摘要
本研究的目的是通过设计专家和质量源于设计（QbD）方法合成和优化装有利培酮（RIS）和槲皮素（QUE）的鼻腔内凝胶固体脂质纳米颗粒（SLN）。方法确定了质量目标产品特征（QTTP）、关键工艺参数（CPP）和关键质量属性（CQAs）。采用普拉克特-伯曼设计法对影响 CPP 和 CQAs 的因素进行了初步筛选。采用溶剂扩散法制备 SLN。通过 22（RIS）和 23（QUE）因子设计对 SLN 进行了优化。温度、辅助表面活性剂的类型、表面活性剂的浓度（%）被确定为独立因素，而粒度、包埋效率（%）则被记录下来。通过分析粒度、PDI、Zeta 电位、傅立叶变换红外光谱、包埋效率、TEM 等对制备的 SLN 进行表征，将合成的 SLN 加入原位凝胶中，对凝胶温度、粘度、体外药物扩散等进行评估。粒径为 157.4 ± 2 nm 153 ± 3 nm。分别为RIS SLN 的 PDI 为 0.261，QUE SLN 为 0.240。EE% 分别为 91.73 ± 2.6%、91.73 ± 2.6%，表明药物封装成功。TEM 研究支持球形性质。DSC 和 FTIR 研究表明药物成功地融入了 SLN。在 18% 浓度的聚氧乙烯中成功加入了 SLN，形成了鼻腔原位凝胶。该研究采用 QbD 方法成功地开发并优化了鼻腔用药中装载 RIS 和 QUE SLN 的 SLN。SLNs 和原位凝胶的组合提供了一种稳定有效的鼻腔给药系统。所开发的 SLNs 和原位凝胶配方有望用于鼻腔给药，通过有效绕过首过代谢和提高药物可用性，为口服给药提供了可行的替代方案。Purpose
The objective of the current study is synthesis and optimization of Nasal Insitu Gel loaded with Risperidone (RIS) and Quercetin (QUE) Solid Lipid Nanoparticles (SLN) by Design Expert and Quality by Design (QbD)Approach.
Method
QTTP (Quality target product profile), critical process parameters (CPP), critical quality attributes (CQAs) were identified. Preliminary screening of factors which affect CPP and CQAs was carried out using Placket Burman design. SLN were prepared by solvent diffusion method. Optimization of SLN was carried by 22 (RIS) and 23 (QUE) factorial designs. Temperature, Type of co-surfactant, Concentration of surfactant (%) were identified as independent factors and responses were recorded against Particle size, % Entrapment Efficiency. Characterization of prepared SLN were done by analysis of particle size, PDI, Zeta Potential, FTIR, Entrapment Efficiency, TEM etc., synthesized SLN were incorporated into Insitu gel which was evaluated for gelation temperature, viscosity, in-vitro drug diffusion etc.
Results
RIS SLN and QUE SLN were successfully synthesized. Particle size was found 157.4 ± 2 nm 153 ± 3 nm. Respectively. PDI was observed 0.261 for RIS SLN and 0.240 and QUE SLN. % EE were obtained 91.73 ± 2.6%, 91.73 ± 2.6% respectively indicated successful drug encapsulation. TEM study supported spherical nature. DSC and FTIR study showed successful incorporation of drugs into SLN. SLN were successfully incorporated into 18% concentration of poloxamer for formation of nasal insitu gel. In-vitro diffusion study revealed sustained and controlled drug release.
Conclusion
The study successfully developed and optimized SLNs loaded with RIS and QUE SLN for nasal administration using the QbD approach. The combination of SLNs and insitu gel provided a stable and effective nasal delivery system. The developed SLNs and insitu gel formulation are promising for nasal administration, offering a viable alternative to oral delivery by effectively bypassing first-pass metabolism and improving drug availability.
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