Predicting local drug availability of locally acting lozenges: From method design to a linear level A IVIVC.

Lozenges are commonly applied in the treatment of sore throat. They often contain drugs intended to exert their effect locally in the oral cavity and throat. In the recent past, an increasing interest in development of generic products for locally acting lozenges could be noted. However, it was not clear, if therapeutic equivalence of locally applied, locally acting lozenges can be predicted based on results from in vitro studies. The aim of the present study was to determine an in vitro model that enables the assessment of local availability and bioequivalence of locally acting lozenges. Two novel in vitro dissolution setups (prototypes I and II) developed for simulating parameters relevant to drug release in the oral cavity, were screened for their biopredictivity. In the first step of the respective study in vitro mass loss and drug release of two marketed flurbiprofen lozenge formulations was determined. Then, an in vivo sucking study was performed to determine in vivo mass loss of the lozenges in 12 healthy volunteers. In the final step in vivo mass loss was correlated with in vitro mass loss resulting in a point to point (level A) correlation both lozenge formulations when using in vitro data obtained in the prototype II-based in vitro setup indicating biopredictivity of this in vitro model.