Process analytical technology as in-process control tool in semi-continuous manufacturing of PLGA/PEG-PLGA microspheres
Nowadays, among 3rd generation drug delivery systems, biodegradable polymeric based long-acting injectable depot has achieved tremendous success in clinical application. So far, there have been two dozen of commercial products of Poly (lactic-co-glycolic acid) microspheres available in the market. R...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023029602 |
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| author | Arfidin Anwar Pengfei Sun Xiaoxu Rong Abdulaziz Arkin Aliya Elham Zilala Yalkun Xun Li Mubarak Iminjan |
| author_facet | Arfidin Anwar Pengfei Sun Xiaoxu Rong Abdulaziz Arkin Aliya Elham Zilala Yalkun Xun Li Mubarak Iminjan |
| author_sort | Arfidin Anwar |
| collection | DOAJ |
| description | Nowadays, among 3rd generation drug delivery systems, biodegradable polymeric based long-acting injectable depot has achieved tremendous success in clinical application. So far, there have been two dozen of commercial products of Poly (lactic-co-glycolic acid) microspheres available in the market. Recently, continuous manufacturing concept has been successfully applied on oral solid formulation from buzzword to reality. However, the polymeric injectable microspheres are still stayed at batch manufacturing phase due to the lack of understanding of knowledge matrix. In this study, micro-mixer as a plug-and-play emulsification modules, Raman spectroscopy and focused beam reflectance measurement as real-time monitoring modules are integrated into a novel semi-continuous manufacturing streamline to provides more efficient upscaling flexibility in microspheres production. In this end to end semi-continuous manufacturing process, amphiphilic block polymer monomethoxy-poly (ethylene glycol) modified PLGA (mPEG-PLGA) was used for encapsulating Gallic acid. Additionally, with guarantee of good robustness, the correlation relationship between critical process parameters, critical material attributes and critical quality attributes were investigated. The time-space evolution process and mechanism for formation of PEG-PLGA microsphere with particular morphology were elaborated. Altogether, this study firstly established semi-continuous manufacturing streamline for PLGA/PEG-PLGA microspheres, which would not only lower the cost of production, narrow process variability and smaller equipment/environmental footprint but also applied in-process control (IPC) and QbD principle on complicated production process of microspheres. Therefore, this study build confidence in the industrial development of PLGA/PEG-PLGA microspheres and establish best practice standards, which might be a quantum leap for developing PLGA microspheres in the future. |
| first_indexed | 2024-03-13T08:25:33Z |
| format | Article |
| id | doaj.art-28265a3a0bb94b42ae09d26e170edc0a |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-13T08:25:33Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-28265a3a0bb94b42ae09d26e170edc0a2023-05-31T04:45:25ZengElsevierHeliyon2405-84402023-05-0195e15753Process analytical technology as in-process control tool in semi-continuous manufacturing of PLGA/PEG-PLGA microspheresArfidin Anwar0Pengfei Sun1Xiaoxu Rong2Abdulaziz Arkin3Aliya Elham4Zilala Yalkun5Xun Li6Mubarak Iminjan7Department of Pharmaceutics and Physical Chemistry, College of Pharmacy, Xinjiang Medical University, Urumqi, 830017, ChinaUniversity of Wisconsin-Madison, Department of Educational Psychology, Madison, USAUniversity of Wisconsin-Madison, Department of Educational Psychology, Madison, USADepartment of Pharmaceutics and Physical Chemistry, College of Pharmacy, Xinjiang Medical University, Urumqi, 830017, ChinaDepartment of Pharmaceutics and Physical Chemistry, College of Pharmacy, Xinjiang Medical University, Urumqi, 830017, ChinaCollege of Pharmacy, Dalian Medical University, Dalian, 116000, ChinaChinese Academy of Science, Department of Chemical Engineering, Beijing, 100190, China; Corresponding author.Department of Pharmaceutics and Physical Chemistry, College of Pharmacy, Xinjiang Medical University, Urumqi, 830017, China; Corresponding author.Nowadays, among 3rd generation drug delivery systems, biodegradable polymeric based long-acting injectable depot has achieved tremendous success in clinical application. So far, there have been two dozen of commercial products of Poly (lactic-co-glycolic acid) microspheres available in the market. Recently, continuous manufacturing concept has been successfully applied on oral solid formulation from buzzword to reality. However, the polymeric injectable microspheres are still stayed at batch manufacturing phase due to the lack of understanding of knowledge matrix. In this study, micro-mixer as a plug-and-play emulsification modules, Raman spectroscopy and focused beam reflectance measurement as real-time monitoring modules are integrated into a novel semi-continuous manufacturing streamline to provides more efficient upscaling flexibility in microspheres production. In this end to end semi-continuous manufacturing process, amphiphilic block polymer monomethoxy-poly (ethylene glycol) modified PLGA (mPEG-PLGA) was used for encapsulating Gallic acid. Additionally, with guarantee of good robustness, the correlation relationship between critical process parameters, critical material attributes and critical quality attributes were investigated. The time-space evolution process and mechanism for formation of PEG-PLGA microsphere with particular morphology were elaborated. Altogether, this study firstly established semi-continuous manufacturing streamline for PLGA/PEG-PLGA microspheres, which would not only lower the cost of production, narrow process variability and smaller equipment/environmental footprint but also applied in-process control (IPC) and QbD principle on complicated production process of microspheres. Therefore, this study build confidence in the industrial development of PLGA/PEG-PLGA microspheres and establish best practice standards, which might be a quantum leap for developing PLGA microspheres in the future.http://www.sciencedirect.com/science/article/pii/S2405844023029602Continuous manufacturingmPEG-PLGA/PLGA, process analytical technologyIn-process controlAnd real-time monitor |
| spellingShingle | Arfidin Anwar Pengfei Sun Xiaoxu Rong Abdulaziz Arkin Aliya Elham Zilala Yalkun Xun Li Mubarak Iminjan Process analytical technology as in-process control tool in semi-continuous manufacturing of PLGA/PEG-PLGA microspheres Heliyon Continuous manufacturing mPEG-PLGA/PLGA, process analytical technology In-process control And real-time monitor |
| title | Process analytical technology as in-process control tool in semi-continuous manufacturing of PLGA/PEG-PLGA microspheres |
| title_full | Process analytical technology as in-process control tool in semi-continuous manufacturing of PLGA/PEG-PLGA microspheres |
| title_fullStr | Process analytical technology as in-process control tool in semi-continuous manufacturing of PLGA/PEG-PLGA microspheres |
| title_full_unstemmed | Process analytical technology as in-process control tool in semi-continuous manufacturing of PLGA/PEG-PLGA microspheres |
| title_short | Process analytical technology as in-process control tool in semi-continuous manufacturing of PLGA/PEG-PLGA microspheres |
| title_sort | process analytical technology as in process control tool in semi continuous manufacturing of plga peg plga microspheres |
| topic | Continuous manufacturing mPEG-PLGA/PLGA, process analytical technology In-process control And real-time monitor |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023029602 |
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