Novel nanostructured lipid carriers with lurasidone hydrochloride for intranasal administration for improved bioavailability

新型纳米结构脂质载体负载盐酸鲁拉西酮,用于鼻内给药以提高生物利用度

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Abstract

AIM: This research aims to develop nanostructured lipid carriers containing Lurasidone hydrochloride (LH) with Quality by Design (QbD) methodology to enhance its bioavailability, given LH's low water solubility (0.224 mg/ml) and bioavailability (9-19%). MATERIAL AND METHODS: The optimized LH-NLC formulation contains Glyceryl monostearate (GMS) as solid lipid, Caproyl 90 as liquid lipid and co-surfactant, and Tween 80 as surfactant. The hot emulsification method was used to formulate the LH-NLC using a three-factor, three-level Box-Behnken design (BBD)for ascertaining functional relationships between particle size and entrapment efficiency (EE). Particle size, polydispersity index (PDI), zeta potential, surface morphology, percentage EE, and in vitro and ex-vivo release were assessed. Wistar rats were used to estimate plasma drug concentration after LH-NLC administration. RESULTS: The developed formulation exhibited a particle size of 190.98 ± 4.72 nm, zeta potential of + 17.47 mV, and encapsulation efficiency of 94 ± 1.26% w/w. LH-NLCs showed a drug release rate of 95.37% within 24 hours. Intranasal administration of LH-NLCs resulted in 5.16 times higher bioavailability compared to intranasally administered lurasidone. CONCLUSION: The study successfully applied QbD methodology to develop NLCs for LH with enhanced bioavailability, demonstrating improved drug entrapment and delivery efficacy for treating psychosis.

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