Self-Nanoemulsifying/ Self-Assembled Cubic Nanoparticles Lyophilized Tablet: A Novel Biphasic Release Approach to Enhance the Bioavailability of a Lipophilic Drug

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2024-10-21 DOI:10.1208/s12249-024-02952-1

Michael M. Farag, Wessam El-Sebaie, Emad B. Basalious, Omaima N. El-Gazayerly

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Abstract

This study aimed to prepare a combined self-nanoemulsifying and self-assembled cubic nanoparticles (SNE/SAC) lyophilized tablet eliciting biphasic release pattern escorted with enhanced bioavailability for drugs hampered with slow dissolution and poor absorption. The antimuscarinic Darifenacin hydrobromide (DRF) was selected as a model drug used to treat overactive bladder-associated nocturia. The DRF-SNE/SAC lyophilized tablet was prepared so that upon reconstitution a mixture of DRF-loaded cubic nanoparticles and nanoemulsion dispersion is obtained. The nanoemulsion portion is responsible for the fast release followed by controlled release of the remaining dose loaded in cubic nanoparticles. A comparative pharmacokinetic study adopting randomized crossover design in male albino rabbits versus marketed product Frequefenacine® tablet was performed. Half of the dose (52.05% ± 4.21%) was rapidly released in the first 4 h followed by sustained release of the remaining drug where (90.16% ± 8.85%) was released in 24 h. The tested system showed 2.45 folds higher % relative bioavailability and 1.57 folds higher C_max with 1.62 longer residence time relative to reference product. The results endow the ability of the developed DRF-SNE/SAC lyophilized tablet to be considered as a propitious approach for the treatment of overactive bladder-associated nocturia without midnight dose administration.

Graphical Abstract

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自纳米乳化/自组装立方纳米颗粒冻干片剂：提高亲脂性药物生物利用度的新型双相释放方法

本研究旨在制备一种自纳米乳化和自组装立方纳米颗粒（SNE/SAC）相结合的冻干片剂，这种片剂具有双相释放模式，并能提高溶解缓慢和吸收不良药物的生物利用度。抗马司卡因药物氢溴酸达非那新（DRF）被选为治疗膀胱过度活动相关性夜尿症的模型药物。制备 DRF-SNE/SAC 冻干片剂的目的是在复溶后获得 DRF 负载立方纳米颗粒和纳米乳液分散体的混合物。纳米乳液部分负责快速释放，然后控制立方纳米颗粒中剩余剂量的释放。研究人员采用随机交叉设计，在雄性白化兔体内进行了一项药代动力学对比研究。一半的剂量（52.05% ± 4.21%）在最初的 4 小时内迅速释放，剩余的药物（90.16% ± 8.85%）在 24 小时内持续释放。与参考产品相比，受试系统的相对生物利用率提高了 2.45 倍，Cmax 提高了 1.57 倍，停留时间延长了 1.62 倍。这些结果表明，所开发的 DRF-SNE/SAC 冻干片剂可被视为治疗膀胱过度活动症相关夜尿的一种有效方法，且无需午夜给药。图解摘要

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.