Spray-drying process for polypeptide
By using a low-temperature spray drying process, controlling the feed and outlet temperatures, and using a specific gas as the atomizing gas, the decomposition of peptide drugs in high-temperature spray drying has been solved, achieving high yield and stability, and improving the safety and efficacy of the drugs.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- SHENZHEN JYMED TECH
- Filing Date
- 2024-11-30
- Publication Date
- 2026-06-04
AI Technical Summary
Existing spray drying technology has a significant impact on the heat sensitivity of peptide drugs under high temperature conditions, leading to problems such as decomposition and polymerization, which affect the safety and efficacy of the drugs, while also resulting in low yield.
The process employs a low-temperature spray drying process, controlling the inlet temperature at 45–81°C, the relative humidity of the atomizing gas at less than 10%, and the outlet temperature at 25–66°C. Compressed air or nitrogen is used as the atomizing gas to ensure that the peptides are not damaged during the spray drying process.
High yield (greater than 93%) of peptides was achieved under low-temperature conditions, while maintaining the stability and activity of the peptides and keeping the impurity content essentially unchanged, thus improving the safety and efficacy of the drug and making it suitable for industrial production.
Smart Images
Figure CN2024135974_04062026_PF_FP_ABST
Abstract
Description
A spray drying process for peptides Technical Field
[0001] This invention relates to the field of spray drying of feed solutions containing peptides. More specifically, this invention relates to a low-temperature spray drying process for feed solutions containing peptides. Technical Background
[0002] Due to their unique heat sensitivity and instability, peptide drugs place high demands on drying technology. The drying process is crucial in production, directly affecting the drug's activity, stability, and bioavailability. Because peptide drugs have short half-lives and are easily degraded at room temperature, the drying process requires precise temperature control and high efficiency. Freeze-drying and spray-drying technologies have become the preferred methods for peptide drug production. Among them, spray-drying technology has attracted much attention due to its high efficiency, continuous production, ease of scaling, and cost-effectiveness. It can protect the active ingredient, precisely control the particle size, morphology, and flowability of the dry powder, while shortening drying time and improving solubility and dispersibility. The particle size of the active pharmaceutical ingredient (API) is crucial in the development of solid dosage forms, affecting key quality attributes, content uniformity, dissolution profiles, and manufacturing processes. For peptide products, good solubility and dispersibility mean higher bioavailability and in vivo absorption efficiency, thereby improving therapeutic effects. Spray-drying technology also enables continuous production, simplifying the preparation of dosage forms such as tablets and capsules.
[0003] Patent CN 113194929B discloses a spray drying process for a feed solution containing smegglutinin, achieving a high product yield. Patent CN102256598A discloses a spray drying method for GLP-1 analogs, yielding products with smaller particle diameters. However, in patent CN 113194929B, the outlet temperature of the spray dryer is 55-90℃, and the inlet temperature is 85-200℃, even reaching as high as 130-150℃; in patent CN102256598A, the temperature of the drying gas is 100-200℃. For heat-sensitive active pharmaceutical ingredients such as peptides, decomposition, polymerization, and oxidation are easily caused by heat. Such high temperatures could potentially generate impurities in the peptides that could affect their safety and efficacy. Summary of the Invention
[0004] To address the aforementioned problems, this invention provides a low-temperature spray drying process for peptides, yielding peptides with stable particle size, low impurity content, and minimal changes in related substances before and after spray drying. To achieve the objectives of this invention, a spray drying process for a feed solution containing peptides is also provided:
[0005] The process mainly involves introducing a feed solution containing a certain concentration of peptides into a spray dryer, and introducing atomizing gas at an atomizing gas flow rate, wherein the feed inlet temperature is 45-81°C and the relative humidity of the atomizing gas is less than 10%.
[0006] In some implementations, the feed inlet temperature is 50–70°C.
[0007] In some implementations, the feed inlet temperature is 50–55°C.
[0008] In some embodiments, the relative humidity of the atomizing gas is 4-10%.
[0009] In some embodiments, the feed solution contains 50–200 g / L of polypeptide.
[0010] In some embodiments, the feed solution contains 70–120 g / L of polypeptide.
[0011] In some implementation schemes, the outlet temperature is also set at 25–66°C.
[0012] In some implementations, the outlet temperature is 25–40°C.
[0013] In some embodiments, the feed solution solvent is water or an aqueous organic solvent.
[0014] In some embodiments, the feed solution solvent is a 30-60% (w / w) aqueous ethanol solution.
[0015] In some embodiments, the feed solution solvent is a 30-60% (w / w) aqueous solution of acetonitrile.
[0016] In some implementations, the atomizing gas is compressed air or nitrogen.
[0017] In some embodiments, the polypeptide is selected from smegglutinin, telpogglutinin, and liraglutinin.
[0018] The polypeptides obtained by the method of the present invention can be used in pharmaceutical compositions together with one or more pharmaceutically acceptable excipients.
[0019] The polypeptides obtained by the method of the present invention can be used together with one or more components in a cosmetic composition.
[0020] The product obtained by the process of the present invention is intended for use in pharmaceutical compositions with one or more pharmaceutically acceptable excipients. In some embodiments, the product obtained by the process of the present invention may be used for subcutaneous administration. In some embodiments, the product obtained by this process may be used for oral administration, for example in tablet form.
[0021] The products obtained through the process of this invention can be used for pharmaceutical purposes.
[0022] The products obtained through the process of this invention can be used in the treatment or prevention of type 2 diabetes and / or obesity.
[0023] In some implementations, as used herein, a specific value given with respect to a number or range can be understood as that specific value or approximately that specific value (e.g., that specific value plus or minus 10%).
[0024] Spray drying is commonly used as a step in the manufacture of active pharmaceutical ingredients (APIs) and pharmaceutical products, and the yield of this process is crucial to the total cost of the final drug product. Several parameters affect the yield obtained; for example, it is generally believed that higher outlet temperatures lead to higher yields. This is because drier particles obtained at higher temperatures are less likely to adhere to the inner wall of the spray dryer upon impact. However, high temperature is one of the key factors affecting peptide stability. Under high-temperature conditions, peptide molecules may undergo a series of changes detrimental to the preservation of their structure and function, such as degradation, aggregation, and conformational changes. These changes may cause peptides to lose their original biological activity or even produce toxic or adverse products.
[0025] The applicant unexpectedly discovered that, using the method of the present invention, peptides can still achieve a high yield after spray drying under low-temperature conditions without compromising their stability, and the related substances remain essentially unchanged, which is highly beneficial for the industrial production of peptides. Beneficial effects:
[0026] This invention performs spray drying at low temperatures, which not only has the advantages of spray drying but also protects the peptides from damage. The content and number of peptide impurities remain essentially unchanged before and after spray drying, and no new impurities are generated. This is significantly better than high-temperature conditions and helps improve the safety and efficacy of the drug.
[0027] Using the method of this invention, while ensuring the quality of polypeptide products, the yield of the products can also be guaranteed, with a yield greater than 93%, which is beneficial for industrial-scale production.
[0028] Using the method of the present invention, the particle size of the dried product is stable with minimal variation, which is beneficial to the stability of subsequent processes. Attached image description:
[0029] Figure 1 is the HPLC chromatogram of semaglutide before spray drying in Example 1 of the present invention;
[0030] Figure 2 is the HPLC chromatogram of smegglutinin after spray drying in Example 1 of the present invention.
[0031] Figure 3 is the HPLC chromatogram of smegglutinin after spray drying in Example 2 of the present invention.
[0032] Figure 4 is the HPLC chromatogram of smegglutinin after spray drying in Example 3 of the present invention.
[0033] Figure 5 shows the HPLC chromatogram of telpoeptide before spray drying in Example 4 of the present invention.
[0034] Figure 6 is the HPLC chromatogram of telpoeptide after spray drying in Example 4 of the present invention;
[0035] Figure 7 is the HPLC chromatogram of telpoeptide after spray drying in Example 5 of the present invention;
[0036] Figure 8 is the HPLC chromatogram of telpoeptide after spray drying in Example 6 of the present invention;
[0037] Figure 9 shows the HPLC chromatogram of smegglutinin after spray drying in Comparative Example 1.
[0038] Figure 10 shows the HPLC chromatogram of telpoeptide after spray drying in Comparative Example 2. Detailed Implementation
[0039] The following embodiments are only some, not all, of the embodiments of the present invention. Therefore, the detailed descriptions of the embodiments provided below are not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.
[0040] Example 1: Spray drying of smegglutinin
[0041] Preparation of test solution
[0042] Take 40.0g of smegglutinin raw material and slowly add it to purified water while stirring. Stir until the solution is completely clear, then dilute the volume to 0.4L with purified water to prepare a 100g / L sample solution. Filter the solution through a 0.22μm filter membrane to obtain the final product.
[0043] HPLC analysis of samples before spray drying
[0044] Take an appropriate amount of the test solution and determine it according to the high performance liquid chromatography method (General Chapter (0512) of the current edition of the Chinese Pharmacopoeia). The HPLC chromatogram and data of smegglutinin are shown in Figure 1 and Table 1, respectively.
[0045] Table 1. HPLC detection results of semaglutide before spray drying.
[0046] Spray drying operation
[0047] The test solution sample was spray-dried using a 2mm orifice dual-fluid nozzle on a QFN-DW-1 spray dryer. The atomizing gas was compressed air, and the drying gas was dehumidified air from a cleanroom.
[0048] Drying parameters: atomization pressure 0.18 MPa, inlet temperature 45℃, induced draft frequency 45 Hz, feed speed 26 rpm. Relative humidity of atomized gas 10%.
[0049] After reaching stable parameters, the peristaltic pump was started to feed the product, and the spray drying process was initiated. The outlet temperature was controlled at 25–30°C, and a cyclone separator was used as the primary powder separation technology to collect the product. At the end of the spray drying operation, smegglutinin was cooled with nitrogen or compressed air to prevent moisture absorption, followed by unloading. 37.24 g of spray-dried smegglutinin was obtained, with a yield of 93.1%.
[0050] HPLC analysis of samples after spray drying
[0051] Following the aforementioned HPLC detection method for samples before spray drying, smegglutinin after spray drying was detected. The HPLC chromatograms and data are shown in Figure 2 and Table 2, respectively.
[0052] Table 2. HPLC detection results of semaglutide after spray drying
[0053] Particle size detection methods and results:
[0054] The particle size distribution of smegglutinin after spray drying was detected by wet dispersion laser diffraction, and the particle size detection results are shown in Table 3.
[0055] Table 3. Particle size detection results of smegglutinin after spray drying.
[0056] Example 2: Spray drying of smegglutinin
[0057] Preparation of test solution
[0058] Take 4600.03g of smegglutide raw material concentrate, with a concentration of 80.00g / L, and use water as the solvent. Filter the solution through a 0.22μm filter membrane to obtain the final product.
[0059] HPLC analysis of samples before spray drying
[0060] According to Example 1, an appropriate amount of the test solution was taken and determined by high performance liquid chromatography (HPLC) according to the current edition of the Chinese Pharmacopoeia, Part IV, General Chapter (0512). The HPLC chromatogram and data of smegglutinin are similar to those in Figure 1 and Table 1, respectively.
[0061] Spray drying operation
[0062] The test solution sample was dried on a QFN-DW-5 spray dryer. The atomizing gas was compressed air, and the drying gas was dehumidified air from a cleanroom.
[0063] Drying parameters: centrifugal frequency 400Hz, inlet temperature 50℃; induced draft frequency 35Hz, feed speed 60rpm. Atomized gas relative humidity 4%.
[0064] After reaching stable parameters, the peristaltic pump was started to feed the product, and the spray drying process was initiated. The outlet temperature was controlled at 25–40°C, and a cyclone separator was used as the primary powder separation technology to collect the product. At the end of the spray drying operation, smegglutinin was cooled with nitrogen or compressed air to prevent moisture absorption, followed by unloading. 4310.03 g of spray-dried smegglutinin was obtained, with a yield of 93.69%.
[0065] HPLC analysis of samples after spray drying
[0066] The spray-dried smegglutinin was detected according to the HPLC detection method in Example 1. The HPLC chromatogram and data are shown in Figure 3 and Table 4, respectively.
[0067] Table 4. HPLC detection results of semaglutide after spray drying
[0068] Particle size detection methods and results:
[0069] According to Example 1, the particle size distribution of smegglutinin after spray drying was detected by wet dispersion laser diffraction, and the particle size detection results are shown in Table 5.
[0070] Table 5. Particle size detection results of smegglutinin after spray drying.
[0071] Example 3: Spray drying of smegglutinin
[0072] Preparation of test solution
[0073] Take 5000.03g of smegglutide raw material concentrate, with a concentration of 200.00g / L, and filter it through a 0.22μm filter membrane.
[0074] HPLC analysis of samples before spray drying
[0075] According to Example 1, an appropriate amount of the test solution was taken and determined by high performance liquid chromatography (HPLC) according to the current edition of the Chinese Pharmacopoeia, Part IV, General Chapter (0512). The HPLC chromatogram and data of smegglutinin are similar to those in Figure 1 and Table 1, respectively.
[0076] Spray drying operation
[0077] The filtered test solution sample was dried on a QFN-DW-5 spray dryer. Nitrogen was used as both the atomizing and drying gas.
[0078] Drying parameters: centrifugal frequency 400Hz, inlet temperature 81℃; induced draft frequency 50Hz, feed speed 70rpm. Relative humidity of atomized gas is 5%.
[0079] After reaching stable parameters, the peristaltic pump was started to feed the product, and the spray drying process was initiated. The outlet temperature was controlled at 25–66°C, and a cyclone separator was used as the primary powder separation technology to collect the product. At the end of the spray drying operation, smegglutinin was cooled with nitrogen or compressed air to prevent moisture absorption, followed by unloading. 4820.03 g of spray-dried smegglutinin was obtained, with a yield of 96.40%.
[0080] HPLC analysis of samples after spray drying
[0081] The spray-dried smegglutinin was detected according to the HPLC detection method in Example 1. The HPLC chromatogram and data are shown in Figure 4 and Table 6, respectively.
[0082] Table 6. HPLC detection results of semaglutide after spray drying
[0083] Particle size detection methods and results:
[0084] According to Example 1, the particle size distribution of smegglutinin after spray drying was detected by wet dispersion laser diffraction, and the particle size detection results are shown in Table 7.
[0085] Table 7. Particle size detection results of smegglutinin after spray drying.
[0086] Example 4: Spray drying of telpoeptide
[0087] Preparation of test solution
[0088] Take 200.01g of telpoeptide raw material and slowly add it to purified water while stirring. Stir until the solution is completely clear, then dilute to 1.8L with purified water to prepare a sample solution of 111.11g / L. Filter the solution through a 0.22μm filter membrane.
[0089] HPLC analysis of samples before spray drying
[0090] Take an appropriate amount of the test solution and determine it according to the high performance liquid chromatography method (General Chapter (0512) of the current edition of the Chinese Pharmacopoeia). The HPLC chromatogram and data of telpolide are shown in Figure 5 and Table 8, respectively.
[0091] Table 8. HPLC detection results of telpolide before spray drying.
[0092] Spray drying operation
[0093] The filtered sample solution was spray-dried using a 2mm orifice dual-fluid nozzle on a QFN-DW-1 spray dryer. The atomizing gas was compressed air, and the drying gas was dehumidified air from a cleanroom.
[0094] Drying parameters: atomization pressure 0.22 MPa, inlet temperature 55℃, induced draft frequency 45 Hz, feed speed 26 rpm. Relative humidity of atomized gas is 2%.
[0095] After reaching stable parameters, the peristaltic pump was started to feed the product, and the spray drying process was initiated. The outlet temperature was controlled at 25–40°C, and a cyclone separator was used as the primary powder separation technology to collect the product. At the end of the spray drying operation, smegglutinin was cooled with nitrogen or compressed air to prevent moisture absorption before unloading. After reaching stable parameters, purified water was switched to the telpolide feed solution, and the spray drying process was initiated again, using a cyclone separator as the primary powder separation technology to collect the product. At the end of the spray drying operation, telpolide was cooled with nitrogen or compressed air to prevent moisture absorption before unloading. 188.20 g of spray-dried telpolide was obtained, with a yield of 94.10%.
[0096] HPLC analysis of samples after spray drying:
[0097] Following the aforementioned HPLC detection method for samples before spray drying, the spray-dried telpolide was detected. The HPLC chromatograms and data are shown in Figure 6 and Table 9, respectively.
[0098] Table 9. HPLC Detection Results of Thiopeptide After Spray Drying
[0099] Particle size detection methods and results:
[0100] The particle size distribution of telpoeptide after spray drying was detected by wet dispersion laser diffraction, and the particle size detection results are shown in Table 10.
[0101] Table 10. Results of particle size analysis of telpoeptide after spray drying.
[0102] Example 5: Spray drying of telpoeptide
[0103] Preparation of test solution
[0104] Take 4000.00g of telpopeptide raw material concentrate, with a concentration of 150.00g / L, and use 40% (w / w) acetonitrile aqueous solution as solvent. Filter the solution through a 0.22μm filter membrane to obtain the final product.
[0105] HPLC analysis of samples before spray drying
[0106] According to Example 4, an appropriate amount of the test solution was taken and determined by high performance liquid chromatography (HPLC) according to the current edition of the Chinese Pharmacopoeia, Part IV, General Chapter (0512). The HPLC chromatogram and data of telpolide are similar to those in Figure 5 and Table 8, respectively.
[0107] Spray drying operation
[0108] The filtered sample solution was dried using a QFN-DW-5 spray dryer. Nitrogen was used as both the atomizing and drying gas.
[0109] Drying parameters: centrifugal frequency 500Hz, inlet temperature 65℃; induced draft frequency 30Hz, feed speed 35rpm. Atomized gas relative humidity 4%.
[0110] After reaching stable parameters, the peristaltic pump was started to feed the product, and the spray drying process was initiated. The outlet temperature was controlled at 25–30°C, and a cyclone separator was used as the primary powder separation technology to collect the product. At the end of the spray drying operation, the telpolide was cooled with nitrogen or compressed air to prevent moisture absorption, followed by unloading. 3816.03 g of spray-dried telpolide was obtained, with a yield of 95.40%.
[0111] HPLC analysis of samples after spray drying:
[0112] Following the HPLC detection method for samples before spray drying in Example 4, the spray-dried telpolide was detected. The HPLC chromatograms and data are shown in Figure 7 and Table 11, respectively.
[0113] Table 11 HPLC detection results of telpolide after spray drying
[0114] Particle size detection methods and results:
[0115] According to Example 4, the particle size distribution of telpoeptide after spray drying was detected by wet dispersion laser diffraction, and the particle size detection results are shown in Table 12.
[0116] Table 12. Results of particle size analysis of telpoeptide after spray drying.
[0117] Example 6: Spray drying of telpoeptide
[0118] Preparation of test solution
[0119] Take 4500.00g of telpopeptide raw material concentrate, with a concentration of 50.00g / L, and filter it through a 0.22μm filter membrane using a 50% (w / w) ethanol aqueous solution as the solvent.
[0120] HPLC analysis of samples before spray drying
[0121] According to Example 4, an appropriate amount of the test solution was taken and determined by high performance liquid chromatography (HPLC) according to the current edition of the Chinese Pharmacopoeia, Part IV, General Chapter (0512). The HPLC chromatogram and data of telpolide are similar to those in Figure 5 and Table 8, respectively.
[0122] Spray drying operation
[0123] The filtered sample solution was dried using a QFN-DW-5 spray dryer. Nitrogen was used as both the atomizing and drying gas.
[0124] Drying parameters: centrifugal frequency 400Hz, inlet temperature 70℃; induced draft frequency 50Hz, feed speed 60rpm. Atomized gas relative humidity 2%.
[0125] After reaching stable parameters, the peristaltic pump was started to feed the product, and the spray drying process was initiated. The outlet temperature was controlled at 25–55°C, and a cyclone separator was used as the primary powder separation technology to collect the product. At the end of the spray drying operation, the telpolide was cooled with nitrogen or compressed air to prevent moisture absorption, followed by unloading. 4248.03 g of spray-dried telpolide was obtained, with a yield of 94.40%.
[0126] HPLC analysis of samples after spray drying:
[0127] Following the HPLC detection method for the sample before spray drying in Example 4, the spray-dried telpolide was detected. The HPLC chromatograms and data are shown in Figure 8 and Table 13, respectively.
[0128] Table 13 HPLC results of telpolide after spray drying
[0129] Particle size detection methods and results:
[0130] According to Example 4, the particle size distribution of telpoeptide after spray drying was detected by wet dispersion laser diffraction, and the particle size detection results are shown in Table 14.
[0131] Table 14. Results of particle size analysis of telpoeptide after spray drying
[0132] Comparative Example 1: Smegglutinin spray-dried
[0133] Preparation of test solution
[0134] Take 4800.03g of smegglutide raw material concentrate, with a concentration of 280.00g / L, and use water as the solvent. Filter the solution through a 0.22μm filter membrane to obtain the final product.
[0135] HPLC analysis of samples before spray drying
[0136] According to Example 1, an appropriate amount of the test solution was taken and determined by high performance liquid chromatography (HPLC) according to the current edition of the Chinese Pharmacopoeia, Part IV, General Chapter (0512). The HPLC chromatogram and data of smegglutinin are similar to those in Figure 1 and Table 1, respectively.
[0137] Spray drying operation
[0138] The test solution sample was dried on a QFN-DW-5 spray dryer. The atomizing gas was compressed air, and the drying gas was dehumidified air from a cleanroom.
[0139] Drying parameters: centrifugal frequency 400Hz, inlet temperature 100℃; induced draft frequency 50Hz, feed speed 100rpm. Relative humidity of atomized gas 15%.
[0140] After reaching stable parameters, the peristaltic pump was started to feed the product, and the spray drying process was initiated. The outlet temperature was controlled at 60–85°C, and a cyclone separator was used as the primary powder separation technology to collect the product. At the end of the spray drying operation, smegglutinin was cooled with nitrogen or compressed air to prevent moisture absorption, followed by unloading. 3379.22 g of spray-dried smegglutinin was obtained, with a yield of 70.40%.
[0141] HPLC analysis of samples after spray drying
[0142] The spray-dried smegglutinin was detected according to the HPLC detection method in Example 1. The HPLC chromatogram and data are shown in Figure 9 and Table 15, respectively.
[0143] Table 15 HPLC Detection Results of Smegglutinin After Spray Drying
[0144] Comparative Example 2: Thilborpeptide spray drying
[0145] Preparation of test solution
[0146] Take 3900.00g of telpopeptide raw material concentrate, with a concentration of 25.00g / L, and filter it through a 0.22μm filter membrane using a 50% (w / w) ethanol aqueous solution as the solvent.
[0147] HPLC analysis of samples before spray drying
[0148] According to Example 4, an appropriate amount of the test solution was taken and determined by high performance liquid chromatography (HPLC) according to the current edition of the Chinese Pharmacopoeia, Part IV, General Chapter (0512). The HPLC chromatogram and data of telpolide are similar to those in Figure 5 and Table 8, respectively.
[0149] Spray drying operation
[0150] The filtered sample solution was dried using a QFN-DW-5 spray dryer. Nitrogen was used as both the atomizing and drying gas.
[0151] Drying parameters: centrifugal frequency 500Hz, inlet temperature 120℃; induced draft frequency 100Hz, feed speed 70rpm. Relative humidity of atomized gas 25%.
[0152] After reaching stable parameters, the peristaltic pump was started to feed the product, and the spray drying process was initiated. The outlet temperature was controlled at 90–105°C, and a cyclone separator was used as the primary powder separation technology to collect the product. At the end of the spray drying operation, smegglutinin was cooled with nitrogen or compressed air to prevent moisture absorption, followed by unloading. 2737.80 g of spray-dried smegglutinin was obtained, with a yield of 70.20%.
[0153] HPLC analysis of samples after spray drying:
[0154] Following the HPLC detection method for samples before spray drying in Example 4, the spray-dried telpolide was detected. The HPLC chromatograms and data are shown in Figure 10 and Table 16, respectively.
[0155] Table 16. HPLC Detection Results of Thiopeptide After Spray Drying
[0156] The HPLC chromatograms and data from Examples 1-6 and Comparative Examples 1-2 show that, compared to before spray drying, the yields of Comparative Examples 1 and 2 were significantly reduced, to only about 70%, and new impurities were generated, with a significant increase in the total amount of impurities. In contrast, the method of the present invention, after spray drying, achieved a yield higher than 93%, with minimal changes in the content and quantity of peptide impurities, and no new impurities were generated. This indicates that the method of the present invention can improve the yield of peptide spray drying while ensuring peptide quality and preventing the generation of new impurities, thus contributing to the safety, efficacy, and stability of the drug. Furthermore, the particle size analysis results from Examples 1-6 show that the particle size of the product dried using the method of the present invention is stable with minimal variation, which is beneficial for the stability of subsequent processes.
Claims
1. A spray drying process for a feed solution containing polypeptides, characterized in that, The process mainly involves introducing a feed solution containing a certain concentration of peptides into a spray dryer, and introducing atomizing gas at an atomizing gas flow rate, wherein the feed inlet temperature is 45-81°C and the relative humidity of the atomizing gas is less than 10%.
2. The spray drying process according to claim 1, characterized in that, The feed inlet temperature is 50–70°C.
3. The spray drying process according to claim 2, characterized in that, The feed inlet temperature is 50–55°C.
4. The spray drying process according to claim 1, characterized in that, The relative humidity of the atomized gas is 4-10%.
5. The spray drying process according to claim 1, characterized in that, The feed solution contains 50–200 g / L of polypeptide.
6. The spray drying process according to any one of claims 5, characterized in that, The feed solution contains 70–120 g / L of polypeptide.
7. The drying process according to claim 1, characterized in that, It also includes an air outlet temperature of 25–66°C.
8. The spray drying process according to claim 7, characterized in that, The temperature at the air outlet is 25–40°C.
9. The spray drying process according to claim 1, characterized in that, The feed solution solvent is water or an aqueous organic solvent.
10. The spray drying process according to claim 9, characterized in that, The feed solution solvent is a 30-60% (w / w) aqueous ethanol solution.
11. The spray drying process according to claim 9, characterized in that, The feed solution solvent is a 30-60% (w / w) aqueous solution of acetonitrile.
12. The spray drying process according to any one of claims 1, characterized in that, The atomizing gas is compressed air or nitrogen.
13. The spray drying process according to claim 1, characterized in that, The polypeptide is selected from smegglutinin, telpogglutinin, and liraglutinin.
14. The polypeptide obtained by spray drying according to claim 1 is used in a pharmaceutical composition together with one or more pharmaceutically acceptable excipients.
15. The polypeptide obtained by spray drying according to claim 1 is used together with one or more components in a cosmetic composition.