Solid self-nanoemulsifying drug delivery systems of nimodipine: development and evaluation

IF 3.4 Q2 PHARMACOLOGY & PHARMACY

Future Journal of Pharmaceutical Sciences Pub Date : 2024-07-10 DOI:10.1186/s43094-024-00653-x

Mohit Kumar, Pooja A. Chawla, Abdul Faruk, Viney Chawla

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Abstract

Background

This study aimed to formulate solid self-nanoemulsifying drug delivery systems (SNEDDS) for nimodipine (NIM). The selection of Cremophor RH 40, Lipoxol 300, and PEG 400 as oil, surfactant, and co-surfactant was based on solubility and self-emulsification assessments. A ternary phase diagram determined the optimal oil to Smix (surfactant/co-surfactant) ratio (40:60). By utilizing liquid SNEDDS (NIM-SNEDDS) as an adsorbate and chitosan EDTA microparticles, developed through spray drying (SD-CHEM) and solvent evaporation (SE-CHEM) as adsorbents, the solid SNEDDS were created (NIM-SD-SSNEDDS and NIM-SE-SSNEDDS, respectively).

Results

Both solid formulations exhibited favourable drug loading (NIM-SD-SSNEDDS = 79.67 ± 2.97%, NIM-SE-SSNEDDS = 77.76 ± 4.29%), excellent flowability, and drug amorphization as per XRD and DSC analysis. Scanning electron microscopy revealed smoothening and filling of adsorbent surfaces by adsorbate (with size range NIM-SD-SSNEDDS = 10–15 μm, NIM-SE-SSNEDDS = 20–25 μm). FTIR confirmed no interaction of drug and excipients. Stability studies demonstrated the physical and thermodynamic stability of reconstituted nanoemulsions with droplet size, PDI, zeta potential, emulsification time, % transmittance and cloud temperature for NIM-SD-SSNEDDS as 247.1 nm, PDI 0.620, 1.353 mV, 38–41 s, 94.64%, 54 °C and for NIM-SE-SSNEDDS as 399.6 nm, PDI 0.821, 1.351 mV, 40–48 s, 92.96%, 49 °C, respectively. FE-SEM images showed globules formed with small sizes, and there was no coalescence evidence, implying the reconstituted nanoemulsions' stability. In vitro dissolution studies revealed a fourfold increase in drug dissolution for NIM-SD-SSNEDDS (84.43%) and NIM-SE-SSNEDDS (76.68%) compared to pure drug (28%). Ex vivo permeation studies indicated almost similar profiles for NIM-SD-SSNEDDS (22.61%) and NIM-SE-SSNEDDS (21.93%) compared to NIM-SNEDDS (25.02%).

Conclusion

NIM-SD-SSNEDDS exhibited superior performance compared to NIM-SE-SSNEDDS, highlighting the efficacy of microparticles developed by the spray drying method (SD-CHEM) as adsorbents for solidification. These results suggest enhanced dissolution and permeation for nimodipine in both the solid SNEDDS.

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尼莫地平固体自纳米乳化给药系统：开发与评估

本研究旨在配制尼莫地平（NIM）的固体自纳米乳化给药系统（SNEDDS）。根据溶解度和自乳化评估结果，选择 Cremophor RH 40、Lipoxol 300 和 PEG 400 作为油、表面活性剂和辅助表面活性剂。三元相图确定了油与 Smix（表面活性剂/辅助表面活性剂）的最佳比例（40:60）。利用液态 SNEDDS（NIM-SNEDDS）作为吸附剂，壳聚糖 EDTA 微颗粒（通过喷雾干燥法（SD-CHEM）和溶剂蒸发法（SE-CHEM）开发）作为吸附剂，制成了固态 SNEDDS（分别为 NIM-SD-SSNEDDS 和 NIM-SE-SSNEDDS）。根据 XRD 和 DSC 分析，两种固体制剂都表现出良好的药物载量（NIM-SD-SSNEDDS = 79.67 ± 2.97%，NIM-SE-SSNEDDS = 77.76 ± 4.29%）、优异的流动性和药物非形态化。扫描电子显微镜显示，吸附剂表面变得平滑，并被吸附物填充（尺寸范围为 NIM-SD-SSNEDDS = 10-15 μm，NIM-SE-SSNEDDS = 20-25 μm）。傅立叶变换红外光谱证实药物与辅料之间没有相互作用。稳定性研究表明，重组纳米乳液具有物理和热力学稳定性，NIM-SD-SSNEDDS 的液滴尺寸、PDI、ZETA 电位、乳化时间、透光率百分比和浊度温度为 247。1 nm、PDI 0.620、1.353 mV、38-41 s、94.64%、54 °C，NIM-SE-SSNEDDS 分别为 399.6 nm、PDI 0.821、1.351 mV、40-48 s、92.96%、49 °C。FE-SEM 图像显示，形成的球状物尺寸较小，没有凝聚迹象，这表明重组纳米乳液具有稳定性。体外溶解研究表明，与纯药物（28%）相比，NIM-SD-SSNEDDS（84.43%）和 NIM-SE-SSNEDDS （76.68%）的药物溶解度提高了四倍。体内外渗透研究表明，NIM-SD-SSNEDDS（22.61%）和 NIM-SE-SSNEDDS （21.93%）的渗透率与 NIM-SNEDDS （25.02%）几乎相似。与 NIM-SE-SSNEDDS 相比，NIM-SD-SSNEDDS 表现出更优越的性能，凸显了喷雾干燥法（SD-CHEM）开发的微粒作为固化吸附剂的功效。这些结果表明，尼莫地平在这两种固体 SNEDDS 中的溶解和渗透性都有所提高。

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来源期刊

Future Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-

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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.