长效注射剂药学研究案例分析及释放特性研究
Case Analysis on Chemical Manufacturing and Control of Long-Acting Injections and Study of Drug Release Characteristics
DOI: 10.12677/pi.2025.145034, PDF,   
作者: 莫宝霞, 汤 佳：国家药品监督管理局药品审评检查大湾区分中心，广东 深圳
关键词: 长效注射剂；药学研究；体外释放；突释效应；粒度；晶型；Long-Acting Injection； Chemical Manufacturing and Control； In Vitro Release； Burst Release； Particle Size； Crystal Form
摘要: 长效注射剂属于复杂注射剂，因其药物释放周期可达几天甚至数月，具有可减少用药频次等优势，在精神分裂等领域得到研究及应用。本文简要总结长效注射剂分类及在中美欧的上市情况，通过调研欧美审评报告，选取注射用双羟萘酸奥氮平作为案例，分析质量研究主要关注点；同时通过调研相关文献，对该类产品的释放特性(如体外释放、突释效应)及与其相关的质量属性(如粒度分布、晶型)进行讨论，以期为国内长效注射剂的研发提供参考。
Abstract: Long-acting injections are a type of complex injection that can release drugs for days or months. Due to the advantages such as reducing medication frequency, long-acting injections have been researched and applied in the treatment of diseases such as schizophrenia. Based on analysis of literatures and review reports of FDA and EMA, this article will introduce the classification of long-acting injections and their approvals in China, US and EU, and analysis the main chemical manufacturing and control research by selecting the olanzapine long-acting injection suspension as a case, and discuss the release characteristic, such as in vitro release and burst release, of long-acting injections and its related critical quality attributes, such as particle size and crystal form, in order to provide references for the research and development of long-acting injections.
文章引用：莫宝霞, 汤佳. 长效注射剂药学研究案例分析及释放特性研究[J]. 药物资讯, 2025, 14(5): 291-298. https://doi.org/10.12677/pi.2025.145034

参考文献

[1] 张汶彦, 胡鑫蕾, 刘莉莎, 等. 长效注射剂的改良与创新: 现状与未来[J]. 药学进展, 2025, 49(3): 187-197.
[2] Forrest, W.P., Reuter, K.G., Shah, V., Kazakevich, I., Heslinga, M., Dudhat, S., et al. (2017) USP Apparatus 4: A Valuable in Vitro Tool to Enable Formulation Development of Long-Acting Parenteral (LAP) Nanosuspension Formulations of Poorly Water-Soluble Compounds. AAPS PharmSciTech, 19, 413-424. [Google Scholar] [CrossRef] [PubMed]
[3] FDA (2009) Chemistry Review of Zyprexa Relprevv.
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022173s000ChemR.pdf
[4] EMA (2009) Zypadhera: EPAR-Public Assessment Report.
https://www.ema.europa.eu/en/documents/overview/zypadhera-epar-summary-public_en.pdf
[5] FDA (2015) Dissolution Methods.
https://www.accessdata.fda.gov/scripts/cder/dissolution/dsp_SearchResults.cfm
[6] 王静文, 文强, 彭玉帅, 等. 长效注射剂体外释放检查方法研究进展[J]. 药物分析杂志, 2024, 44(11): 1842-1851.
[7] Shen, J. and Burgess, D.J. (2012) Accelerated In-Vitro Release Testing Methods for Extended-Release Parenteral Dosage Forms. Journal of Pharmacy and Pharmacology, 64, 986-996. [Google Scholar] [CrossRef] [PubMed]
[8] Burgess, D.J., Crommelin, D.J.A., Hussain, A.S. and Chen, M. (2004) Assuring Quality and Performance of Sustained and Controlled Release Parenterals: EUFEPS Workshop Report. AAPS PharmSci, 6, 100-111. [Google Scholar] [CrossRef] [PubMed]
[9] Martinez, M., Rathbone, M., Burgess, D. and Huynh, M. (2008) In Vitro and in Vivo Considerations Associated with Parenteral Sustained Release Products: A Review Based Upon Information Presented and Points Expressed at the 2007 Controlled Release Society Annual Meeting. Journal of Controlled Release, 129, 79-87. [Google Scholar] [CrossRef] [PubMed]
[10] Siewert, M., Dressman, J., Brown, C. and Shah, V. (2003) FIP/AAPS Guidelines for Dissolution/in Vitro Release Testing of Novel/Special Dosage Forms. Dissolution Technologies, 10, 6-15. [Google Scholar] [CrossRef] 
[11] D’Souza, S.S., Faraj, J.A. and DeLuca, P.P. (2005) A Model-Dependent Approach to Correlate Accelerated with Real-Time Release from Biodegradable Microspheres. AAPS PharmSciTech, 6, E553-E564. [Google Scholar] [CrossRef] [PubMed]
[12] Rawat, A., Bhardwaj, U. and Burgess, D.J. (2012) Comparison of in Vitro—in Vivo Release of Risperdal® Consta® Microspheres. International Journal of Pharmaceutics, 434, 115-121. [Google Scholar] [CrossRef] [PubMed]
[13] FDA.USP < 1088 > (2021) In Vitro and in Vivo Evaluation of Oral Dosage Forms.
https://online.uspnf.com/uspnf/document/1_GUID-0818140F-BBE0-4124-96DB-4A37CBF25659_4_en-US?source=Search%20Results&highlight=1088
[14] Li, M. (2017) Biorelevant Dissolution Testing for in Vitro in Vivo Correlation/Relationship (IVIVC-R) Development: Regulatory Perspective. Division of Biopharmaceutics U.S. FDA/CDER/OPQ/ONDP.
[15] FDA (2005) Chemistry Review of Invega Trinza (3 Months).
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207946Orig1s000ChemR.pdf
[16] FDA (2009) Chemistry Review of Invega Sustenna (1 Months).
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022264s000chemr.pdf
[17] FDA (1997) Extended Release Oral Dosage Forms-Development, Evaluation, and Application of IVIVC Correlation.
https://www.fda.gov/media/70939/download
[18] FDA (2013) Chemistry Review of Abilify Maintena KIT.
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/202971Orig1s000ChemR.pdf
[19] FDA (2015) Chemistry Review of Aristada.
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207533Orig1s000ChemR.pdf
[20] 张聪. 美金刚长效注射剂的研究[D]: [硕士学位论文]. 无锡: 江南大学, 2021.