Development of an in vitro solubility test as a tool for predicting lung retention of poorly water soluble compounds



Development of an In Vitro Solubility Test as a Tool for Predicting Lung Retention of Poorly Water Soluble Compounds

Stefani Mariarita1, Cesari Nicola 1, Corsaletti Roberto1, Fioni Alessandro1, Saccani Francesca1, Volta Roberta1, Brogin Giandomenico1 & Puccini Paola1

1Chiesi Farmaceutici S.p.A., Largo Belloli 11/A, Parma, 43122, Italy


Background: The prediction of pulmonary exposure after inhalation of a drug is one of the key objectives for the success of a novel inhalable drug candidate. This study focuses on the determination of an apparent solubility (Sapp) value that may be used to study the impact of solubility on the drug candidate lung mean retention time (MRT) in order to support lead candidate selection. Methods: An in vitro solubility test in simulated lung fluid (SLF) was developed to measure Sapp. The Sapp value was determined by the diffusion of the dissolved amount from a drug-saturated solution through a membrane, which provides the separation between the donor and the receiver (sampling) compartments. In order to evaluate the validity of the test, different compounds with poor water solubility and different solid state were tested. Results: The test can provide different values of Sapp for the same compound, based on the different solid states of the powder. The values correlated well with the in vivo lung mean residence time (MRT) after intra-tracheal administration in rats. Conclusion: The Sapp value seems promising in predicting the impact of solubility on drug candidate lung MRT in the drug discovery phase.