Ghose Debashish, Patra Chinam Niranjan, Ravi Kumar Bera Varaha Venkata, Swain Suryakanta, Jena Bikash Ranjan, Choudhury Punam, Shree Dipthi
Roland Institute of Pharmaceutical Sciences, Berhampur (Affiliated to Biju Patnaik University of Technology, Rourkela), Odisha, India
Department of Pharmacy, School of Health Sciences, The Assam Kaziranga University, Jorhat, Assam, India
Turk J Pharm Sci. 2021 Sep 1;18(4):452-464. doi: 10.4274/tjps.galenos.2020.08522.
The aim of the present work was to prepare QbD enabled optimization, and to improve the oral bioavailability of freeze-dried polymeric nanoparticles of cinacalcet hydrochloride manufactured by nanoprecipitation and ultrasonication methods using polymers PLGA, and poloxamer-188.
The initial screening and optimization were carried out for the formulations by employing Taguchi and Box-Behnken Designs. The FT-IR and DSC revealed no interactions and had no incompatibility among the selected drug and polymers. The nanoparticles were characterized for % drug release, particle size analysis, zeta potential, PDI, SEM, TEM, P-XRD, TGA, DTA, , and drug release study.
drug release study showed sustained release of the drug from the optimized batch by diffusion mechanism. The optimized nanoparticle formulation was recognized by numerical and graphical methods using validation of the experimental model. The optimized batch was stable as per the ICH stability guidelines for 6 months with no considerable alternation noticed in particle size, entrapment efficiency, and drug release. The pharmacokinetic parameters of AUC and Cmax data for the optimized formulation increased 3- and 2.9-folds compared to the pure-drug suspension.
The prepared polymeric nanoparticles formulation is an alternative delivery system for enhanced therapeutic efficacy and bioavailability potential of a model drug to manage long-term normocalcemia in patients with preliminary hyperparathyroidism.
本研究旨在采用质量源于设计（QbD）方法进行优化，以提高通过纳米沉淀法和超声法，使用聚乳酸-羟基乙酸共聚物（PLGA）和泊洛沙姆-188制备的盐酸西那卡塞冻干聚合物纳米粒的口服生物利用度。
采用田口设计和Box-Behnken设计对制剂进行初步筛选和优化。傅里叶变换红外光谱（FT-IR）和差示扫描量热法（DSC）显示所选药物与聚合物之间无相互作用且无不相容性。对纳米粒进行了药物释放率、粒径分析、zeta电位、多分散指数（PDI）、扫描电子显微镜（SEM）、透射电子显微镜（TEM）、粉末X射线衍射（P-XRD）、热重分析（TGA）、差热分析（DTA）以及药物释放研究等表征。
药物释放研究表明，优化批次的药物通过扩散机制实现持续释放。通过实验模型验证，采用数值和图形方法确定了优化的纳米粒制剂。根据国际协调理事会（ICH）稳定性指南，优化批次在6个月内稳定，粒径、包封率和药物释放均未出现明显变化。与纯药物混悬液相比，优化制剂的药时曲线下面积（AUC）和血药浓度峰值（Cmax）的药代动力学参数分别提高了3倍和2.9倍。
所制备的聚合物纳米粒制剂是一种替代给药系统，可提高模型药物的治疗效果和生物利用度潜力，用于治疗初发性甲状旁腺功能亢进患者的长期血钙正常。
