How Do Orodispersible Tablets Behave in an In Vitro Oral Cavity Model: A Pilot Study.

Orodispersible tablets (ODTs) offer rapid disintegration of the dosage form when placed on the tongue, which leads to fast release of the active pharmaceutical ingredient. Despite increased use in diverse patient populations, there have been numerous challenges associated with ODTs. One such concern is the lack of standardised assessment of disintegration behaviour. In the European Pharmacopoeia, 'orodispersibles' are defined as such if disintegration time is faster than 3 min. Common in vitro measurement methods only provide single time point data and have limited physiological accuracy. To determine more bio-predictive disintegration kinetics, a bench-top in vitro oral cavity model (OCM) was modified and piloted to assess disintegration of three ODTs of differing hardness. All ODTs disintegrated similarly within the OCM-surface breakdown/swelling, initial 'wash away' and final 'wash away'. The distinct advantage presented within this pilot study using the OCM is the opportunity to ascertain disintegration behaviour profiles of ODTs by evaluating changes in the observable area during simulated oral processing. The model could be implemented as a decision-support tool during the early stages of the drug design process to improve acceptability and further understand ODT disintegration behaviour.

Experimental and Computational Investigation of the IDDSI Flow Test of Liquids Used in Dysphagia Management.

The International Dysphagia Diet Standardisation Initiative (IDDSI) flow test, using a standard 10-mL syringe, is being adopted in many countries for clinical measurement of the consistency of drinks. The working hypothesis is that thickening drinks to retard flow can be advantageous for individuals who struggle to cope with thin drinks. This study assesses how the IDDSI test relates to rheology and clinical knowledge of physiological flows during swallowing. With no pre-existing analytical solution for internal flow through the syringe, a computational model was designed, incorporating rheometry data from a variety of Newtonian and non-Newtonian liquids. The computational model was validated experimentally across the range of liquids but the technique showed limitations in simulating dripping and cohesiveness. Gum-based liquids which were strongly shear-thinning (0.12 < n < 0.25) showed plug-flow characteristics with 90% of the shear occurring in only 22% of the radial dimension. Shear rates were maximal at the nozzle outlet (> 60 times higher than the barrel) and reached 7400/s for the thinnest gum-based liquid. Shear rheology data alone was unable to describe the flow of these drinks. The flow conditions in the test varied according to the type and consistency of liquid, relating to the desired clinical effect.

In Vitro Oral Cavity Model for Screening the Disintegration Behavior of Orodispersible Films: A Bespoke Design.

The availability of biorelevant methods for the disintegration study of pharmaceutical orodispersible dosage forms is required. The disintegration of orodispersibles should be assessed using in vitro methods that can combine biorelevant volumes of disintegration medium and mechanical stresses mimicking in vivo conditions. This study proposes an adaptation of a mechanical oral cavity model for the disintegration study of orodispersible films. A periodic compression is applied to the sample in the presence of a biorelevant volume of artificial salivary fluid. Four orodispersible film samples (P1, C1, P2, and C2), differing in polymer type and molecular weight, and Listerine® were tested and filmed during disintegration. An image analysis program was developed for the determination of the volume reduction of the film matrix over time, as a descriptor of film disintegration behavior. Samples P1 and Listerine® showed a volume reduction at 180 s of >90%, C1, P2, and C2 were 85%, 48%, and 37%, respectively. The model was able to detect differences in the disintegration behavior of the 4 samples, and results were comparable with the benchmark product. The concept of disintegration behavior of orodispersible films was introduced for the first time as an informative method for the study of orodispersible dosage form.