Synergistic effect of miscible cellulose-based microparticles and pH modulators on the bioavailability of a weakly...

This study aimed to evaluate the miscibility of cellulose derivatives to improve the release rate and stability of microparticles containing the weakly basic drug itraconazole (ITZ). We also investigated the effect of some organic acids on the microenvironmental pH (pH_m) and the release rate of ITZ from the cellulose-based microparticles. The synergistic effect of cellulose-based microparticles and pH_m modulators on the bioavailability of ITZ compared with the reference product was investigated in a rabbit model. Differential scanning calorimetry and Fourier-transform infrared spectroscopy (FTIR) analysis showed that ITZ, hydroxypropyl methylcellulose, and hydroxypropyl methylcellulose phthalate were miscible at a ratio of 1.5:3:1 (w/w/w), and the stability of the microparticles was maintained for 6 months under accelerated conditions. In addition, X-ray diffraction, FTIR, and scanning electron microscopy were used to characterize the properties of the microparticles. Through the titration technique and determination of pH_m, the combination of fumaric acid and maleic acid (1:2, w/w) was found to be the most effective pH_m modulator for microparticles. The integration of cellulose-based microparticles and pH_m modulators showed a synergistic effect on the flux and relative bioavailability of ITZ and its active metabolite OH-ITZ (182.60 % and 217.67 %, respectively) when compared with the reference product.