Title:Design Optimization and Evaluation of Solid Lipid Nanoparticles of
Azelnidipine for the Treatment of Hypertension
Volume: 18
Issue: 1
Author(s): Tejas Dugad and Abhishek Kanugo*
Affiliation:
- Department of Pharmacy, SVKM’s NMIMS School of Pharmacy and Technology Management Shirpur, Dhule, 425405,
India
Keywords:
Solid lipid nanoparticles, Azelnidipine, hypertension, Box-Behnken design, oral delivery, DSC.
Abstract:
Background: Solid lipid nanoparticles (SLN) are the most promising lipid-based drug delivery
to enhance poorly water-soluble molecules' solubility, bioavailability, and therapeutic efficacy.
Azelnidipine (AZN) is a calcium channel blocker widely recommended for treating high blood pressure,
but its activity is restricted due to high lipophilicity and poor solubility in the GIT. The current
research focused on developing the SLN of AZN and thereby improving the absorption, bioavailability,
and therapeutic efficacy in hypertension which is a leading cause of death worldwide. Recent patents
on SLN were available as U.S. Patent,10,973,798B2, U.S. Patent 10,251,960B2, U.S. Patent
2021/0069121A1, U.S. Patent 2022/0151945A1.
Methods: SLN was developed by hot melt emulsification and ultrasonication method using glyceryl
monostearate (GMS) as solid lipid and Poloxamer 188 as a surfactant to stabilize colloidal dispersion.
Results: Box-Behnken model was utilized, which predicted 13 batches in which concentration of GMS
(X1), Poloxamer 188 (X2) and sonication time (X3) were considered independent parameters. The particle
size (Y1) and entrapment efficiency (Y2) were dependable parameters, and optimized batch F2
showed a particle size of 166.4 nm, polydispersity index of 0.40 and zeta potential of -13.7 mV. The
entrapment efficiency was observed at 86.21%. FTIR spectra confirm the identity and compatibility
with the formulation components. The differential scanning calorimetry (DSC) confirmed the absence
of melting point and interpreted that AZN was entirely incorporated in the lipid matrix and transformed
from crystalline to amorphous. The ANOVA for the particle size (p-value: 0.0203), % EE (p-value:
0.0271) was found significant. The in-vitro drug release showed a sustained release pattern for about
12 h. The AZN-loaded SLN was lyophilized and intended for oral delivery.
Conclusion: AZN-loaded SLN was developed by the hot melt emulsification method, which accelerated
the solubility and bioavailability and was released sustainably for treating hypertension.