ABSTRACT
INTRODUCTION Freeze-drying of pharmaceutical and biological solutions to produce an elegant stable powder has been a standard practice employed to manufacture many marketed pharmaceutical and biological products for over 50 years. The vast majority of these products are lyophilized from simple aqueous solutions. Water is typically the only solvent of significant quantity that is present, which must be removed from the solution via the freeze-drying process. However, frozen water (ice) is not the only frozen liquid that can sublime under reduced pressures. Numerous organic and mineral solvents have been shown to possess this property (1). It is also noteworthy that during the freeze-drying of pharmaceutical or biological products it is not unusual for small quantities of organic solvents to be present in either the active pharmaceutical ingredient or one of the excipients. These low levels of organic solvent are commonly found because they may be carried through as part of the manufacture of these individual components since the ingredient may be precipitated, crystallized, or spray dried from organic solvents. Therefore, many freeze-dried products may be dried from solutions, which contain low levels of a variety of organic solvents. Additionally, there may be instances where freeze-drying from substantial quantities of organic solvents or mixtures of water and organic solvent may offer the formulation scientist advantages over simply drying from an aqueous solution. An example of at least one pharmaceutical product on the market that has utilized an organic cosolvent system during freeze-drying is CAVERJECT1
Sterile Powder (2,3). This particular product has been successfully manufactured by freeze-drying from a 20% vol/vol tert-butanol/water cosolvent system. Another example is the anticancer drug Imexon. This drug, which is undergoing clinical testing, utilized dimethyl sulfoxide (DMSO) as a formulation vehicle prior to lyophilization (4).
