The focus of this research work was to develop a melt granulation technique to enhance solubility,\ndissolution rate and associated flowability concerns of Ibuprofen. Hydrophilic excipients like xylitol\nand lactose anhydrous were added to the binary mixture of conventional low melting surfactant\nPoloxamer 407 and Ibuprofen. Physical mixtures of Ibuprofen and Poloxamer 407 were prepared\nin ratios of 1:0.25, 1:0.5 and 1:0.75 using a water-jacketed high shear mixer. For each ratio of\nIbuprofen and Poloxamer 407, xylitol and lactose anhydrous were added separately at two levels\n(75 mg and 150 mg) per unit dose containing 200 mg drug. Phase solubility studies revealed\nlinearity in drug solubility enhancement with Poloxamer 407 concentration. In vitro dissolution\nstudies were carried out for drug, physical mixtures (PM) and melt granules (MG) for all ratios in\nde-ionized water and 0.1 N HCl (pH=1.2). Solid state characterization was performed using Fourier\ntransform infrared spectroscopy (FTIR), modulated differential scanning calorimetry (mDSC) and\n powder X-ray diffraction (PXRD) methodologies. Powder rheology studies were performed\nconventionally by measuring Carr�s index and Hausner�s ratio. Basic flowability energy values were\ncalculated using a powder rheometer to corroborate flowability data measured by conventional\nmethods. Particle morphological studies were done by Scanning electron microscope (SEM) and\nFluid imaging technologies. In-vitro dissolution studies showed approximately 7 fold drug release in\nwater and 19 fold drug release in acidic media for MG 1:0.75 at hydrophilic excipient level of 150\nmg compared to that of neat Ibuprofen in respective dissolution media. mDSC and PXRD data\nconfirms crystalline nature of drug in the formulations. FTIR data confirms no interactions between\ndrug and excipients used during processing. Particle morphology analysis confirms absence of\nrhombic Ibuprofen crystals in formulations. Dissolution rate and solubility enhancement was seen\ndue to synergistic effects of Poloxamer 407 and hydrophilic excipients incorporated in formulations.
Loading....