Dosage forms freeze-dried formulations

Final dosage form The finished formulated product it may be freeze-dried and contain excipients, which should have been shown not to affect stability adversely. 

Hyperspectral imaging of freeze-dried solid-dosage formulations have been recently published [135]. The ability to characterize both the morphological and chemical properties of a freeze-dried formulation is a critical element to the complete description the dosage forms studied. 

Vries et al. [3.59] described the development of a stable parenteral dosage form of the cytotoxic drug E 09. E 09 dissolves poorly in water and its solution is unstable. With the addition of 200 mg of lactose per vial containing 8 mg of E 09, an optimum formulation was developed with respect to solubility, dosage of E 09 and length of the freeze drying cycle. DSC studies have been used to select the most effective parameters. The freeze dried product remains stable for 1 year when stored at 4 °C in a dark environment. 

Although excipients are the non-active ingredients, they are indispensable for the successful production of acceptable solid dosage forms. The important roles played by excipients in tablets and capsules, freeze-dried, and spray-dried powders, as well as powder aerosol formulations, were discussed. Some recent applications of excipients in controlled, release formulations for biologicals were also highlighted. Finally, incompatibility problems attributable to excipients were considered with an emphasis on the indirect role of excipients through moisture distribution. 

Lyophilization (Freeze Drying) Lyophilization is most frequently used for heat-labile dosage forms that are unstable in aqueous formulation. The principle of lyophilization can be seen by reference to the phase equilibrium diagram for water (Fig. 15). Water at atmospheric pressure and ambient temperatures is stable in its liquid phase at lOO C the liquid phase attains an equilibrium with its vapor phase. Above 100 C water is stable in its vapor phase. At atmospheric pressures and 0 C the solid (ice) and liquid phases of water are in equilibrium with each other. At vacuum pressures a temperature (the eutectic point) can be reached where the three phases, solid, liquid, and vapor are all in equilibrium with each other. At even lower temperatures and pressures the solid phase comes into equilibrium with the liquid phase. The significance of this is that an aqueous solution can be concentrated by evaporation (sublimation) at low pressures without any necessity for significant heat input. 

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