Characterization, optimisation and process robustness of a co-processed mannitol for the development of orally disintegrating tablets

Abstract

This is a study to fully assess a commercially available co-processed mannitol for its usefulness as an off-the-shelf excipient for developing orally disintegrating tablets (ODTs) by direct compression on a pilot scale (up to 4 kg). This work encompassed material characterization, formulation optimisation and process robustness. Overall, this co-processed mannitol possessed favourable physical attributes including low hygroscopicity and compactibility. Two design-of-experiments (DoEs) were used to screen and optimise the placebo formulation. Xylitol and crospovidone concentrations were found to have the most significant impact on disintegration time (p < 0.05). Higher xylitol concentrations retarded disintegration. Avicel PH102 promoted faster disintegration than PH101, at higher levels of xylitol. Without xylitol, higher crospovidone concentrations yielded faster disintegration and reduced tablet friability. Lubrication sensitivity studies were later conducted at two fill loads, three levels for lubricant concentration and number of blend rotations. Even at 75% fill load, the design space plot showed that 1.5% lubricant and 300 blend revolutions were sufficient to manufacture ODTs with ≤ 0.1% friability and disintegrated within 15 s. This study also describes results using a modified disintegration method based on the texture analyzer as an alternative to the USP method.

Keywords::

• Orally disintegrating tablets
• modified disintegration method
• lubricant sensitivity
• design space
• process robustness

Acknowledgements

The authors acknowledge Marie Pang and Jasminder Chana for their assistance with part of the data collection. DrPaul Goggin is thanked for his support of the Royal Pharmaceutical Society of Great Britain (RPSGB) pre-registration pharmacist program of which Marie Pang and Jasminder Chana were part of. Thomas Millgate is thanked for the statistical analysis, Gema Gelayo and Annmarie Gambrill for their contribution towards the modified disintegration method and Lincoln Bird for general analytical discussion.