Extrusion as a process for the manufacture of completely water-soluble tablets for both small molecules and proteins

Abstract

Biologically active proteins and peptides are utilized for a variety of medical purposes, ranging from diagnostic tests to therapeutic medicines. Since the stability of these compounds in solutions is often limited, a rapidly soluble, stabilized solid form would be highly advantageous. A simple extrusion process is proposed as a method of manufacture for completely water soluble tablets, suitable for proteins and peptides. The objectives of this research were to determine the feasibility of manufacturing a completely water-soluble tablet by a mass extrusion process, and to examine the stability of a biologically active protein incorporated into the extruded tablets. Placebo tablets were manufactured by the addition of a solvent to a melted blend of polyethylene glycols, cooling and extruding through a round orifice. The resultant cylinder of product was dried and cut into segments to create tablets. Mixture experimental designs were used to examine the effects of each component, including a soluble marker compound in one study. Tablets containing a protein were manufactured in a similar manner, using an aqueous solution of the protein lysozyme. The activity of lysozyme was measured by a standard turbidity test, and the content of protein was measured by HPLC. The stability of the protein, both immediately after manufacture and over a two-month period, was examined. Completely water soluble tablets with acceptable characteristics were manufactured by mass extrusion on a small scale using a solvent-based process. General regions of extrudability were identified efficiently using a mixture design approach. The regions changed significantly with the presence of a soluble marker compound. The extrusion process is a simple procedure covering a broad range of applications: stabilization of a protein is one application. The protein lysozyme was incorporated into the extruded tablets and retained 100% activity after processing. Over two months, however, the protein degraded 20-45%, depending on the storage condition. This degradation rate of the protein in the tablets was approximately the same as that of lysozyme in solution. Alternative vehicles, soluble stabilizers, and proteins with various degradation pathways should be examined to improve the stability profile of the delivery system for proteins.