Effect of blending conditions on the tabletting performance of paracetamol–polyvinylpyrrolidone mixture
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AbstractMonoclinic paracetamol is notorious as a poorly compactible model drug that exhibits reduced plastic deformation, resulting in fragile tablets with high capping tendency during tabletting. Polyvinylpyrrolidone is a polymer that can act as effective additive to improve the stability and physicomechanical properties of paracetamol, since it could adsorb onto the surfaces of paracetamol crystals via hydrogen bonding. It is surprising however that the role of blending process on paracetamol–polyvinylpyrrolidone (PA–PVP) interactions and the tableting performance of PA–PVP mixture is ignored in many studies. Therefore, the purpose of this study was to investigate the influence of blending conditions of the physicochemical and mechanical properties of PA–PVP mixtures (95:5, w:w). PA–PVP mixtures were prepared using low shear (using V–shaped mixer for 30 min), medium shear (hand blending for 10 min), and dry high shear (Tefal high speed blender, Berkshire, UK, for 1 min) blending conditions. The high shear blender consists of two faced flat knife-like blades (6.5 cm × 1.5 cm) rotating at ~500 rpm in a bowel of 186 cm2). The results showed that all PA–PVP mixtures demonstrated improved tabletting compared to commercial paracetamol, regardless of the blending method. PA–PVP mixtures processed using high shear blending conditions demonstrated the best compactibility at a range of compaction pressures. For example, the mixtures processed using lower shear, medium shear and high shear blending conditions produced tablets with tensile strengths of 0.37 MPa, 0.38 MPa, and 1.36 MPa respectively. Fourier transform infrared spectroscopy analysis showed that, with the increase in blending shear, there was a reduction in absorption intensities (i.e. increased band broadening) between 3150 cm-1 and 3250 cm-1 compared to the sharp peak observed with the commercial drug. This could be due to the higher level of hydrogen bond interaction obtained in the PA–PVP mixture processed by high shear blending in comparison to the mixtures processed by low and medium shear blending. Powder X-Ray diffraction analyses showed PA–PVP mixture processed by high shear blending to have a slightly reduced degree of crystallinity compared to the mixtures processed by low and medium shear blending. PA–PVP mixture processed using dry high shear blending showed higher bulk porosity than the mixtures processed using low shear and medium shear blending, as indicated by its lower bulk density (0.31 ± 0.01 g/cm3 versus (0.66 to 0.69) g/cm3). Particle blending is a critical process during the preparation of interactive mixtures for tableting. Blending alters the physicochemical and mechanical properties of PA–PVP mixture. Future studies will concentrate on engineering paracetamol-polyvinylpyrrolidone mixtures with optimised physicochemical and mechanical properties.
TypeMeetings and Proceedings
Description1st International Electronic Conference on Oral Drug Delivery