Development of buccal application forms is gaining increasing interest in recent years, mostly driven by the insight that enabling formulations may help to overcome limitations as well as the need for patient-oriented medicines. A key characteristic of dosage forms is whether they can grant absorption of therapeutically relevant doses across the limited absorption area in the mouth and realistic time window. Despite the generally accepted paradigm to replace or at least reduce animal experiments, current transport studies towards oromucosal drug delivery still are dominated by in vivo or ex vivo animal studies. Only few groups have published pioneering transport experiments with alternative models avoiding the use of animals. The few studies indicate that there is increasing justification for the use of artificial membranes to replace the classical cell- and tissue-based systems. The artificial membranes need to be biomimetic and distinguish transport kinetics of dissociation states and molecule flexibility. It appears that dissociation states may be distinguished by silicone membranes, as well as by phospholipid based models (PAMPA variants and Permeapad®). Regarding other molecule properties such as flexibility, data are available demonstrating excellent IVIVR. Aim of the current review is to make the scientific community dealing with oromucosal drug formulation development aware of the opportunities provided by non-cellular artificial membranes.