Purpose

The present study is aimed at developing liposomal nanovesicular system of teriparatide employing the use of ethanol injection method for providing sustained release in the treatment of osteoporosis.

Methods

Formulation development was carried out systematically by employing Quality by Design (QbD) approach. The developed system was evaluated for various physicochemical characterizations.

Results

The developed liposomal formulation exhibited particle size of approximately 186.9 ± 2.20 nm. Cryogenic field emission scanning electron microscopy (Cryo-FE-SEM) analysis revealed spherical morphology of the liposomes. The % encapsulation efficiency (% EE) was found to be 46.52% and polydispersity index (PDI) to be 0.149 ± 0.02, suggesting narrow particle size distribution of the developed liposomal formulation. Circular dichroism study revealed intact structure of drug in the formulation. Haemolysis assay was performed and the no significant lysis of RBC was observed up to the concentration of 10 µg/ml of formulation. The developed formulation took almost 24 h to release 50% of the encapsulated teriparatide while it took 36 h to release about 90% of the drug. Furthermore, results of cell viability study suggest that encapsulation of teriparatide into the liposomes is not affecting its safety.

Conclusion

The implementation of the QbD concept in the development of teriparatide-loaded liposomes enhanced understanding of the manufacturing process and the influence of formulation parameters on the quality attributes of liposomes.

中文翻译：

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采用质量设计方法治疗骨质疏松症的特立帕肽负载纳米脂质体的系统开发和优化

目的

本研究旨在开发特立帕肽脂质体纳米囊泡系统，采用乙醇注射法在骨质疏松症治疗中提供缓释。

方法

通过采用质量源于设计 (QbD) 方法系统地进行配方开发。对开发的系统进行了各种物理化学表征的评估。

结果

开发的脂质体制剂的粒径约为 186.9 ± 2.20 nm。低温场发射扫描电子显微镜 (Cryo-FE-SEM) 分析揭示了脂质体的球形形态。发现 % 包封效率 (% EE) 为 46.52%，多分散指数 (PDI) 为 0.149 ± 0.02，表明开发的脂质体制剂的粒度分布窄。圆二色性研究揭示了制剂中药物的完整结构。进行了溶血测定，并且在高达 10 µg/ml 制剂的浓度下没有观察到 RBC 的显着溶解。开发的制剂需要将近 24 小时才能释放 50% 的包封特立帕肽，而需要 36 小时才能释放约 90% 的药物。此外，

结论

QbD 概念在特立帕肽负载脂质体开发中的实施增强了对制造过程和制剂参数对脂质体质量属性影响的理解。