• Part of the book series (AAPS, volume 3) Abstract A growing number of new therapeutic molecules are limited by low or erratic bioavailability due to poor water solubility. Because of the clinical demand for new and more efficacious anti-cancer, antiviral, and anti-infective drugs, many of these new drugs must be formulated for injection. Poor water solubility can be addressed by a range of formulation approaches such as pH manipulation, salt formation, and cosolvent and surfactant addition, or by more advanced techniques such as complexation, liposomal encapsulation, or nanosuspension. While remaining focused on drug solubility, issues such as buffering, tonicity, sterility, and drug ­product stability also must be considered when formulating injectable products. This chapter outlines a formulator’s approach toward development of an injectable drug product containing an active ingredient with poor solubility.

Marketed injectable products, listings of GRAS excipients, and techniques for enhancing solubility are offered as case studies to assist in the formulation process. Method • Prepare solutions of varying concentrations of PS80 (0, 2.5, 5, 10, and 20%) in citrate buffer with a pH of 4.3 and 8.4. • Perform solubility study by placing 0.5 mL of each solution into vials with excess flavopiridol. • Attach vials to rotator, place at 25°C, and rotate at 20 rpm for 6 days or until equilibrium solubility is achieved. (Note: The drug is stable for >2 months under these conditions). • Filter samples through 0.45-μm syringe filter membrane and check final solution pH. • Perform HPLC analysis of samples for potency (solubility) of flavopiridol.

Results • The solubility of flavopiridol in solution without surfactant was 1.37 mM and 0.055 mM at pH 4.3 and 8.4, respectively. • The solubility of a drug in the micelle is influenced by the micellar partition coefficient and drug water solubility. • Increasing the concentration of PS80 resulted in a substantial linear increase in drug solubility. The increase was considerably greater (up to ∼27 mM at 20% PS80) at pH 4.3, where the majority of drug is ionized. • Solubilization of the ionized drug by PS80 is more critical than that of the unionized species for increasing the overall solubility due to the increased water solubility resulting from the increased solubility of drug in the micelles. Download Free Grewe Scanner Interface Professional Development on this page. Pyramid Principle Minto Pdf Creator there. Method Capsule 2Solubilization of a PWS Drug using a Combination of Cosolvent and Surfactant. Method • Determine the solubility of ENA in cosolvent–water solutions with concentrations up to 50% (w/v).