Can formulation and drug delivery reduce attrition during drug discovery and development--review of feasibility,benefits and challenges

Drug discovery and development has become longer and costlier process.The fear of failure and stringent regulatory review process is driving pharmaceutical companies towards“me too”drugs and improved generics(505(b)(2))fillings.The discontinuance of molecules at late stage clinical trials is common these years.The molecules are withdrawn at various stages of discovery and development process for reasons such as poor ADME properties,lack of efficacy and safety reasons.Hence this review focuses on possible applications of formulation and drug delivery to salvage molecules and improve the drugability.The formulation and drug delivery technologies are suitable for addressing various issues contributing to attrition are discussed in detail.

Flow behavior and deposition study of pollen-shape carrier particles in an idealized inhalation path model

Pollen-shape （spiked sphere） hydroxyapatite （HA） particles for drug carrier application are studied. The particle shape and size effect on flow characteristics and deposition are assessed. The pollen-shape HA particles are synthesized to have comparable size as typical carrier particles with mean diameter of 30-50 μm and effective density less than 0.3 g/cm^3. The flow behaviors of HA and commonly used lactose （LA） carrier particles are characterized by the Carr＇s compressibility index （CI）. The HA particles have lower CI than the LA particles for the same size range. The flow fields of HA and LA carrier particles are measured in an idealized inhalation path model using particle image velocimetry （PLY） technique. The particle streamlines indicate that a large portion of particles may deposit at the bending section due to inertial impaction and gravitational deposition. The flow field result shows that HA particles give smaller separation regions than the LA particles for the same size range. The pollen-shape HA particles are found to be able to follow the gas flow in the model and minimize undesired deposition. Deposition result confirms the bending section to have the most deposition. Deposition is found to be a function of particle properties. An empirical correlation is derived for the deposition efficiency of the pollen-shape particles as a function of particles Stokes number.