Tailoring lipid nanoconstructs for the oral delivery of Paliperidone: Formulation, Optimization and In vitro evaluation,Chemistry and Physics of Lipids

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Tailoring lipid nanoconstructs for the oral delivery of Paliperidone: Formulation, Optimization and In vitro evaluation
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2020-11-02 , DOI: 10.1016/j.chemphyslip.2020.105005
Saleha Rehman ₁ , Bushra Nabi ₁ , Sanjula Baboota ₁ , Javed Ali ₁

Affiliation

Purpose

The present research work involves Quality by Design (QbD)-based fabrication of lipid nanoconstructs (LNC) of paliperidone (PPD) bearing superior biopharmaceutical attributes.

Methods

LNC of paliperidone was prepared by melt emulsification-probe sonication and high-pressure homogenization method followed by optimization using QbD approach. Preparing LNC by both these methods will give the benefit of identifying the best optimized formulation which will be further evaluated for in vitro studies.

Results

The best optimized formulation was obtained using melt emulsification-probe sonication technique with small particle size (86.35 nm), high entrapment efficiency (90.07%), and high loading capacity (8.49%). The drug release from LNC was found to be 5, 8, and 9-folds greater than drug suspension in pH 1.2, 6.8, and 7.4 respectively (p < 0.001). Stability studies of LNC in simulated gastric fluid pH 1.2 and fasted state simulated intestinal fluid depicted no alteration in particle size and polydispersity index of LNC but were found to increase in fed state simulated intestinal fluid. The drug permeability through rat intestine for LNC was found to be approximately 6-folds (p < 0.05) greater as compared to the drug suspension which was further confirmed by confocal microscopy. The in vitro lipolysis study presented significantly highest solubilization (p < 0.001) in the aqueous phase thereby anticipating higher in vivo absorption.

Conclusion

Thus, it was concluded that LNC bears the knack of improving the solubilization and permeation potential of an otherwise hydrophobic drug, paliperidone.”

中文翻译：

为帕利哌酮口服给药定制脂质纳米结构：配方、优化和体外评估

目的

目前的研究工作涉及基于设计质量 (QbD) 的帕潘立酮 (PPD) 脂质纳米结构 (LNC) 的制造，具有卓越的生物制药特性。

方法

通过熔体乳化-探针超声和高压均质法制备帕潘立酮的 LNC，然后使用 QbD 方法进行优化。通过这两种方法制备 LNC 将有助于确定最佳优化配方，并将进一步评估体外研究。

结果

使用熔体乳化-探针超声技术获得最佳优化配方，具有小粒径 (86.35 nm)、高包封率 (90.07%) 和高负载能力 (8.49%)。发现 LNC 的药物释放量分别是 pH 1.2、6.8 和 7.4 中的药物悬浮液的 5、8 和 9 倍（p < 0.001）。LNC 在模拟胃液 pH 1.2 和禁食状态模拟肠液中的稳定性研究表明 LNC 的粒径和多分散指数没有变化，但发现在进食状态模拟肠液中增加。发现 LNC 通过大鼠肠道的药物渗透性与药物悬浮液相比大约高 6 倍 ( p < 0.05)，共聚焦显微镜进一步证实了这一点。这体外脂解研究表明在水相中的溶解度显着最高（p < 0.001），因此预计体内吸收率更高。