Abstract
Abstract: :
Purpose:The ocular bioavailability of some drugs, e.g. Fluorescein, can be increased significantly by adminstration in an ophthalmic lyophilisate carrier (1,2), but the adhesion between the lyophilisate and the carrier is variable if it is freeze–dried in a conventinal batch process. Neither the freezing nor the drying process be controlled with the degree of precision required for this drug delivery system when temperature profiles in the drying chamber depend upon the location of samples on shelves. Methods: A new lyophilization technique where only one unit is frozen and dried in a small chamber at any time under closely controlled conditions (3,4) solves this problem. Lyophilization is converted to a quasi–continuous operation by simultaneous, time–staggered operation of several drying chambers and the cycle time for each drop is reduced to less than 20 min ( about 1/50 of the batch process) by reducing the residual gas pressure to less than 10–2 mbar, minimizing the distance between the condenser surface and the samples and supplying the heat of sublimation directly to the frozen drops by radiation. Results: The surface temperature of the lyophilisates measured by their infrared emission is used for feedback–control of freezing and drying. The adhesion between the lyophilisates and the carrier membranes depends upon the freezing rate, which is controlled by the rate of evacuation. Condenser surfaces with accumulated ice can be replaced periodically and de–iced offline so that the length of production runs is not limited by technical constraints. Conclusions:The development of the fast precision freeze drying technique is a prerequisite for the reproducible manufacturing of ophthalmic lyophilisate carriers on an industrial scale. Since the volume of production is controlled by the addition or removal of more chambers of the same dimensions to or from an automated loading system and by the length of production runs, there is no need for a process scale–up. A modification of the FPFD process is particularly suited for sensitive proteins and other biotechnology products in containers. References: 1. Lux A et al. Br.J.Ophthalmol.. 87(3) 436 (2003) 2. Süverkrüp R et al. US patent 6,228,381 (8 May 2001) 3. Süverkrüp R et al. Patent application PCT EP/ 10359 (18 September 2003). 4. Maier S: Doctoral dissertation, Bonn 2003
Keywords: pharmacology • conjunctiva • cornea: clinical science