A novel Posaconazole oral formulation using spray dried solid dispersion technology: in-vitro and in-vivo study

SD (solid dispersion) technology is one of the well-recognized solubility enhancement methods; but the use of versatile carriers in ASD (amorphous SD) to achieve the added advantage of modified release along with solubility improvement is an emerging area of exploration. Spray drying is a widely used technology with excellent scalability and product attributes. The SD carriers explored were Soluplus^®, possessing excellent solubilization properties that may enhance bioavailability and is suitable for innovative processing, and Gelucire 43/01, a lipid polymer utilized in a non-effervescent-based floating gastro-retentive DDS for the modified release of API. The CPPs of spray drying were screened during preliminary trials, and the formulation variables were optimized using a 3² Full Factorial Design. All nine batches were evaluated for % yield, % drug content, flow properties, floating behavior, saturation solubility, and in-vitro drug release in 0.1 N HCl. The optimized batch characterized based on DSC (differential scanning calorimetry) and PXRD (powder X-ray diffraction) confirmed the amorphous nature of entrapped drug in SDD (spray-dried dispersion). Particle size analysis and SEM (scanning electron microscopy) demonstrated micron size irregular shaped particles. Residual solvent analysis by GCMS-HS confirmed the elimination of organic solvents from SDD. The optimized batch was found stable after 6 months stability study as per ICH guidelines. In-vivo roentgenography study in New Zealand white rabbit showed the residence of SDD in gastric environment for sufficient time. The pharmacokinetic study was performed in male Sprague-Dawley rats to determine the bioavailability of developed SDD based product in fasting and fed conditions, and to compare the data with marketed Noxafil formulation. The current research is focused on the development of a novel ternary SDD (spray-dried dispersion)-based gastro-retentive formulation for an anti-fungal drug Posaconazole.