Title:Improved Transdermal Delivery of Anti-hypertensive Drug Loaded
Nanostructured Lipid Carriers: Statistical Design, Optimization, Depiction
and Pharmacokinetic Assessment
Volume: 19
Issue: 7
Author(s): Ananda Kumar Chettupalli*, Purnachandra Rao Avula and Vivek Chauhan
Affiliation:
- Department of Pharmaceutics, Center for nano medicine, School of Pharmacy, Anurag University, Venkatapur, Ghatkesar,
Medchal, Hyderabad, Telangana, 500088, India
Keywords:
Lercanidipine, nanostructured lipid carriers, hot homogenization, ultrasonication technique, ex vivo gastrointestinal, permeability experiments, Box-Behnken study design, pharmacodynamic research.
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.
