Delivery of poorly soluble compound has become a major challenge in the pharmaceutical industry, especially in discovery. Many enabling formulation technologies can help to improve the solubility of these drug candidates. However, every compound/project is unique. Take away the best formulation strategy and technique to use that is compound value appropriate, development phase appropriate.
Salts present a unique opportunity at fixing solubility/dissolution related exposure and/or solid form related challenges. However the drive to progress molecules with low basic pKa (to address safety concerns) in the discovery setting increases risks associated with the design of a robust solid dosage form (namely disproportionation to the base as drug substance or drug product). Relationship between pKa, pHmax, and salt disproportionation will be discussed. How to assess this risk and mitigation strategies will be presented
The presentation will be focused in the areas of protein drug delivery, device design and development and the increasing importance of software/connectivity for future delivery devices.
Therapeutic peptides, proteins, and macromolecular drugs represent highly efficacious approaches for the pharmacologic treatment of human diseases. However, current administration of such drugs continues to be bolus injection which is inconvenient, painful and can lead to variable dosing. In this talk, I will discuss nanoporous materials that can be used to deliver proteins to the eye as well as nanostructured surfaces that enhance the permeability of macromolecules across epithelial cells in response to direct contact. New systems that can deliver proteins and peptides in a stable and controlled manner will have great potential to impact therapeutic development in the future
Phlebitis of a parental formulation is one of the main concerns for patient compliance. It has two major causes, one is the physical precipitation of the compound in blood stream after administration, and another one is chemically irritation due to the compound chemical entity.
In this study, the phlebitis issue of phase I formulation of compound A was due to its poor solubility. Physical precipitation occurred after formulation intravenous injection. In order to minimize precipitation induced phlebitis, pH combination with cosolvents, surfactants, and Cyclodextrins were used to screen the formulation. L-lactic acid and D-Glucuronic acid are the two counter ions show better solubility of compound A. Both hydroxyl- β-cyclodextrin (HP-β-CD) and sulfobutylether- β-cyclodextrin (SBE- β-CD) have shown further enhancement of the solubility combining with either lactic acid or glucuronic acid. An in vitro dynamic precipitation and an in vivo rabbit ear models have been used to investigate the potential of precipitation and phlebitis of the promising new formulations, there is a correlation between in vitro and in vivo findings. Based on both in vitro and in vivo data, the formulation composed of 40% SBE--β-CD, 50mM Glucuronic acid, and 13mg/ml compounds A has shown significant improvement of phlebitis compared to phase 1 formulation.