CONTEXT: Flutamide (FLT) has poor aqueous solubility and low oral bioavailability. OBJECTIVE: Lyophilization monophase solution was used for preparing lyophilized dispersions of FLT with polyols and amino acids to increase its poor dissolution. METHODS: Physical properties and dissolution behavior of their physical mixtures and lyophilized dispersions were investigated. RESULTS AND DISCUSSION: The carriers increased the aqueous solubility of FLT but to a limited extent with arginine and glycine showing a linear A(L)-phase solubility diagrams. Gas chromatography indicated that residual tertiary butyl alcohol was in range of 0.007-0.023% (w/w) in the dispersions. In all dispersions, the crystal structure of FLT was confirmed using differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy. However, the percent drug crystallinity was found to decrease with increasing the carrier content. Infrared spectroscopy revealed no interaction between drug and carriers. The particle size of FLT dispersions ranged between 0.61 and 1.81 μm, with a high surface area (293.93-465.37 m(2)/g) and porosity (447.69-754.33 e(-3) mL/g). In addition, the poor flow properties of FLT were improved but to a limited extent. FLT dissolution from the dispersions was enhanced with 46.35% and 36.43% of FLT dissolved after 30 minutes from 1:5 FLT-mannitol and FLT-trehalose dispersions, respectively, compared with only 13.45% of pure FLT. On the other hand, after 30 minutes 38.57% and 46.78% of FLT was dissolved from 1:3 FLT-arginine and FLT-glycine dispersions, respectively. CONCLUSION: These data suggest that polyols and amino acids might be useful adjuncts in preparation of immediate-release formulations of FLT.
CONTEXT: Flutamide (FLT) has poor aqueous solubility and low oral bioavailability. OBJECTIVE: Lyophilization monophase solution was used for preparing lyophilized dispersions of FLT with polyols and amino acids to increase its poor dissolution. METHODS: Physical properties and dissolution behavior of their physical mixtures and lyophilized dispersions were investigated. RESULTS AND DISCUSSION: The carriers increased the aqueous solubility of FLT but to a limited extent with arginine and glycine showing a linear A(L)-phase solubility diagrams. Gas chromatography indicated that residual tertiary butyl alcohol was in range of 0.007-0.023% (w/w) in the dispersions. In all dispersions, the crystal structure of FLT was confirmed using differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy. However, the percent drug crystallinity was found to decrease with increasing the carrier content. Infrared spectroscopy revealed no interaction between drug and carriers. The particle size of FLT dispersions ranged between 0.61 and 1.81 μm, with a high surface area (293.93-465.37 m(2)/g) and porosity (447.69-754.33 e(-3) mL/g). In addition, the poor flow properties of FLT were improved but to a limited extent. FLT dissolution from the dispersions was enhanced with 46.35% and 36.43% of FLT dissolved after 30 minutes from 1:5 FLT-mannitol and FLT-trehalose dispersions, respectively, compared with only 13.45% of pure FLT. On the other hand, after 30 minutes 38.57% and 46.78% of FLT was dissolved from 1:3 FLT-arginine and FLT-glycine dispersions, respectively. CONCLUSION: These data suggest that polyols and amino acids might be useful adjuncts in preparation of immediate-release formulations of FLT.
Authors: Ahmed O Elzoghby; Shaimaa K Mostafa; Maged W Helmy; Maha A ElDemellawy; Salah A Sheweita Journal: Pharm Res Date: 2017-06-22 Impact factor: 4.200