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Current Drug Delivery

Author(s): Priyanka Maurya, Pawan Pandey, Samipta Singh, Alka Sonkar, Sonali Singh and Shubhini A. Saraf*

DOI: 10.2174/1567201818666210729104351

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Appraisal of Felodipine Nanocrystals for Solubility Enhancement and Pharmacodynamic Parameters on Cadmium Chloride Induced Hypertension in Rats

Page: [625 - 634] Pages: 10

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Abstract

Aim: Felodipine (FDP), an antihypertensive drug possesses low water solubility and extensive first-pass metabolism leading to poor bioavailability. This impelled us to improve its solubility, bioavailability, and pharmacodynamic properties through the Nanocrystal (NC) approach.

Methods: FDP-NC were prepared with Poloxamer F125 (PXM) by the antisolvent precipitation method. The experimental setup aimed at fine-tuning polymer concentration, the proportion of antisolvent to solvent, and the duration of ultrasonication for NC formulation.

Results: Optimized formulation was characterized for particle size, solubility, and PDI. Particle reduction of 74.96 times was achieved with a 9X solubility enhancement as equated to pure FDP. The morphology of NC was found to be crystalline through scanning electron microscopy observation. The formation of the crystal lattice in FDP-NC was further substantiated by the XRD and DSC results. Lowering of the heat of fusion of FDP-NC is a clear indication of size reduction. The stability studies showed no substantial change in physical parameters of the FDP-NC as assessed by particle size, zeta potential, and drug content.

Conclusion: The crystalline nature and improved solubility of FDP-NC improve the dissolution profile and pharmacodynamic data. The stability study data ensure that FDP-NC can be safely stored at 25°C. It is revealed that FDP-NC had a better release profile and improved pharmacodynamic effects as evident from better control over heart rate than FDP.

Keywords: Antisolvent precipitation, cadmium chloride, felodipine, heart rate variability, heat of fusion, crystallinity.

Graphical Abstract

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