Design Optimization and Evaluation of Solid Lipid Nanoparticles of Azelnidipine for the Treatment of Hypertension.

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.