ElectrosprayedShellac–Salt Nanoparticles forImproved Intestinal Dissolution and pH-Responsive Drug Release

Abstract This study aimed to develop and optimize shellac–salt (SHL–salt) nanoparticles using the electrospraying technique. A central composite design (CCD) was employed to systematically evaluate the effects of shellac concentration, salt conversion degree, and applied electrical voltage on the average particle size, size distribution, and solubility of the prepared nanoparticles. The optimized formulation─comprising 20% (w/w) shellac, 100% salt conversion degree, and an applied voltage of 15 kV─produced nanoparticles with an average particle size of 758.00 nm and a narrow size distribution of approximately 94.44 nm, along with markedly enhanced solubility at intestinal pH 6.8. Diclofenac sodium (DS) was selected as a model drug to assess encapsulation efficiency, drug loading capacity, and drug release behavior following incorporation into the nanoparticle matrix. The optimized nanoparticles exhibited high encapsulation efficiency (97.63%) with a drug loading capacity of 4.88%. Physicochemical characterization using powder X-ray diffractometry (PXRD) and Fourier-transform infrared spectroscopy (FTIR) confirmed that DS was present in an amorphous state and molecularly dispersed within the shellac–salt matrix. In vitro dissolution studies under simulated gastrointestinal conditions showed no drug release in acidic medium; however, DS-loaded shellac–salt nanoparticles exhibited significantly faster drug release at intestinal pH compared with DS-loaded shellac acid nanoparticles. In summary, the application of CCD-based statistical optimization enabled the successful fabrication of drug-loaded shellac nanoparticles, demonstrating their potential as promising carriers for improved intestinal dissolution.