Solid dispersion of β-lapachone in PVP K30 and PEG 6000 by spray drying technique

Abstract

Beta-lapachone (βlap) is a naphthoquinone derived from Lapachol, a substance extracted from the Bignoniaceae family of trees, genus Tabebuia; found in the Northern and Northeastern regions of Brazil. βlap shows excellent pharmacological activity as an antiparasitic, antitumor, and anti-inflammatory drug, but its water solubility is low, which decreases its bioavailability. This work aims to evaluate the solubility and dissolution rate of βlap from solid dispersions obtained by the Spray Drying technique and compare them with the physical mixture (PM) of compounds. βlap solid dispersions were prepared with polyethylene glycol (PEG 6000) and polyvinylpyrrolidone (PVP K30) at 1: 2 (w/w) ratio and characterized by thermal analysis [differential scanning calorimetry (DSC)], X-ray powder diffraction (XRPD), Fourier transform infrared (FTIR), Scanning electron microscopy (SEM), solubility tests, dissolution profile assays and analyzed by mathematical models to link to the system properties. βlap/PVP solid dispersion provided a 15-fold increase in dissolution rate compared to pristine βlap in the first 5 min. The release constants obtained from Korsmeyer–Peppas and Weibull models demonstrate that βlap is released more rapidly from the PVP system produced by Spray Drying than by PM. The thermal analysis suggests that the βlap was successfully encapsulated into spherical shape and uniform size distribution microparticles produced by SD/PVP, as shown by the SEM technique. In addition, it afforded about 9-fold higher solubility than the free βlap. The results of DSC and XRD showed a tendency of the βlap crystallinity to decrease. FTIR showed intermolecular interaction between drug and polymer molecules (PVP and PEG). Thus, the results suggest that βlap/PVP-based solid dispersions can be successfully applied in pharmaceutical formulations.