Multi-nozzle spray dryer and method for scaling up spray drying of inhalation powders

Abstract

This invention provides a spray dryer for preparing particles for inhalation, the spray dryer comprising a multi-nozzle device including multiple single nozzles suitable for preparing inhaled powder, and wherein the drying gas flow rate is greater than about 80 kg / h. Furthermore, a method is provided for scaling up a spray drying process for preparing particles for inhalation relative to each other from a smaller-scale spray dryer to a larger-scale spray dryer, the method comprising applying a multi-nozzle device including single nozzles suitable for preparing inhaled powder in the larger-scale spray dryer, wherein the number of nozzles in the larger spray dryer is determined by the ratio of the drying gas flow rate of the larger-scale spray dryer to the drying gas flow rate of the smaller-scale spray dryer.

Description

[0001] This application is a divisional application of the invention patent application filed on March 30, 2015, with application number 201580023072.0, entitled "Multi-nozzle spray dryer, method for amplifying spray drying of powder, multi-nozzle device and application of multi-nozzle in spray dryer". Technical Field

[0002] This invention belongs to the technical field of drying methods. More specifically, this invention belongs to the technical field of spray drying of active pharmaceutical ingredients (APIs), pharmaceutical intermediates, and pharmaceutical products intended for inhalation administration. The active pharmaceutical ingredients (APIs), pharmaceutical intermediates, and pharmaceutical products can be organic compounds. Background Technology

[0003] The development of a manufacturing process for spray-dried inhaled powders involves two challenging constraints: i) the need for very small particle sizes (with an average diameter of less than 5 micrometers, typically less than 3 micrometers); and ii) the requirement that particle size should not increase during scale-up (although in reality, most spray-dried powders for oral dosage forms tend to increase in particle size during scale-up). These constraints present significant challenges during development because current nebulization systems lose efficiency when increased production volumes must be managed after scale-up. This loss of efficiency necessitates the use of larger volumes of gas for nebulization, leading to varying challenges depending on the type of nebulization system used:

[0004] a) In the case of a dual-fluid external mixing nozzle (for high consumption of atomized gas at low pressure), the flow rate of the atomized gas may increase to such an extent that the size of the drying chamber and the rest of the process flow may become too small for the process (because the atomized gas flow rate requirement can theoretically increase to 30-50% of the total gas flow rate requirement in the spray dryer).

[0005] b) For dual-fluid internal mixing nozzles (low-consumption of atomizing gas under high pressure), an increase in the atomizing gas flow rate can promote this increase in pressure drop in the nozzle, making it possible that the pressure of the gas supply line may often require very complex and expensive upgrades.

[0006] While these challenges can be overcome through engineering upgrades to the spray dryer process, more difficult challenges remain because droplet sizes may still be outside the expected range after scale-up. It is not uncommon for nozzles used in smaller-scale applications to be unsuitable for larger-scale applications due to exceeding their operating range. Furthermore, selecting new nozzles is often complex, time-consuming, and expensive, requiring extensive testing. Moreover, there is no guarantee that such process development activities will lead to the successful identification of suitable candidate nozzles, as there are physical limitations to atomizing high-flow-rate liquids into small droplets within the target suction range. Therefore, current methods for controlling particle size within the suction range after scale-up are limited by nozzle design (external or internal mixing, and nozzle model) and atomizing gas flow rate. Different options for controlling particle size could involve reducing the solids concentration in the feed mixture, but this is not recommended because it adversely affects process throughput and cycle time, ultimately impacting its feasibility from a process economic perspective.

[0007] The concept of using multi-nozzle atomization to combine high feed capacity and fine atomization with pressure nozzles and dual-fluid nozzles is known in the art [Green, D; Perry, R. "Perry's chemical engineers' handbook" (2008)]. Spray drying literature includes further examples of the use of multi-nozzle arrangements. For example, US 2002 / 0007869 discloses a multi-nozzle electro-spraying method for producing nanoparticles in high-volume production.

[0008] WO 03 / 090893 discloses a process that uses a multi-nozzle device to promote powder agglomeration by reintroducing fine powder near the main spray plume, wherein there is negligible product deposit on the wall.

[0009] US 2007 / 0148325 discloses a granulation method for producing fine waterborne particles using a number of nozzles equivalent to those of conventional designs.

[0010] The paper by Turton et al. [Turton, R; Cheng, X. "The scale-up of spray coating processes for granular solid and tablets"; Powder Technology 150 (2005) 78-85] discloses a spray coating process for granular solids and tablets that utilizes multiple nozzles to cover a wide area.

[0011] US 8524279 discloses a method primarily for use with inhaled products, reporting the use of a multi-nozzle atomizer comprising a central gas nozzle and a plurality of atomizing nozzles surrounding such central gas nozzle. The central gas nozzle is used to minimize spray plume interactions and control the final powder characteristics, while the feed mixture is atomized in the atomizing nozzles.

[0012] While most of these examples disclose multi-nozzle systems aimed at increasing process throughput and, in some cases, producing particles within an inhalable range, a need remains in inhalation spray drying for a simple means of controlling particle size after scale-up. The invention disclosed herein overcomes the disadvantages identified in the prior art by using multiple off-the-shelf nozzles with low throughput. The ratio between liquid and atomizing gas flow rates can be kept constant across the nozzle dryer scale in each nozzle, resulting in droplets of similar size across the scale and eliminating the challenges encountered during scale-up as described previously. This allows for direct process scale-up because the operating conditions used at smaller scales can be directly applied to larger-scale spray dryers, since each nozzle across the scale is geometrically identical. In this way, the single scale-up action to be performed would be: to increase the number of nozzles to be used proportionally to the scale of the spray drying unit. Therefore, the ideas disclosed herein include two innovative concepts that overcome the limitations present in the prior art and accelerate process development:

[0013] 1) The ability to generate particles within an aspirable range (i.e., characterized by a volume distribution with an average geometric size of less than 5 micrometers), regardless of the required production volume; this key performance criterion is not disclosed in currently available high-volume multi-nozzle systems in the art, and

[0014] 2) Using the same nozzles, regardless of scale (only changing the number of nozzles, not the model and type), the target particle size range can be achieved. When it is necessary to increase production beyond a certain range, different variants / models of currently available multi-nozzle systems can be considered.

[0015] Therefore, conventional drug spray drying methods for producing inhaled powders are limited in meeting key quality attributes (i.e., regarding particle size distribution) when higher production volumes are required; the proposed concept is expected to overcome this limitation and further accelerate process development. Summary of the Invention

[0016] According to one aspect of the invention, a spray dryer for preparing particles for inhalation is provided, the spray dryer comprising a multi-nozzle device including a plurality of single nozzles suitable for preparing inhaled powder, wherein the drying gas flow rate of the spray dryer is greater than about 80 kg / h.

[0017] According to another aspect of the invention, a method is provided for scaling up a spray drying process for preparing particles for inhalation from a smaller-scale spray dryer to a larger-scale spray dryer relative to each other, the method comprising applying a multi-nozzle arrangement comprising a single nozzle suitable for preparing inhaled powder in the larger-scale spray dryer, wherein the smaller-scale spray dryer comprises a number of m nozzles, while the larger-scale spray dryer comprises a number of n nozzles, and wherein n is determined by the ratio of the drying gas flow rate of the larger-scale spray dryer to the drying gas flow rate of the smaller-scale spray dryer. The drying gas flow rate may be referred to as the nominal drying gas flow rate.

[0018] According to another aspect of the invention, a multi-nozzle device for use in a spray dryer is provided, the multi-nozzle device being manufactured according to the method described above, wherein the multi-nozzle device comprises a plurality of single nozzles suitable for preparing inhaled powder.

[0019] According to another aspect of the invention, the application of multiple single nozzles suitable for preparing inhaled powders in a spray dryer is provided, wherein the drying gas flow rate of the spray dryer is greater than about 80 kg / h.

[0020] The nozzle suitable for preparing particles for inhalation can be used to prepare particles for inhalation containing an active pharmaceutical ingredient, a pharmaceutical intermediate, or a pharmaceutical product—optionally, an organic active pharmaceutical ingredient, a pharmaceutical intermediate, or a pharmaceutical product. The particles for inhalation have an average particle size of less than about 5 micrometers, preferably less than about 3 micrometers.

[0021] In the method of the present invention, n can be equal to the ratio of the drying gas flow rate of the larger-scale spray dryer to the drying gas flow rate of the smaller-scale spray dryer, rounded up or down to the nearest integer. Furthermore, in the method of the present invention, m is between 1 and 4, optionally m = 1, 2, or 3, and n is between 2 and 16, preferably n = 2, 3, 4, 5, 8, 10, or 16. In fact, the number of single nozzles used in the spray dryer, multi-nozzle device, and application of the present invention can also be between 2 and 16, preferably n = 2, 3, 4, 5, 8, 10, or 16.

[0022] Smaller-scale spray dryers can have a drying gas flow rate from about 20 kg / h to about 120 kg / h, preferably from about 40 kg / h to about 80 kg / h, and most preferably about 40 kg / h. According to the spray dryer used in the first aspect of the invention, larger spray dryers can have a drying gas flow rate greater than about 80 kg / h. Optionally, the drying gas flow rate of the spray dryer can be greater than about 120 kg / h, or greater than about 150 kg / h. The drying gas flow rate of the spray dryer can be about 360 kg / h, about 650 kg / h, or about 1250 kg / h.

[0023] The single nozzle used in the method and apparatus of the present invention can be a dual-fluid external or internal mixing nozzle, preferably a dual-fluid external mixing nozzle. The liquid feed stream and the atomizing gas stream can be homogeneously distributed among the n single nozzles.

[0024] In some embodiments of the method of the present invention, the drying gas flow rate of the smaller-scale spray dryer is about 80 kg / h, and the drying gas flow rate of the larger spray dryer is about 360 kg / h, with m = 1 and n = 4. Alternatively, the drying gas flow rate of the larger spray dryer is about 650 kg / h, with m = 1 and n = 8.

[0025] This invention incorporates the innovative concept of using multiple nozzles simultaneously. Preferably, all nozzles are of the same type, and they can be selected from any readily available, commercially available nozzles typically used on small-sized spray dryers (e.g., size 1 (SD1), where a nominal dry gas flow rate of approximately 80 kg / h corresponds to this size). The invention ensures that the particle size distribution obtained at the SD1 scale by a single specific nozzle is identical to the particle size distribution obtained at larger-scale (e.g., size 2 (SD2) or size 3 (SD3) scales, where a nominal dry gas flow rate of approximately 360 kg / h or approximately 650 kg / h corresponds to size 2 or size 3 respectively) without significant development effort (i.e., without changing the nozzle type but only through an increase in the number of nozzles used).

[0026] "Small spray dryer" or "small-scale spray dryer" refers to a spray dryer designed for typical use in laboratory settings or pilot-scale applications, with a typical nominal gas flow rate of 20 to 120 kg / h, preferably 40 to 80 kg / h. Examples of such spray dryers include, but are not limited to, the BUCHI Model B-290 with a typical nominal gas flow rate of about 20 to 40 kg / h, the Niro Mobile Minor with a typical nominal gas flow rate of about 40 to 120 kg / h, and SPX's Anhydro spray dryer with a typical nominal gas flow rate of about 35 to 150 kg / h.

[0027] "Large spray dryer" refers to a spray dryer designed for use in industrial settings (even if the unit is a small production unit) with a typical nominal flow gas rate >80 kg / h. Examples of such spray dryers include, but are not limited to, the Niro spray dryers of sizes 2, 3, and 4 (or upgraded units of size 1 prepared for handling larger drying gas flow rates) with typical nominal gas flow rates of about 360, 650, and 1250 kg / h, and SPX's Anhydro spray dryer with typical nominal gas flow rates of about 400 to 2500 kg / h. Attached Figure Description

[0028] Figure 1 This is a representation of a multi-nozzle atomizer intended for use in a spray dryer of the SD2 scale (external view and liquid circuit view).

[0029] Figure 2 This is a side view of the spray plume from a multi-nozzle atomizer in an SD2-scale spray dryer.

[0030] Figure 3 The results of a computational fluid dynamics (CFD) simulation close to the nozzle are shown.

[0031] Figure 4 This is a top view of the spray plume from a multi-nozzle atomizer in an SD2-scale spray dryer.

[0032] Figure 5 The results of a computational fluid dynamics (CFD) simulation above the drying chamber are shown.

[0033] Figure 6 The multi-nozzle system used in laboratory experiments is shown:

[0034] 1- Solution Feed

[0035] 2-Gas Supply

[0036] Figure 7 and Figure 8 This shows an optical microscope image of particles obtained in a laboratory experiment.

[0037] Figure 9 The images show scanning electron microscope images of particles obtained in the SD1 unit experiment (left side - multi-nozzle atomizer operated with 2 nozzles, right side - multi-nozzle atomizer operated with 1 nozzle).

[0038] Figure 10 The particle size distribution of the particles obtained in the SD1 unit experiment is shown (left side - multi-nozzle atomizer operated with 2 nozzles, right side - multi-nozzle atomizer operated with 1 nozzle).

[0039] Figure 11 Scanning electron microscope images of particles obtained in commercial-scale spray dryer experiments are shown. Detailed Implementation

[0040] Referring now to the invention in more detail, the spray dryers, methods, apparatus, and applications of the present invention utilize multiple single nozzles of the type used in smaller-scale spray dryers for preparing inhaled powder to match the drying gas flow rate of larger spray dryers. For example, for a single nozzle of a typical spray dryer (SD1) with a gas flow rate of about 80 kg / h, four nozzles can be used for a spray dryer (SD2) with a drying gas flow rate of about 360 kg / h, or eight nozzles can be used for a spray dryer (SD3) with a drying gas flow rate of about 650 kg / h. Figure 1 A possible configuration of the apparatus for generating larger SD2 scales is shown.

[0041] This means that the number of single nozzles used in a larger-scale spray dryer is determined by the ratio of the drying gas flow rate of the larger-scale spray dryer to that of the smaller-scale spray dryer.

[0042] More specifically, the present invention provides an apparatus whose dimensions allow for the positioning of n single nozzles within a spray drying chamber, and whose dimensions are the same as or similar to those of conventional off-the-shelf atomizing systems, thereby avoiding expensive retrofits of spray dryers or complex assembly processes prone to human error – see [link to related document]. Figure 1 and Figure 2 Therefore, the device of the present invention can be used in existing manufacturing plants, replacing existing atomization systems.

[0043] Due to the symmetrical geometry of the device, the distribution of the liquid feed and atomizing gas flow is as follows: Figure 1 The n single nozzles shown should be uniform. This makes it possible to produce a set of identical sprays and ensures that the droplet size is the same from one single nozzle to another, and therefore does not affect the final particle size distribution of the obtained powder.

[0044] The shape, size, and positioning of the device do not significantly affect, for example Figure 3 The drying gas flow pattern within the spray drying chamber shown avoids any disruption to the gas distribution and all the typical operational problems that arise from it. Furthermore, the spray angle of each individual nozzle (relative to each other) can be arranged such that significant spray overlap does not occur (which can lead to droplet coalescence and thus an increase in particle size) – see [link to relevant documentation]. Figure 4 For example, in Figure 5 As shown, the spray angle of each individual nozzle (relative to the chamber) can be arranged such that the spray penetration will not cause droplets (or wet particles) to impact the walls of the equipment (which can lead to production loss and product degradation). Figure 5It is also shown that the spray shape does not need to be affected, thus avoiding secondary atomization (which can lead to droplet coalescence and splitting, accompanied by subsequent effects on the final particle size). Furthermore, those skilled in the art can easily design other nozzle configurations. For example, those skilled in the art can arrange a set of four nozzles to guide the spray from a single point in four different directions, or can design two sets of two nozzles to guide the spray from two different points in two different directions.

[0045] The advantages of this invention include, but are not limited to, the simplification (to a large extent) of scaling up the inhalation of powder in spray drying, because it involves no development (or minimal development) since operating conditions from smaller scales can be kept approximately constant. Essentially, the single scaling-up action required would be: increasing the number of nozzles used. Another advantage of this invention is that it can be used as an enabling technology because there is currently no scale-up method in the art for inhaling powder when moving to larger-scale spray dryers (e.g., SD2 or larger). Similarly, the lack of suitable nozzles for inhaling powder is known because nozzle manufacturers do not guarantee the target particle size, reducing the applicability of current technology.

[0046] To provide a more complete understanding of the present invention, the following embodiments are included by way of illustration only.

[0047] Example

[0048] Example 1

[0049] This example considers a scaled-down version of the invention (such as...) Figure 6 (As shown) to demonstrate proof of concept.

[0050] A feed mixture (total solids concentration approximately 2.5% w / w) was prepared by dissolving 1.2 g of lysine and 4.8 g of trehalose in 234 g of water. This excipient system is known to produce amorphous powders, where particle size is highly sensitive to variations in atomization conditions. Therefore, this excipient system is ideal for the current proof-of-concept.

[0051] The feed solution was processed using a laboratory-scale spray dryer (BUCHI model B-290 Advanced). In Test #1, the BUCHI unit was equipped with a single two-fluid nozzle, with a nozzle cap and diameter of 1.4 mm and 0.7 mm, respectively. In Test #2, the BUCHI unit was equipped with a pair of two-fluid nozzles ( Figure 6 Each nozzle has a nozzle cap of 1.4 and 0.7 mm and a diameter (i.e., the same as the nozzle of test #1).

[0052] During the first test, the flow rate of the solution supplied to a single nozzle was approximately 3 g / min, and the flow rate of the atomizing gas supplied to a single nozzle was approximately 9 g / min (equivalent to 30 mm in the rotor flowmeter).

[0053] During the second test, the flow rate of the solution supplied to the device (a pair of nozzles) was 6 g / min, and the flow rate of the atomizing gas supplied to the device was approximately 20 g / min (equivalent to 60 mm in the rotor flowmeter).

[0054] Based on the above conditions, each nozzle was used (independent of the test) under similar atomization conditions (atomization ratio = F_atomiz / F_feed (F_atomiz / F_feed) is approximately 3).

[0055] The applied heat distribution (i.e., the relationship between T_in and T_out) was similar in both tests (because significantly different heat distributions could affect particle formation). The small difference stemmed from the fact that in test #2, twice the amount of solvent was evaporated at the same dry gas flow rate, thus requiring a slightly higher inlet temperature (in order to achieve thermodynamic equilibrium).

[0056]

[0057] Note: F_drying - drying gas flow rate; F_feed - solution flow rate; R_atomization - atomization ratio; T_in - inlet drying temperature; T_out - outlet drying temperature.

[0058] As from Figure 7 (Single nozzle) and Figure 8 (A pair of nozzles) It can be seen that when comparing the powder obtained via “single nozzle” and “a pair of nozzles”, the particle size distribution and morphology are the same, indicating the success of the current proof of concept and demonstrating the feasibility of the multi-nozzle concept in this way, which can achieve all the previous purposes and objectives.

[0059] Example 2

[0060] This example considers the multi-nozzle atomizer of the present invention utilized in the SD1 unit. Figure 1 The example shown demonstrates a proof of concept.

[0061] A feed mixture (total solids concentration of approximately 3.5% w / w) was prepared by dissolving 1.225 kg of leucine and 4.9 kg of trehalose in 33.8 kg of ethanol and 135.1 kg of water.

[0062] The SD1 unit, operating at a nominal dry gas flow rate of approximately 110 kg / h, was used to process the aforementioned feed solution. In Test #1, the SD1 unit was equipped with a multi-nozzle atomizer operating with 2 Niro ETFN nozzles (orifice = 0.5 mm) and a special housing for uniform liquid and gas distribution. In Test #2, the SD1 unit was equipped with a multi-nozzle atomizer operating with 1 Niro ETFN nozzle (orifice = 0.5 mm).

[0063] During the first test, the flow rate of the solution supplied to the two nozzles of the multi-nozzle atomizer was approximately 2 kg / h, and the flow rate of the atomizing gas supplied to the device was approximately 20 kg / h.

[0064] During the second test, the flow rate of the solution supplied to a single nozzle of the multi-nozzle atomizer was 1 kg / h, and the flow rate of the atomizing gas supplied to the device was approximately 10 kg / h.

[0065] Based on the above conditions, each nozzle was used (independent of the test) under similar atomization conditions (atomization ratio = F_atomization / F_feed is approximately 10).

[0066] The difference in the heat distribution applied in the two tests (i.e., the relationship between T_in and T_out) stems from the fact that in test #1, twice the amount of solvent evaporates at the same dry gas flow rate, thus requiring a higher inlet temperature (in order to achieve thermodynamic equilibrium).

[0067]

[0068] As from Figure 9 and Figure 10 As can be seen, when comparing powders, the morphology and particle size distribution are the same, indicating the success of the current proof of concept and demonstrating the feasibility of the multi-nozzle concept in this way, which can achieve all previous purposes and objectives.

[0069] Example 3

[0070] This example is illustrated by considering the multi-nozzle atomizer of the present invention used in commercial-scale spray dryer units. Figure 1 The example shown demonstrates a proof-of-concept.

[0071] A feed mixture (total solids concentration of approximately 3.5% w / w) was prepared by dissolving 1.225 kg of leucine and 4.9 kg of trehalose in 33.8 kg of ethanol and 135.1 kg of water.

[0072] The above feed solution was processed using the SD2, which operates at a nominal dry gas flow rate of approximately 360 kg / h. The SD2 unit is equipped with a special housing for a multi-nozzle atomizer operating with 4 NIRO ETFN nozzles (orifice = 0.5 mm) to ensure uniform liquid and gas distribution.

[0073] During the test, the flow rate of the solution supplied to the multi-nozzle atomizer was approximately 8 kg / h, and the flow rate of the atomizing gas supplied to the device was approximately 20 g / h.

[0074]

[0075] As from Figure 11 (The multi-nozzle atomizer with 4 nozzles) shows that the particle size distribution and morphology are the same as the powder generated in Example 2, indicating the success of the current proof of concept and demonstrating the feasibility of the multi-nozzle concept in this way, which can achieve all the previous purposes and objectives.

[0076] While the foregoing written description of the invention enables those skilled in the art to make and use the invention as currently considered the best implementation thereof, those skilled in the art will understand and appreciate the existence of variations, combinations, and equivalents of the specific embodiments, methods, and examples of the invention herein. Therefore, the invention should not be limited to the foregoing embodiments, methods, and examples, but rather to all embodiments and methods within the scope and spirit of the claimed invention.

Claims

1. A method for scaling up a spray drying process for preparing particles for inhalation from a smaller-scale spray dryer to a larger-scale spray dryer relative to each other, wherein, The particle size distribution of particles prepared by a larger-scale spray dryer is the same as that of particles prepared by a smaller-scale spray dryer. The method includes applying a multi-nozzle device in the larger-scale spray dryer, comprising a single nozzle suitable for preparing inhaled powder, wherein the smaller-scale spray dryer comprises m nozzles and the larger-scale spray dryer comprises n nozzles. Where n is determined by scaling m by a ratio that is the ratio of the drying gas flow rate of the larger-scale spray dryer to the drying gas flow rate of the smaller-scale spray dryer, the ratio being rounded up or down to the nearest integer. The n nozzles are configured to prevent significant jet overlap during use, thus avoiding droplet coalescence and consequently preventing particle size increase; and all individual nozzles are of the same type. The liquid feed stream and atomizing gas stream are uniformly distributed among the n nozzles. The spray angle of each individual nozzle relative to the chamber is arranged so that the spray penetration will not cause droplets or wet particles to impact the walls of the equipment, in order to avoid production loss and product deterioration.

2. The method of claim 1, wherein the ratio of the drying gas flow rate of the larger-scale spray dryer to the drying gas flow rate of the smaller-scale spray dryer is rounded down to an integer.

3. The method according to claim 1 or 2, wherein the drying gas flow rate of the smaller-scale spray dryer is from 20 kg / h to 120 kg / h.

4. The method according to claim 1 or 2, wherein the drying gas flow rate of the smaller-scale spray dryer is from 40 kg / h to 80 kg / h.

5. The method according to claim 1 or 2, wherein the drying gas flow rate of the smaller-scale spray dryer is 40 kg / h.

6. The method according to claim 1 or 2, wherein the drying gas flow rate of the larger spray dryer is greater than 80 kg / h, greater than 120 kg / h, or greater than 150 kg / h.

7. The method according to claim 1 or 2, wherein the drying gas flow rate of the larger spray dryer is 360 kg / h, 650 kg / h, or 1250 kg / h.

8. The method according to claim 1 or 2, wherein m is between 1 and 4.

9. The method according to claim 1 or 2, wherein m = 1, 2 or 3.

10. The method according to claim 1 or 2, wherein n is between 2 and 16.

11. The method according to claim 1 or 2, wherein n = 2 or 3 or 4 or 5 or 8 or 10 or 16.

12. The method according to claim 1 or 2, wherein the drying gas flow rate of the smaller spray dryer is 80 kg / h, and the drying gas flow rate of the larger spray dryer is 360 kg / h, and m = 1 and n = 4, or the drying gas flow rate of the larger spray dryer is 650 kg / h, and m = 1 and n = 8.

13. The method according to claim 1 or 2, wherein the particles for inhalation comprise an active pharmaceutical ingredient, a pharmaceutical intermediate, or a pharmaceutical product.

14. The method according to claim 1 or 2, wherein the particles for inhalation comprise an organic active pharmaceutical ingredient, a pharmaceutical intermediate, or a pharmaceutical product.

15. The method according to claim 1 or 2, wherein the particles have an average particle size of less than 5 micrometers.

16. The method according to claim 1 or 2, wherein the particles have an average particle size of less than 3 micrometers.

17. The method according to claim 1 or 2, wherein the single nozzle is a dual-fluid external or internal mixing nozzle.

18. The method according to claim 1 or 2, wherein the single nozzle is a dual-fluid external mixing nozzle.

19. The method according to claim 1 or 2, wherein the liquid feed stream and the atomizing gas stream are homogeneously distributed between the single nozzle.

20. The method according to claim 1 or 2, further comprising: The number of nozzles used in the larger-scale spray dryer is increased by the ratio of the drying gas flow rate of the larger-scale spray dryer to the drying gas flow rate of the smaller-scale spray dryer, the ratio being rounded up or down to an integer.

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