Investigation of Mirabegron-loaded Nanostructured Lipid Carriers for Improved Bioabsorption: Formulation, Statistical Optimization, and In-Vivo Evaluation

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2024-09-25 DOI:10.1208/s12249-024-02944-1

Pranav Shah, Mansi Patel, Yashwini Kansara, Bhavin Vyas, Pintu Prajapati, Madhulika Pradhan, Sanyog Jain

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Abstract

Overactive bladder (OAB) is a usual medical syndrome that affects the bladder, and Mirabegron (MBG) is preferred medicine for its control. Currently, available marketed formulations (MYRBETRIQ® granules and MYRBETRIQ® ER tablets) suffer from low bioavailability (29–35%) hampering their therapeutic effectiveness and compromising patient compliance. By creating MBG nanostructured lipid carriers (MBG-NLCs) for improved systemic availability and drug release, specifically in oral administration of OAB treatment, this study aimed to address these issues. MBG-NLCs were fabricated using a hot-melt ultrasonication technique. MBG-GMS; MBG-oleic acid interaction was assessed by in silico molecular docking. QbD relied on the concentration of Span 80 (X1) and homogenizer speed (X2) as critical material attribute (CMA) and critical process parameter (CPP) respectively, while critical quality attributes (CQA) such as particle size (Y1) and cumulative drug release at 24 h (Y2) were estimated as dependent variables. 32 factorial design was utilized to investigate the interconnection in variables that are dependent and independents. Optimized MBG-NLCs with a particle size of 194.4 ± 2.25 nm were suitable for lymphatic uptake. A PDI score of 0.275 ± 0.02 and zeta potential of -36.2 ± 0.721 mV indicated a uniform monodisperse system with stable dispersion properties. MBG-NLCs exhibited entrapment efficiency of 77.3 ± 1.17% and a sustained release in SIF of 94.75 ± 1.60% for 24 h. MBG-NLCs exhibited the Higuchi model with diffusion as a release mechanism. A pharmacokinetic study in Wistar rats exhibited a 1.67-fold higher bioavailability as compared to MBG suspension. Hence, MBG-NLCs hold promise for treating OAB by improving MBG’s oral bio absorption.

Graphical Abstract

Abstract Image

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用于改善生物吸收的米拉贝琼纳米结构脂质载体的研究：配方、统计优化和体内评估

膀胱过度活动症（OAB）是一种影响膀胱的常见内科综合征，米拉贝琼（MBG）是控制该病的首选药物。目前，市场上现有的制剂（MYRBETRIQ® 颗粒剂和 MYRBETRIQ® ER 片剂）生物利用度低（29%-35%），影响了其治疗效果，并降低了患者的依从性。本研究旨在通过制造 MBG 纳米结构脂质载体（MBG-NLCs）来改善全身可用性和药物释放，特别是在口服治疗 OAB 时，从而解决这些问题。本研究采用热熔超声技术制备了 MBG-NLC。通过硅学分子对接评估了 MBG-GMS；MBG-油酸的相互作用。QbD 依靠斯盘 80 的浓度（X1）和均质器速度（X2）分别作为关键材料属性（CMA）和关键工艺参数（CPP），而粒度（Y1）和 24 小时累积药物释放量（Y2）等关键质量属性（CQA）则作为因变量进行估算。采用 32 因式设计来研究因变量和自变量之间的相互联系。优化后的 MBG-NLCs 的粒径为 194.4 ± 2.25 nm，适合淋巴吸收。PDI 分数为 0.275 ± 0.02，zeta 电位为 -36.2 ± 0.721 mV，表明这是一种具有稳定分散特性的均匀单分散体系。MBG-NLCs 的夹持效率为 77.3 ± 1.17%，在 SIF 中 24 小时的持续释放率为 94.75 ± 1.60%。在 Wistar 大鼠体内进行的药代动力学研究表明，生物利用率比 MBG 悬浮液高 1.67 倍。因此，MBG-NLCs 有望通过改善 MBG 的口服生物吸收率来治疗 OAB。

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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.