The ideal parenteral formulation should comprise an isotonic solution with pH close to the physiological value of 7.4, and contain only pharmaceutically acceptable ingredients. Meeting these criteria, however, is very often precluded by the low aqueous solubility of the drug. The number of poorly soluble drugs has increased dramatically during the last few decades and resulted in a great variety of parenteral products: in addition to simple solutions, these include microemulsions, emulsions, liposomes, particulate systems, complexes, etc.
When the parent drug is a weak base or acid, the solubility problem can be readily overcome by simple adjustment of the pH to low or high values and salt formation. However, preparing a solution of the drug alone rarely results in a robust formulation as small variations in pH may lead to drug precipitation. In addition, extreme pH values are harmful to patients and might require more complicated ways of administration, such as premixing of stock solutions in the administration set prior to infusion in the body (Y-setup).
The present work describes some of the most common problems related to colloid and interface science when developing an i.v. formulation. The focus is mainly on drugs with extremely low solubility and high melting point (strong crystal lattice). The behavior of both ionizable and nonionizable molecules is examined and analyzed. The paper also presents a critical discussion of each step of the formulation development process, including the in-vitro studies needed to evaluate the formulation behavior in the administration sets.