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Current Drug Therapy

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ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

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Research Article

Improved Transdermal Delivery of Anti-hypertensive Drug Loaded Nanostructured Lipid Carriers: Statistical Design, Optimization, Depiction and Pharmacokinetic Assessment

Author(s): Ananda Kumar Chettupalli*, Purnachandra Rao Avula and Vivek Chauhan

Volume 19, Issue 7, 2024

Published on: 27 November, 2023

Page: [828 - 845] Pages: 18

DOI: 10.2174/0115748855267831231113112445

Price: $65

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Abstract

Background: The vasoselective calcium-channel blocker lercanidipine hydrochloride (LCH) is poorly absorbed orally (only 10% bioavailability) owing to its low solubility and hepatic metabolism. Because of the LCH's poor solubility and permeability, bioavailability is low and very variable, stable aqueous liquid formulations are challenging to create, and a uniform distribution of the medication is almost impossible to produce.

Objectives: The purpose of this research was to see whether an approach involving the development of nanostructured lipid carriers (NLCs) might be used to create an effective, innovative oral formulation of LCH. The efficacy of several synthetic and natural liquid lipids was compared using a hot homogenization-ultrasonication strategy.

Methods: Following initial improvements with hot homogenization and ultrasonication, the LCHloaded NLCs formulation was fine-tuned by Box-Behnken statistical analysis. The optimal LCHNLCs composition includes the lipid phase (2-4% w/v) of stearic acid and oleic acid, the surfactants poloxamer 188 (1%) and Tween 80(1%), and other ingredients.

Results: The optimized NLCs formulation was found to have mean vesicle sizes of 128.72 ± 1.59 nm, polydispersity indices of 0.169 ± 0.06, zeta potentials of -36.81 ± 0.42 mV, and entrapment efficiencies of 79.84 ± 0.11%. The optimized NLCs formulation released much more LCH (88.74 ± 4.62) than the LCH-suspension (36.84 ± 0.37%) in in-vitro drug release experiments lasting up to 24 hours. Ex vivo studies on the ability of LCH-NLCs to pass through the gut showed that drug permeation was much better than it was with plain LCH-solution. The in vivo pharmacodynamic analysis demonstrated that, compared to conventional LCH-suspension, NLCs released LCH more slowly and steadily over a longer time period.

Conclusion: These findings provide additional evidence that NLCs have great promise as a drug delivery technology for the treatment of hypertension, just as they show promise as a controlled release formulation for the treatment of LCH.

Keywords: Lercanidipine, nanostructured lipid carriers, hot homogenization, ultrasonication technique, ex vivo gastrointestinal, permeability experiments, Box-Behnken study design, pharmacodynamic research.

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