In vitro assays are an important part in drug development, as they often allow prediction of the behavior of a new drug or drug formulation in patients without performing studies in humans or animals. This study is interested in developing and validating an in vitro assay that predicts the dissolution rate of particles of orally inhaled drug products (OIDP) in the lung, thereby allowing predictions of the in vivo behavior of inhaled drug formulations as it relates to the interrelationship between drug/formulation properties, dissolution of drug in the pulmonary lining fluid and the pulmonary effects and, after absorption, systemic side effects. The proposed study can be divided into three parts: First, the proposed dissolution device will be optimized with respect to the dissolution medium to be used (a dissolution medium reflecting the conditions in the lung is desired), drug amount and mechanism of applying drug to testing device , design of the overall dissolution device and other factors. After optimization of the system, the second part of the study will assess a wide range of commercially available and experimental drug formulations that differ in physicochemical properties, delivery (metered dose inhaler, dry powder inhaler nebulizer), formulation (solution, powder, suspension) and physicochemical properties of the drug compound (hydrophilic, lipophilic....). In the third step of the proposed work, pharmacokinetic studies present in the literature will be analyzed with respect to the rate with which OIDPs enter the systemic circulations in humans. These data are than correlated to data generated within the dissolution test experiments. It is intended to provide a strong relationship between in vitro dissolution data and in vivo absorption properties of OIDPs.
Development of inhaled drugs is complex as indicated by the very limited availability of generic inhalation drug products. This proposal is interested in developing an in vitro tool that would facilitate the successful development of inhalation drugs by predicting its performance in patients from in vitro experiments. The tool is intended to help optimizing formulation development and insure the quality of the product during the manufacturing.