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

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).

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Materials

The formulations also contained a combination of two of the following fillers — microcrystalline cellulose (MCC) (Avicel® PH-102, FMC International), mannitol (Pearlitol® 200 SD, Roquette), lactose (FastFlo® 316, Foremost Farms USA), and dibasic calcium phosphate anhydrous (DCPA) (Anhydrous Emcompress ®, JRS Pharma). Croscarmellose sodium (CCS) (FMC International) and magnesium stearate (Mallinckrodt) were added to each formulation as a disintegrant and a lubricant, respectively.

Natalie Maclean, Ibrahim Khadra, James Mann, Alexander Abbott, Heather Mead, Daniel Markl, Formulation-dependent stability mechanisms affecting dissolution performance of directly compressed griseofulvin tablets, International Journal of Pharmaceutics, Volume 631, 2023, 122473, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2022.122473.

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