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Nanoscience & Nanotechnology-Asia

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ISSN (Print): 2210-6812
ISSN (Online): 2210-6820

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Research Article

Development of Surface Modified and Aqueous Re-dispersible Nanocrystal using Pluronic F-68 and Suitable Cryoprotectant for Accelerating the Dissolution Rate of Cilnidipine

Author(s): Vijay Agarwal*, Nitin Kaushik and Surya Goel

Volume 13, Issue 5, 2023

Published on: 25 July, 2023

Article ID: e220623218147 Pages: 10

DOI: 10.2174/2210681213666230622100611

Price: $65

Abstract

Background: The research on poorly aqueous-soluble drugs of BCS class II such as Cilnidipine (CLD) demands significant improvement in their aqueous solubility and dissolution rate. Such requirements may be fulfilled by adapting the nanocrystal approach with considering the various challenges.

Objective: The prime purpose of this research work was to develop, optimize and characterize the nanocrystal of the poorly aqueous soluble drug (CLD) using the antisolvent-precipitation ultrasonication method. Such a method was followed for rapid re-dispersion of drugs in water with improving their dissolution rate.

Methods: In this study, the different nanosuspension formulations were prepared using varying concentrations of three stabilizers - Pluronic F-68, Pluronic F-127, and HPMC-15cps, as selected stabilizer candidates. The selected and optimized formulation was followed by a lyophilization process with the incorporation of two selected distinct cryoprotectants - Mannitol and Lactose. The obtained nanocrystals were evaluated for their physical appearance, aqueous re-dispersibility, and particle size. Additionally, the optimized nanoformulation was also evaluated for morphology, dissolution rate, assay, drug entrapment efficiency, and drug loading content. The in vitro dissolution of optimized drug nanocrystal was done in the phosphate buffer solution of pH 6.8 and compared with bulk CLD and a physical mixture of CLD and pluronic F-68.

Results: For optimizing drug nanosuspension, the effect of pluronic F-68 and cilnidipine concentration was investigated, and the optimal values were 0.3% w/v and 5 mg/ml, respectively. Mannitol-containing nanocrystals exhibited a white crystalline powder having a particle size of 154 nm and a good polydispersity index (0.217). Nanocrystals also demonstrated an excellent re-dispersibility in deionized water after manual shaking and no particles were observed at the bottom of the container till 15 days. Such optimized formulation also indicated an increase in dissolution rate in comparison to bulk CLD and their physical mixture with pluronic F-68. It released approximately 72.25% of the drug within 90 minutes while bulk CLD and physical mixture released only 31.24% and 30.37% of the drug, respectively at the same time. The drug assay method indicated that only 92% of the drug was present in optimized nanocrystals after the transformation of nanosuspension into nanocrystals which was less than the initial amount. In this research, the experimental work also analyzed that optimized nanocrystal has only 28.6% of drug loading content.

Conclusion: The selected method and cryoprotectant have ability to develop the aqueous re-dispersible nanocrystal for enhancing the dissolution rate and water solubility of CLD-like poorly soluble drugs.

Keywords: Nanosuspension, nanocrystals, cilnidipine, lyophilization, dissolution rate, stability.

Graphical Abstract

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