Development of novel lipid matrix for improved sustained release effect of a hydrophilic drug via response surface methodology

Abstract

The aim of this research was the constitution of the lipid matrix to achieve a sustained release effect of a hydrophilic drug by incorporating it into the lipid nanocarriers. Isoniazid (INH) was used as a model drug. Response Surface Methodology (RSM)-Central Composite Rotatable Design (CCRD) model was employed for this purpose. The formulation parameters were investigated for their effect on response variables of nanostructured lipid carrier (NLC) formulation. The optimized formulation was found to have encapsulation efficiency (EE) of 72.39 ± 1.39%, drug loading (DL) of 15.93 ± 0.30%, in vitro drug release (DR) of 66.35 ± 1.44%, and mean particle size (PS) of 306.4 ± 3.53 nm. Differential scanning calorimetry (DSC) and X-ray Diffraction pattern (XRD) analysis showed the loss of crystallinity of isoniazid in INH-NLC formulation. Transmission electron microscopy (TEM) images indicated that nanoparticles were loaded with drug and of slightly irregular shape. The release kinetics showed the highest R2 value for the Higuchi square root model resulted in a diffusion-controlled sustained drug release mechanism. The zeta potential (ZP) and polydispersity index (PDI) were found to be +19.08 ± 1.73 mV and 0.539 ± 0.06, respectively. Stability studies revealed that the formulations were most stable at all temperature conditions during a 6 months study. This study reports the successful constitution of the lipid matrix for pulmonary delivery to achieve a better-sustained release effect over 24 h and could be efficient in reducing the drug dose and regulating the dosage regimens.