Research and development of phamaceutical dosage forms.

The development of a suitable formulation and a freeze-dry cycle for a pharmaceutical dosage form requires knowledge of some basic properties such as (1) eutectic temperature, if one exists, (2) temperature effect on solubility, (3) degree of supercooling, (4) heat transfer properties of the frozen product and (5) equipment design and equipment capability. Basic work with several inorganic and organic salts shows that eutectic temperature is a function of the melting point and the differential heat of solution of a drug. From a knowledge of these parameters, a mathematical expression can be used to estimate eutectic temperature. The desired characteristics which can be achieved by proper formulation of the solution to be freeze-dried and by employing optimum freeze-drying cycles include an intact cake, sufficient strength, uniform color and rapid reconstitution. By utilizing resistivity measurements to determine eutectic temperature and supercooling properties it is possible to reformulate products, increase batch sizes and reduce overall times for freeze-drying cycles.