Evidence-Based Nanoscopic and Molecular Framework for Excipient Functionality in Compressed Orally Disintegrating Tablets

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.

A pragmatic approach for engineering porous mannitol and mechanistic evaluation of particle performance

“…Particle Size measurements were carried out using Sympatec (Clausthal-Zellerfeld, Germany) laser diffraction particle size analyzer according to the experimental procedure detailed in [20]. Volume mean diameter (VMD) was recorded.…”

“…Each powder (1000 mg) or tablet (500 mg) was placed into a micro sample cell and assessed for true volume and in turn true density. Detailed methodology is reported elsewhere [20]. Bulk density measurement for tablet was carried out and porosity (ε) calculated using Eq.…”

Predictive model for tensile strength of pharmaceutical tablets based on local hardness measurements

“…For example, it is well known that the macroscopic dissolution of tablets depends on the physicochemical properties of the micrometric powders such as contact angle, surface area and particle size (Tran et al, 2015;Leonardi and Salomon, 2013). In the same way, recent studies have been conducted on mechanical properties (Tejedor et al, 2015;Al-Khattawi et al, 2014;Sun, 2011;Narayan and Hancock, 2003). However, the relationship between mechanical properties at different scale is not yet fully understood.…”

Microparticle surface layering through dry coating: impact of moisture content and process parameters on the properties of orally disintegrating tablets

“…In addition, previous research from our group has stated that the needle shape of the particles of mannitol results in its low compactability . To further support the fragmentation pattern, AFM topographical analysis was performed which showed a considerable number of asperities that were liable to damage when slight force was applied using the AFM cantilever.…”

“…Good flow properties are a requirement for the successful manufacturing of tablets as it affects mixing, content uniformity, tablet compression and scale‐up operations . Flow properties of the materials tested were primarily affected by the size and shape of the particles within the powder, which in turn affected the cohesivity and the mechanical interlocking between the particles . Flow properties were evaluated before mixing/tabletting was carried out for the different MCC powders.…”