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

 Maclean, Natalie, Ibrahim Khadra, James Mann, Alexander Abbott, Heather Mead, and Daniel Markl. "Formulation-dependent stability mechanisms affecting dissolution performance of directly compressed griseofulvin tablets." International Journal of Pharmaceutics 631 (2023): 122473.

full paper can be found at

https://www.sciencedirect.com/science/article/pii/S0378517322010286

Abstract

During drug product development, stability studies are used to ensure that the safety and efficacy of a product are not affected during storage. Any change in the dissolution performance of a product must be investigated, as this may indicate a change in the bioavailability. In this study, three different griseofulvin formulations were prepared containing microcrystalline cellulose (MCC) with either mannitol, lactose monohydrate, or dibasic calcium phosphate anhydrous (DCPA). The tensile strength, porosity, contact angle, disintegration time, and dissolution rate were measured after storage under five different accelerated temperature and humidity conditions for 1, 2, and 4 weeks. The dissolution rate was found to decrease after storage for all three batches, with the change in dissolution rate strongly correlating with the storage humidity. 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).

Terahertz spectroscopy

Terahertz time-domain spectroscopy was performed using a TeraPulse Lx Spectrometer (TeraView Ltd). The sample chamber was purged with nitrogen to remove moisture from the air during analysis. Samples were analysed using an optical delay of 200 ps and 30 averages. From the terahertz measurements, the refractive index and loss coefficient were obtained. Based on the spectra obtained, a frequency of 0.8 THz was selected for comparing the change in refractive index and loss coefficient across different conditions and timepoints. This frequency was selected as this point was free from peaks (caused by the tablet components) for all formulations.