Abstract
The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2–10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale.
Highlights
The inclusion of excipient in formulations has seen an evolution from the traditional concept of inert component alongside the active ingredient to the functional and essential constituent of pharmaceutical dosage forms [1]
Nano forces and surface energies obtained from atomic force microscopy (AFM) measurements were compared to the bulk tablet characteristics including their influence on tabletability, Heckel profiles and solid state polymorphic and thermal properties
Functionalised Atomic force microscopy (AFM) probe with an excipient/active pharmaceutical ingredients (APIs) particle was used to obtain force-distance curves when indented upon another particle
Summary
The inclusion of excipient in formulations has seen an evolution from the traditional concept of inert component alongside the active ingredient to the functional and essential constituent of pharmaceutical dosage forms [1]. The widely utilised model of Heckel (1961) for powder deformation under pressure provided the scientific community with an important tool for understanding the mechanical properties of excipients [6]. Evidence of the micro/nanoscale features and adhesion forces of tableting excipients is crucial to develop a mechanistic understanding of their functionality in formulation development of ODTs. The study investigates interparticulate adhesive/cohesive interactions of commonly used ODT excipients including microcrystalline cellulose (MCC) and D-mannitol to understand the mechanisms affecting product functionality. Two model active pharmaceutical ingredients (APIs) with different mechanical and physico-chemical properties were chosen to investigate the adhesion within tablets. Nano forces and surface energies obtained from atomic force microscopy (AFM) measurements were compared to the bulk tablet characteristics including their influence on tabletability, Heckel profiles and solid state polymorphic and thermal properties. Surface topography and particle roughness were examined using AFM and SEM for the nano and microscopic features respectively
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