Abstract
The RPMI 2650 and Calu-3 cell lines have been previously evaluated as models of the nasal and airway epithelial barrier, and they have demonstrated the potential to be used in drug permeation studies. However, limited data exist on the utilization of these two cell models for the assessment of nasal formulations. In our study, we tested these cell lines for the evaluation of in vitro permeation of intranasally administered drugs having a local and systemic effect from different solution- and suspension-based formulations to observe how the effects of formulations reflect on the measured in vitro drug permeability. Both models were shown to be sufficiently discriminative and able to reveal the effect of formulation compositions on drug permeability, as they demonstrated differences in the in vitro drug permeation comparable to the in vivo bioavailability. Good correlation with the available bioavailability data was also established for a limited number of drugs formulated as intranasal solutions. The investigated cell lines can be applied to the evaluation of in vitro permeation of intranasally administered drugs with a local and systemic effect from solution- and suspension-based formulations.
Highlights
When drugs are administered nasally to achieve a local or a systemic effect, it is difficult to clinically observe their interaction with the nasal mucosa in terms of uptake into or diffusion through the epithelium
The RPMI 2650 and Calu-3 cell lines are among the simplest models applicable, and we have previously demonstrated that these two cell lines grown at an air–liquid (A–L) interface are highly useful for distinguishing the permeability of low or moderately permeable compounds dissolved in pure balanced salt solution from the permeability of those with high permeability designation [7,8]
The analogy of utilizing the biopharmaceutical classification system (BCS) with the gastrointestinal absorption, which is very helpful with the permeability classification of orally administered drugs, is not truly applicable to the intranasally administered formulations, since the dilution of the formulation on the nasal mucosa is much lower compared to the intestinal situation
Summary
When drugs are administered nasally to achieve a local or a systemic effect, it is difficult to clinically observe their interaction with the nasal mucosa in terms of uptake into or diffusion through the epithelium. Performing permeability studies is necessary to predict nasal drug absorption and elucidate the transport mechanisms through the nasal epithelial barrier. While the biopharmaceutical classification can be convenient to estimate the systemic absorption, which can indicate efficacy, or the undesired systemic exposure indicating safety of an intranasally administered drug, in vitro models of the nasal mucosa are needed for formulation development of novel and generic drugs. The analogy of utilizing the biopharmaceutical classification system (BCS) with the gastrointestinal absorption, which is very helpful with the permeability classification of orally administered drugs, is not truly applicable to the intranasally administered formulations, since the dilution of the formulation on the nasal mucosa is much lower compared to the intestinal situation
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