Design and utilization of the drug-excipient chemical compatibility automated system.

To accelerate clinical formulation development, an excipient compatibility screen should be conducted as early as possible and it must be rapid, robust and resource sparing. This however, does not describe the traditional excipient compatibility testing approach, requiring many tedious and labor intensive manual operations. This study focused on transforming traditional practices into a completely automated screening process to increase sample throughput and realign resources to more urgent areas, while maintaining quality. Using the developed system, a complete on-line performance study was conducted whereby drug-excipient mixtures were weighed, blended and subjected to accelerated stress stability for up to 1 month, followed by sample extraction and HPLC analysis. Compared to off-line traditional study protocols, the system provided similar relative rank order results with equivalent precision and accuracy, while increasing sample throughput. The designed system offers a resource sparing primary screen for drug-excipient chemical compatibility for solid dosage form development. This approach allows risk assessment analysis, based upon formulation complexity, to be conducted prior to the commitment of resources and candidate selection for clinical development.

The road map to oral bioavailability: an industrial perspective.

Optimisation of oral bioavailability is a continuing challenge for the pharmaceutical and biotechnology industries. The number of potential drug candidates requiring in vivo evaluation has significantly increased with the advent of combinatorial chemistry. In addition, drug discovery programmes are increasingly forced into more lipophilic and lower solubility chemical space. To aid in the use of in vitro and in silico tools as well as reduce the number of in vivo studies required, a team-based discussion tool is proposed that provides a 'road map' to guide the selection of profiling assays that should be considered when optimising oral bioavailability. This road map divides the factors that contribute to poor oral bioavailability into two interrelated categories: absorption and metabolism. This road map provides an interface for cross discipline discussions and a systematic approach to the experimentation that drives the drug discovery process towards a common goal - acceptable oral bioavailability using minimal resources in an acceptable time frame.