supply, there is a local increase in the film thickness that creates larger particles during atomization. Figure 2A shows an example of an eccentric supply onto the supply receiving surface (112) from a supply outlet (111) slightly offset from the center, where a non-uniform spiral (90) of the supply is generated across the entire supply receiving surface (112), resulting in the discharge of droplets (92) of non-uniform size from the surface. The eccentric supply is evident in many existing designs where the rotatable disk is driven from below and the supply is poured onto the disk surface from above by a non-connected supply outlet (111). Alignment of the supply outlet (111) and the center of rotation of the rotatable disk (110) is particularly difficult in the melt spray coagulation (MSC) process, in which the rotatable disk (110) is positioned at the top of a large process vessel, and as a result, droplets that fall like rain and solidify in the air are generated within the vessel where they are collected as solid particles at the base. Since the rotatable disk (110) must be positioned at the top of a large process vessel, it is supported and driven from below by a long shaft (e.g., 2 - 3 m in length). The presence of the long shaft makes it difficult to align the rotatable disk (110) with the non-connected supply outlet (111) at the top of the large process vessel.

[0040] This configuration, in which the drive shaft lumen (202) supplies the supply to the center of the supply receiving surface (112) by an upward attachment from the hollow drive shaft (200) to the rotatable disk (110), ensures that the supply is concentric or coaxial with the axes of rotation (A-A', B-B').

[0041] The liquid supply may be any that can be atomized. Preferably, the liquid supply is a melt supply. Melt supplies are typically used in spray coagulation processes for producing multi-particles. The melt supply may be a homogeneous solution or suspension. The melt supply has a viscosity of 1 - 1000 cP, preferably about 40 - 400 cP.

[0042] The liquid supply, especially the molten supply, may contain one or more active agents. An active agent is a component that has a desired physiological effect on animals, preferably mammals, including but not limited to humans. The "activity" referred to herein may be targeted at humans only.

[0043] Non-limiting examples of active agents include vitamins or provitamins A, B, C, D, E, PP, and their esters, carotenoids, anti-radical substances, hydroxy acids, preservatives, molecules acting on pigmentation or inflammation, biological extracts, antioxidants, cells and cell organelles, antibiotics, macrolides, antifungal agents, itraconazole, ketoconazole, anthelmintics, antimalarials, adsorbents, hormones and their derivatives, nicotine, antihistamines, steroid and non-steroid anti-inflammatory agents, ibuprofen, naproxen, cortisone and its derivatives, anti-allergic agents, antihistamines, analgesics, local anesthetics, antiviral agents, antibodies and molecules acting on the immune system, cell growth inhibitors and anticancer agents, antihyperlipidemic agents, vasodilators, vasoconstrictors, inhibitors of angiotensin-converting enzyme and phosphodiesterase, fenofibrate and its derivatives, statins, nitrate derivatives and antianginal agents, beta blockers, calcium inhibitors, antidiuretics and diuretics, bronchodilators, opiates and their derivatives, barbiturates, benzodiazepines, molecules acting on the central nervous system, nucleic acids, peptides, anthracene compounds, paraffin oil, polyethylene glycol, inorganic salts, antispasmodics, gastric acid secretion inhibitors, clay gastric dressings and polyvinylpyrrolidone, aluminum salts, calcium carbonate, magnesium carbonate, starch, derivatives of benzimidazole, and combinations of the foregoing, including but not limited to drugs, supplements, and nutraceuticals.

[0044] Other non-limiting examples of the active agent include dextromethorphan, phenergan, guaifenesin, loratadine, sildenafil, vardenafil, tadafil, olanzapine, risperidone, famotidine, loperamide, sumatriptan, ondansetron, cetirizine, desloratadine, rizatriptan, piroxicam, paracetamol, phloroglucinol, nicergoline, metopimazine, dihydroergotamine, mirtazapine, clozapine, sumatriptan, prednisolone, levodopa, carbidopa, lamotrigine, ibuprofen, oxycodone, diphenhydramine, ramosetron, tramadol, zolpidem, fluoxetine, thiamine, and combinations thereof.

[0045] The active agent is preferably crystalline (having a higher melting point than the excipient), but may be amorphous. The active agent may be soluble or insoluble in the excipient (preferably insoluble). The active agent is typically homogeneous when mixed with the molten excipient. Preferably, the active agent has a particle size of less than 50 μm. The active agent may be present in an amount of multi-particles of 60% w / w.

[0046] The liquid feed, more specifically the molten feed, may contain one or more excipients (also known as matrix materials). The excipient binds to at least the active agent and, if present, the pore former. The presence of the excipient creates smooth round balls upon solidification of the molten feed containing the active agent. The excipient may be solid at room temperature. The excipient may be liquid above room temperature. The excipient may have a melting point in the range of 45 to 95 °C. Preferably, the excipient has a lower melting point than the active agent. The excipient may rapidly solidify to form a solid. The excipient may be present in an amount of multi-particles of at least 30% w / w.

[0047] Non-limiting examples of the excipient include one or more of the following. - Highly purified forms of waxes such as carnauba wax, white and yellow beeswax, microcrystalline wax, candelilla wax, and paraffin wax - Long-chain alcohols such as stearyl alcohol, cetyl alcohol, and polyethylene glycol - Polyethylene glycol, - Poloxamer, - Polyoxyethylene alkyl ether, - Mixtures of monoalkyl glycerides, dialkyl glycerides, and trialkyl glycerides, including glyceryl monooleate, glyceryl monostearate, glyceryl distearate, glyceryl palmitostearate, polyethoxylated castor oil derivatives, glyceryl monobehenate, glyceryl dibehenate, and glyceryl triehenate, glyceryl tristearate, glyceryl tripalmitate, and hydrogenated vegetable oils such as hydrogenated cottonseed oil and hydrogenated castor oil, long-chain fatty acid esters (also known as fats), - Glycolated fatty acid esters such as polyethylene glycol stearate and polyethylene glycol distearate, - Fatty acid esters from short-chain to medium-chain, such as isopropyl palmitate, isopropyl myristate, triethyl citrate, lecithin, triacetin, and dibutyl sebacate, - Polysorbate, - Carboxylic acids such as stearic acid, benzoic acid, citric acid, fumaric acid, lactic acid, maleic acid, palmitic acid, caprylic acid, capric acid, lauric acid, arachidic acid, behenic acid, and lignoceric acid, - Polyoxyl glycerides such as stearoyl polyoxyl glyceride (Gelucire50 / 13) and lauroyl polyoxyl glyceride (Gelucire44 / 14), - Polyglycerol esters of fatty acids.

[0048] Particularly preferred excipients are alkyl-containing glycerols such as a mixture of monoglyceryl behenate, diglyceryl behenate, and triglyceryl behenate (Compritol 888), glyceryl tristearate (Dynasan 118), hydrogenated cottonseed oil (Lubritab), hydrogenated castor oil (Kolliwax HCO), stearyl alcohol (Kolliwax SA), stearic acid and palmitic acid 50 (Kolliwax S), carnauba wax, candelilla wax, stearoyl polyoxyl glyceride (Gelucire 50 / 13), polyglycerol esters of fatty acids, etc.

[0049] Examples of excipients that are lipid matrix materials are known in the art and are described, for example, in WO2015 / 189726 or its equivalents, which are incorporated herein by reference, for example, US2017 / 0112762. WO2015 / 189726 describes examples of lipid matrix materials that may be suitable as excipients in the formation of multiparticulates in paragraphs

[0049] to

[0065] .

[0050] The liquid feed, which is a melt feed, may contain one or more pore formers (also known as dissolution promoters). The pore former is a water-soluble material that increases the rate of water uptake by the core by increasing the effective water permeability of the multiparticulates. The pore former can, for example, cause the formation of pores or channels throughout the excipient material. The pore former may be solid at room temperature. The pore former may be liquid above room temperature. The pore former may have a melting point in the range of 45 to 95 °C. Preferably, the pore former has a lower melting point than the active agent. The pore former may be water-soluble. The pore former can increase the uptake of water into the core to enhance the dissolution of the active agent. The pore former may be present in an amount of 5 to 30% w / w of the multiparticulates. Preferably, the pore former dissolves in the excipient in the molten state and phase-separates in the solid state.

[0051] Non-limiting examples of pore-forming agents include poloxamers such as Kolliphor P188 and Kolliphor P407, alcohols such as stearyl alcohol, cetyl alcohol, and polyethylene glycol, povidone, doxartate salts, polyglycerol esters of fatty acids, polyoxyethylene alkyl ethers, polyoxyethylene alkyl esters, alkyl polyglycol ethers, polyoxyethylene castor oil derivatives, polysorbates, sodium lauryl sulfate, sorbitan monoesters, monoalkyl glycerides, dialkyl glycerides, and trialkyl glycerides, and mixtures of mono-fatty acid esters and di-fatty acid esters of polyethylene glycol, sugars such as glucose, xylitol, sorbitol, and maltitol, salts such as sodium chloride, potassium chloride, lithium chloride, calcium chloride, magnesium chloride, sodium sulfate, potassium sulfate, sodium carbonate, magnesium sulfate, and potassium phosphate, amino acids such as alanine and glycine, and one or more of their mixtures.

[0052] Preferred dissolution promoters include poloxamers (Kolliphor P407), polyglycerol esters of fatty acids, and alkyl polyglycol ethers.

[0053] The liquid feed, particularly the melt feed, may contain one or more other ingredients. Non-limiting examples of other ingredients include the following. - One or more swelling agents for rupturing the core and promoting the immediate release of the drug. Non-limiting examples of swelling agents include sodium starch glycolate, croscarmellose sodium, and crospovidone. - One or more release-modifying materials for delaying dissolution. Non-limiting examples of release-modifying materials include the following. - Dialkyl phthalates such as dibutyl phthalate, - Hydrocarbon waxes such as carnauba wax, candelilla wax, beeswax, microcrystalline wax, and paraffin wax, - One or more viscosity modifiers for changing the viscosity of the molten feed to enable suitable atomization. - Viscosity-reducing excipients, for example, stearyl alcohol, cetyl alcohol, low molecular weight polyethylene glycol, isopropyl alcohol, water - Viscosity-increasing excipients such as microcrystalline wax, paraffin wax, high molecular weight polyethylene glycol, poloxamer, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, silicon dioxide, microcrystalline cellulose, magnesium silicate, sugars, and salts.

[0054] The liquid feed, which is a molten feed, may contain one or more of i) at least one active agent, ii) at least one excipient, iii) at least one pore-forming agent, and iv) at least one other component. Preferably, the liquid feed, which is a molten feed, contains i), ii), optionally iii), and optionally iv). Preferably, the liquid feed, which is a molten feed, contains i), ii), iii), and optionally iv). Preferably, the liquid feed contains i), ii), iii), and iv). The liquid feed forms multiparticles according to the method described herein.

[0055] The multiparticles formed by the method of the present disclosure may contain one or more active ingredients, optionally one or more pore-forming agents, and optionally one or more other components encapsulated in a continuous phase of one or more excipients, and the aforementioned components are present in the molten feed described elsewhere herein. The multiparticles may have a particle size of less than 150 μm and up to about 3 mm. The multiparticles may have a particle size and particle distribution according to the intended use. In pharmacological applications, for example, the particle size ranges from about 100 to about 500 μm. The span of the particle size distribution may be from 0.6 to 0.9.

[0056] The subsequent solid multiparticles may be coated. Non-limiting examples of coatings include the following. - Cosmetic coatings to provide a specific appearance - An enteric coating for delaying oral release to provide taste masking. - An enteric coating for protecting the active agent from an acidic environment or delaying drug release in the stomach.

[0057] The number of rotatable disks (110) attached to the hollow drive shaft (200) may be only one. The number of supply receiving surfaces (112) may be only one. The rotatable disk (110) may be formed from a single part. The supply receiving surface (112) may be formed from a single part. The supply receiving surface (112) includes a peripheral (32) flare portion (114) that gradually slopes in the central (30) and downward (22) directions toward the central well (116). Exemplary rotatable disks (110) are shown in FIGS. 3A - 3C.

[0058] The well (116) is configured to receive and hold the centrifuged supply along the peripheral flare portion (114) outside the well (116). The well (116) has a cup shape that substantially coincides with an inner portion having a substantially vertical wall, and the vertical wall transitions to the outer flare portion (114) of the disk (110). At least a part (e.g., the whole or a substantial part) of the supply receiving surface of the well (116) may be steeper than at least a part (e.g., the whole or a substantial part) of the supply receiving surface of the flare portion (114). The steepness of the surface is determined by its inclination compared to the rotation axis (B - B') of the rotatable disk, and the steeper surface is more parallel to the rotation axis (B - B'). The supply receiving surface of the well (116) may include a side wall (120), and all or a substantial part of it is parallel to the rotation axis (B - B') of the rotatable disk or is inclined at an angle of less than ±10 degrees. More than 50%, preferably more than 75% of the height (Wh) of the well (116) may have a side wall parallel to the rotation axis (B - B') of the rotatable disk (110).

[0059] The supply-receiving surface of the well (116) extends further downward (22) toward the well base end (117). The supply-receiving surface of the well base end (117) is sealed to hold the supply within the well (116). The well base end (117) may be sealed by the surface of the well (116) being continuous in the central direction (30), or by another element such as a hollow drive shaft (200) or a shaft plug (250) that cooperates with the rotatable disk (110).

[0060] By providing the well (116) in the rotatable disk (110), a vortex of the supply is easily formed using the well (116) having a center aligned with the rotation axis (A-A’) of the hollow drive shaft (200) and the rotation axis (B-B’) of the rotatable disk (110).

[0061] The inventors have found that the vortex created within the well (116) smooths out non-uniform flow into the well (116), thereby diffusing the supply in a more uniform manner across the entire supply-receiving surface (112) and resulting in a narrower size distribution of the particles. The geometric shape of the well (116) helps to uniformly redistribute the molten supply from some disturbances that may occur due to the hollow drive shaft lumen (202) or the pillar (212). Figures 2B (planar well floor) and 2C (concave well floor) each show a rotatable disk (110) having a well (116) that exhibits good performance (supply rate 10 Kg / hour, disk speed 3000 rpm) with a minimal supply-deficient area across the entire supply-receiving surface.

[0062] The well floor surface (118) is formed where the well base end (117) is sealed. The well floor surface (118) may be circular. The well floor surface (118) may be flat. The well floor surface (118) may be concave. The well floor surface (118) may be formed by the continuity of the wall of the well (116) in the direction of the center (30) (for example, FIG. 3A). The well floor surface (118) may be formed by a part of the hollow drive shaft (200) (for example, FIG. 3C). The well floor surface (118) may be formed by the main body (252) of the shaft plug (250). The well base end (117) may be provided with an opening (130) for removably attaching to the hollow drive shaft (200).

[0063] The side wall (120) of the well (116) may be connected to the well floor surface (118) via a second transition part (124) (for example, FIG. 3A). The second transition part may have a profile of an arc or a linear inclination. As a pointer, when the diameter of the rotatable disk (110) is 101.6 mm, the radius of the second transition part arc can be 2 to 12 mm.

[0064] The supply-receiving surface (112) of the flare part (114) may be curved or straight. When the flare part (114) is curved, the flare part (114) may be an arc. The supply-receiving surface of the flare part (114) may be smooth.

[0065] The supply-receiving surface (112) of the flare part (114) may be provided with a plurality of radial channels (160, -a, -b). The radial channels (160, -a, -b) are conduits for the molten supply, open on the upper (20) side, and open at both the peripheral (32) and the central (30) ends. The radial channels (160, -a, -b) are configured to guide the molten supply from the well (116) to the periphery of the flare part (114). Exemplary rotatable disks (110) with radial channels (160, -a, -b) are shown in FIGS. 11 and 12.

[0066] The radial channels (160, -a, -b) may be formed, for example, as channels protruding above the upper (20) surface of the flare portion (114), as shown in FIG. 12. The radial channels (160, -a, -b) may be formed as grooves below the upper (20) surface of the flare portion (114).

[0067] The radial channels (160, -a, -b) are aligned with a line (168) extending radially outward from the axis of rotation (B - B’) of the rotatable disk (110) (see FIG. 11A). The peripheral ends of the radial channels (160, -a, -b) may contact the periphery (32) of the flare portion (114) of the rotatable disk (110). The central ends of the radial channels (160, -a, -b) may or may not contact the central (32) edge of the well (116) of the rotatable disk (110). The annular buffer region (162) of the flare portion (114) extending outward from the well (116) may be devoid of the radial channels (160, -a, -b). The radial channels (160, -a, -b) are preferably limited to the flare portion (114).

[0068] The radial channels (160, -a, -b) may have a radial cross-section (170) which is a cross-section (b - b in FIG. 11A) perpendicular to the central radial line (168) of the channel (see FIG. 11B). The radial cross-section (170) may have a rectangular (elongated rectangular) form. The long edges of the rectangle may be parallel to the axis of rotation (B - B’) of the rotatable disk (110). The size of the cross-section may vary in the direction from the center (30) to the periphery (32) of the radial channel. The change in size may be gradual.

[0069] Preferably, the size of the cross-section (170) gradually decreases in the circumferential direction (32) from the center (30) of the radial channel. Preferably, the width (Cw) of the cross-section (170) gradually decreases in the circumferential direction (32) from the center (30) of the radial channel. The height (Hw) of the cross-section (170) may be constant in the circumferential direction (32) from the center (30) of the radial channel. The circumferential annular boundary (164) of the flare portion (114) may have a reduced cross-sectional height compared to the cross-section of the remaining portion of the radial channel. This may be due to the flattening of the top of the channel in the circumferential annular boundary (164). The radial channels (160, -a, -b) are preferably evenly distributed around the axis of rotation (B-B’) of the rotatable disk (110). The radial channels are dimensioned to maintain the flow of the melt feed within the area of the channel, i.e., without overflowing from the upwardly open side. Radial channels that provide a higher melt feed throughput than can be obtained with a smooth flare disk surface design while maintaining ideal atomization.

[0070] The circumferential rim of the rotatable disk (110) may terminate at an angle of less than 10 degrees (e.g., 3 to 5 degrees) above a plane perpendicular to the axis of rotation (B-B’) of the rotatable disk (110). The flare portion (114) may or may not be connected to the well via a first transition portion (122) (e.g., FIG. 3A). The first transition portion (122) may have an arcuate profile.

[0071] The feed receiving surface (112) may be made of any suitable material that maintains its shape integrity under rotation and has other properties such as durability and corrosion resistance. Examples of suitable materials include stainless steel, high-temperature thermoplastics (e.g., Teflon, PEEK), coated materials such as coated aluminum (anodized, polymer coating, or others), and coated steel.

[0072] The rotatable disk (110) may be provided with a heating element (180) configured to controllably generate heat in order to adjust the temperature of the supply receiving surface (112). The heating element may be an induction heating element (180’) configured to heat using wireless induction heating. The induction coil may emit energy in the form of a rapidly alternating magnetic field and may be provided above or below the rotatable disk (110). The induction heating element (180’) is heated by eddy currents induced by the electromagnetic field. The material of the rotatable disk itself may form the induction heating element (180’), or a separate induction heating element (180’) may be provided and attached, for example, on the lower side of the rotatable disk. An exemplary heating element (180) as a separate induction heating element (180’) is shown in FIG. 3D. The induction heating element (180’) may include any material suitable for induction heating, such as stainless steel, iron, or an alloy thereof. The rotatable disk (110) may be provided with one or more temperature sensors, optionally wirelessly. The one or more temperature sensors may be disposed on the lower side of the rotatable disk (110), for example, within the cavity or bore of the heating element (180) or the induction heating element (180’). The wireless temperature sensor may use Bluetooth (e.g., BLE), or RFID.

[0073] One skilled in the art can prepare a rotatable disk (110) according to the requirements of flow rate and particle size. As a guide, the supply-receiving surface of the rotatable disk (110) may have a diameter (Dd) of 101.6 mm, and the supply-receiving surface of the well may have a diameter (Wd) of 30 mm. The dimensional indicators are shown in Figure 3A. The arc radius may be 63.5 mm. The peripheral rim of the rotatable disk (110) may terminate at an angle of less than 10 degrees (e.g., 3 - 5 degrees) above a plane perpendicular to the axis of rotation (B - B’) of the rotatable disk (110). The height (Wh) of the supply-receiving surface of the well (the distance between the top of the well sidewall (120) and the well floor (118)) may be 4 - 5 mm. The arc radius of the first transition portion (122) may be 8 - 12 mm, e.g., 10 mm. The second transition portion may have a profile of an arc or a linear slope. The arc radius of the second transition portion may be 2 - 12 mm. The width (Cw) of the radial channel at the peripheral (32) edge of the flare portion (114) may be 200 - 500 μm (see Figure 11B). The width (Cw) of the radial channel cross-section (170) at the central (30) end of the disk may be 1 - 2 μm. The transition from the peripheral width (Cw) to the central edge may be gradual. The height (Ch) of the radial channel cross-section (170) at the periphery is preferably configured to be large enough, e.g., 1 mm or more, to prevent the molten supply from flowing over the wall. The radial channel cross-section height (Ch) may be constant in the radial direction, and the radial channel cross-section height (Ch) may taper off (i.e., decrease) together with the profile of the disk surface at the peripheral annular boundary (164). For example, the top surface of the channel may be flattened at the peripheral annular boundary (164). The number of radial channels (160, -a, -b) may be 50 - 500, e.g., 80 - 100. It is understood that the dimensions of the rotatable disk (110) may be enlarged or reduced according to the desired flow rates of the supply and the product.

[0074] The hollow drive shaft (200) transmits torque to the rotatable disk (110). The torque is optionally provided from the motor unit (300) to the hollow drive shaft (200) via an outer support shaft (270) (see below for details). The lumen (202) of the hollow drive shaft (200) transports the supply to the aperture (110) in the downward (22) direction for passage across the entire supply receiving surface (112) of the rotatable disk (110). The lumen (202) of the hollow drive shaft (200) is aligned with the axis of rotation (B-B’) of the rotatable disk (110), such that the liquid supply is intensively supplied into the wells (116) of the supply receiving surface (112).

[0075] The hollow drive shaft (200) may be provided with one or more O-rings to seal the exterior of the hollow drive shaft (200) against the lumen wall of the outer support shaft (270).

[0076] The hollow drive shaft (200) may be made of any suitable material that maintains its shape integrity under rotation and has other properties such as rigidity and durability. Other qualities include compatibility with the liquid supply, e.g., low toxicity and chemical stability. Examples of suitable materials include stainless steel and Teflon-coated materials.

[0077] The hollow drive shaft (200) is vertically elongated. The hollow drive shaft (200) may have an effective height (Seh) measured from the well floor surface (118) to the upper (20) end (see Figure 4A). Generally, a reduced effective height (Seh) is preferred to reduce vibration and instability at high rotational speeds. The hollow drive shaft (200) may have a wall thickness (St) (see Figure 4B). The hollow drive shaft (200) may have a lumen diameter (Sd) (see Figure 4B). As a non-limiting guideline, the effective height (Seh) may be 200 - 400 mm, the wall thickness (St) may be 1 - 5 mm, and the lumen diameter (Sd) may be 10 - 25 mm.

[0078] The hollow drive shaft (200) comprises a distributor (204) at or towards its lower (22) end configured for the regulation of the outward flow of the liquid supply. The distributor (204) comprises a plurality of apertures (210) disposed around the circumference of the lower end (22) of the hollow drive shaft (200) for the outflow of the molten supply. Pillars (212, a, b) are disposed between adjacent pairs of apertures (210, a, b), and the pillars are configured to minimally impede the flow of the liquid supply from the well (116) to the flare portion (114) of the supply receiving surface (112). The pillar (212) may have a longitudinal axis disposed in the direction of the A-A' axis or with an inclination of less than 10 degrees.

[0079] The distributor (204) may be disposed with a plurality of apertures (210). Exemplary apertures (210) are shown in FIGS. 4A-4D. The number of apertures (210) in the hollow drive shaft (200) may be, for example, between 2 and 24 such as 3-9, preferably 6. The apertures (210) may be evenly disposed around the circumference towards the lower end (22) of the hollow drive shaft (200). Each aperture (210) may have the same shape and dimensions. Each aperture (210) may have an aperture height (Ah) in the axial (A-A') direction and an aperture width (Aw) in a plane perpendicular to the axial (A-A') direction, as shown in FIG. 4D.

[0080] Each aperture (210) may have two opposing parallel straight side edges (e.g., 216, b; 218, a in FIGS. 4C and 4D). The straight side edges may be parallel to the axial direction (A-A'). The side edges (e.g., 216, b; 218, a) may be separated by the aperture width (Aw). Each aperture (210) may have opposing upper and lower edges (e.g., 224, 226). The upper and lower edges (e.g., 224, 226) may be parallel to a plane perpendicular to the axial direction (A-A'). The upper and lower edges (e.g., 224, 226) may be separated by the aperture height (Ah). The corners (228, a-d) of each aperture (210) may be rounded.

[0081] The aperture (210) may be positioned at the same axial position of the hollow drive shaft (200). The aperture (210) may be positioned on the hollow drive shaft (200) at an axial position of the hollow drive shaft (200) such that the axial height (Ah) of the aperture (210) is within the axial height (Wh) of the well, preferably within the axial span between the top of the well sidewall (120) and the well floor (118).

[0082] The pillars (212, a, b) may have a cross-section. The cross-section of the pillars (212, a, b) is a section taken across a plane (e.g., in FIGS. 4A, D-D') perpendicular to the axis of rotation (A-A') of the hollow drive shaft (200). The cross-section of the pillars (212, a, b) can be seen in FIGS. 4B and 4C. The cross-section of the pillars (212, a, b) may have a pillar outer edge (214, a), two pillar side edges (216, a, b; 218, a, b), and optionally a pillar inner edge (220, a). The pillar outer edge (214, a) is provided on the outer surface of the hollow drive shaft (200) and is typically rounded (convex) to correspond to the rounded outer surface of the hollow drive shaft (200). The pillar side edges (216, a, b; 218, a, b) are formed by the thickness of the wall of the hollow drive shaft (200) and are typically straight. The pillar inner edge (220, a) is provided on the inner surface of the hollow drive shaft (200) and may be rounded (concave) to correspond to the rounded inner surface of the hollow drive shaft (200).

[0083] The pillar (212) in the cross-section is parallel to the axis of rotation (A-A') of the hollow drive shaft (200) and may have a plane of symmetry (222) that intersects it.

[0084] The side edges (e.g., 216,b and 218b) of the same pillar (e.g., 212,b) may converge in a direction towards the center (30) of the hollow drive shaft (200). In other words, the axes that are parallel to and in contact with the pillar side edges (e.g., 216,b and 218b) intersect towards the center (30) (not the periphery 32) of the hollow drive shaft (200). They intersect at an angle of alpha (α). The side edges (e.g., 216,b and 218b) of the same pillar (e.g., 212,b) may be arranged at an angle alpha (α) to each other and formed towards the center (30) of the hollow drive shaft (200). The angle alpha (α) can be less than 180 degrees, preferably 10 to 80 degrees. When there are six apertures, alpha is preferably 60 degrees. The side edges of adjacent pillars to each other (e.g., 218,a and 216,b), i.e., the side edges of the pillars forming the aperture (210), may be parallel to each other (see Fig. 4C).

[0085] The inventors have found that when the side edges (e.g., 216,b and 218b) of the same pillar (e.g., 212,b) converge in a direction towards the center (30) of the hollow drive shaft (200) (not the periphery 32), there are fewer shortage regions on the supply-receiving surface compared to other configurations. Fig. 5A shows the flow across the entire supply-receiving surface, where the side edges of the same symmetric pillars converge in a direction towards the center of the hollow drive shaft (Fig. 5A’), and the shortage region (94) is narrow and faint. Fig. 5B shows the flow across the entire supply-receiving surface, where the side edges of the same pillar converge in a direction towards the periphery of the hollow drive shaft (Fig. 5B’), and the shortage region (94) is more and prominent. Fig. 5C shows the flow across the entire supply-receiving surface, where the pillars are asymmetric (Fig. 5C’), and the shortage region (94) is very prominent.

[0086] The geometric shape of the combination of pillars, wells, and intensively aligned feeds creates a uniform film of liquid feed on the disk surface, which leads to a well-defined and narrow atomization profile and robust particle size control. In particular, for high throughput with several melt feeds, it can be problematic to obtain the desired particle size and size distribution. The top drive, distributor, and rotatable disk configuration that aligns the disk with the delivery of the melt feed to the disk improves the uniformity of the melt feed across the spinning disk. The use of radial grooves on the feed receiving surface of the disk maintains ideal atomization by inducing ligament formation (rather than sheeting) at higher throughput. At higher flow rates, a standard disk can exhibit sheeting (inferior atomization), while a channelized disk exhibits a ligament regime (superior atomization).

[0087] The hollow drive shaft (200) may be removably attachable to the rotatable disk (110) at its lower (22) end. The hollow drive shaft (200) passes through an opening (130) in the well base end (117) of the rotatable disk (110) and is attached to the rotatable disk (110) using one or more joints. The hollow drive shaft (200) may comprise one or more sealing elements (206) (e.g., O-rings) to seal the exterior of the hollow drive shaft (200) against the feed receiving surface of the well (216). The hollow drive shaft (200) may be attached to the rotatable disk (110) using any means including one or more fixtures (e.g., bolts). The hollow drive shaft (200) may be attached to the rotatable disk (110) using a shaft plug (250) that clamps components together via a bayonet joint or flange end of the hollow drive shaft (200).

[0088] A shaft plug (250) having a plug head (254) and a plug body (252) attached to the plug head (254) may be provided. Exemplary shaft plugs are shown in FIGS. 7A - 7C and FIG. 6D. The plug body (252) can be inserted upward (22) into the lumen (202) of the hollow drive shaft (200) at the lower end (22) of the hollow drive shaft (200) and fits in a sealed manner. The plug body (252) may be provided with one or more O - rings (258) for sealing the plug body (252) against the wall of the hollow drive shaft (200). The top surface of the plug body (252) may form the well floor surface (118). In FIG. 7A, the plug body (252) lacks a plug key, and the plug key can be used where the hollow drive shaft (200) and the rotatable disk (110) lack the bayonet joint described later. In FIGS. 7B and 7C, a plug key (256) is provided for rotating the bayonet joint at the location where the aforementioned bayonet joint exists.

[0089] The plug head (254) can be attached to the rotatable disk (110) from the lower side (22). The plug head (254) may be provided with one or more passages (258) to enable attachment to the rotatable disk (110) using one of a plurality of fixtures (260) such as retaining bolts. Tightening the plug head (254) and the rotatable disk (110) with the fixture (260) clamps the plug body (252) in place and seals the well (116).

[0090] At the location where the bayonet joint described later exists, the plug head (254) also provides a grip for rotation of the plug key (254) and clamps the bayonet joints (140, 240) together.

[0091] Where the hollow drive shaft (200) has a flange end, the plug head (254) clamps the flange portion against an annular ring disposed between the upper (20) end of the flange and the lower (22) end of the rotatable disk (110), thereby attaching the hollow drive shaft (200) to the rotatable disk (110).

[0092] The bayonet joints (140, 240) may be provided at the lower ends (22) of the hollow drive shaft (200) and the rotatable disk (110), particularly within the well (116). Exemplary bayonet joints are shown in FIGS. 6A - 6C. The bayonet joint may include a set of spaced projections (240) provided on the outside of the hollow drive shaft (200) and a complementary set of spaced projections (140) provided on the inside of the well (116) towards the base end (117). Each of the spaced projections (140, 240) can slide past each other when they are aligned with the gaps between the corresponding portions of the projections (140, 240). Each of the spaced projections (140, 240) engages and prevents sliding apart when they are aligned together. In other words, the bayonet joint in the first position allows the hollow drive shaft (200) to be inserted downward (22) through an opening (130) in the rotatable disk (110), and in the second position, prevents removal of the hollow drive shaft (200) in the upward (20) direction through the opening (130) in the rotatable disk (110). The movement between the first and second positions is effected by rotation of the hollow drive shaft (200) about its axis (A - A').

[0093] The plug key (256) fixedly arranged with respect to the plug head (254) may be provided on the plug body (252) attached to the plug head. The plug key may comprise one or more protrusions (e.g., radial protrusions) from the plug body (252). The plug key (254) engages with one or more slots (242) on the hollow drive shaft (200). The one or more slots may be provided at the lower (22) edge of the hollow drive shaft (200). Engagement of the plug key (254) with the one or more slots enables the hollow drive shaft (200) to be turned relative to the rotatable disk (110) while the hollow drive shaft (200) is positioned at the well (116) opening (130). The plug key (254) enables bayonet joint engagement and disengagement.

[0094] It is understood that there may be cases where there is no bayonet joint at the lower end (22) of the hollow drive shaft (200) and the rotatable disk (110). In this case, the plug key is not required on the plug body (252).

[0095] The shaft plug (250) may be made of any suitable material that maintains its shape integrity under rotation and has other properties such as durability and corrosion resistance. Other qualities include compatibility with the liquid supply, e.g., low toxicity and chemical stability. Examples of suitable materials include stainless steel and Teflon coating materials.

[0096] The hollow drive shaft (200) may be removably attachable at its upper (20) end to a releasable mounting base (350). Exemplary releasable mounting bases are shown in FIGS. 9A-9E. At the upper end, the hollow drive shaft (200) may include an annular groove (208). The annular groove (208) engages with the releasable mounting base (350). The releasable mounting base (350) may include a spring latch (352) and a push slider (354), and the annular groove engages with the spring latch (352), thereby maintaining the fixed axial position of the hollow drive shaft (200). In FIG. 9B, the spring latch (352) is first engaged with the annular groove (208). The push slider (354) may be configured to slide perpendicular to the axis of rotation (A-A') of the hollow drive shaft and has a deployed position and a released position. The push slider (354) may be provided with a protrusion (356) configured to engage with the annular groove (208) in the deployed position. In FIG. 9B, the push slider (354) is in the released position. In FIG. 9C, the push slider (354) has been moved to the deployed position. In FIG. 9D, the push slider (354) is in the deployed position. The annular groove (208) may engage with the spring latch (352) at one circumferential portion and with the push slider (354) at another circumferential portion. The releasable mounting base (350) enables the hollow drive shaft (200) to be quickly and securely removably attached to the chassis assembly (320).

[0097] The push slider (354) may be lockable in the deployed position by one or more fasteners (e.g., screw fasteners). The one or more screw fasteners may further raise the push slider (354) and the spring latch (352) in the upward direction, where the push slider (354) and the spring latch (352) engage with a distance limiter, and the friction between the distance limiter and the push slider (354) / spring latch (352) ensures that the latter maintains its fixed position.

[0098] The push slider (354) may be guarded at the deployment position by a hub element mounting block (360) (see FIG. 9E). The hub element mounting block (360) may include a flap-shaped body that defines a receiving space (362). The push slider (354) at the deployment position and the spring latch (352) (latched onto the annular groove of the biasing hollow drive shaft (200)) in the biased state may be fitted and engaged in the receiving space (362) of the hub element mounting block (360), thereby preventing the push slider (354) from moving to the release position while the hub element mounting block (360) is in a predetermined position. The hub element mounting block (360) may be attachable to the chassis assembly (320). The releasable mounting base (350) may rotate relative to the chassis assembly (320). The releasable mounting base (350) may be provided in a (axial) rotational relationship fixed to the outer support shaft (270) (described later).

[0099] The element mounting block (320) of the hub element mounting block (360) may be utilized as a removable safety lock to prevent the push slider (356) from moving to the release position during operation. In situations where the fastener may loosen, the friction between the distance limiter and the push slider (354) is released, and the centrifugal force generated by the rotating hollow drive shaft (200) displaces it radially and pushes the slider (354) outward. The hub element mounting block (360) functions as a stop member to prevent the push slider (354) from completely releasing the hollow drive shaft (200). When the collision between the hub element mounting block (360) and the push slider (354) is repeated, an audible alert is generated to warn the operator to safely stop the rotation induced by the motor unit (300). Thus, the hub element mounting block (360) prevents damage caused by the high-speed release of the hollow drive shaft (200) and the rotatable disk (110).

[0100] The spinning disk atomizer (100) may further include a hollow outer support shaft (270) having a longitudinal shaft lumen (272) for receiving a hollow drive shaft (200). An exemplary outer support shaft (270) is shown in FIGS. 8A and 8B. The outer support shaft (270) may be non-removably coupled (except for inspection and repair) to the torque output portion of the motor unit (300). The lumen (272) of the outer support shaft (270) may be configured to fit and receive the drive shaft (200). The outer support shaft (270) may be supported on one or more bearings (e.g., roller bearings) by a part of the chassis assembly (320) (which supports the stationary part).

[0101] The chassis assembly (320) is the static part of the spinning disk atomizer (100) that supports one or more parts of the spinning disk atomizer (100). The chassis assembly (320) may be a single part or may be composed of one or more parts that are firmly and permanently attached to each other (during the service life).

[0102] The outer support shaft (270) rotates along the axis of rotation (A-A') of the hollow drive shaft (200). The rotation of the outer support shaft (270) about the axis (A-A') due to the torque output of the motor unit (300) causes the rotation of the hollow drive shaft (200). Torque is transmitted from the outer support shaft (270) to the hollow drive shaft (200) by frictional force. The outer support shaft (270) may be arranged in a fixed (axial) rotational relationship with respect to the releasable mounting base (350), and the torque path may sequentially follow the motor unit (300) - outer support shaft (270) - releasable mounting base (350) - hollow drive shaft (202).

[0103] The outer support shaft (270) may be made of any suitable material that maintains its shape integrity under rotation and has other properties such as rigidity and durability. Examples of suitable materials include brass, stainless steel, aluminum (coated or uncoated), steel (coated or uncoated), and polymeric materials.

[0104] The spinning disk atomizer (100) may further include a static (non-rotating) rigid product supply tube (232) that extends downward (22) toward the aperture (210) within the lumen (202) of the drive shaft (200). Exemplary rigid product supply tubes (232) are shown in FIGS. 8A and 8B. The rigid product supply tube (232) has an axial lumen (233) for passage of the supply to the aperture (232). The rigid product supply tube (232) may not extend axially (A-A') within the axial region occupied by the distributor (204) or the aperture (210). The rigid product supply tube (232) may terminate, for example, above the distributor (204) or the aperture (210) by a distance exceeding 1 - 25 mm. The product supply tube unit (230) may be dimensioned such that there is a gap between the drive shaft (200) and the outer surface of the product supply tube (232). The product supply tube unit (230) has a supply inlet (234). The supply inlet (234) conveys the supply to the rigid product supply tube (232).

[0105] The hub element may be provided, for example, by one or more retaining bolts, for attaching the product supply tube (230) to the chassis assembly (320). The rigid product supply tube (232) may be firmly attached to the hub element at its upper (20) end. The hub element may optionally be removably attached to the chassis assembly (320) via a hub element mounting block (360). The supply inlet (234) of the product supply tube (230) may be integrated with or supported by the hub element.

[0106] The outer support shaft (270) may be made of any suitable material having the required properties of rigidity, durability, and thermal conductivity. Examples of suitable materials include stainless steel.

[0107] The spinning disk atomizer (100) may further include a heating element tube (236) for heating at least a portion of the rigid product supply tube (232). An exemplary rigid product supply tube (232) is shown in FIGS. 8A and 8B. The heating element tube (236) includes an electric heating element and has a tubular form with a lumen into which the rigid product supply tube (232) fits. The heating element tube (236) may be flexible. The electrical cable for supplying power to the heating element tube (236) may exit through a hub element. The heating element tube (236) may extend beyond 90% of the axial length of the rigid product supply tube (232). The heating element tube (236) may be attached to the hub element at the upper end (20).

[0108] The spinning disk atomizer (100) may further include an optical camera configured to capture at least a portion of the supply receiving surface and one or more images of the supply particles being sprayed from the supply receiving surface during spraying. The optical camera may be configured to capture the peripheral portion (32) of the supply receiving surface. The optical camera may be linked to a trigger configured to trigger image capture according to the angular rotational position of the rotatable disk.

[0109] The spinning disk atomizer (100) may be attached to and disposed in a process vessel (400). In particular, the spinning disk atomizer (100) may be attached to the upper end (top) of the process vessel. An exemplary process vessel (400) is shown in FIG. 10. The process vessel has a containment wall (402) that surrounds a vessel volume (404) in which particles ejected from a rotatable disk (110) can undergo a conversion (e.g., solidification) and fall toward a base (406) where they are collected. An outlet (408) of the vessel (400) removes the formed product. The spinning disk atomizer (100) may be configured to be partially inserted into the process vessel (400), with the rotatable disk (110) embedded within the vessel volume (404) and the upper end (20) of the spinning disk atomizer (100) being outside the vessel (400) or the vessel volume (404). A system including the spinning disk atomizer (100) and the process vessel may be provided.

[0110] Figures 13A - 17B show another embodiment of the spinning disk atomizer (100) that includes an alternative connection system between a hollow shaft (200) and a disk (110). Unless otherwise described below, the structure and operation of the spinning disk atomizer in this embodiment may be the same as that described in other embodiments. For example, the geometry of the fluid path, upper disk surface, pillars, and windows may be the same as the geometry of other embodiments described herein.

[0111] Figures 13A - 13B show cross - sectional views of a hollow drive shaft (200) having a flange (500) fixed to the hollow drive shaft (200) at the lower end of the hollow drive shaft. The flange (500) can be fixed to the hollow drive shaft (200) in any suitable manner. Preferably, the flange is welded to the bottom of the hollow drive shaft. However, it should be understood that the flange can be integrally formed with the hollow drive shaft (e.g., machined from a single piece) or coupled to the shaft by any other suitable fastener.

[0112] As shown in FIGS. 13A - 13B, the disk 110 can be received on the upper surface 502 of the flange (500). In some embodiments, the upper surface 502 can be flat so as to engage the corresponding shaped lower surface of the disk (110). Alternatively, other shapes of the upper surface of the flange and the lower surface of the disk can be provided as long as the surfaces engage with each other correspondingly to enable the connections described herein.

[0113] To fix the disk (110) to the hollow drive shaft (200), the opening (504) (FIG. 16B) in the disk (100) can be placed over the hollow drive shaft (200), and the disk (110) can be lowered from the upper part of the shaft until the lower surface of the disk is seated on the upper surface (502) of the flange (500). Then, the shaft plug (506) can be positioned under the bottom surface (508) of the flange (500), and the shaft plug can be fixed to the flange and the disk (110).

[0114] As shown in FIGS. 13A - 13B, the shaft plug (506) is positioned below the flange and the disk is positioned above the flange. In some embodiments, since the connection (described in more detail below) between the upper surface of the flange and the lower surface of the disk provides sufficient sealing, there is no need to provide an additional sealing member (e.g., an O - ring) between the shaft and the disk. As shown in FIGS. 13A and 17B, for example, a sealing member (510), e.g., an O - ring, can be provided to achieve a tighter seal between the plug and the inner surface of the shaft. FIG. 13B also shows a cover 512 that can include one or more sensors (e.g., temperature sensors) as described above.

[0115] Figures 14A - 14B are cross - sectional views showing an exemplary fastener system for fixing a shaft plug (506) to a flange (500) and a disk (110). The shaft plug (506) can have one or more first openings (512) corresponding to a second opening (514) in the flange and a third opening (516) in the disk (110). One or more fasteners (518) can extend through their respective corresponding openings as shown in Figures 14A - 14B and can fix them together. For example, the fastener (518) can extend through the first opening (512), the second opening (514), and the third opening (516), and can be a screw that engages with the threaded portion of the third opening (516) and optionally with one or more of the first and second openings.

[0116] Figure 17A shows a plurality of first openings (512) in the shaft plug (506). In some embodiments, the number of corresponding openings in each structure can vary and can be one or more. Preferably, the number of openings provided in each structure is from 1 to 4, and preferably includes at least 2 or at least 3 openings.

[0117] Figures 15A - 15C show a plurality of second openings (514) in the flange (500). As discussed above, the number of second openings can vary, but three second openings are shown in the figures. As can be seen in Figures 15A - 15C and as described in other embodiments, a plurality of apertures (210) can be disposed around the circumference of the lower end of the hollow drive shaft (200) for the outflow of the molten feed. The flange (500) is located below the plurality of apertures (210).

[0118] Figures 16A - 16C show a plurality of third openings (516) in the disk (110). Three third openings are shown in these figures corresponding to the number of first and second openings in Figures 15A - 15C and 17A. The third opening can have internal threading that engages a fastener (e.g., a screw) to fix the shaft plug (506) to the flange (500) and the third opening (516) of the disk (110).

[0119] The alternative connection system shown in Figures 13A - 17B can offer several advantages over other systems. While maintaining the desirable features of the spinning disk atomizer described herein that use other connection methods, this connection method can provide improved operational safety because the disk cannot fall from the flange even if the fastener fails. Additionally, in some embodiments, the alternative connection system can allow for lighter and shorter connection components, thereby reducing potentially undesirable off - axis vibrations at higher rotational speeds.

[0120] Provided herein is the use of the spinning disk atomizer (100) described herein for a melt spray coagulation (MSC) process. Provided herein is the use of the spinning disk atomizer (100) described herein for generating multi - particles from a melt feed.

[0121] Considering numerous possible embodiments to which the principles of the disclosed invention can be applied, it should be recognized that the illustrated embodiments are merely preferred examples of the invention and should not be regarded as limiting the scope of the invention. Rather, the scope of the invention is defined by the claims. Accordingly, we claim as our invention all that falls within the scope and spirit of these claims.

Claims

Claim 1 A method for producing multi-particles, comprising: providing a molten feed comprising an active ingredient and an excipient; providing a spinning disk atomizer (100), wherein the spinning disk atomizer (100) comprises: a rotatable disk (110) having a feed receiving surface (112) and a rotation axis (B-B'), wherein the feed receiving surface defines a well (116) centered about the rotation axis (B-B'); and providing a hollow drive shaft (200) having a longitudinal shaft lumen (202) and a rotation axis (A-A'), and attached to the rotatable disk (110); inducing the molten feed through the longitudinal shaft lumen (202) onto the feed receiving surface (112) and atomizing the molten feed from the rotatable disk (110) to form solid multi-particles; wherein the rotation axes of the hollow drive shaft (A-A') and the rotatable disk (B-B') are coaxial, and a lower end portion (22) of the hollow drive shaft (200) is provided with a distributor (204) for regulating the flow of the molten feed into the well (116), and the distributor (204) and the well (116) are configured together to provide a substantially radially uniform outward flow of the molten feed across the entire feed receiving surface (112); A method wherein the number of rotatable disks (110) is one and the number of feed receiving surfaces (112) is one. Claim 2 The method according to claim 1, wherein the feed receiving surface (112) comprises a peripheral flare portion (114) that gradually slopes in a central (30) and downward (22) direction towards the well (116), the well (116) extends further downward (22) towards a well base end portion (117), and at least a portion of the feed receiving surface of the well (116) is steeper than at least a portion of the feed receiving surface of the flare portion (114). Claim 3 The flare portion (114) of the supply-receiving surface (112) includes a plurality of radial channels (160, -a, -b), each channel being a conduit for the molten supply, open on the upper (20) side, open at both the peripheral (32) and central (30) ends, and configured to direct the molten supply from the well (116) to the periphery of the flare portion (114), the method according to claim 2.

4. The rotatable disk (110) is provided on the lower side with a heating element (180) configured to adjust the temperature of the supply-receiving surface, the method according to any one of claims 1 to 3.

5. The distributor (204) includes a plurality of apertures (210) disposed around the circumference of the lower end (22) of the hollow drive shaft (200) for the outflow of the molten supply, the method according to any one of claims 1 to 4.

6. Pillars (212, a, b) are disposed between adjacent pairs of apertures (210, a, b), the pillars (212, a, b) having, in cross-section, pillar outer edges (214, a), two pillar side edges (216, a, b; 218, a, b), and optionally a pillar inner edge (220, a), the pillar side edges (216, b and 218b) of the pillar (212, b) converging in a direction towards the center (30) of the hollow drive shaft (200), the method according to claim 5.

7. The hollow drive shaft is removably attachable to the lower end of the hollow drive shaft through an opening (130) in the well base end (117) of the rotatable disk (110), the method according to claim 2 or 3.

8. The hollow drive shaft has a flange (500) at the lower end of the hollow drive shaft, the upper surface of the flange being configured to receive the lower surface of the rotatable disk, the method according to any one of claims 1 to 6.

9. A shaft plug engages the lower surface of the flange, and the rotatable disk is fixed to the flange by a plurality of fasteners extending through a plurality of first openings in the shaft plug, a plurality of second openings in the flange, and a plurality of third openings in the rotatable disk, the method according to claim 8.

10. The method according to any one of claims 1 to 9, wherein the hollow drive shaft (200) is removably attachable to a releasable mounting base (350) at an upper end portion.

11. The method according to any one of claims 1 to 10, wherein the spinning disk atomizer (100) further comprises a hollow outer support shaft (270) having a longitudinal shaft lumen (272) for receiving the hollow drive shaft (200).

12. The method according to any one of claims 1 to 11, wherein the spinning disk atomizer (100) further comprises an optical camera configured to capture during atomization one or more images of at least a part of the supply receiving surface and supply particles being atomized from the supply receiving surface (112).

13. The method according to any one of claims 1 to 12, wherein the spinning disk atomizer (100) is configured to be partially inserted into a process vessel (400) having a vessel volume (404) in which particles ejected from the rotatable disk (110) can undergo conversion, the rotatable disk (110) being embedded in the vessel volume, and an upper end portion of the spinning disk atomizer being outside the process vessel.

14. The molten feed comprises at least one active ingredient and at least one excipient, Optionally, the at least one excipient is a mixture of monoglyceryl behenate, diglyceryl behenate, and triglyceryl behenate (Compritol 888), glyceryl tristearate (Dynasan 118), hydrogenated cottonseed oil (Lubritab), hydrogenated castor oil (Kolliwax HCO), stearyl alcohol (Kolliwax SA), stearic acid and palmitic acid 50 (Kolliwax S), carnauba wax, candelilla wax, stearoyl polyoxyl glyceride (Gelucire 50 / 13), or a polyglycerol ester of a fatty acid, etc., an alkyl-containing glycerol, the method according to any one of claims 1 to 13.

15. The method according to any one of claims 1 to 14, wherein the molten feed further comprises at least one of a pore former, a swelling agent, a release modifying material, and a viscosity modifying agent.

16. The method according to any one of claims 1 to 15, wherein the multi-particles have a particle size range of 100 μm to a maximum of about 3 mm.

Images