TRANSFORMING GROWTH-FACTOR-ALPHA (TGF-ALPHA) IN A SEMISOLID DOSAGE FORM - PRESERVATIVE AND VEHICLE SELECTION

The selection of an ideal semisolid vehicle for growth factors present s a challenge. Some antimicrobial agents are known to delay wound heal ing. The objective of this investigation was to identify appropriate p reservatives and vehicles for TGF-alpha. Criteria for acceptance are n oninterference with the mitogenic activity of TGF-alpha as well as ade quate product preservation. Vehicles considered were o/w creams, ointm ents, and a gel. Combinations of six preservatives were tested. Select ion was determined using both microbial preservative challenge and TGF -alpha mitogenic assay. In the former, 10 species of microorganisms we re inoculated into formulation samples. At selected time intervals, it was determined whether colonies decreased, increased, or remained con stant. In the mitogenic assay, samples of either preservatives or form ulation prototypes were introduced to TGF-alpha-stimulated fibroblast cell cultures. Mitogenesis was determined by measuring H-3-dThd uptake into newly synthesized DNA. As preservatives, sorbic acid and quatern ium-15 appear to satisfy both selection criteria. A thermosetting gel appears most promising as vehicle.