Enhancing the Dissolution of Oral Dasatinib Tablets Using Zein–Hydroxypropyl Methylcellulose Solid Dispersions
Abstract
Zein has been used in several pharmaceutical applications because of its unique composition. It is an amphiphilic molecule that is biodegradable, biocompatible, and has adhesive, matrix-forming, and film-coating properties, making it a promising pharmaceutical excipient. Zein-based formulations have been investigated in tablet-coating, nanoparticulate delivery systems, and controlled-release formulations. However, to date, very few studies have been performed on the inclusion of zein in solid dispersion formulations to enhance drug dissolution. This study aimed to improve the dissolution of the weakly basic and poorly soluble oral dasatinib (used as a model) using zein–hydroxypropyl methylcellulose (HPMC) solid dispersion to achieve rapid disintegration and dissolution in the gastric pH. Using the spray-drying technique, four solid dispersions were prepared with different zein, HPMC, and dasatinib ratios. Subsequently, five different tablets were directly compressed using the previously prepared solid dispersions along with basic excipients. Various in vitro characterization analyses were performed to predict their behavior in vivo. Particle size measurement, tablet weight variation and content assay, disintegration, and dissolution studies were also performed. The results indicated that zein solid dispersion improved the disintegration and dissolution of dasatinib in the gastric media by reducing the drug particle size and the formation of the dasatinib amorphous state. Moreover, the tablets exhibited desirable properties in terms of high drug content, friability, and tensile strength. In conclusion, tablets comprising zein–HPMC solid dispersion showed improved properties; however, including a higher ratio of zein in the solid dispersion adversely affected the disintegration and release properties of formulations.
