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

Abstract

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 films 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 behaviour. Samples P1, and Listerine  showed a volume reduction at 180s of > 90%, C1, P2, and C2 were 85%, 48%, and 37% respectively. The model was able to detect differences in the disintegration behaviour of the four samples, and results were comparable with the benchmark product. The concept of disintegration behaviour of orodispersible films was introduced for the first time as an informative method for the study of orodispersible dosage form.

Image Analysis: A Versatile Tool in the Manufacturing and Quality Control of Pharmaceutical Dosage Forms

“…Redfearn et al studied orodispersible films in an in vitro oral model where image analysis was used to determine the volume reduction of the film matrix over time, which well describes the disintegration behavior of the film [ 77 ].…”

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

“…The OCM was re-programmed from the previous study [ 16 ] to perform regular compressions of the compliant silicone tongue against the hard palate. This motion simulated typical oral manipulation.…”

“…The accelerated testing conditions of the European Pharmacopoeia method expose all ODT surfaces to continuous fluid movement while the OCM method ensures that, like the human oral cavity, only a single large surface is exposed to SSF. Furthermore, drawing a direct comparison with other in vitro techniques for measuring disintegration time might not be appropriate because the measurement end points differ considerably [ 16 ].…”

“…As a result, a thin layer of SSF formed on the tongue surface with a continuous flow down the tongue in the anterior to posterior direction. Visual measurements of ODT disintegration within the cavity allowed for disintegration-time profiles to be established, which is an improvement on current in vitro tests that report a single degradation time [16]. A mobile phone (Apple iPhone X, Apple Inc., Cupertino, CA, USA) recording at 30 frames per second (fps) was positioned above the acrylic plate facing downwards.…”

“…To ascertain these more bio-predictive disintegration kinetics, a bench-top in vitro oral cavity model (OCM), previously developed to assess the flow properties of non-Newtonian fluids during swallowing [ 15 ], and modified to study orodispersible films (ODFs) under biorelevant mechanical stimulation and synthetic saliva interactions [ 16 ] was used.…”