Development of Dosage Forms and Delivery Systems for Anti Tumor Agents

The offerors propose to furnish all services, qualified personnel, materials, equipment, and facilities not otherwise provided by the Government (compounds assigned by the Government to be studied will be provided by the NCI) as needed to perform the work described in the following outline: 1. Determine the solubility profile of the supplied bulk drug substance in various physiologically acceptable aqueous vehicles and certain water miscible and least-toxic organic solvents. 2. Develop novel approaches for intravenous delivery of drugs exhibiting inadequate solubility and/or stability in aqueous solutions. 3. Develop suitable stability-indicating assays to detect the bulk drug substance subject to a variety of experimental conditions including the formulation per se, heat, light, oxygen, moisture, and other parameters. 4. Prepare kinetic profiles to predict the stability of the drug substance in solid state, in various physiologically acceptable aqueous vehicles and certain organic solvents. Determinations of pKa and partition coefficient of drug substances will also be performed. 5. Apply the solubility and stability enhancement approaches when needed to prepare experimental dosage formulations on a small scale (50-150 units) for subsequent therapeutic and toxicological evaluation by the NCI in animals. Pack, label and ship the experimental products according to procedures supplied by the Government. 6. Evaluate the experimental dosage form under simulated use conditions (i.e., completeness and clarity of the reconstituted solution after freeze drying, stability of this solution per se and after dilution with intravenous fluids in glass bottles and in polyvinylchloride (PVC) bags. 7. Carry out a short term stability study of the finished dosage form under accelerated stability condition at 50°C, 37°C, and 25°C and under refrigeration conditions for 1 year.