Purpose

The current study entails the design, development, and optimization of nasal mucoadhesive microspheres of lercanidipine with improved systemic bioavailability for the management of hypertension.

Methods

Mucoadhesive microspheres of lercanidipine were prepared by solvent evaporation and polymerization method using bovine serum albumin (BSA) as the carrier and glutaraldehyde as the chelating agent. For screening the material and process variables, Taguchi design revealed the major influence of BSA concentration and glutaraldehyde volume as the critical factors for the preparation of microspheres. These factors were systematically optimized using Central Composite design to evaluate the particle size, entrapment efficiency, and in vitro drug release from the microspheres as the response variables.

Results

The optimized microspheres were prepared using 4.4% BSA and 0.25-mL glutaraldehyde, and stirring speed at 1500 rpm, which exhibited particle size of 34 μm, entrapment efficiency of 88.6%, Q_6h of 94.67%, T_60% of 3.2 h, and bioadhesion efficiency of 93.2%. In vivo pharmacokinetics in rabbits showed remarkable superiority of the optimized nasal microspheres (p < 0.001) with nearly eightfold improvement in the drug absorption parameters vis-à-vis the pure drug lercanidipine. Accelerated stability studies for 6 months demonstrated nearly similar drug release profiles at different time intervals, indicating the robustness of the optimized formulation.

Conclusions

In a nutshell, the present studies resulted in the successful development of optimized lercanidipine microspheres for nasal delivery.

中文翻译：

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乐卡地平的鼻粘膜粘附微球具有增强的全身生物利用度和降压活性

目的

当前的研究涉及乐卡地平鼻粘膜粘附微球的设计，开发和优化，其具有改善的系统生物利用度，可用于治疗高血压。

方法

以牛血清白蛋白（BSA）为载体，戊二醛为螯合剂，通过溶剂蒸发和聚合法制备了乐卡地平的粘膜粘附微球。为了筛选材料和工艺变量，Taguchi设计揭示了BSA浓度和戊二醛体积的主要影响是制备微球的关键因素。使用中央复合材料设计系统地优化了这些因素，以评估粒径，包封效率和微球的体外药物释放作为响应变量。

结果

使用4.4％BSA和0.25 mL戊二醛，以1500 rpm的搅拌速度制备了优化的微球，其粒径为34μm，包封率为88.6％，Q _6h为94.67％，T _60％为3.2 h，并且生物粘附效率为93.2％。兔子体内的药物动力学显示，优化的鼻腔微球具有明显的优越性（p  <0.001），相对于纯药物lercanidipine而言，药物吸收参数提高了近八倍。六个月的加速稳定性研究表明，不同时间间隔的药物释放曲线几乎相似，表明优化制剂的耐用性。

结论

简而言之，本研究成功地开发了用于鼻腔输送的优化的lercanidipine微球。