A new freeze-drying technique for processing biological materials

Abstract

Wet granulation and dry blending are standard techniques used in tablet formulation. Both techniques impose limitations on the ability to produce homogeneous tablets with rapid dissolution and controllability of the matrix for active ingredients. This report describes the development and application of a new freeze-system using a swirling bath of Freon-12 to process sensitive biological materials. The frozen beads produced with this process are subsequently freeze-dried and may be used to produce precise tablets. The ultra rapid freezing (7-14 milliseconds) provided by the Freon-12 process yiels amorphous homogeneous spheres by retarding component migration which permits precise control of pH and redox potential in the final product. Dissolution of tablets prepared by this Du Pont process is so rapid (8-12 seconds) that a special testing technique is required for measurement of dissolution time. Improved recoveries of activity have been demonstrated for sensitive biological materials compared to conventional freeze-drying. The optimization of droplet sizes is controlled by injection rate, stream diameter and surface velocity of the Freon-12 bath. Droplet size control permits attainment of weight precision in the range of 0.6 +/- 0.06% for a final 50 mg tablet. This compares with a tablet weight precision of 1% to 2% typical of dry blending and wet granulating. Potential applications of this technology include pharmaceuticals and the production of ultra precise reagent tablets for the Du Pont Automatic Clinical Analyser.