中国临床药理学杂志

长效注射液帕利哌酮棕榈酸酯的体内外相关性研究

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金雄 ¹ , 于盼盼 ² , 付龙 ² , 吴科衡 ³ , 李学 ³ , 徐坚 ² , 刘波 ¹

中国临床药理学杂志 | 研究方法 2025,41(7): 1002-1007

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中国临床药理学杂志 |研究方法 2025 , 41 (7) : 1002 -1007

长效注射液帕利哌酮棕榈酸酯的体内外相关性研究

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金雄¹, 于盼盼², 付龙², 吴科衡³, 李学³, 徐坚², 刘波¹

作者信息

^1.武汉工程大学化工与制药学院，湖北武汉 430000

^2.丽珠医药集团股份有限公司，广东珠海 519000

^3.英翰医药科技（上海）有限公司，上海 200000

通讯作者:

刘波，正高级工程师 MP: 18971321466 E-mail: 513839739@qq.com

作者简介:

金雄（1998-），男，研究生硕士，主要从事长效注射液的相关研究

Research on in vitro-in vivo correlation of paliperidone palmitate, a long-acting injection

Xiong JIN¹, Pan-pan YU², Long FU², Ke-heng WU³, Xue LI³, Jian XU², Bo LIU¹

Affiliations

^1.College of Chemical and Pharmaceutical Engineering, Wuhan Institute of Technology, Wuhan 430000, Hubei Province, China

^2.Livzon Pharmaceutical Group Inc, Zhuhai 519000, Guangdong Province, China

^3.Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd, Shanghai 200000, China

出版时间: 2025-04-17 doi: 10.13699/j.cnki.1001-6821.2025.07.019

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摘要

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目的

探索体外溶出数据和动物的体内数据的相关性。

方法

体外方法：用碱性明胶先制备明胶水溶液，再把帕利哌酮棕榈酸酯加入溶液里面混匀后，在冰箱冷藏1~2 h得到明胶水凝胶，然后将水凝胶放到桨法溶出仪进行溶出实验，用高效液相色谱仪检测药物浓度，并计算释放度。体内方法：将帕利哌酮棕榈酸酯通过肌内注射到比格犬体内后开始计时，分别于给药前0 h和给药后6 h~36 d进行采血，用液相色谱-串联质谱联用技术检测血药浓度，并绘制血药浓度-时间曲线。最后将得到的体外数据通过威布尔函数进行拟合、体内数据通过内尔松-瓦格纳法和曲线下面积法进行转换，建立图表来评估体内和体外药物释放的相关性。

结果

体外的释放度在第13天接近100%，体内的释放度在第30~36天接近100%。内尔松-瓦格纳法和曲线下面积法都得出了体内与体外是有相关性的结论。

结论

通过药物的体外溶出数据和动物的体内数据建立体内外相关性是可行的。

关键词

帕利哌酮棕榈酸酯 / 长效注射剂 / 体外溶出 / 体内释放 / 体内外相关性

Abstract

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Objective

To establish in vitro and in vivo correlations from in vitro dissolution data and in vivo data from animals.

Methods

In vitro method: an aqueous gelatin solution was first prepared with alkaline gelatin, paliperidone palmitate was added into the solution and mixed well, gelatin hydrogel was obtained by refrigerating in the refrigerator for 1-2 h. The hydrogel was put into paddle dissolution apparatus for dissolution experiments, the concentration of the drug was detected by high-performance liquid chromatography and the degree of release was calculated. In vivo method: Timing was started after paliperidone palmitate was injected into Beagle dogs via intramuscular injection, blood was collected at 0 h before and 6 h-36 d after drug administration, respectively, the blood concentration was detected by liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique and the blood concentration-time curve was plotted. Finally, the obtained in vitro data were fitted by Weibull function, the in vivo data were transformed by Nelson-Wagner method and area under the curve method. Graphs were constructed to evaluate the correlation between in vivo and in vitro drug release.

Results

The in vitro release was approaching 100% by day 13, while the in vivo release was approaching 100% by day 30-36. Both Nelson-Wagner method and area under the curve method yielded that in vivo and in vitro were correlated.

Conclusion

It is feasible to establish in vitro correlations from in vivo dissolution data and in vivo data from animals.

Key words

paliperidone palmitate / long-acting injectables / in vitro dissolution / in vivo release / in vitro-in vivo correlation

引用本文

金雄, 于盼盼, 付龙, 吴科衡, 李学, 徐坚, 刘波. 长效注射液帕利哌酮棕榈酸酯的体内外相关性研究. 中国临床药理学杂志, 2025 , 41 (7) : 1002 -1007 . DOI: 10.13699/j.cnki.1001-6821.2025.07.019

Xiong JIN, Pan-pan YU, Long FU, Ke-heng WU, Xue LI, Jian XU, Bo LIU. Research on in vitro-in vivo correlation of paliperidone palmitate, a long-acting injection[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (7) : 1002 -1007 . DOI: 10.13699/j.cnki.1001-6821.2025.07.019

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2025年第41卷第7期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.07.019

接收时间：2024-10-22
首发时间：2026-08-04
出版时间：2025-04-17

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收稿日期：2024-10-22

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作者信息

^1.武汉工程大学化工与制药学院，湖北武汉 430000

^2.丽珠医药集团股份有限公司，广东珠海 519000

^3.英翰医药科技（上海）有限公司，上海 200000

通讯作者:

刘波，正高级工程师 MP: 18971321466 E-mail: 513839739@qq.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.07.019

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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