WO2025133729A1

WO2025133729A1 - Process for preparation of glp-1 peptides and dual glp-1/gip peptides having controlled particle size

Info

Publication number: WO2025133729A1
Application number: PCT/IB2024/058419
Authority: WO
Inventors: Offir BAREL; Abed Masarwa; Oshrat FRENKEL
Original assignee: Assia Chemical Industries Ltd.
Priority date: 2023-12-18
Filing date: 2024-08-29
Publication date: 2025-06-26

Abstract

The present disclosure relates to processes for preparation of a peptide powder, and the preparation of peptide particles, for example a GLP-1 peptide such as Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide, and/or a salt thereof; particularly Liraglutide and Semaglutide and salts thereof; preferably Semaglutide and salts thereof, and more preferably Semaglutide or a Dual GIP/GLP-1 peptide such as Tirzepatide. More specifically, the disclosure relates to a process comprising spray drying of a solution comprising the peptide using an ultrasonic nozzle. The disclosure further relates to GLP-1 peptides, particularly wherein the GLP-1 peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide, and/or a salt thereof; preferably selected from Liraglutide and Semaglutide, and a salt thereof; and more preferably Semaglutide and a salt thereof, and most preferably Semaglutide, obtainable by said process and its use in medicine and cosmetic treatment.

Description

PROCESS FOR PREPARATION OF GLP-1 PEPTIDES AND DUAL GLP-l/GIP PEPTIDES HAVING CONTROLLED PARTICLE SIZE

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of, and priority to, U.S. Provisional Patent Application Serial No. 63/611,267 filed on December 18, 2023. The entire contents of the foregoing application are incorporated by reference herein.

FIELD OF THE DISCLOSURE

[0002] The present disclosure relates to processes for preparation of a peptide powder, and the preparation of peptide particles, for example a GLP-1 peptide such as Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide, and/or a salt thereof; particularly Liraglutide and Semaglutide and salts thereof; preferably Semaglutide and salts thereof, and more preferably Semaglutide or a Dual GIP/GLP-1 peptide such as Tirzepatide. More specifically, the disclosure relates to a process comprising spray drying of a solution comprising the peptide using an ultrasonic nozzle. The disclosure further relates to GLP-1 peptides, particularly wherein the GLP-1 peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide, and/or a salt thereof; preferably selected from Liraglutide and Semaglutide, and a salt thereof; and more preferably Semaglutide and a salt thereof, and most preferably Semaglutide, obtainable by said process and its use in medicine and cosmetic treatment.

BACKGROUND OF THE DISCLOSURE

[0003] Glucagon-like peptide 1 (GLP-1) encompasses peptides such as Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide, represent a class of drugs that can be used to treat type 2 diabetes. These GLP-1 agonists improve blood sugar control and may also be used for the treatment of overweight or obesity since they can assist with weight loss through appetite suppression. GLP-1 agonists can also be used in cosmetic weight loss in non-overweight non- obese subjects. Dual GIP/GLP-1 peptides such as Tirzepatide, represent a class of drugs that can be used to treat type 2 diabetes and Obesity.

[0004] Synthetic peptide drugs such as GLP-1 peptides Dual GIP/GLP-1 peptides are typically manufactured using multistep solid phase synthesis. The resulting peptides are typically purified by HPLC, and the products isolated primarily by lyophilization or by spray drying in order to remove the chromatography solvents and buffers.

[0005] Lyophilization and spray drying are well-known processes used for the solidification of unstable or biopharmaceutical formulations. However, the products (lyophilizates) produced by lyophilization are generally characterized by low bulk density. Lyophilized particles of an active pharmaceutical ingredient (“API”) having low bulk density may display poor or limited flowability, which may ultimately result in difficulties in milling processes, as well as difficulties in blending during the manufacture of a pharmaceutical composition. In the case of peptides such as GLP-1 peptides or dual GIP/GLP-1 peptides, where the drugs are typically administered in relatively low doses, content uniformity in a solid dosage form is of particular importance. Content uniformity is particularly difficult to control in the case of poorly flowable substances and/or substances having unsuitable particle size distribution. However, preparation of a solid dosage form particularly of peptides such as GLP-1 peptides or dual GIP/GLP-1 peptides generally requires an API having a specific particle size distribution (“PSD”) and other characteristics that cannot be controlled by lyophilization. Thus, prior art lyophilization processes which are typically used in the preparation of peptides such as GLP-1 peptides or dual GIP/GLP-1 peptides result in the production of fluffy and non-fl owable materials. The lyophilized products typically do not have the required small particle sizes for the final dosage form in the case of low dose drugs, such as the GLP-1 peptides and are not good candidates for particle size reduction steps such as milling or sieving.

[0006] The problems associated with lyophilized materials having poor flowability have generally been difficult to resolve. Indeed, the difficulties of processing prior art lyophilizates, which are typically fluffy and non-flowable materials are well known and investigators have been prompted to seek alternatives to the freeze drying process. This problem is especially acute when the lyophilizates are peptides. A common technology for obtaining powders of, e.g. peptides, is through spray drying processes. However, whilst spray drying is a useful method to form a product which does not suffer from the above-discussed issues of fluffy or non-flowable materials commonly obtained from lyophilization, there are other problems associated with spray drying, particularly in the production of, e.g. peptides. In particular, spray drying technology requires preparation of a feed solution comprising the API and exposure of the API-containing feed solution to heat, which can be especially detrimental for the API purity over time (for example due to decomposition), especially in large scale during spray drying of drug substances. Despite the high temperature of the drying gas, spray drying is suitable for heat sensitive peptides because of the cooling effect of the evaporating solvent which keeps the droplet temperature relatively low and the high temperature exposure time short. Such spray drying processes are disclosed in International Publications Nos. WO 2020/127950, WO 2020/187712 and WO 2021/043803 that disclose a bi-fluid spray drying processes using a liquid/gas atomizing nozzle. However, a major drawback of the spray drying process is the low yield obtained due to material loss, which is particularly undesirable in the cases of high cost APIs such as peptides. For at least these reasons, there is still a need for additional processes for preparation of APIs such as peptides and particular GLP-1 peptides or dual GIP/GLP-1 peptides having controlled PSDs that will be suitable in large scale production.

SUMMARY OF THE DISCLOSURE

[0007] Peptides may undergo structural changes such as cleavage when processed using ultrasonic waves. Ultrasonic waves can also generate localized heating due to energy absorption, which may also affect peptide stability, particularly if the temperature rises significantly. For this reason, ultrasonic atomization is typically used in the food industry such as for encapsulation and food hygiene (enzyme and microbial inactivation). Moreover, known applications in the pharmaceutical industry are generally limited to encapsulation of drugs and/or preparation of solid dispersions that include stabilizing agents rather than in the production of the pure API (e.g. by spray drying). Typically, bi-fluid nozzles are employed in the production of therapeutic peptide APIs by spray drying. Moreover, spray drying of peptide-based products typically includes the use of stabilizers in order to minimize peptide denaturation during production.

[0008] It has unexpectedly been found that using ultrasonic nozzle in the spray drying process can be successfully used to prepare peptide products, particularly peptide drugs. The process advantageously provides peptide particles of high purity, acceptable levels of residual solvents (according to ICH guidelines) in high yields and also having controlled particle size distribution and narrow span. The process is robust and advantageously produces peptide particles having larger size spheres compared to the product obtained in processes wherein the bi-fluid atomizing nozzles is used. The process disclosed in any aspect or embodiment herein enables the production of these sensitive active agents in unexpectedly high yields, low moisture content and with a low content of residual solvents. Moreover, the use of an ultrasonic nozzle in the spray drying process as described in the processes of the present disclosure yields a product having a lower content of fine particles and thus mechanical loss of material is avoided or minimized, thereby providing a dramatically better yield than the known processes using a bi-fluid nozzle. Further, the products obtained from prior art spray drying processes using a bi-fluid nozzle typically contain high residual solvent and/or high residual moisture, and hence a secondary drying step, such as vacuum drying, is often required to further reduce residual solvent and/or residual moisture levels, particularly the former in order for the drug product to comply with ICH guidelines for residual solvent levels. The processes of the present disclosure can provide highly pure products having low level of residual solvent and lower water content compared to the previously disclosed processes that use a bi-fluid nozzle. The process enables the spray drying of peptides without the need to include stabilizers, and advantageously the products are obtainable in surprisingly high yield. Moreover, the disclosed process enables the production of a spray dried peptide with sufficiently low residual solvent and moisture content without the requirement to carry out a secondary drying step.

[0009] The present disclosure relates to a process for spray drying a feed solution comprising a peptide (preferably a GLP-1 or dual GIP/GLP-1 peptide), and one or more solvents, wherein the process comprises introducing the feed solution comprising one or more solvents and a peptide, into a spray dryer equipped with an ultrasonic nozzle. The ultrasonic nozzle atomizes the feed solution to form a spray.

[0010] According to any aspect or embodiment of the disclosure, the feed solution may consist essentially of, or consist of, the peptide and the one or more solvents. For example, feed solutions may consist essentially of the peptide, and salts or other impurities that may be present in the peptide during its manufacture or purification. Typically, impurities such as salts or peptide impurities may be present in the peptide. Suitable feed solutions may include solutions obtained as an eluant from chromatographic purification of the peptide or following isolation of the peptide from the eluant. The feed solutions according to any aspect or embodiment of the present disclosure do not contain added pharmaceutical excipients. The peptide used in feed solutions employed according to any aspect or embodiment of the present disclosure can be obtained by any suitable process, for example, either directly from the chromatographic purification of the peptide (e.g. as the eluted fractions), or may be obtained following isolation of the solid peptide (typically having a purity of about 80 to about 100%, or about 85% to about 100%, or about 90% to about 100%, or about 95% to about 100%) from a chromatographic purification process. Preferably, according to any aspect or embodiment of the disclosure, peptide is obtained following isolation of the solid peptide (typically having a purity of about 80 to about 100%, or about 85% to about 100%, or about 90% to about 100%, or about 95% to about 100%) from a chromatographic purification process.

[0011] According to any aspect or embodiment of the present disclosure, the feed solution may be prepared by combining the peptide (which may typically have a purity of about 80 to about 100%, or about 85% to about 100%, or about 90% to about 100%, or about 95% to about 100%) with the one or more solvents. The feed solution may contain small amounts of salt if the pH is required to be adjusted. According to any aspect or embodiment, the feed solution preferably does not comprise added pharmaceutical excipients.

[0012] The present disclosure relates to a process for spray drying a feed solution comprising a peptide, preferably wherein the peptide is a GLP-1 peptide, wherein the process comprises introducing the feed solution comprising the peptide, preferably the GLP-1 peptide or dual GIP/GLP-1 peptide in a solvent into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate, wherein the ultrasonic nozzle power is in the range of 1-50 W.

[0013] In any aspect or embodiment, the feed solution comprises a peptide, preferably a GLP-1 peptide, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide or Semaglutide, or a salt thereof; preferably selected from Liraglutide and Semaglutide, and a salt thereof; more preferably Semaglutide, or a salt thereof; and most preferably Semaglutide or dual GIP/GLP-1 peptide, preferably Tirzepatide, and one or more solvents; wherein the concentration (w/w) of the peptide in the solution is not less than about 0.5% particularly the concentration of the peptide may range from: about 1% (w/w) to about 50% w/w), about 1.5% (w/w) to about 20% (w/w), about 2% to about 15% (w/w), or more particularly, the concentration of the peptide is from about 2 % (w/w) to about 6% (w/w); and wherein the solution has a pH of about 5 to about 10, preferably to about 6 to about 9, and more preferably about 7 to about 8.5.

[0014] According to any aspect or embodiment of the disclosure, the peptide is Semaglutide, or a salt thereof, preferably Semaglutide, and the concentration of Semaglutide in the feed solution is: about 1 % to about 25%, about 1.5% to about 25%, about 1.5% w/w to about 22% w/w, about 1 % to about 20%, about 1% (w/w) to about 15% w/w), or about 1.5% (w/w) to about 10% (w/w), or about 2% (w/w) to about 20% w/w). In embodiments, the feed solution comprises Semaglutide, and one or more solvents; wherein the concentration (w/w) of the peptide in the solution is not less than about 0.5 % particularly the concentration of the peptide may range from: about 1% (w/w) to about 15% w/w), about 1.5% (w/w) to about 10% (w/w), about 2% to about 8% (w/w), or more particularly, the concentration of the peptide is from about 2 % (w/w) to about 6% (w/w); and wherein the solution has a pH of about 5 to about 10, preferably to about 6 to about 9, and more preferably about 7 to about 8, about 7.1 to about 7.5 or about 7.3. Alternatively, according to any embodiment where the peptide is Semaglutide, the pH of the feed solution is about 7.0 to about 7.5, or about 7.2 to about 7.5. According to any embodiment, the power input to the ultrasonic nozzle may be in the range of: about 1 W to about 50 W, about 1 W to about 40 W, about 1 W to about 30 W, about 1 W to about 20 W, about 1 W to about 10 W, about 1 W to about 8 W, about 1 W to about 7 W, about 2 W to about 7 W, about 1 W to about 6 W, about 1 W to about 5 W, or about 2 W to about 5 W, and preferably about 2W. According to any embodiment where the peptide is Semaglutide, the one or more solvents consists essentially of, or consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is: about 0.6 g/min to about 10 g/min, about 0.6 g/min to about 5 g/min, aboutl ml/min to about 10 ml/min, preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 180 °C, preferably from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C. According to any embodiment where the peptide is Semaglutide, the one or more solvents in the feed solution consists essentially of, or consists of, acetonitrile and water wherein acetonitrile is present at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 0.6 g/min to about 10 g/min, about 0.6 g/min to about 5 g/min, about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and preferably the inlet temperature is about 130 °C. According to any embodiment where the peptide is Semaglutide, the one or more solvents in the feed solution consists essentially of, or consists of, acetonitrile and water wherein acetonitrile is present at a concentration of about 15% to about 60%, about 15% to about 50%, about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 150 °C (or about 120 °C to about 140 °C, or 130 °C).

[0015] In embodiments, the feed solution comprises Tirzepatide, and one or more solvents; wherein the concentration (w/w) of the peptide in the solution is not less than about 0.5 % particularly the concentration of the peptide may range from: about 1% (w/w) to about 50% w/w), about 1.5% (w/w) to about 30% (w/w), about 5% to about 20% (w/w) and wherein the solution has a pH of about 5 to about 10, preferably to about 6 to about 9, and more preferably about 7 to about 8.5 or about 7.5 to about 8.5. Alternatively, in any embodiment the feed solution comprises Tirzepatide or a salt thereof, preferably Tirzepatide, wherein the concentration of Tirzepatide in the feed solution is: about 1% to about 25%, about 1% to about 20%, 1% (w/w) to about 15% w/w), about 1.5% (w/w) to about 30% (w/w), about 5 % to about 20% (w/w), about 2% (w/w) to about 6% (w/w). According to any embodiment wherein the peptide in the feed solution is Tirzepatide, the pH of the feed solution may be: about 5 to about 10, preferably to about 6 to about 9, preferably about 7 to about 8.5, more preferably 7.5 to about 8.5. According to any embodiment wherein the peptide in the feed solution is Tirzepatide, the ultrasonic nozzle power is in the range of 1-10 W, or in the range of 1-7 W, or in the range of 1-3 W. According to any embodiment wherein the peptide in the feed solution is Tirzepatide, the one or more solvents in the feed solution consists essentially of, and preferably consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 30% (w/w) to about 50% (w/w); the feed flow rate is from about 0.5 g/min to about 10 g/min, about 0.5 g/min to about 5 g/min, about 0.5 ml/min to about 3 ml/min, preferably from about 0.5 ml/min to about 2 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 180 °C, preferably from about 120 °C to about 150 °C. According to any embodiment wherein the peptide in the feed solution is Tirzepatide, the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 30% (w/w) to about 50% (w/w); the feed flow rate is from about 0.5 g/min to about 10 g/min, about 0.5 g/min to about 5 g/min, about 0.5 ml/min to about 3 ml/min, about 0.5 ml/min to about 2 ml/min; and the inlet temperature is from about 120 °C to about 150 °C. According to any embodiment wherein the peptide is Tirzepatide, the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of about 15% to about 60%, about 15% to about 50%, about 30% (w/w) to about 50% (w/w), the feed flow rate is from about 0.5 ml/min to about 5 ml/min or about 0.5 to about 2 ml/min; and the inlet temperature is from about 120 °C to about 150 °C. According to any embodiment wherein the peptide in the feed solution is Tirzepatide, the obtained product may have a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, about 20 to about 40 pm, or about 10 pm to about 30 pm.

[0016] The peptide particles produced by the spray drying process equipped with the ultrasonic nozzle described herein advantageously have a robust morphology and are characterized by spherical particles having a narrow span and a narrow portion of fine particles compared to the particles obtained in by spray drying using the conventional nozzle that has at least two-fluid entry channels.

[0017] According to any aspect or embodiment of the disclosed process, the particles obtained are characterized by a D(90) of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm.

[0018] In embodiments of the disclosed process, the Semaglutide particles obtained are characterized by a D(90) of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm.

[0019] In yet another aspect the disclosure further relates to a spray drying process for preparation of a peptide, preferably a GLP-1 peptide, wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide or Semaglutide, or a salt thereof; preferably selected from Liraglutide and Semaglutide, and a salt thereof; more preferably Semaglutide, or a salt thereof or a dual GLP-1 /GIP peptide, preferably Tirzepatide; wherein the peptide particles have a PSD characterized by a D(90) value of: not more than 120 um ± 20%, not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 30 um ± 20%; or a D(90) of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm., wherein the process comprises introducing the feed solution comprising the peptide, preferably the GLP-1 peptide or dual GLP-l/GLP peptide in a solvent into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate, wherein the ultrasonic nozzle power is in the range of 1-50 W.

[0020] In embodiments the disclosure further relates to a spray drying process for preparation of Semaglutide, or a salt thereof wherein the Semaglutide particles have a PSD characterized by a D(90) value of: not more than 60 um ± 20%, not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, wherein the process comprises introducing the feed solution comprising Semaglutide or salt thereof in a solvent into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate, wherein the ultrasonic nozzle power is in the range of 1-50 W.

[0021] The process according to any aspect or embodiment disclosed herein may further comprise combining the spray dried peptide with at least one pharmaceutically acceptable excipient to form a pharmaceutical composition.

[0022] In yet another aspect the present disclosure provides peptide particles, preferably GLP-1 peptide particles, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, not more than 80 um ± 20%; preferably not more than 50 um ± 20%; more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by a process according to any aspect or embodiment of the disclosure. [0023] In embodiments the present disclosure provides particles of Semaglutide or a salt thereof; preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; not more than 30 um ± 20%; more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by a process according to any aspect or embodiment of the disclosure.

[0024] The present disclosure also provides the use of peptide particles, preferably GLP-1 peptide particles, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%; preferably not more than 50 um ± 30%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by the processes of the disclosure in the preparation of pharmaceutical compositions and/or formulations or dietary compositions.

[0025] The present disclosure also provides the use of particles of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; not more than 30 um ± 20%; more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by the processes of the disclosure in the preparation of pharmaceutical compositions and/or formulations or dietary compositions.

[0026] The present disclosure also provides peptide particles, preferably GLP-1 peptide particles, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%; preferably not more than 50 um ± 20%; more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm., obtainable by any of the processes of the disclosure for use in the preparation of pharmaceutical compositions and/or formulations or dietary compositions.

[0027] The present disclosure also provides particles of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; preferably not more than 30 um ± 20%more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by any of the processes of the disclosure for use in the preparation of pharmaceutical compositions and/or formulations or dietary compositions.

[0028] The present disclosure further includes processes for the preparation of the above mentioned pharmaceutical composition or pharmaceutical formulation, or dietary composition, preferably for oral administration and more preferably wherein the pharmaceutical formulation is a tablet a GLP-1 peptide, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof ; and most preferably Semaglutide or a dual GLP-l/GIP peptide, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; wherein the process comprises combining the GLP-1 peptide particles, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%; preferably not more than 50 um ± 20% more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by any of the processes of the present disclosure with at least one pharmaceutically acceptable excipient.

[0029] The present disclosure further includes processes for the preparation of the above mentioned pharmaceutical composition or pharmaceutical formulation, or dietary composition, preferably for oral administration and more preferably wherein the pharmaceutical formulation is a tablet comprising Semaglutide or a salt thereof; and most preferably Semaglutide; wherein the process comprises combining Semaglutide particles having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; not more than 30 um ± 20%; more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by any of the processes of the present disclosure with at least one pharmaceutically acceptable excipient.

[0030] The present disclosure provides GLP-1 peptide particles, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein and the pharmaceutical compositions or formulations, may be used as medicaments, such as for the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes.

[0031] The present disclosure provides particles of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein and the pharmaceutical compositions or formulations, may be used as medicaments, such as for the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes.

[0032] The present disclosure provides GLP-1 peptide particles, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein and the compositions or formulations comprising the GLP-1 peptide particles or the dual GLP-1 /GIP peptide particles having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein for cosmetic weight loss in non-overweight non-obese subjects.

[0033] The present disclosure provides particles of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein and the compositions or formulations comprising Semaglutide particles having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein for cosmetic weight loss in non-overweight non-obese subjects.

[0034] The present disclosure also provides methods for the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes, by administering a therapeutically effective amount of GLP-1 peptide particles, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein, or at least one of the above pharmaceutical compositions or pharmaceutical formulation, to a subject suffering from type 2 diabetes, overweight or obesity, and preferably type 2 diabetes, or otherwise in need of the treatment.

[0035] The present disclosure also provides methods for the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes, by administering a therapeutically effective amount of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein, or at least one of the above pharmaceutical compositions or pharmaceutical formulation, to a subject suffering from type 2 diabetes, overweight or obesity, and preferably type 2 diabetes, or otherwise in need of the treatment.

[0036] The present disclosure further provides methods for cosmetic weight loss in nonoverweight non-obese subjects comprising administering an effective amount of GLP-1 peptide particles, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein.

[0037] The present disclosure further provides methods for cosmetic weight loss in nonoverweight non-obese subjects comprising administering an effective amount of Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein.

[0038] The present disclosure also provides use of GLP-1 peptide particles, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by the processes of the present disclosure or at least one of the above pharmaceutical compositions, for the manufacture of medicaments for treating type 2 diabetes, overweight or obesity and preferably type 2 diabetes.

[0039] The present disclosure also provides use of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by the processes of the present disclosure or at least one of the above pharmaceutical compositions, for the manufacture of medicaments for treating type 2 diabetes, overweight or obesity and preferably type 2 diabetes. [0040] The present disclosure also provides uses of GLP-1 peptide particles, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by any of the processes of present disclosure or at least one of the above pharmaceutical compositions, for the manufacture of compositions of formulations for cosmetic weight loss, i.e. weight loss in non-overweight, non-obese subjects.

[0041] The present disclosure also provides use of particles of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by any of the processes of present disclosure or at least one of the above pharmaceutical compositions, for the manufacture of compositions or formulations for cosmetic weight loss, i.e. weight loss in non-overweight, non- obese subjects

BRIEF DESCRIPTION OE THE DRAWINGS

[0042] Figure 1 shows scanning electron microscopy (SEM) images of Semaglutide particles prepared by spray drying using an ultrasonic nozzle according to Example 1 : xl500 (Figure 1A); x5000 (Figure IB). [0043] Figure 2 shows scanning electron microscopy (SEM) images of Semaglutide particles prepared by spray drying using a Bi fluid nozzle according to Reference example 1 : xl500 (Figure 2A); x5000 (Figure 2B).

[0044] Figure 3 shows scanning electron microscopy (SEM) images of Semaglutide particles prepared by spray drying using a Bi fluid nozzle according to Reference Example 3: xl500 (Figure 3A); x5000 (Figure 3B).

[0045] Figure 4 shows scanning electron microscopy (SEM) images of Tirzepatide particles prepared by spray drying using an ultrasonic nozzle according to Example 5b: xl 500 (Figure 4A); x5000 (Figure 4B).

DETAILED DESCRIPTION OF THE DISCLOSURE

[0046] As used herein, the term “room temperature” refers to a temperature of about 20°C to about 30°C, about 22°C to about 27°C, or about 25 °C.

[0047] As used herein, the term “GLP-1 peptide” refers to a compound which fully or partially activates the human GLP-1 receptor. In some embodiments the GLP-1 peptide is a GLP-1 analogue optionally comprising one substituent. The term "analogue" refers to a GLP-1 peptide wherein at least one amino acid residue of the peptide has been substituted with another amino acid residue and/or wherein at least one amino acid residue has been deleted from the peptide and/or at least one amino acid residue has been added to the peptide and/or wherein at least one amino acid has been modified. In some embodiments the GLP-1 peptide comprises one substituent which is covalently attached to the peptide. As used herein, the term "GLP-1 peptide" is meant to also include dual glucagon-like peptide- 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonists such as Glucagon-like peptide 1 (GLP-1) peptides such as Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide, and salts thereof. Particularly preferred GLP-1 peptides according to any aspect or embodiment of the present invention are: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide.

[0048] As used herein, the term "dual GLP-1 /GIP receptor agonists" refers to dual incretin peptide mimetic compounds that agonize receptors for both glucagon-like peptide- 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonists such as Tirzepatide. [0049] As used herein, particle size distribution is determined by means of laser diffractometry. More specifically, unless otherwise indicated, the particle size was determined using a Mastersizer 3000 from Malvern Instruments. Preferably, particle size and particle size distribution are determined by laser light diffraction, using Mie theory, and Isopar-G dispersant (isoparaffinic fluid (CAS No) 64742-48-9)) refractive index 1.42.

[0050] It will be understood that the term “D(90)” (or D0.9 or Dv0.9) as used herein refers to a particle size distribution where 90% of the volume of particles have a diameter lower than the D(90) value. Similarly, “D(50)” (or “D0.5” or “Dv0.5”) and “D(10)” (or “D0.1” or “DvO.1”) refer to particle size distributions where 50% and 10% respectively, of the volume of particles have a diameter lower than the specified D(50) or D(10) value.

[0051] As used herein, reference to a (w/w) concentration is to be understood as a reference to concentration based on the weight of the solution of peptide and solvent(s).

[0052] Thus, for example, reference to a w/w concentration of peptide, relates to the concentration based on the weight of the solution of peptide and solvent(s).

[0053] As used herein, reference to a (w/w) concentration of a specified solvent in the one or more solvents, is understood to refer to the concentration of the specified solvent based on the total weight of the one or more solvents.

[0054] As used herein, obesity encompasses obese and severely obese classes of subjects.

Obesity is defined in adult humans as a BMI of 30 to 39.9. Severely obese is defined in adult humans as a BMI of 40 or above.

[0055] As used herein, overweight is defined in adult humans as a BMI of 25 to 29.9.

[0056] As used herein, cosmetic weight loss is understood to mean weight loss in nonoverweight, non-obese subjects. For example, cosmetic weight loss optionally refers to weight loss in subjects having a body mass index (BMI) of: 18.5 to 24.9, 19 to 24, 20 to 23.5, or 21.0 to 23.

[0057] The present disclosure relates to a process for spray drying a feed solution comprising a peptide (preferably a GLP-1 or dual GIP/GLP-1 peptide), and one or more solvents, wherein the process comprises introducing the feed solution into a spray dryer equipped with an ultrasonic nozzle.

[0058] The feed solution may comprise the peptide (preferably a GLP-1 or a dual GIP/GLP-1 peptide) and the one or more solvents; or the feed solution may consists essentially of the peptide (preferably a GLP-1 or a dual GIP/GLP-1 peptide) and the one or more solvents; or wherein the feed solution consists of the peptide (preferably a GLP-1 or a dual GIP/GLP-1 peptide) and the one or more solvents.

[0059] According to any aspect or embodiment of the present disclosure, the feed solution may preferably be prepared by combining the peptide with the one or more solvents. The feed solution may additionally contain small amounts of salt if the pH is required to be adjusted. According to any aspect or embodiment, the feed solution preferably does not comprise added pharmaceutical excipients.

[0060] The present disclosure relates to processes for spray drying a feed solution comprising a peptide, preferably a GLP-1 peptide, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; wherein the process comprises introducing the feed solution comprising the peptide, preferably the GLP-1 peptide, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; in a solvent into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate, wherein the ultrasonic nozzle power is in the range of 1-50 W, 1-40W, 1-30W, 1-20W, preferably 1-10W, more preferably 1-5W or about 2W.

[0061] The present disclosure relates to processes for spray drying a feed solution comprising Semaglutide or a salt thereof; and most preferably Semaglutide wherein the process comprises introducing the feed solution comprising Semaglutide or a salt thereof; and most preferably Semaglutide; in a solvent into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate, wherein the ultrasonic nozzle power is in the range of 1-50 W, 1-40W, 1-30W, 1-20W, preferably 1-10W, more preferably 1-5W or about 2W.

[0062] The present disclosure relates to processes for spray drying a feed solution comprising Tirzepatide or a salt thereof; and most preferably Tirzepatide wherein the process comprises introducing the feed solution comprising Tirzepatide or a salt thereof; and most preferably Tirzepatide; in a solvent into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate, wherein the ultrasonic nozzle power is in the range of 1-50 W, 1-40W, 1-30W, 1-20W, preferably 1-10W, more preferably 1-5W or about 2W.

[0063] In yet another aspect the disclosure further relates to a spray drying process for preparation of a peptide, preferably a GLP-1 peptide, wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide or Semaglutide, or a salt thereof; preferably selected from Liraglutide and Semaglutide, and a salt thereof; more preferably Semaglutide, or a salt thereof and most preferably Semaglutide or a dual GLP-l/GIP peptide, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; wherein the peptide particles have a PSD characterized by a D(90) value of: not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, wherein the process comprises introducing the feed solution comprising the peptide, preferably the GLP-1 peptide or the dual GLP-1 /GIP peptide in a solvent into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate, wherein the ultrasonic nozzle power is in the range of 1-50 W, 1-40W, 1-30W, 1-20W, preferably 1-10W, more preferably 1-5W or about 2W.

[0064] In yet another aspect the disclosure further relates to a spray drying process for preparation of Semaglutide, or a salt thereof and most preferably Semaglutide wherein the peptide particles have a PSD characterized by a D(90) value of: not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm [0065] to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, wherein the process comprises introducing the feed solution comprising Semaglutide or a salt thereof in a solvent into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate, wherein the ultrasonic nozzle power is in the range of 1-50 W, 1-40W, 1-30W, 1-20W, preferably 1-10W, more preferably 1-5W or about 2W.

[0066] another aspect the disclosure further relates to a spray drying process for preparation of Tirzepatide, or a salt thereof and most preferably Tirzepatide wherein the peptide particles have a PSD characterized by a D(90) value of: not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, wherein the process comprises introducing the feed solution comprising Tirzepatide or a salt thereof in a solvent into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate, wherein the ultrasonic nozzle power is in the range of 1-50 W, 1-40W, 1-30W, 1-20W, preferably 1-10W, more preferably 1-5W or about 2W.

[0067] In any aspect or embodiment, the feed solution comprises a peptide, preferably a GLP-1 peptide, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide or Semaglutide, or a salt thereof; preferably selected from Liraglutide and Semaglutide, and a salt thereof; more preferably Semaglutide, or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide and one or more solvents: wherein the concentration (w/w) of the peptide in the feed solution is not less than about 0.5%, particularly the concentration of the peptide may range from: about 1% (w/w) to about 50% w/w), about 1.5% (w/w) to about 20% (w/w), about 2% to about 15% (w/w), or more particularly, the concentration of the peptide is from about 2. % (w/w) to about 6% (w/w)].

[0068] In any aspect or embodiment, the feed solution comprises Semaglutide, or a salt thereof; and most preferably Semaglutide and one or more solvents: wherein the concentration (w/w) of the peptide in the feed solution is not less than about 0.5%, particularly the concentration of the peptide may range from: about 1% (w/w) to about 15% (w/w), about 1.5% (w/w) to about 10% (w/w), about 2% to about 8% (w/w), or more particularly, the concentration of the peptide is from about 2. % (w/w) to about 6% (w/w)]. Optionally, the concentration of the peptide in the feed solution is: about 1% (w/w) to about 30% (w/w), about 1% (w/w) to about 25% (w/w), or about 2% (w/w) to about 20% (w/w).

[0069] In any aspect or embodiment, the feed solution comprises Tirzepatide, or a salt thereof; and most preferably Tirzepatide and one or more solvents: wherein the concentration (w/w) of the peptide in the feed solution is not less than about 0.5%, particularly the concentration of the peptide may range from: about 1% (w/w) to about 15% (w/w), about 1.5% (w/w) to about 10% (w/w), about 2% to about 8% (w/w), or more particularly, the concentration of the peptide is from about 2. % (w/w) to about 6% (w/w)]. Optionally, the concentration of the peptide in the feed solution is: about 1% (w/w) to about 30% (w/w), about 1% (w/w) to about 25% (w/w), or about 2% (w/w) to about 20% (w/w).

[0070] In any aspect or embodiment the solvents of the feed solution may be one or more selected from the list consisting of ethanol, isopropanol (IP A), acetonitrile and water. In any aspect or embodiment, the one or more solvents of the feed solution are selected from the group consisting of isopropanol, acetonitrile and water.

[0071] In any aspect or embodiment, the solvent is a mixture of water and at least one of: ethanol, isopropanol and acetonitrile; or wherein the solvent is a mixture of water and at least one of isopropanol and acetonitrile; and more particularly wherein the solvent is a mixture of water and acetonitrile.

[0072] Preferably, the solvent of the feed solution comprises up to 80% of water. In particular embodiments, the solvent of the feed solution may comprise about 0 to about 80% of water and up to about 100% (w/w), preferably up to about 40% (w/w) of any one or a mixture of acetonitrile, IPA and ethanol. In a specific embodiment the feed solution comprises water and about 15% (w/w) to about 25% (w/w) of acetonitrile, more preferably the feed solution comprises water and about 20% (w/w) of acetonitrile. In particularly preferred embodiments, the feed solution essentially consists of (and preferably consists of) acetonitrile and water, preferably wherein acetonitrile is present at about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and most preferably about 20% (w/w).

[0073] According to any aspect or embodiment, the one or more solvents in the feed solution may comprise, consist essentially of, or consists of, up to 80% (w/w) water, and preferably: 5% (w/w) to 80% (w/w) water, 10% (w/w) to 80% (w/w) water, 20% (w/w) to 80% (w/w) water, or 30% (w/w) to 80% (w/w) water.

[0074] According to any aspect or embodiment, the one or more solvents in the feed solution comprises, consists essentially of, or consists of: up to about 100% (w/w), up to about 90% (w/w), up to about 80% (w/w), up to about 70% (w/w), up to about 60% (w/w), up to about 50% (w/w), and preferably up to about 40% (w/w) of any one or a mixture of acetonitrile, IPA and ethanol, with any remainder being water; or wherein the one or more solvents in the feed solution comprises up to about 40% (w/w) of any one or a mixture of acetonitrile and IPA), with the remainder being water. 1 [0075] According to any aspect or embodiment, the one or more solvents in the feed solution comprises, consists essentially of, or consists of: from 5% (w/w) to 100% (w/w), from 10% (w/w) to 90% (w/w), from 20% (w/w) to 80% (w/w), or from 20% (w/w) to 70% (w/w), of any one or a mixture of acetonitrile, IPA and ethanol, with any remainder being water; or wherein the one or more solvents in the feed solution comprises from 5% (w/w) to 100% (w/w), from 10% (w/w) to 90% (w/w), from 20% (w/w) to 80% (w/w), or from 20% (w/w) to 70% (w/w), of any one or a mixture of acetonitrile, and IPA, with any remainder being water.

[0076] According to any aspect or embodiment, the one or more solvents in the feed solution comprises, consists essentially of, or consists of, water, and: up to about 90% (w/w), up to about 80% (w/w), up to about 70% (w/w), up to about 60% (w/w), up to about 50% (w/w), or up to about 40% (w/w), of any one or a mixture of acetonitrile, IPA and ethanol, or wherein the one or more solvents in the feed solution comprises water and: up to about 90% (w/w), up to about 80% (w/w), up to about 70% (w/w), up to about 60% (w/w), up to about 50% (w/w), or up to about 40% (w/w), of any one or a mixture of acetonitrile and IPA).

[0077] According to any aspect or embodiment, the one or more solvents in the feed solution comprises, consists essentially of, or consists of, water, and: from 5% (w/w) to 90% (w/w) of any one or a mixture of acetonitrile, IPA and ethanol; or wherein the one or more solvents in the feed solution comprises water and: from 5% (w/w) to 90% (w/w), from 10% (w/w) to 90% (w/w), or from 20% (w/w) to 80% (w/w) of any one or a mixture of acetonitrile, and IPA.

[0078] According to any aspect or embodiment, the one or more solvents in the feed solution comprises, consists essentially of, or consists of, water and one of: acetonitrile, IPA or ethanol (preferably acetonitrile or IPA); or wherein the one or more solvents in the feed solution comprises, consists essentially of, or consists of, either water and acetonitrile, or water and isopropanol.

[0079] According to any aspect or embodiment, the one or more solvents in the feed solution consists essentially of, or consists of, acetonitrile and water.

[0080] According to any aspect or embodiment, the one or more solvents in the feed solution consists essentially of, or consists of, acetonitrile and water in a w/w ratio of: 10:90 to 90: 10, 15:85 to 80:20, 20:80 to 75:25, or 20:80 to 70:30.

[0081] According to any aspect or embodiment, the one or more solvents in the feed solution consists essentially of, and preferably consists of, acetonitrile and water, wherein acetonitrile is present in the one or more solvents at a concentration of: about 10% (w/w) to about 90% (w/w), about 15% (w/w) to about 75% (w/w), about 20% (w/w) to about 70% (w/w), or wherein the acetonitrile is present in the one or more solvents of the feed solution at a concentration of: about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w).

[0082] In any aspect or embodiment the pH of the feed solution comprising a peptide, preferably a GLP-1 peptide, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide or Semaglutide, or a salt thereof; preferably selected from Liraglutide and Semaglutide, and a salt thereof; more preferably Semaglutide, or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide may be: about 5.6 to about 9, more preferably about 7 to about 8.5; or the pH may be about 7.0 to about 8.0, about 7.1 to about 7.8, or about 7.2 to about 7.5. If necessary, the pH may be adjusted to within the specified ranges by any suitable basic agent such as but not limited to sodium bicarbonate, ammonium acetate, phosphate buffer, ammonium hydroxide or NaOH. In embodiments the pH is adjusted by ammonium hydroxide, preferably 25% (w/w) solution of ammonium hydroxide or NaOH, to provide the feed solution.

[0083] In embodiment the pH of the feed solution comprising Semaglutide, or a salt thereof; preferably Semaglutide may be about 5.6 to about 9, more preferably about 7 to about 8, about 7.1 to about 7.5 or about 7.3.

[0084] In embodiment the pH of the feed solution comprising Tirzepatide, or a salt thereof; preferably Semaglutide may be about 5.6 to about 9, more preferably about 7 to about 8, about 7.1 to about 7.5 or about 7.3.

[0085] In any aspect or embodiment, the feed flow rate is from about 1 ml/min to about 35 ml/min, preferably from about 1 ml/min to about 20 ml/min, more preferably from about 1 ml/min to about 10 ml/min. Even more preferably from about 1 ml/min to about 5 ml/min. In particular embodiments, the feed flow rate ranges from about 1 ml/min to about 2.5 ml/min and even more particularly the feed flow rate is about 1.5 ml/min.

[0086] In any aspect or embodiment, the feed solution flow rate may be: about 0.5 ml/min to about 50 ml/min, about 0.5 ml /min to about 25 ml /min, about 0.6 ml/min to about 15 ml/min, about 0.6 ml/min to about 10 ml/min, about 0.6 g ml/min to about 5 ml/min about 0.6 ml/min to about 4 ml/min, about 0.8 ml/min to about 3 ml/min, or about 0.5 ml/min to about 2.8 ml/min. [0087] In any aspect or embodiment, the inlet temperature is from about 100 °C to about 180 °C. Preferably the inlet temperature is from about 120 °C to about 160 °C and more preferably the inlet temperature is about 130 °C.

[0088] In any aspect or embodiment, the inlet temperature may be: about 110 °C to about 190 °C, about 115 °C to about 190 °C, about 120 °C to about 180 °C, about 120 °C to about 170 °C, about 120 °C to about 160 °C, or about 120 °C to about 155 °C, about 120 °C to about 152 °C, and optionally about 120 °C to about 140 °C.

[0089] In any aspect or embodiment, the outlet temperature is from about 40 °C to about 100 °C. Preferably the outlet temperature is from about 50 °C to about 80 °C and more preferably the outlet temperature is from about 60 °C to about 70 °C.

[0090] In any aspect or embodiment, the outlet temperature is: about 50 °C to about 100 °C, about 60 °C to about 95 °C, about 65 °C to about 95 °C, about 70 °C to about 95 °C, or about 75 °C to about 95 °C.

[0091] According to any aspect or embodiment, the aspirator gas flow may be: about 0.1 m³/h to about 10 m³/h, about 0.1 m³/h to about 5 m³/h, about 0.1 m³/h to about 2.5 m³/h, about 0.15 m³/h to about 2.0 m³/h, about 0.15 m³/h to about 1.5 m³/h, about 0.15 m³/h to about 1.0 m³/h, about 0.2 m³/h to about 0.8 m³/h, about 0.25 m³/h to about 0.6 m³/h, about 0.3 m³/h to about 0.5 m³/h, about 0.35 m³/h to about 0.5 m³/h, or about 0.4 m³/h to about 0.5 m³/h, about 0.1 m³/h to about 2.5 m³/h.

[0092] According to any aspect or embodiment of the disclosure, the ultrasonic nozzle frequency is: about 21 kHz to about 140 kHz, about 21 kHz to about 130 kHz, about 21 kHz to about 120 kHz, about 25 kHz to about 100 kHz, about 25 kHz to about 90 kHz, about 25 kHz to about 80 kHz, about 25 kHz to about 75 kHz, about 25 kHz to about 65 kHz, or about 25 kHz to about 60 kHz.

[0093] According to any aspect or embodiment of the disclosure ultrasonic nozzle power (i.e. the power input to the ultrasonic nozzle) is: about 1 W to about 50 W, about 1 W to about 40 W, about 1 W to about 30 W, about 1 W to about 20 W, about 1 W to about 10 W, about 1 W to about 8 W, about 1 W to about 7 W, about 2 W to about 7 W, about 1 W to about 6 W, about 1 W to about 5 W, or about 2 W to about 5 W.

[0094] In yet another aspect the present disclosure provides peptide particles, preferably GLP-1 peptide particles, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm, or about 10 to about 30 pm, obtainable by any of the processes disclosed herein.

[0095] In embodiments the present disclosure provides particles of Semaglutide or a salt thereof; preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; not more than 30 um ± 20%; more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by a process according to any aspect or embodiment of the disclosure.

[0096] In embodiments the present disclosure provides particles of Tirzepatide or a salt thereof; preferably Tirzepatide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; not more than 30 um ± 20%; more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by a process according to any aspect or embodiment of the disclosure.

[0097] The present disclosure also provides the use of peptide particles, preferably GLP-1 peptide particles, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of: about 8 pm to about 150 pm, about 10 m to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm, or about 10 to about 30 pm, obtainable by the processes of the disclosure in the preparation of pharmaceutical compositions and/or formulations.

[0098] The present disclosure also provides the use of particles of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; not more than 30 um ± 20%; more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by the processes of the disclosure in the preparation of pharmaceutical compositions and/or formulations or dietary compositions.

[0099] The present disclosure also provides the use of particles of Tirzepatide or a salt thereof; and most preferably Tirzepatide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; not more than 30 um ± 20%; more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by the processes of the disclosure in the preparation of pharmaceutical compositions and/or formulations or dietary compositions.

[00100] The present disclosure also provides the peptide particles, preferably GLP-1 peptide particles, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm, or about 10 to about 30 pm, obtainable by the processes of the disclosure for use in the preparation of pharmaceutical compositions and/or formulations or dietary compositions. [00101] The present disclosure also provides particles of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; preferably not more than 30 um ± 20%more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm., obtainable by any of the processes of the disclosure for use in the preparation of pharmaceutical compositions and/or formulations or dietary compositions.

[00102] The present disclosure also provides particles of Tirzepatide or a salt thereof; and most preferably Tirzepatide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; preferably not more than 30 um ± 20%more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm., obtainable by any of the processes of the disclosure for use in the preparation of pharmaceutical compositions and/or formulations or dietary compositions.

[00103] The present disclosure further includes processes for the preparation of the above mentioned pharmaceutical composition, or pharmaceutical formulation, or dietary composition preferably for oral administration and more preferably wherein the pharmaceutical formulation is a tablet a comprising a GLP-1 peptide, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; wherein the process comprises combining the GLP-1 peptide particles, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-l/GIP peptide, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 m, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm, or about 10 to about 30 pm, obtainable by any of the processes of the present disclosure with at least one pharmaceutically acceptable excipient.

[00104] The present disclosure further includes processes for the preparation of the above mentioned pharmaceutical composition or pharmaceutical formulation, or dietary composition, preferably for oral administration and more preferably wherein the pharmaceutical formulation is a tablet comprising Semaglutide or a salt thereof; and most preferably Semaglutide; wherein the process comprises combining Semaglutide particles having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; not more than 30 um ± 20%; more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by any of the processes of the present disclosure with at least one pharmaceutically acceptable excipient.

[00105] The present disclosure further includes processes for the preparation of the above mentioned pharmaceutical composition or pharmaceutical formulation, or dietary composition, preferably for oral administration and more preferably wherein the pharmaceutical formulation is a tablet comprising Tirzepatide or a salt thereof; and most preferably Tirzepatide; wherein the process comprises combining Tirzepatide particles having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%; not more than 30 um ± 20%; more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by any of the processes of the present disclosure with at least one pharmaceutically acceptable excipient.

[00106] The present disclosure provides GLP-1 peptide particles, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 m to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm, or about 10 to about 30 pm, obtainable by any of the processes described herein and the pharmaceutical compositions or formulations may be used as medicaments, such as for the treatment of patients suffering from type 2 diabetes, overweight or obesity, preferably type 2 diabetes or for the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly- controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin.

[00107] The present disclosure provides particles of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein and the pharmaceutical compositions or formulations, may be used as medicaments, such as for the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes or for the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly- controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin.

[00108] The present disclosure provides particles of Tirzepatide or a salt thereof; and most preferably Tirzepatide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein and the pharmaceutical compositions or formulations, may be used as medicaments, such as for the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes or for the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly- controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin.

[00109] The present disclosure provides GLP-1 peptide particles, particularly Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide particles, and more preferably Semaglutide or salt thereof, most preferably Semaglutide particles or a dual GLP-l/GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm, or about 10 to about 30 pm, obtainable by any of the processes described herein, and the compositions or formulations comprising the GLP-1 peptide particles or the dual GLP-1 /GIP peptide particles having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein for cosmetic weight loss in non-overweight non-obese subjects.

[00110] The present disclosure provides particles of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein and the compositions or formulations comprising Semaglutide particles having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein for cosmetic weight loss in non-overweight non-obese subjects.

[00111] The present disclosure provides particles of Tirzepatide or a salt thereof; and most preferably Tirzepatide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein and the compositions or formulations comprising Tirzepatide particles having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein for cosmetic weight loss in non-overweight non-obese subjects.

[00112] The present disclosure also provides methods for the treatment of patients with type 2 diabetes, overweight or obesity, preferably type 2 diabetes or for the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin by administering a therapeutically effective amount of GLP-1 peptide particles, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm, or about 10 to about 30 pm, obtainable by the processes described herein, or at least one of the above pharmaceutical compositions, to a subject suffering from type 2 diabetes, overweight or obesity, preferably type 2 diabetes, or for the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Librosis or Cystic Librosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAELD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin or otherwise in need of the treatment.

[00113] The present disclosure also provides methods for the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes, or for the treatment of

Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Librosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFUD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin by administering a therapeutically effective amount of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein, or at least one of the above pharmaceutical compositions or pharmaceutical formulation, to a subject suffering from type 2 diabetes, overweight or obesity, and preferably type 2 diabetes, or for the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly- controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin or otherwise in need of the treatment.

[00114] The present disclosure also provides methods for the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes, or for the treatment of

Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin by administering a therapeutically effective amount of Tirzepatide or a salt thereof; and most preferably Tirzepatide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein, or at least one of the above pharmaceutical compositions or pharmaceutical formulation, to a subject suffering from type 2 diabetes, overweight or obesity, and preferably type 2 diabetes, or for the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly- controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin or otherwise in need of the treatment.

[00115] The present disclosure further provides methods for cosmetic weight loss in nonoverweight non-obese subjects comprising administering an effective amount of GLP-1 peptide particles, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein.

[00116] The present disclosure further provides methods for cosmetic weight loss in nonoverweight non-obese subjects comprising administering an effective amount of Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein. [00117] The present disclosure further provides methods for cosmetic weight loss in nonoverweight non-obese subjects comprising administering an effective amount of Tirzepatide, or a salt thereof; more preferably Tirzepatide or a salt thereof; and most preferably Tirzepatide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable according to any of the processes described herein. The present disclosure also provides GLP-1 peptide particles, particularly wherein the peptide is selected from: Liraglutide, Dulaglutide, Exanetide, Lixisenatide and Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by the processes of the present disclosure or at least one of the above pharmaceutical compositions, for the manufacture of medicaments for treating type 2 diabetes, overweight or obesity and preferably type 2 diabetes or for the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Eibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin or otherwise in need of the treatment. [00118] The present disclosure also provides use of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by the processes of the present disclosure or at least one of the above pharmaceutical compositions, for the manufacture of medicaments for treating type 2 diabetes, overweight or obesity and preferably type 2 diabetes or for the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly- controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin or otherwise in need of the treatment.

[00119] The present disclosure also provides use of Tirzepatide or a salt thereof; and most preferably Tirzepatide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by the processes of the present disclosure or at least one of the above pharmaceutical compositions, for the manufacture of medicaments for treating type 2 diabetes, overweight or obesity and preferably type 2 diabetes or for the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly- controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin or otherwise in need of the treatment. The present disclosure also provides uses of GLP-1 peptide particles, particularly wherein the peptide is selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferable Tirzepatide; having a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 30 um ± 20%; or a D(90) value of: about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by any of the processes of present disclosure or at least one of the above pharmaceutical compositions, for the manufacture of compositions of formulations for cosmetic weight loss, i.e. weight loss in non-overweight, non-obese subjects.

[00120] The present disclosure also provides use of particles of Semaglutide or a salt thereof; and most preferably Semaglutide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by any of the processes of present disclosure or at least one of the above pharmaceutical compositions, for the manufacture of compositions or formulations for cosmetic weight loss, i.e. weight loss in non- overweight, non-obese subjects.

[00121] The present disclosure also provides use of particles of Tirzepatide or a salt thereof; and most preferably Tirzepatide; having a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%; or a D(90) value of: about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, or about 20 to about 40 pm or about 10 pm to about 30 pm, obtainable by any of the processes of present disclosure or at least one of the above pharmaceutical compositions, for the manufacture of compositions or formulations for cosmetic weight loss, i.e. weight loss in non- overweight, non-obese subjects. [00122] The present disclosure also provides uses of the peptide particles obtained by the methods of the present disclosure or at least one of the above described dietary compositions for cosmetic weight loss in non-overweight non-obese subjects.

METHODS

PSD method:

[00123] Instrumentation: Malvern Laser Diffraction Mastersizer 3000, Hydro Mv cell Measuring range: 0.01 - 3500 mcm

Analysis model: Mie Theory

Powder RI: 1.488, Absorption: 1

Dispersant name: Isopar-G

Dispersant RI: 1.42

Speed rate of the flow cell: 2500

Internal Sonication: 1 minute

Recirculation time: 1 minute

SEM

[00124] SEM micrographs were taken on Phenom Pro, scanning microscope at 10 kV, low current. Samples were sputtered with gold by Denton Desk V sputter coater.

SPAN calculation:

(Dv0.9-Dv0.1) / Dv0.5

Gas flow

In Example 1 and Reference Example 1, the gas flow was originally measured in mm (height of the column in the rotameter). In the rest of the examples, the gas flow was measured in m³/hour. The measurement of the height in mm is equivalent to the measurement in m³/hour and these measures can be interconverted. The conversion table for conversion of the measured height to the gas flow in liters/hour is presented below. Further division by 1000 to get the number in m³/hour.

[00125] The term "Open loop" means that the system is open to the vent and not connected to a solvent trap.

EXAMPLES

[00126] Semaglutide may be prepared for example according to any method known in the art. Concentrations of solvent as indicated, refer to the % w/w in the solvent mixture.

Example 1: Spray drying of Semaglutide solution using an Ultrasonic nozzle

[00127] 55 grams of Semaglutide was dissolved in a mixture of 550 grams Acetonitrile and 2200 grams water and the pH was adjusted to 7.3 by dropwise addition of 2.7 grams of 25% Ammonium hydroxide solution. The solution obtained was filtered using a 0.2 micron nylon filter at room temperature (Semaglutide cone. 2% w/w, ACN 20% w/w). The solution was sprayed in a Buchi B-290 lab spray drying instrument equipped with an ultrasonic nozzle.

Reference Example 1: Spray drying of Semaglutide solution using a bi-fluid nozzle

[00128] 50 grams of Semaglutide was dissolving in a mixture of 500 grams Acetonitrile and 2000 grams water and the pH was adjusted to 7.3 by dropwise addition of 2.5 grams of 25% Ammonium hydroxide solution. The solution obtained was filtered using a 0.2 micron nylon filter at room temperature (Semaglutide cone. 2% w/w, ACN 20% w/w). The solution was sprayed in a Buchi B-290 lab spray drying instrument equipped with a bi-fluid nozzle.

[00129] The above data shows that under comparable operating conditions, the use of an ultrasonic nozzle (Example 1) compared with a bi-fluid nozzle (Reference Example 1) advantageously achieves a product having a lower Span (i.e. tighter particle size distribution), with fewer small particles, and a low moisture content (0.9% compared to 1.6%) to be prepared in exceptionally high yield of 96% compared with the yield of only 85% obtained using a bifluid nozzle. Moreover, the product obtained using an ultrasonic nozzle has a very high purity as well as a low residual solvent content, which is well below the ICH Guidelines limit of 410 ppm. Example 2: Spray drying a Semaglutide solution using an Ultrasonic Nozzle

[00130] 55 grams of Semaglutide was dissolved in a mixture of 550 grams Acetonitrile and 2200 grams water (Semaglutide cone.: 2% w/w; ACN: water: 20%: 80% w/w, corresponding to cone, of ACN: 20% w/w in the ACN/water mixture) and the pH was adjusted to 7.3 by dropwise addition of 2.7 grams of 25% Ammonium hydroxide solution. The resulting solution was filtered at room temperature (0.2 micron nylon filter). The solution was sprayed in a Buchi B-290 lab spray drying instrument equipped with a Buchi 60 kHz ultrasonic nozzle with variable power (1-50W), according to the following conditions:

Reference Example 2: Spray drying of Semaglutide solution using a bi-fluid nozzle

[00131] Semaglutide (50 g) was dissolved in a mixture of Acetonitrile (500 g) and water (2000 g), and the pH was adjusted to 7.3 by dropwise addition of 2.5 grams of 25% ammonium hydroxide solution. The solution was filtered at room temperature (0.2 micron nylon filter) (Semaglutide cone. 2% w/w, ACN: water: 20%: 80% w/w, corresponding to an ACN concentration of 20% in the ACN/water mixture). The solution was sprayed in a Buchi B-290 lab spray drying instrument equipped with a bi-fluid nozzle, 0.7 mm inside diameter and 10 cap 1.5 mm in diameter under the following conditions:

Reference Example 3: Spray drying of Semaglutide solution using a bi-fluid nozzle

[00132] Semaglutide (2.0 g) was dissolved in a mixture of Acetonitrile (53.0 g) and water (30.7 g), and the pH was adjusted to 7.3 by dropwise addition of 7.7g 0. IN NaOH solution (Semaglutide cone. 2.1% w/w; ACN: water ratio - 58%: 32% (w/w), corresponding to an ACN cone, of 58%). The solution was sprayed in a Buchi B-290 lab spray drying instrument equipped with a Bi fluid nozzle (the nozzle consists of the nozzle tip with a 0.7 mm diameter hole and the nozzle cap (1.4 or 1.5 mm in diameter), under the following conditions:

A SEM micrograph of the product obtained in Example 3 is shown in Figure 3.

Example 3: Spray drying Semaglutide solutions using an Ultrasonic Nozzle

[00133] Semaglutide (1-4 g) was dissolved in a mixture of acetonitrile and water and the pH was adjusted to 7.2-7.6 by dropwise addition of 0. IN NaOH solution. The solution was sprayed in a ProCepT Spray Dryer 4M8-TriX industrial spray drying instrument equipped with an ultrasonic nozzle [Sonozap Ultrasonic atomizer 25 KHz with variable power (1-10 W)] (Semaglutide cone. 2-20% w/w, ACN 50-80% w/w) using the conditions set out below:

Example 4 : Spray drying of Semaglutide solutions using an Ultrasonic Nozzle

[00134] 1 -4 grams of Semaglutide was dissolved in a mixture of Acetonitrile and water and the pH was adjusted to 7.2.-7.6 dropwise addition of 0. IN NaOH solution. The solution (Semaglutide cone. 2-20% w/w, ACN 50-80% w/w) was spray dried in a ProCepT Spray Dryer 4M8-TriX industrial spray drying instrument equipped with equipped with an ultrasonic nozzle [Sonozap Ultrasonic atomizer 25 KHz with variable power (1-10 W)] using the following conditions:

[00135] The particle size distribution of the product from Examples 4a-4e are presented below. The Span is calculated as (D0.9 - DO.I)/DO.5 and provides a comparison of the particle size uniformity - a greater number indicates a lower (i.e. less favorable) particle size uniformity:

Example 5: Spray drying of Tirzepatide solutions using an Ultrasonic Nozzle

[00136] Tirzepatide (1 g) was dissolved in a mixture of Acetonitrile and water and the pH was adjusted to 7.5-8.2 dropwise addition of 0. IN NaOH solution. The solution obtained was filtered using a 0.2 micron nylon filter at room temperature (TZP cone. 2-20% w/w based on the feed solution, ACN concentration 50-70% w/w - see table below). The solution was sprayed in a Buchi B-290 lab spray drying instrument equipped with an ultrasonic nozzle having a nozzle frequency of 60 kHz and variable power (1-50 W) according to following parameters:

[00137] Tirzepatide particles were obtained in yields of > 80%. The particle size distribution of the product from Examples 5a-5d are presented below. The Span is calculated as (DO.9 - DO.I)/DO.5 and provides a comparison of the particle size uniformity - a greater number indicates a lower (i.e. less favorable) particle size uniformity:

A SEM micrograph of the product obtained in Example 5a is shown in Figure 4. [00138] Further aspects and embodiments of the disclosure are described in the following numbered clauses:

1. A process for spray drying a feed solution comprising a peptide wherein the process comprises introducing the feed solution comprising one or more solvents and a peptide, into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate wherein the ultrasonic nozzle power is in the range of 1-50 W, 1-40W, 1-30W, 1-20W, preferably 1-10W, more preferably 1- 5W or about 2W.

2. A process according to Clause 1, wherein the concentration of the peptide in feed solution is from: about 1% (w/w) to about 50% w/w), about 1.5% (w/w) to about 20% (w/w), about 2 % to about 15% (w/w), about 2% (w/w) to about 6% (w/w).

3. A process according to Clause 1 or 2, wherein the one or more solvents are selected from the group consisting of ethanol, isopropanol (IP A), acetonitrile and water.

4. A process according to Clause 1, 2 or 3, wherein the one or more solvents comprises up to 80% (w/w) water.

5. A process according to any of Clauses 1, 2, 3 or 4, wherein the one or more solvents comprise optionally water and up to about 100% (w/w), preferably up to about 40% (w/w) of any one or a mixture of acetonitrile, IPA and ethanol.

6. A process according to any of Clauses 1, 2, 3, 4 or 5, wherein the one or more solvents consists essentially of, and preferably consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w). 7. A process according to any of Clauses 1, 2, 3, 4, 5 or 6, wherein the pH of the feed solution is: about 5 to about 10, preferably to about 6 to about 9, more preferably about 7 to about 8.5.

8. A process according to any of Clauses 1- 7, wherein the pH of the solution is adjusted if necessary using a base, preferably selected from the group consisting of: sodium bicarbonate, ammonium acetate, phosphate buffer, ammonium hydroxide or NaOH, preferably wherein the pH is adjusted by addition of ammonium hydroxide or NaOH, more preferably by addition of a 25% (w/w) solution of ammonium hydroxide or NaOH.

9. A process according to any of Clauses 1- 8, wherein the feed flow rate is from about 1 ml/min to about 50 ml/min, preferably from about 1 ml/min to about 30 ml/min, from about 1 ml/min to about 10 ml/min, more preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min.

10. A process according to any of Clauses 1- 9, wherein the inlet temperature is from about 120 °C to about 180 °C, preferably from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

11. A process according to any of Clauses 1- 10, wherein the aspirator gas flow is from about 20 m³/h to about 50 m³/h, preferably from about 25 m³/h to about 35 m³/h and more preferably about 35 m³/h.

12. A process according to any of Clauses 1-11 wherein the obtained product has a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, about 20 to about 40 pm, about 10 pm to about 30 pm. 13. A process according to any one of Clauses 1-12 wherein the peptide is a GLP-1 peptide, preferably selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferably Tirzepatide.

14. A process according to Clause 13 wherein the peptide is Semaglutide or salt thereof, preferably Semaglutide and the concentration of Semaglutide or salt thereof in the feed solution is from about 1% (w/w) to about 15% w/w), about 1.5% (w/w) to about 10% (w/w), about 2 % to about 8% (w/w), about 2% (w/w) to about 6% (w/w).

15. A process according to Clause 14 wherein the pH of the feed solution is: about 6 to about 9, preferably to about 7 to about 8, more preferably about 7.3.

16. A process according to Clause 15 wherein the ultrasonic nozzle power is in the range of 1-10 W, preferably about 2W; or wherein the ultrasonic nozzle power is in the range of about 1 W to about 8 W, or about 2 W to about 7 W.

17. A process according to any of Clauses 14, 15 or 16 wherein the one or more solvents consists essentially of, and preferably consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 1 ml/min to about 10 ml/min, preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 180 °C, preferably from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

18. A process according to any of Clauses 14-17 wherein the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of: about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

19. A process according to any of Clauses 14-18 wherein the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

20. A process according to any of Clauses 14-19 wherein the obtained product has a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, about 20 to about 40 pm, about 10 pm to about 30 pm.

21. A process according to Clause 13 wherein the peptide is Tirzepatide or salt thereof, preferably Tirzepatide and the concentration of Tirzepatide in the feed solution is from about 1% (w/w) to about 15% w/w), about 1.5% (w/w) to about 30% (w/w), about 5 % to about 20% (w/w), about 2% (w/w) to about 6% (w/w).

22. A process according to Clause 21 wherein the pH of the feed solution is: about 5 to about 10, preferably to about 6 to about 9, preferably about 7 to about 8.5, more preferably 7.5 to about 8.5.

23. A process according to Clause 21 or 22 wherein the ultrasonic nozzle power is in the range of 1-10 W, preferably about 1-3W.

24. A process according to any of Clauses 21, 22 or 23 wherein the one or more solvents consists essentially of, and preferably consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% (w/w) to about 70% (w/w), more preferably about 15% (w/w) to about 60% (w/w), and more preferably about 30% (w/w) to about 60%(w/w) and particularly about 50%; the feed flow rate is from about 1 ml/min to about 10 ml/min, preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min; and the inlet temperature is from about 120 °C to about 180 °C, preferably from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

25. A process according to any of Clauses 21- 24 wherein the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of: about 15% (w/w) to about 70% (w/w), more preferably about 15% (w/w) to about 60% (w/w), and particularly about 30% (w/w) to about 60%(w/w) and particularly about 50%; the feed flow rate is from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

26. A process according to any of Clauses 21-25 wherein the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of about 50% (w/w); the feed flow rate is from about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

27. A process according to any of Clauses 21-26 wherein the obtained product has a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, about 20 to about 40 pm, about 10 pm to about 30 pm.

28. Peptide particles produced by any one of the processes of any one of Clauses 1-27.

29. A pharmaceutical composition, pharmaceutical formulation, or dietary composition, preferably a pharmaceutical composition or pharmaceutical formulation, comprising peptide particles according to Clause 28. 30. Peptide particles according to Clause 28, for use in the preparation of a pharmaceutical composition, pharmaceutical formulation, or a dietary composition.

31. A process for the preparation of a pharmaceutical composition, a pharmaceutical formulation, or a dietary composition as defined in Clause 29, comprising combining the peptide particles obtained by any one of the processes of clauses 1 -27 with at least one pharmaceutically acceptable excipient.

32. Peptide particles according to Clause 28, a pharmaceutical composition or pharmaceutical formulation thereof according to Clause 29, for use in the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes or in the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysisdependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin.

33. Peptide particles according to Clause 28, or dietary composition according to Clause 29, for cosmetic weight loss in non-overweight non-obese subjects.

34. A method for treating type 2 diabetes, overweight or obesity, and preferably type 2 diabetes or Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin comprising administering an effective amount of peptide particles according to Clause 28, or dietary composition according to Clause 29.

35. A method for cosmetic weight loss in non-overweight non-obese subjects comprising by administering an effective amount of GLP-1 peptide particles according to Clause 28, or dietary composition according to Clause 29.

[00139] Yet further aspects and embodiments of the disclosure are described in the following numbered clauses 1A-49A:

1A. A process for spray drying a feed solution comprising a peptide (preferably a GLP-1 or dual GIP/GLP-1 peptide), and one or more solvents, wherein the process comprises introducing the feed solution into a spray dryer equipped with an ultrasonic nozzle.

2A. A process according to Clause 1 A, wherein the feed solution comprises the peptide (preferably a GLP-1 or a dual GIP/GLP-1 peptide) and the one or more solvents; or wherein the feed solution consists essentially of the peptide (preferably a GLP-1 or a dual GIP/GLP-1 peptide) and the one or more solvents; or wherein the feed solution consists of the peptide (preferably a GLP-1 or a dual GIP/GLP-1 peptide) and the one or more solvents.

3 A. A process according to Clause 1 A or 2A, wherein the concentration of the peptide in the feed solution is from: about 1% (w/w) to about 50% w/w), about 1.5% (w/w) to about 20% (w/w), about 2 % to about 15% (w/w), about 2% (w/w) to about 6% (w/w), or wherein the concentration of the peptide in the feed solution is: about 1% (w/w) to about 30% (w/w), about 1% (w/w) to about 25% (w/w), or about 2% (w/w) to about 20% (w/w).

4A. A process according to any of Clauses 1 A, 2A or 3 A, wherein the one or more solvents are selected from the group consisting of ethanol, isopropanol (IP A), acetonitrile and water, and preferably isopropanol, acetonitrile and water. 5 A. A process according to any of Clauses 1A, 2 A, 3 A, or 4A, wherein the solvent is a mixture of water and at least one of: ethanol, isopropanol and acetonitrile; or wherein the solvent is a mixture of water and at least one of isopropanol and acetonitrile; and more particularly wherein the solvent is a mixture of water and acetonitrile.

6A. A process according to Clause 1A, 2A, 3 A, 4A, or 5 A, wherein the one or more solvents comprises, consists essentially of, or consists of, up to 80% (w/w) water, and preferably: 5% (w/w) to 80% (w/w) water, 10% (w/w) to 80% (w/w) water, 20% (w/w) to 80% (w/w) water, or 30% (w/w) to 80% (w/w) water.

7A. A process according to any of Clauses 1 A, 2 A, 3A,4A, or 5 A, wherein the one or more solvents comprises, consists essentially of, or consists of: up to about 100% (w/w), up to about 90% (w/w), up to about 80% (w/w), up to about 70% (w/w), up to about 60% (w/w), up to about 50% (w/w), and preferably up to about 40% (w/w) of any one or a mixture of acetonitrile, IPA and ethanol, with any remainder being water; or wherein the solvent comprises up to about 40% (w/w) of any one or a mixture of acetonitrile and IPA), with the remainder being water.

8A. A process according to any of Clauses 1A, 2A, 3A, 4A, or 5A, wherein the one or more solvents comprises, consists essentially of, or consists of: from 5% (w/w) to 100% (w/w), from 10% (w/w) to 90% (w/w), from 20% (w/w) to 80% (w/w), or from 20% (w/w) to 70% (w/w), of any one or a mixture of acetonitrile, IPA and ethanol, with any remainder being water; or wherein the one or more solvents comprises from 5% (w/w) to 100% (w/w), from 10% (w/w) to 90% (w/w), from 20% (w/w) to 80% (w/w), or from 20% (w/w) to 70% (w/w), of any one or a mixture of acetonitrile, and IPA, with any remainder being water.

9A. A process according to any of Clauses 1A, 2A, 3A, 4A, or 5A, wherein the one or more solvents comprises, consists essentially of, or consists of, water, and: up to about 90% (w/w), up to about 80% (w/w), up to about 70% (w/w), up to about 60% (w/w), up to about 50% (w/w), or up to about 40% (w/w), of any one or a mixture of acetonitrile, IPA and ethanol, or wherein the one or more solvents comprises water and: up to about 90% (w/w), up to about 80% (w/w), up to about 70% (w/w), up to about 60% (w/w), up to about 50% (w/w), or up to about 40% (w/w), of any one or a mixture of acetonitrile and IP A).

10A. A process according to any of Clauses 1A, 2A, 3A, 4A, or 5A, wherein the one or more solvents comprises, consists essentially of, or consists of, water, and: from 5% (w/w) to 90% (w/w) of any one or a mixture of acetonitrile, IPA and ethanol; or wherein the one or more solvents comprises water and: from 5% (w/w) to 90% (w/w), from 10% (w/w) to 90% (w/w), or from 20% (w/w) to 80% (w/w) of any one or a mixture of acetonitrile, and IPA.

11 A. A process according to any of Clauses 1 A, 2 A, 3 A, 4A, 5 A, 6 A, 7A, 8 A, 9A, or 10A, wherein the one or more solvents comprises, consists essentially of, or consists of, water and one of: acetonitrile, IPA or ethanol (preferably acetonitrile or IPA); or wherein the one or more solvents comprises, consists essentially of, or consists of, either water and acetonitrile, or water and isopropanol.

12A. A process according to any of Clauses 1A, 2 A, 3 A, 4A, 5 A, 6 A, 7A, 8 A, 9A, 10A, or 11 A, wherein the one or more solvents consists essentially of, or consists of, acetonitrile and water.

13 A. A process according to Clause 12A, wherein the one or more solvents consists essentially of, or consists of, acetonitrile and water in a w/w ratio of: 10:90 to 90: 10, 15:85 to 80:20, 20:80 to 75:25, or 20:80 to 70:30.

14A. A process according to any of Clauses 1 A, 2 A, 3 A, 4A, 5 A, wherein the one or more solvents consists essentially of, and preferably consists of, acetonitrile and water, wherein acetonitrile is present in the one or more solvents at a concentration of: about 10% (w/w) to about 90% (w/w), about 15% (w/w) to about 75% (w/w), about 20% (w/w) to about 70% (w/w), or wherein the acetonitrile is present in the one or more solvents at a concentration of: about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w). 15 A. A process according to any of Clauses 1A, 2 A, 3 A, 4A, 5 A 6 A, 7A, 8 A, 9 A, 10 A, 11 A, 12A, 13A, or 14A, wherein the pH of the feed solution is: about 5 to about 10, preferably to about 6 to about 9, more preferably about 7 to about 8.5, about 7.0 to about 8.0, about 7.1 to about 7.8, or about 7.2 to about 7.5.

16A. A process according to any of Clauses 1A, 2 A, 3 A, 4A, 5 A, 6 A, 7A, 8 A, 9A, 10A, 11A, 12A, 13 A, 14A, or 15 A, wherein the pH of the solution is adjusted if necessary using a base, preferably selected from the group consisting of: sodium bicarbonate, ammonium acetate, phosphate buffer, ammonium hydroxide or NaOH, preferably wherein the pH is adjusted by addition of ammonium hydroxide or NaOH, more preferably by addition of a 25% (w/w) solution of ammonium hydroxide or NaOH.

17A. A process according to any of Clauses 1A, 2 A, 3 A, 4A, 5 A, 6 A, 7A, 8 A, 9A, 10A, 11A, 12A, 13A, 14A, 15A, or 16A, wherein the feed solution flow rate is: about 0.5 ml/min to about 50 ml/min, about 0.5 ml /min to about 25 ml /min, about 0.6 ml/min to about 15 ml/min, about 0.6 ml/min to about 10 ml/min, about 0.6 g ml/min to about 5 ml/min about 0.6 ml/min to about 4 ml/min, about 0.8 ml/min to about 3 ml/min, about 0.5 ml/min to about 2.8 ml/min; or wherein the feed solution flow rate is: from about 1 ml/min to about 50 ml/min, preferably from about 1 ml/min to about 30 ml/min, from about 1 ml/min to about 10 ml/min, more preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min, or about 1.5 ml/min.

18 A. A process according to any of Clauses 1A, 2 A, 3 A, 4A, 5 A, 6 A, 7A, 8 A, 9A, 10A, 11A, 12A, 13 A, 14A, 15 A, 16A, or 17A, wherein the inlet temperature is : from about 110 °C to about 190 °C, about 115 °C to about 190 °C, from about 120 °C to about 180 °C, about 120 °C to about 170 °C, about 120 °C to about 160 °C, or about 120 °C to about 155 °C, about 120 °C to about 152 °C, optionally about 120 °C to about 140 °C.

19A. A process according to any of Clauses 1A, 2 A, 3 A, 4A, 5 A, 6 A, 7A, 8 A, 9A, 10A, 11A, 12A, 13A, 14A, 15A, 16A, 17A, or 18A, wherein the outlet temperature is: about 50 °C to about 100 °C, about 60 °C to about 95 °C, about 65 °C to about 95 °C, about 70 °C to about 95 °C, or about 75 °C to about 95 °C. 20A. A process according to any of Clauses 1A, 2 A, 3 A, 4A, 5 A, 6 A, 7A, 8 A, 9A, 10A, 11A, 12A, 13A, 14A, 15A, 16A, 17A, 18A, or 19A, wherein the aspirator gas flow is: about 0.1 m³/h to about 10 m³/h, about 0.1 m³/h to about 5 m³/h, about 0.1 m³/h to about 2.5 m³/h, about 0.15 m³/h to about 2.0 m³/h, about 0.15 m³/h to about 1.5 m³/h, about 0.15 m³/h to about 1.0 m³/h, about 0.2 m³/h to about 0.8 m³/h, about 0.25 m³/h to about 0.6 m³/h, about 0.3 m³/h to about 0.5 m³/h, about 0.35 m³/h to about 0.5 m³/h, or about 0.4 m³/h to about 0.5 m³/h, about 0.1 m³/h to about 2.5 m³/h.

21 A. A process according to any of Clauses 1A, 2 A, 3 A, 4A, 5 A, 6 A, 7A, 8 A, 9A, 10A, 11A, 12A, 13A, 14A, 15A, 16A, 17A, 18A, 19A, or 20A, wherein the nozzle frequency is: about 21 kHz to about 140 kHz, about 21 kHz to about 130 kHz, about 25 kHz to about 100 kHz, about 25 kHz to about 90 kHz, about 25 kHz to about 80 kHz, about 25 kHz to about 75 kHz, about 25 kHz to about 65 kHz, or about 25 kHz to about 60 kHz.

22A. A process according to any of Clauses 1A, 2 A, 3 A, 4A, 5 A, 6 A, 7A, 8 A, 9A, 10A, 11 A, 12A, 13A, 14A, 15A, 16A, 17A, 18A, 19A, 20A, or 21A, wherein the ultrasonic nozzle power is: about 1 W to about 50 W, about 1 W to about 40 W, about 1 W to about 30 W, about 1 W to about 20 W, about 1 W to about 10 W, about 1 W to about 8 W, about 1 W to about 7 W, about 2 W to about 7 W, about 1 W to about 6 W, about 1 W to about 5 W, or about 2 W to about 5 W.

23 A. A process according to any of Clauses 1A, 2A, 3 A, 4A, 5A, 6A, 7A, 8A, 9A, 10A, 11A, 12A, 13A, 14A, 15A, 16A, 17A, 18A, 19A, 20A, 21A, or 22A, wherein the obtained product has a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, about 20 to about 40 pm, or about 10 pm to about 30 pm.

24A. A process according to any one of Clauses 1 A-23A wherein the peptide is a GLP-1 peptide, preferably selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide; or wherein the peptide is a dual GLP-l/GIP peptide, preferably Tirzepatide or salt thereof, and more preferably Tirzepatide.

25 A. A process according to Clause 24A wherein the peptide is Semaglutide or salt thereof, preferably Semaglutide and the concentration of Semaglutide or salt thereof in the feed solution is: about 1% to about 25%, about 1.5% to about 25%, about 1.5% w/w to about 22% w/w, about 1% to about 20%, about 1% (w/w) to about 15% w/w), or about 1.5% (w/w) to about 10% (w/w), or about 2% (w/w) to about 20% w/w).

26A. A process according to any of Clause 25 A wherein the pH of the feed solution is: about 6 to about 9, preferably to about 7 to about 8, about 7.0 to about 7.5, or about 7.2 to about 7.53.

27A. A process according to Clause 25A or Clause 26A wherein the ultrasonic nozzle power is in the range of: about 1 W to about 50 W, about 1 W to about 40 W, about 1 W to about 30 W, about 1 W to about 20 W, about 1 W to about 10 W, about 1 W to about 8 W, about 1 W to about 7 W, about 2 W to about 7 W, about 1 W to about 6 W, about 1 W to about 5 W, or about 2 W to about 5 W, or about 2W.

28A. A process according to any of Clauses 25A, 26A or 27A, wherein the one or more solvents consists essentially of, or consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is: about 0.6 ml/min to about 10 ml/min, about 0.6 ml/min to about 5 ml/min, about 1 ml/min to about 3 ml/min, about 1 ml/min to about 10 ml/min, preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 180 °C, preferably from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C. 29A. A process according to any of Clauses 25A, 26A, 27 A, or 28A, wherein the one or more solvents consists essentially of, or consists of, acetonitrile and water wherein acetonitrile is present in the one or more solvents at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 0.6 ml/min to about 10 ml/min, about 0.6 ml/min to about 5 ml/min, about 1 ml/min to about 3 ml/min, about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

30A. A process according to any of Clauses 25A, 26A, 27 A, 28A, or 29A, wherein the one or more solvents consists essentially of, or consists of, acetonitrile and water wherein acetonitrile is present at a concentration of about 15% to about 60%, about 15% to about 50%, about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is about 0.6 ml/min to about 5 ml/min, about 1 ml/min to about 3, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 150 °C (or about 120 °C to about 140 °C, or 130 °C).

31 A. A process according to any of Clauses 25 A, 26A, 27 A, 28 A, 29 A, or 30A, wherein the obtained product has a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, about 20 to about 40 pm, about 10 pm to about 30 pm.

32A. A process according to Clause 24A wherein the peptide is Tirzepatide or salt thereof, preferably Tirzepatide and the concentration of Tirzepatide in the feed solution is from about 1% to about 25%, about 1% to about 20%, 1% (w/w) to about 15% w/w), about 1.5% (w/w) to about 30% (w/w), about 5 % to about 20% (w/w), about 2% (w/w) to about 6% (w/w). 33A. A process according to any of Clause 32A wherein the pH of the feed solution is: about 5 to about 10, preferably to about 6 to about 9, preferably about 7 to about 8.5, more preferably 7.5 to about 8.5.

34A. A process according to Clause 32A or Clause 33 A, wherein the ultrasonic nozzle power is in the range of 1-10 W, or in the range of 1-7 W, or in the range of 1-3 W.

35A. A process according to any of Clauses 32A, 33A or 34A, wherein the one or more solvents consists essentially of, and preferably consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 30% (w/w) to about 50% (w/w).

36A. A process according to any of Clauses 32A, 33A, 34A, or 35A , wherein the feed flow rate is from about 0.5 g/min to about 10 g/min, about 0.5 g/min to about 5 g/min, about 0.5 ml/min to about 3 ml/min, preferably from about 0.5 ml/min to about 2 ml/min, about 0.5 ml/min to about 1.5 ml/min, about 0.5 ml/min to about 1.2 ml/min, about 0.5 ml/min to about 1.0 ml/min, about 0.6 ml/min to about 0.9 ml/min, or about 0.7 ml/min to about 0.8 ml/min.

37A. A process according to any of Clauses 32A, 33A, 34A, 35A, or 36A, wherein the inlet temperature is from: about 120 °C to about 180 °C, about 120 °C to about 170 °C, about 120 °C to about 160 °C, about 125 °C to about 155 °C, or about 128 °C to about 150 °C.

38A. A process according to any of Clauses 32A, 33A, 34A, 35A, 36A, or 37A, wherein the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 30% (w/w) to about 50% (w/w); the feed flow rate is from about 0.5 g/min to about 10 g/min, about 0.5 g/min to about 5 g/min, about 0.5 ml/min to about 3 ml/min, about 0.5 ml/min to about 2 ml/min; and the inlet temperature is from about 120 °C to about 150 °C.

39A. A process according to any of Clauses 32A, 33A, 34A, 35A, 36A, 37A, or 38A, wherein the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of about 15% to about 60%, about 15% to about 50%, about 30% (w/w) to about 50% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 0.5 ml/min to about 5 ml/min or about 0.5 to about 2 ml/min; and the inlet temperature is from about 120 °C to about 150 °C.

40A. A process according to any of Clauses 32A, 33A, 34A, 35A, 36A, 37A, 38A, or 39A, wherein the obtained product has a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, about 20 to about 40 pm, or about 10 pm to about 30 pm.

41 A. A process according to any of Clauses 1A-40A, further comprising combining the spray dried peptide with at least one pharmaceutically acceptable excipient to form a pharmaceutical composition.

42A. Peptide particles produced by any one of the processes of any one of Clauses 1A-40A.

43 A. A pharmaceutical composition, pharmaceutical formulation, or dietary composition, preferably a pharmaceutical composition or pharmaceutical formulation, comprising peptide particles according to Clause 42A.

44A. Peptide particles according to Clause 42A, for use in the preparation of a pharmaceutical composition, pharmaceutical formulation, or a dietary composition.

45A. A process for the preparation of a pharmaceutical composition, a pharmaceutical formulation, or a dietary composition as defined in Clause 43 A, comprising combining the peptide particles obtained by any one of the processes of clauses 1 A-40A with at least one pharmaceutically acceptable excipient.

46A. Peptide particles according to Clause 42A, a pharmaceutical composition or pharmaceutical formulation, or a dietary composition thereof according to Clause 43 A, for use in the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes or in the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin.

47A. Peptide particles according to Clause 42A, or dietary composition according to Clause 43 A, for cosmetic weight loss in non-overweight non-obese subjects.

48A. A method for treating type 2 diabetes, overweight or obesity, and preferably type 2 diabetes or in the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly- controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin comprising administering an effective amount of GLP-1 peptide particles or GLP-l/GIP peptide particles according to Clause 42A, or a pharmaceutical composition, a pharmaceutical formulation or a dietary composition according to Clause 43 A.

49A. A method for cosmetic weight loss in non-overweight non-obese subjects comprising by administering an effective amount of GLP-1 peptide particles according to Clause 42A, or dietary composition according to Clause 43 A.

Claims

1. A process for spray drying a feed solution comprising a peptide wherein the process comprises introducing the feed solution comprising one or more solvents and a peptide, into a spray dryer equipped with an ultrasonic nozzle at a feed flow rate, wherein the ultrasonic nozzle power is in the range of 1-50 W, 1-40W, 1-30W, 1-20W, preferably 1-10W, more preferably 1- 5W or about 2W.

2. A process according to Claim 1, wherein the concentration of the peptide in feed solution is from: about 1% (w/w) to about 50% w/w), about 1.5% (w/w) to about 20% (w/w), about 2 % to about 15% (w/w), or about 2% (w/w) to about 6% (w/w).

3. A process according to Claim 1 or 2, wherein the one or more solvents are selected from the group consisting of ethanol, isopropanol (IP A), acetonitrile and water.

4. A process according to Claim 1, 2, or 3, wherein the one or more solvents comprises up to 80% (w/w) water.

5. A process according to any of Claims 1, 2, 3, or 4, wherein the one or more solvents comprise optionally water and up to about 100% (w/w), preferably up to about 40% (w/w) of any one or a mixture of acetonitrile, IPA and ethanol.

6. A process according to any of Claims 1, 2, 3, 4, or 5, wherein the one or more solvents consists essentially of, and preferably consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w).

7. A process according to any of Claims 1, 2, 3, 4, 5, or 6, wherein the pH of the feed solution is: about 5 to about 10, preferably to about 6 to about 9, more preferably about 7 to about 8.5.

8. A process according to any of Claims 1-7, wherein the pH of the solution is adjusted if necessary using a base, preferably selected from the group consisting of: sodium bicarbonate, ammonium acetate, phosphate buffer, ammonium hydroxide or NaOH, preferably wherein the pH is adjusted by addition of ammonium hydroxide or NaOH, more preferably by addition of a 25% (w/w) solution of ammonium hydroxide or NaOH.

9. A process according to any of Claims 1-8, wherein the feed flow rate is from about 1 ml/min to about 50 ml/min, preferably from about 1 ml/min to about 30 ml/min, from about 1 ml/min to about 10 ml/min, more preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min, or about 1.5 ml/min.

10. A process according to any of Claims 1-9, wherein the inlet temperature is from about 120 °C to about 180 °C, preferably from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

11. A process according to any of Claims 1-10, wherein the aspirator gas flow is from about 20 m³/h to about 50 m³/h, preferably from about 25 m³/h to about 35 m³/h and more preferably about 35 m³/h.

12. A process according to any of Claims 1-11, wherein the obtained product has a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, about 20 to about 40 pm, or about 10 pm to about 30 pm.

13. A process according to any one of Claims 1-12, wherein the peptide is a GLP-1 peptide, preferably selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide or a dual GLP-1 /GIP peptide particles, preferably Tirzepatide or salt thereof, and most preferably Tirzepatide.

14. A process according to Claim 13, wherein the peptide is Semaglutide or salt thereof, preferably Semaglutide and the concentration of Semaglutide or salt thereof in the feed solution is from about 1% (w/w) to about 15% w/w), about 1.5% (w/w) to about 10% (w/w), about 2 % to about 8% (w/w), or about 2% (w/w) to about 6% (w/w).

15. A process according to any of Claim 14, wherein the pH of the feed solution is: about 6 to about 9, preferably to about 7 to about 8, more preferably about 7.3.

16. A process according to Claim 15, wherein the ultrasonic nozzle power is in the range of 1-10 W, preferably about 2W; or wherein the ultrasonic nozzle power is in the range of about 1 W to about 8 W, or about 2 W to about 7 W.

17. A process according to any of Claims 14, 15, or 16 wherein the one or more solvents consists essentially of, and preferably consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 1 ml/min to about 10 ml/min, preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 180 °C, preferably from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

18. A process according to any of Claims 14-17, wherein the one or more solvents consists essentially of acetonitrile and water, wherein acetonitrile is present at a concentration of: about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

19. A process according to any of Claims 14-18, wherein the one or more solvents consists essentially of acetonitrile and water, wherein acetonitrile is present at a concentration of about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

20. A process according to any of Claims 14-19, wherein the obtained product has a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, about 20 to about 40 pm, or about 10 pm to about 30 pm.

21. A process according to Claim 13, wherein the peptide is Tirzepatide or salt thereof, preferably Tirzepatide and the concentration of Tirzepatide in the feed solution is from about 1% (w/w) to about 15% w/w), about 1.5% (w/w) to about 30% (w/w), about 5 % to about 20% (w/w), or about 2% (w/w) to about 6% (w/w).

22. A process according to any of Claim 21, wherein the pH of the feed solution is: about 5 to about 10, preferably to about 6 to about 9, preferably about 7 to about 8.5, more preferably 7.5 to about 8.5.

23. A process according to Claim 21 or Claim 22, wherein the ultrasonic nozzle power is in the range of 1-10 W, preferably about 1-3W.

24. A process according to any of Claims 21, 22, or 23, wherein the one or more solvents consists essentially of, and preferably consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% (w/w) to about 70% (w/w), more preferably about 15% (w/w) to about 60% (w/w), and more preferably about 30% (w/w) to about 60%(w/w) and particularly about 50%; the feed flow rate is from about 1 ml/min to about 10 ml/min, preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min; and the inlet temperature is from about 120 °C to about 180 °C, preferably from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

25. A process according to any of Claims 21-24 wherein the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of: about 15% (w/w) to about 70% (w/w), more preferably about 15% (w/w) to about 60% (w/w), and particularly about 30% (w/w) to about 60%(w/w) and particularly about 50%; the feed flow rate is from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

26. A process according to any of Claims 21-25, wherein the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of about 50% (w/w); the feed flow rate is from about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

27. A process according to any of Claims 21-26, wherein the obtained product has a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, about 20 to about 40 pm, or about 10 pm to about 30 pm.

28. Peptide particles produced by any one of the processes of any one of Claims 1-27.

29. A pharmaceutical composition, pharmaceutical formulation, or dietary composition, preferably a pharmaceutical composition or pharmaceutical formulation, comprising peptide particles according to Claim 28.

30. Peptide particles according to Claim 28, for use in the preparation of a pharmaceutical composition, pharmaceutical formulation, or a dietary composition.

31. A process for the preparation of a pharmaceutical composition, a pharmaceutical formulation, or a dietary composition as defined in Claim 29, comprising combining the peptide particles obtained by any one of the processes of Claims 1-27 with at least one pharmaceutically acceptable excipient.

32. Peptide particles according to Claim 28, a pharmaceutical composition or pharmaceutical formulation thereof according to Claim 29, for use in the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes or in the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysisdependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, or obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin

33. Peptide particles according to Claim 28, or dietary composition according to Claim 29, for cosmetic weight loss in non-overweight non-obese subjects.

34. A method for treating type 2 diabetes, overweight or obesity, and preferably type 2 diabetes or Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, or obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin comprising administering an effective amount of peptide particles according to Claim 28, or dietary composition according to Claim 29.

35. A method for cosmetic weight loss in non-overweight non-obese subjects comprising by administering an effective amount of GLP-1 peptide particles according to Claim 28, or dietary composition according to Claim 29.

36. A process for spray drying a feed solution comprising a peptide (preferably a GLP-1 or dual GIP/GLP-1 peptide), and one or more solvents, wherein the process comprises introducing the feed solution into a spray dryer equipped with an ultrasonic nozzle.

37. A process according to Claim 36, wherein the feed solution comprises the peptide (preferably a GLP-1 or a dual GIP/GLP-1 peptide) and the one or more solvents; or wherein the feed solution consists essentially of the peptide (preferably a GLP-1 or a dual GIP/GLP-1 peptide) and the one or more solvents; or wherein the feed solution consists of the peptide (preferably a GLP-1 or a dual GIP/GLP-1 peptide) and the one or more solvents.

38. A process according to Claim 36 or 37, wherein the concentration of the peptide in the feed solution is from: about 1% (w/w) to about 50% w/w), about 1.5% (w/w) to about 20% (w/w), about 2 % to about 15% (w/w), about 2% (w/w) to about 6% (w/w), or wherein the concentration of the peptide in the feed solution is: about 1% (w/w) to about 30% (w/w), about 1% (w/w) to about 25% (w/w), or about 2% (w/w) to about 20% (w/w).

39. A process according to any of Claims 36, 37, or 38, wherein the one or more solvents are selected from the group consisting of ethanol, isopropanol (IP A), acetonitrile and water, and preferably isopropanol, acetonitrile and water.

40. A process according to any of Claims 36, 37, 38, or 39, wherein the solvent is a mixture of water and at least one of: ethanol, isopropanol and acetonitrile; or wherein the solvent is a mixture of water and at least one of isopropanol and acetonitrile; and more particularly wherein the solvent is a mixture of water and acetonitrile.

41. A process according to Claim 36, 37, 38, 39, or 40, wherein the one or more solvents comprises, consists essentially of, or consists of, up to 80% (w/w) water, and preferably: 5% (w/w) to 80% (w/w) water, 10% (w/w) to 80% (w/w) water, 20% (w/w) to 80% (w/w) water, or 30% (w/w) to 80% (w/w) water.

42. A process according to any of Claims 36, 37, 38, 39, or 40, wherein the one or more solvents comprises, consists essentially of, or consists of: up to about 100% (w/w), up to about 90% (w/w), up to about 80% (w/w), up to about 70% (w/w), up to about 60% (w/w), up to about 50% (w/w), and preferably up to about 40% (w/w) of any one or a mixture of acetonitrile, IPA and ethanol, with any remainder being water; or wherein the solvent comprises up to about 40% (w/w) of any one or a mixture of acetonitrile and IPA), with the remainder being water.

43. A process according to any of Claims 36, 37, 38, 39, or 40, wherein the one or more solvents comprises, consists essentially of, or consists of: from 5% (w/w) to 100% (w/w), from 10% (w/w) to 90% (w/w), from 20% (w/w) to 80% (w/w), or from 20% (w/w) to 70% (w/w), of any one or a mixture of acetonitrile, IPA and ethanol, with any remainder being water; or wherein the one or more solvents comprises from 5% (w/w) to 100% (w/w), from 10% (w/w) to 90% (w/w), from 20% (w/w) to 80% (w/w), or from 20% (w/w) to 70% (w/w), of any one or a mixture of acetonitrile, and IPA, with any remainder being water.

44. A process according to any of Claims 36, 37, 38, 39, or 40, wherein the one or more solvents comprises, consists essentially of, or consists of, water, and: up to about 90% (w/w), up to about 80% (w/w), up to about 70% (w/w), up to about 60% (w/w), up to about 50% (w/w), or up to about 40% (w/w), of any one or a mixture of acetonitrile, IPA and ethanol, or wherein the one or more solvents comprises water and: up to about 90% (w/w), up to about 80% (w/w), up to about 70% (w/w), up to about 60% (w/w), up to about 50% (w/w), or up to about 40% (w/w), of any one or a mixture of acetonitrile and IPA).

45. A process according to any of Claims 36, 37, 38, 39, or 40, wherein the one or more solvents comprises, consists essentially of, or consists of, water, and: from 5% (w/w) to 90% (w/w) of any one or a mixture of acetonitrile, IPA and ethanol; or wherein the one or more solvents comprises water and: from 5% (w/w) to 90% (w/w), from 10% (w/w) to 90% (w/w), or from 20% (w/w) to 80% (w/w) of any one or a mixture of acetonitrile, and IPA.

46. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, or 45, wherein the one or more solvents comprises, consists essentially of, or consists of, water and one of: acetonitrile, IPA or ethanol (preferably acetonitrile or IP A); or wherein the one or more solvents comprises, consists essentially of, or consists of, either water and acetonitrile, or water and isopropanol.

47. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, or 46, wherein the one or more solvents consists essentially of, or consists of, acetonitrile and water.

48. A process according to Claim 47, wherein the one or more solvents consists essentially of, or consists of, acetonitrile and water in a w/w ratio of: 10:90 to 90: 10, 15:85 to 80:20, 20:80 to 75:25, or 20:80 to 70:30.

49. A process according to any of Claims 36, 37, 38, 39, or 40, wherein the one or more solvents consists essentially of, and preferably consists of, acetonitrile and water, wherein acetonitrile is present in the one or more solvents at a concentration of: about 10% (w/w) to about 90% (w/w), about 15% (w/w) to about 75% (w/w), about 20% (w/w) to about 70% (w/w), or wherein the acetonitrile is present in the one or more solvents at a concentration of: about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w).

50. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, or 49, wherein the pH of the feed solution is: about 5 to about 10, preferably to about 6 to about 9, more preferably about 7 to about 8.5, about 7.0 to about 8.0, about 7.1 to about 7.8, or about 7.2 to about 7.5.

51. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50, wherein the pH of the solution is adjusted if necessary using a base, preferably selected from the group consisting of: sodium bicarbonate, ammonium acetate, phosphate buffer, ammonium hydroxide or NaOH, preferably wherein the pH is adjusted by addition of ammonium hydroxide or NaOH, more preferably by addition of a 25% (w/w) solution of ammonium hydroxide or NaOH.

52. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51, wherein the feed solution flow rate is: about 0.5 ml/min to about 50 ml/min, about 0.5 ml /min to about 25 ml /min, about 0.6 ml/min to about 15 ml/min, about 0.6 ml/min to about 10 ml/min, about 0.6 g ml/min to about 5 ml/min about 0.6 ml/min to about 4 ml/min, about 0.8 ml/min to about 3 ml/min, about 0.5 ml/min to about 2.8 ml/min; or wherein the feed solution flow rate is: from about 1 ml/min to about 50 ml/min, preferably from about 1 ml/min to about 30 ml/min, from about 1 ml/min to about 10 ml/min, more preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min, or about 1.5 ml/min.

53. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, or 52, wherein the inlet temperature is: from about 110 °C to about 190 °C, about 115 °C to about 190 °C, from about 120 °C to about 180 °C, about 120 °C to about 170 °C, about 120 °C to about 160 °C, or about 120 °C to about 155 °C, about 120 °C to about 152 °C, optionally about 120 °C to about 140 °C.

54. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, or 53, wherein the outlet temperature is: about 50 °C to about 100 °C, about 60 °C to about 95 °C, about 65 °C to about 95 °C, about 70 °C to about 95 °C, or about 75 °C to about 95 °C.

55. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, or 54, wherein the aspirator gas flow is: about 0.1 m³/h to about 10 m³/h, about 0.1 m³/h to about 5 m³/h, about 0.1 m³/h to about 2.5 m³/h, about 0.15 m³/h to about 2.0 m³/h, about 0.15 m³/h to about 1.5 m³/h, about 0.15 m³/h to about 1.0 m³/h, about 0.2 m³/h to about 0.8 m³/h, about 0.25 m³/h to about 0.6 m³/h, about 0.3 m³/h to about 0.5 m³/h, about 0.35 m³/h to about 0.5 m³/h, or about 0.4 m³/h to about 0.5 m³/h, about 0.1 m³/h to about 2.5 m³/h.

56. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, or 55, wherein the nozzle frequency is: about 21 kHz to about 140 kHz, about 21 kHz to about 130 kHz, about 25 kHz to about 100 kHz, about 25 kHz to about 90 kHz, about 25 kHz to about 80 kHz, about 25 kHz to about 75 kHz, about 25 kHz to about 65 kHz, or about 25 kHz to about 60 kHz.

57. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55 or 56, wherein the ultrasonic nozzle power is: about 1 W to about 50 W, about 1 W to about 40 W, about 1 W to about 30 W, about 1 W to about 20 W, about 1 W to about 10 W, about 1 W to about 8 W, about 1 W to about 7 W, about 2 W to about 7 W, about 1 W to about 6 W, about 1 W to about 5 W, or about 2 W to about 5 W.

58. A process according to any of Claims 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, or 57, wherein the obtained product has a PSD characterized by a D(90) value of not more than 120 um ± 20%, preferably not more than 80 um ± 20%, preferably not more than 50 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 150 pm, about 10 pm to about 120 pm, about 15 pm to about 100 pm, about 20 pm to about 80 pm, about 20 to about 40 pm, or about 10 pm to about 30 pm.

59. A process according to any one of Claims 36-58, wherein the peptide is a GLP-1 peptide, preferably selected from Liraglutide, Dulaglutide, Exanetide, Lixisenatide and/or Semaglutide or a salt thereof; preferably Liraglutide and Semaglutide, or a salt thereof; more preferably Semaglutide or a salt thereof; and most preferably Semaglutide; or wherein the peptide is a dual GLP-l/GIP peptide, preferably Tirzepatide or salt thereof, and more preferably Tirzepatide.

60. A process according to Claim 59 wherein the peptide is Semaglutide or salt thereof, preferably Semaglutide and the concentration of Semaglutide or salt thereof in the feed solution is: about 1% to about 25%, about 1.5% to about 25%, about 1.5% w/w to about 22% w/w, about 1% to about 20%, about 1% (w/w) to about 15% w/w), or about 1.5% (w/w) to about 10% (w/w), or about 2% (w/w) to about 20% w/w).

1

61. A process according to any of Claim 60, wherein the pH of the feed solution is: about 6 to about 9, preferably to about 7 to about 8, about 7.0 to about 7.5, or about 7.2 to about 7.5.

62. A process according to Claim 60 or Claim 61, wherein the ultrasonic nozzle power is in the range of: about 1 W to about 50 W, about 1 W to about 40 W, about 1 W to about 30 W, about 1 W to about 20 W, about 1 W to about 10 W, about 1 W to about 8 W, about 1 W to about 7 W, about 2 W to about 7 W, about 1 W to about 6 W, about 1 W to about 5 W, or about 2 W to about 5 W, or about 2W.

63. A process according to any of Claims 60, 61, or 62, wherein the one or more solvents consists essentially of, or consists of, acetonitrile and water, more preferably wherein acetonitrile is present in the one or more solvents at a concentration (w/w) of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is: about 0.6 ml/min to about 10 ml/min, about 0.6 ml/min to about 5 ml/min, about 1 ml/min to about 3 ml/min, about 1 ml/min to about 10 ml/min, preferably from about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 180 °C, preferably from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

64. A process according to any of Claims 60, 61, 62, or 63, wherein the one or more solvents consists essentially of, or consists of, acetonitrile and water wherein acetonitrile is present at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 15% (w/w) to about 25% (w/w), more preferably about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 0.6 ml/min to about 10 ml/min, about 0.6 ml/min to about 5 ml/min, about 1 ml/min to about 3 ml/min, about 1 ml/min to about 5 ml/min, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 140 °C and more preferably the inlet temperature is about 130 °C.

65. A process according to any of Claims 60, 61, 62, 63, or 64 wherein the one or more solvents consists essentially of, or consists of, acetonitrile and water wherein acetonitrile is present at a concentration of about 15% to about 60%, about 15% to about 50%, about 18% (w/w) to about 22% (w/w), and particularly about 20% (w/w); the feed flow rate is about 0.6 ml/min to about 5 ml/min, about 1 ml/min to about 3, about 1 ml/min to about 2.5 ml/min or about 1.5 ml/min; and the inlet temperature is from about 120 °C to about 150 °C (or about 120 °C to about 140 °C, or 130 °C).

66. A process according to any of Claims 60, 61, 62, 63, 64, or 65 wherein the obtained product has a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, about 20 to about 40 pm, about 10 pm to about 30 pm.

67. A process according to Claim 59, wherein the peptide is Tirzepatide or salt thereof, preferably Tirzepatide and the concentration of Tirzepatide in the feed solution is from about 1% to about 25%, about 1% to about 20%, 1% (w/w) to about 15% w/w), about 1.5% (w/w) to about 30% (w/w), about 5 % to about 20% (w/w), about 2% (w/w) to about 6% (w/w).

68. A process according to any of Claim 67 wherein the pH of the feed solution is: about 5 to about 10, preferably to about 6 to about 9, preferably about 7 to about 8.5, more preferably 7.5 to about 8.5.

69. A process according to Claim 67 or Claim 68, wherein the ultrasonic nozzle power is in the range of 1-10 W, or in the range of 1-7 W, or in the range of 1-3 W.

70. A process according to any of Claims 67, 68, or 69, wherein the one or more solvents consists essentially of, and preferably consists of, acetonitrile and water, more preferably wherein acetonitrile is present at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, or about 30% (w/w) to about 50% (w/w).

71. A process according to any of Claims 67, 68, 69, or 70, wherein the feed flow rate is from about 0.5 g/min to about 10 g/min, about 0.5 g/min to about 5 g/min, about 0.5 ml/min to about 3 ml/min, preferably from about 0.5 ml/min to about 2 ml/min, about 0.5 ml/min to about 1.5 ml/min, about 0.5 ml/min to about 1.2 ml/min, about 0.5 ml/min to about 1.0 ml/min, about 0.6 ml/min to about 0.9 ml/min, or about 0.7 ml/min to about 0.8 ml/min.

72. A process according to any of Claims 67, 68, 69, 70, or 71, wherein the inlet temperature is from: about 120 °C to about 180 °C, about 120 °C to about 170°C, about 120 °C to about 160 °C, about 125 °C to about 155 °C, or about 128 °C to about 150°C.

73. A process according to any of Claims 67, 68, 69, 70, 71, or 72. wherein the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of: about 15% to about 70%, about 15% to about 60%, about 15% to about 50%, about 30% (w/w) to about 50% (w/w); the feed flow rate is from about 0.5 g/min to about 10 g/min, about 0.5 g/min to about 5 g/min, about 0.5 ml/min to about 3 ml/min, about 0.5 ml/min to about 2 ml/min; and the inlet temperature is from about 120 °C to about 150 °C.

74. A process according to any of Claims 67, 68, 69, 70, 71, 72, or 73, wherein the one or more solvents consists essentially of acetonitrile and water wherein acetonitrile is present at a concentration of about 15% to about 60%, about 15% to about 50%, about 30% (w/w) to about 50% (w/w), and particularly about 20% (w/w); the feed flow rate is from about 0.5 ml/min to about 5 ml/min or about 0.5 to about 2 ml/min; and the inlet temperature is from about 120 °C to about 150 °C.

75. A process according to any of Claims 67, 68, 69, 70, 71, 72, 73, or 74 , wherein the obtained product has a PSD characterized by a D(90) value of not more than 60 um ± 20%, preferably not more than 40 um ± 20%, preferably not more than 30 um ± 20%, more preferably not more than 20 um ± 20%, or a PSD characterized by a D(90) value of about 8 pm to about 80 pm, about 10 pm to about 70 pm, about 15 pm to about 65 pm, about 20 pm to about 60 pm, about 20 to about 40 pm, or about 10 pm to about 30 pm.

76. A process according to any of Claims 36-75, further comprising combining the spray dried peptide with at least one pharmaceutically acceptable excipient to form a pharmaceutical composition.

77. Peptide particles produced by any one of the processes of any one of Claims 36-75.

78. A pharmaceutical composition, pharmaceutical formulation, or dietary composition, preferably a pharmaceutical composition or pharmaceutical formulation, comprising peptide particles according to Claim 77.

79. Peptide particles according to Claim 77, for use in the preparation of a pharmaceutical composition, pharmaceutical formulation, or a dietary composition.

80. A process for the preparation of a pharmaceutical composition, a pharmaceutical formulation, or a dietary composition as defined in Claim 78, comprising combining the peptide particles obtained by any one of the processes of Claims 36-75 with at least one pharmaceutically acceptable excipient.

81. Peptide particles according to Claim 77, a pharmaceutical composition or pharmaceutical formulation, or a dietary composition thereof according to Claim 78, for use in the treatment of type 2 diabetes, overweight or obesity, and preferably type 2 diabetes or in the treatment of Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly-controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin.

82. Peptide particles according to Claim 77, or dietary composition according to Claim 78, for cosmetic weight loss in non-overweight non-obese subjects.

83. A method for treating type 2 diabetes, overweight or obesity, and preferably type 2 diabetes or treating Systemic Scleroderma, obesity and polycystic ovarian syndrome, Atherosclerosis or Cardiovascular Diseases in people with type 2 diabetes and/or obesity, Chronic Kidney Disease or dialysis-dependent end-stage kidney disease in T2DM and overweight/obesity, Cystic Fibrosis or Cystic Fibrosis-related Diabetes, Advanced Lung Disease, NASH - Nonalcoholic Steatohepatitis or NAFLD or Liver Transplant Recipients with poorly- controlled Diabetes Mellitus, Addiction Alcohol Use Disorder, Tobacco Use Disorder Nicotine Addiction, or obesity in patients with schizophrenia-spectrum disorder who did not demonstrate adequate weight loss on metformin comprising administering an effective amount of GLP-1 peptide particles or GLP-l/GIP peptide particles according to Claim 77, or a pharmaceutical composition, a pharmaceutical formulation or a dietary composition according to Claim 78.

84. A method for cosmetic weight loss in non-overweight non-obese subjects comprising by administering an effective amount of GLP-1 peptide particles according to Claim 77, or dietary composition according to Claim 78.