The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of\ncommonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to\nelucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum\nproduct functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion\nforces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface\ntopography images (100 nm2ââ?¬â??10 mm2) and roughness data were acquired from AFM tapping mode. AFM data were related\nto ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration\ntesting, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and\nphysical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of\ntablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to\nmechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid\nstate investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during\ncompression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro\nfibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and\nmodel drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials\non the macro scale.
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