佩米替尼超小型自纳米乳化给药系统的配方开发、优化与表征

IF 3.4 Q2 PHARMACOLOGY & PHARMACY
Muthadi Radhika Reddy, Kumar Shiva Gubbiyappa
{"title":"佩米替尼超小型自纳米乳化给药系统的配方开发、优化与表征","authors":"Muthadi Radhika Reddy,&nbsp;Kumar Shiva Gubbiyappa","doi":"10.1186/s43094-022-00434-4","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Pemigatinib is a small molecule tyrosine kinase inhibitor of fibroblast growth factor receptor inhibitors. The oral bioavailability of Pemigatinib is constricted due to its limited solubility at physiological pH. It is essential to develop a novel formulation of Pemigatinib to improve the intrinsic solubility and to reduce the pharmacokinetic variability. Self-nanoemulsifying drug delivery system is an effective, smart and more adequate formulation approach for poorly soluble drugs. Different from conventional self-nanoemulsifying drug delivery system, a supersaturable self-nanoemulsifying drug delivery system of Pemigatinib was prepared by using a supersaturation promoter.</p><h3>Results</h3><p>Among all the oils, Captex® 300 have shown maximum solubility of Pemigatinib. Considering the solubilization potential and emulsification ability Kolliphor®RH 40 was selected as surfactant. Transcutol®HP was selected as co-surfactant. The composition of oil, surfactant and co-surfactant was identified using phase diagrams and further adjusted by simplex-lattice design. HPMC K4M as precipitation inhibitor at 5% concentration resulted in effective supersaturating with increased self-emulsification time. The droplet of sSNEDDS ranges from 166.78 ± 3.14 to 178.86 ± 1.24 nm with PDI 0.212 – 0.256, which is significantly smaller than that observed with plain SNEDDS. TEM images revealed the spherical shape of the nanodroplets. The final optimized formulation formed spontaneous nanoemulsion within 15 secs when added to physiological fluids. The percent transmittance of the diluted formulation was found to be 99.12 ± 0.46. The viscosity was found to be 574 ± 26 centipoises indicating the good flow ability. FTIR and DSC studies indicated the amorphization of the drug. The dissolution profile of sSNEDDS indicated the faster release of drug compared to both pure drug suspension and SNEDDS formulation. The drug release rate is directly proportional to the concentration of the drug. The drug release from the insoluble matrix is a square root of time-dependent Fickian diffusion process. The formulation was found to be stable and transparent at all pH values and the percent transmittance was more than 95%. Any kind of separation or precipitation was not observed at different temperatures cycles. No significant difference was observed with all the samples exposed at different storage conditions.</p><h3>Conclusions</h3><p>This study demonstrated the feasibility of stabilizing and improving the in-vitro performance of self-nanoemulsifying drug delivery systems of Pemigatinib by incorporating HPMC K4M as precipitation inhibitor.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"8 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-022-00434-4","citationCount":"1","resultStr":"{\"title\":\"Formulation development, optimization and characterization of Pemigatinib-loaded supersaturable self-nanoemulsifying drug delivery systems\",\"authors\":\"Muthadi Radhika Reddy,&nbsp;Kumar Shiva Gubbiyappa\",\"doi\":\"10.1186/s43094-022-00434-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Pemigatinib is a small molecule tyrosine kinase inhibitor of fibroblast growth factor receptor inhibitors. The oral bioavailability of Pemigatinib is constricted due to its limited solubility at physiological pH. It is essential to develop a novel formulation of Pemigatinib to improve the intrinsic solubility and to reduce the pharmacokinetic variability. Self-nanoemulsifying drug delivery system is an effective, smart and more adequate formulation approach for poorly soluble drugs. Different from conventional self-nanoemulsifying drug delivery system, a supersaturable self-nanoemulsifying drug delivery system of Pemigatinib was prepared by using a supersaturation promoter.</p><h3>Results</h3><p>Among all the oils, Captex® 300 have shown maximum solubility of Pemigatinib. Considering the solubilization potential and emulsification ability Kolliphor®RH 40 was selected as surfactant. Transcutol®HP was selected as co-surfactant. The composition of oil, surfactant and co-surfactant was identified using phase diagrams and further adjusted by simplex-lattice design. HPMC K4M as precipitation inhibitor at 5% concentration resulted in effective supersaturating with increased self-emulsification time. The droplet of sSNEDDS ranges from 166.78 ± 3.14 to 178.86 ± 1.24 nm with PDI 0.212 – 0.256, which is significantly smaller than that observed with plain SNEDDS. TEM images revealed the spherical shape of the nanodroplets. The final optimized formulation formed spontaneous nanoemulsion within 15 secs when added to physiological fluids. The percent transmittance of the diluted formulation was found to be 99.12 ± 0.46. The viscosity was found to be 574 ± 26 centipoises indicating the good flow ability. FTIR and DSC studies indicated the amorphization of the drug. The dissolution profile of sSNEDDS indicated the faster release of drug compared to both pure drug suspension and SNEDDS formulation. The drug release rate is directly proportional to the concentration of the drug. The drug release from the insoluble matrix is a square root of time-dependent Fickian diffusion process. The formulation was found to be stable and transparent at all pH values and the percent transmittance was more than 95%. Any kind of separation or precipitation was not observed at different temperatures cycles. No significant difference was observed with all the samples exposed at different storage conditions.</p><h3>Conclusions</h3><p>This study demonstrated the feasibility of stabilizing and improving the in-vitro performance of self-nanoemulsifying drug delivery systems of Pemigatinib by incorporating HPMC K4M as precipitation inhibitor.</p></div>\",\"PeriodicalId\":577,\"journal\":{\"name\":\"Future Journal of Pharmaceutical Sciences\",\"volume\":\"8 1\",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2022-11-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-022-00434-4\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Future Journal of Pharmaceutical Sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://link.springer.com/article/10.1186/s43094-022-00434-4\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future Journal of Pharmaceutical Sciences","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1186/s43094-022-00434-4","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 1

摘要

pemigatinib是一种小分子酪氨酸激酶抑制剂的成纤维细胞生长因子受体抑制剂。由于其在生理ph值下的溶解度有限,Pemigatinib的口服生物利用度受到限制。开发一种新的Pemigatinib配方以提高其固有溶解度并减少药代动力学变异性是必要的。自纳米乳化给药系统是一种有效的、智能的、更合适的难溶性药物配制方法。与传统的自纳米乳化给药系统不同,采用过饱和促进剂制备了一种过饱和的Pemigatinib自纳米乳化给药系统。结果Captex®300对Pemigatinib的溶解度最大。考虑到增溶潜力和乳化能力,选择Kolliphor®RH 40作为表面活性剂。选择Transcutol®HP作为助表面活性剂。采用相图法确定了油、表面活性剂和助表面活性剂的组成,并通过单纯点阵设计进行了进一步调整。5%浓度的HPMC K4M作为沉淀抑制剂,随着自乳化时间的延长,可实现有效的过饱和。sSNEDDS的微滴范围为166.78±3.14 ~ 178.86±1.24 nm, PDI为0.212 ~ 0.256,明显小于普通SNEDDS。TEM图像显示纳米液滴呈球形。最终优化的配方在加入生理液体15秒内形成自发纳米乳。稀释后的溶液透光率为99.12±0.46。粘度为574±26厘泊,具有良好的流动性。FTIR和DSC研究表明药物的非晶化。溶出度曲线表明,与纯药物混悬液和SNEDDS制剂相比,其药物释放速度更快。药物释放率与药物浓度成正比。药物从不溶性基质中的释放是随时间变化的菲克扩散过程的平方根。结果表明,该配方在所有pH值下均稳定透明,透过率均大于95%。在不同的温度循环中没有观察到任何形式的分离或沉淀。在不同的贮藏条件下,所有样品均无显著差异。结论采用HPMC K4M作为沉淀抑制剂,稳定和提高Pemigatinib自纳米乳化给药系统的体外性能是可行的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Formulation development, optimization and characterization of Pemigatinib-loaded supersaturable self-nanoemulsifying drug delivery systems

Background

Pemigatinib is a small molecule tyrosine kinase inhibitor of fibroblast growth factor receptor inhibitors. The oral bioavailability of Pemigatinib is constricted due to its limited solubility at physiological pH. It is essential to develop a novel formulation of Pemigatinib to improve the intrinsic solubility and to reduce the pharmacokinetic variability. Self-nanoemulsifying drug delivery system is an effective, smart and more adequate formulation approach for poorly soluble drugs. Different from conventional self-nanoemulsifying drug delivery system, a supersaturable self-nanoemulsifying drug delivery system of Pemigatinib was prepared by using a supersaturation promoter.

Results

Among all the oils, Captex® 300 have shown maximum solubility of Pemigatinib. Considering the solubilization potential and emulsification ability Kolliphor®RH 40 was selected as surfactant. Transcutol®HP was selected as co-surfactant. The composition of oil, surfactant and co-surfactant was identified using phase diagrams and further adjusted by simplex-lattice design. HPMC K4M as precipitation inhibitor at 5% concentration resulted in effective supersaturating with increased self-emulsification time. The droplet of sSNEDDS ranges from 166.78 ± 3.14 to 178.86 ± 1.24 nm with PDI 0.212 – 0.256, which is significantly smaller than that observed with plain SNEDDS. TEM images revealed the spherical shape of the nanodroplets. The final optimized formulation formed spontaneous nanoemulsion within 15 secs when added to physiological fluids. The percent transmittance of the diluted formulation was found to be 99.12 ± 0.46. The viscosity was found to be 574 ± 26 centipoises indicating the good flow ability. FTIR and DSC studies indicated the amorphization of the drug. The dissolution profile of sSNEDDS indicated the faster release of drug compared to both pure drug suspension and SNEDDS formulation. The drug release rate is directly proportional to the concentration of the drug. The drug release from the insoluble matrix is a square root of time-dependent Fickian diffusion process. The formulation was found to be stable and transparent at all pH values and the percent transmittance was more than 95%. Any kind of separation or precipitation was not observed at different temperatures cycles. No significant difference was observed with all the samples exposed at different storage conditions.

Conclusions

This study demonstrated the feasibility of stabilizing and improving the in-vitro performance of self-nanoemulsifying drug delivery systems of Pemigatinib by incorporating HPMC K4M as precipitation inhibitor.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
44
审稿时长
23 weeks
期刊介绍: Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信