Conceptualisation, Development, Fabrication and In Vivo Validation of a Novel Disintegration Tester for Orally Disintegrating Tablets

Abstract

Disintegration time is the key critical quality attribute for a tablet classed as an Orally Disintegrating Tablet (ODT). The currently accepted in vitro testing regimen for ODTs is the standard United States Pharmacopeia (USP) test for disintegration of immediate release tablets, which requires a large volume along with repeated submergence of the dosage form within the disintegration medium. The aim of this study was to develop an in vivo relevant ODT disintegration test that mimicked the environment of the oral cavity, including lower volume of disintegration medium, with relevant temperature and humidity that represent the conditions of the mouth. The results showed that the newly developed Aston test was able to differentiate between different ODTs with small disintegration time windows, as well as between immediate release tablets and ODTs. The Aston test provided higher correlations between ODT properties and disintegration time compared to the USP test method and most significantly, resulted in a linear in vitro / in vivo correlation (IVIVC) (R 2 value of 0.98) compared with a “hockey stick” profile of the USP test. This study therefore concluded that the newly developed Aston test is an accurate, repeatable, relevant and robust test method for assessing ODT disintegration time which will provide the pharmaceutical industry and regulatory authorities across the world with a pragmatic ODT testing regime.

Digital Image Disintegration Analysis: a Novel Quality Control Method for Fast Disintegrating Tablets

“…Higher gelatin to D-mannitol ratio in tablets has been observed to result in a longer disintegration time (37,38), although the basis of this effect was not investigated. The disintegration process starts by wetting (39) and FDT will be wetted by saliva and moisture absorbed from air, which has a humidity of 90 to 95% in the oral cavity (18). Moisture uptake is enhanced by higher gelatin concentrations in edible films due to the amorphous nature of this polymer (40).…”

“…Over the last 20 years, efforts have been made to design in-vitro procedures resembling the in-vivo disintegration environment of FDTs, such approaches have been based on texture analysis (TA) (13), CCD cameras (charged-coupled device) ( 14), Kyoto models (KYO) (15), charged-coupled devices (16), Tricorptesters (17) and the Aston test (18). There are limitations associated with all of the recent in-vitro Fig.…”

“…Other disintegration assays such as Tricorptester and the Aston tests use a flow of disintegration medium of 6 mL/min and 10 mL/min, respectively (17,18). Such flows of disintegration medium overestimate the volume that a tablet will be exposed to in the timeframe in which it disintegrates.…”

“…Such flows of disintegration medium overestimate the volume that a tablet will be exposed to in the timeframe in which it disintegrates. Finally, many of the new assays model the process of disintegration with the incorporation of a mechanical perturbation to replicate forces associated with mastication, such as the TA test (5 kg over 60 s) and the Aston test (50 g for a fixed time) (13,16,18). The disintegration measurement while applying a force on the formulation does not replicate the disintegration forces encountered during clinical use.…”

Recent Formulation Advances and Therapeutic Usefulness of Orally Disintegrating Tablets (ODTs)

“…Furthermore, the Aston test was able to differentiate between different ODTs with small disintegration time windows, as well as between immediate release tablets and ODTs. As per the researchers, this newly developed Aston test provided higher correlations between ODT properties and disintegration time compared to the USP test method and resulted in a linear in vitro/in vivo correlation compared with a “hockey stick” profile of the USP test [ 60 ].…”