Investigating the role of excipients on the physical stability of directly compressed tablets

Abstract

Stability studies are an integral part of the drug development process for any drug product. In addition to monitoring chemical degradation, the physical stability of a drug product must also be evaluated to ensure that the drug release and performance is not affected by storage. In this study, directly compressed tablets of 16 different formulations were exposed to an accelerated stability program to quantify changes in tablet breaking force, porosity, contact angle and disintegration time. Tablets were exposed to five different storage conditions from 37 ∘ C /30% relative humidity (RH) to 70 ∘ C /75%RH with testing after 2 and 4 weeks of storage. Each formulation contained two different fillers (47% w /w each), a disintegrant (5% w /w) and magnesium stearate (1% w/w). The results show that tablets stored at high humidity show increases in porosity and decreases in tensile strength, particularly if they contain a highly hygroscopic filler such as microcrystalline cellulose (MCC). For tablets stored at high temperature, the most commonly affected property was the tablet wettability, measured by sessile drop contact angle measurements. These results are considered in combination with the performance-controlling disintegration mechanism (Maclean et al., 2021) to identify the critical properties which influence the performance after storage.

The Effect of Humidity on the Dissolution Kinetics and Tablet Properties of Immediate-Release Tablet Formulation Containing Lamotrigine

“…Lower humidity in long term stability studies is 35%; in this study was lower humidity was adjusted at 30%. Generally, humidity conditions were chosen based on the study Maclean et al, where the role of excipients in the physical stability of tablets was investigated after being exposed to humidity of 30% and 75% [ 17 ]. A research protocol was created to uniquely mimic most possible conditions after repackaging the drug into dose administration aids (DAAs) in continental Europe.…”

Formulation-dependent stability mechanisms affecting dissolution performance of directly compressed griseofulvin tablets

“…was composed of a 1:1 ratio of two different fillers -MCC/mannitol, MCC/lactose, or MCC/DCPA. These formulations were selected to mimic the formulations of placebo tablets which were previously characterised with respect to their disintegration mechanism and physical stability (Maclean et al, 2021(Maclean et al, , 2022. Blends were prepared by mixing the fillers, disintegrant and griseofulvin in a bin blender (AB-015 bin blender, Pharmatech, UK) for 20 min with a blend speed of 20 rpm and agitator speed of 200 rpm.…”

“…The griseofulvin tablets were formulated to correspond to previous work on placebo tablets (Maclean et al, 2021(Maclean et al, , 2022Markl et al, 2021), which investigated the performance-and stability-controlling disintegration mechanisms of placebo tablets. The formulations selected maintained the same concentrations of disintegrant and lubricant (5% and 1% wt., respectively) and a filler ratio of 1:1, however, the total concentration of filler was reduced to allow 30% wt.…”

“…Previously, the change in physical properties and disintegration performance of 16 different placebo formulations was investigated before and after storage under five different temperature and humidity conditions (Maclean et al, 2021(Maclean et al, , 2022. It was found that the changes in disintegration could be related to the performance-controlling disintegration mechanism of the tablets prior to storage, for example, whether tablet disintegration was driven by swelling, dissolution of soluble fillers, or wettability and liquid-uptake.…”

“…The changes in physical properties of each formulation were found to relate to either the premature swelling (MCC/DCPA, MCC/lactose) or dissolution (MCC/mannitol) of particles during storage. These results are also discussed with consideration of the performance-and stability-controlling mechanisms of placebo tablets of the same formulations (Maclean et al, 2021;Maclean et al, 2022).…”